The World Market For Cardiovascular Diagnostics

Cardiovascular Diagnostics
5th
CARDIOVASCULAR DIAGNOSTICS
A KALORAMA INFORMATION MARKET INTELLIGENCE REPORT
The Cardiovascular Diagnostics Market has been prepared by Kalorama
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Copyright 2013 Kalorama Information

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Table of Contents
ii
C
CHAPTER ONE: EXECUTIVE SUMMARY ..........................................................1

Industry at a Glance ........................................................................................................... 1
Scope and Methodology ...................................................................................................... 3
Size and Growth of the Market ......................................................................................... 4
Key Issues and Trends Affecting the Market ................................................................... 6
Leading Market Participants ............................................................................................. 6
CHAPTER TWO: INDUSTRY OVERVIEW ..........................................................9

Introduction ......................................................................................................................... 9
Cardiovascular Anatomy .................................................................................................. 9
Heart............................................................................................................................. 9
Circulatory System ..................................................................................................... 11
Cardiac Cycle.................................................................................................................. 12
Coronary Circulation ...................................................................................................... 13
Cardiac Myocytes ........................................................................................................... 16
Molecular Contraction .................................................................................................... 16
Diseases of the Heart ......................................................................................................... 17
Ischemic Heart Disease................................................................................................... 17
Etiology ...................................................................................................................... 17
Pathophysiology ......................................................................................................... 17
Atherosclerosis ........................................................................................................... 18
Angina Pectoris .......................................................................................................... 21
Acute Ischemia and Myocardial Infarction Chronic .................................................. 22
Chronic Ischemic Cardiomyopathy ............................................................................ 23
Sudden Cardiac Death ............................................................................................... 23
Diagnostic Tests ......................................................................................................... 23
Valvular and Endocardial Diseases ................................................................................ 24
Mitral Valve Disorders ............................................................................................... 25
Aortic Valve Disorders ............................................................................................... 25
Rheumatic Heart Disease ........................................................................................... 26
Endocarditis ............................................................................................................... 26
Pericardial Diseases ........................................................................................................ 27
Pericardial Effusion ................................................................................................... 27
Pericarditis ................................................................................................................. 27
Myocardial Diseases ....................................................................................................... 27
Myocarditis................................................................................................................. 28
Cardiomyopathy ......................................................................................................... 28
Congenital Heart Diseases .............................................................................................. 28
Atrial Septal Defect .................................................................................................... 29
Ventral Septal Defect.................................................................................................. 29
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iii
Pulmonary Stenosis..................................................................................................... 30
Aortic Stenosis ............................................................................................................ 30
Coarctation of the Aorta ............................................................................................. 30
Patent Ductus Arteriosus ............................................................................................ 30
Truncus Arteriosus ...................................................................................................... 31
Transposition of the Great Arteries ............................................................................ 31
Tricuspid Atresia......................................................................................................... 31
Congestive Heart Failure................................................................................................. 32
Etiology ....................................................................................................................... 32
Diagnostic Tests .......................................................................................................... 32
Cardiac Dysrhythmias ..................................................................................................... 33
Diagnostic Tests .......................................................................................................... 33
Hypertension ................................................................................................................... 33
Risk Factors ................................................................................................................ 34
Effects of High Blood Pressure ................................................................................... 35
CHAPTER THREE: ELECTROCARDIOGRAPHY ...........................................37

Introduction ....................................................................................................................... 37
Market Size and Growth................................................................................................... 40
CHAPTER FOUR: CARDIAC DIAGNOSTIC IMAGING ..................................43

Non-Invasive Cardiac Imaging ........................................................................................ 43
X-Ray .............................................................................................................................. 43
MRI ................................................................................................................................. 45
Ultrasound ....................................................................................................................... 47
Computed Tomography................................................................................................... 47
Electron Beam Computed Tomography ...................................................................... 48
Dual Source Computed Tomography.......................................................................... 49
Nuclear Cardiography ..................................................................................................... 49
Invasive Transcatheter Cardiac Imaging ........................................................................ 52
Cardiac Catheterization/Angiography Products .............................................................. 52
Intravascular Ultrasound ................................................................................................. 55
Optical Coherence Tomography ..................................................................................... 56
Electrophysiology ........................................................................................................... 57
Market Size and Growth................................................................................................... 58
Noninvasive Imaging ...................................................................................................... 58
Invasive Transcatheter Imaging ...................................................................................... 59
CHAPTER FIVE: CARDIAC DIAGNOSTIC POINT OF CARE TESTING ....63

Coagulation Testing ........................................................................................................ 64
Cholesterol Testing ......................................................................................................... 65
Total Cardiac Diagnostic Point-of- Care Market Size and Growth ............................. 68

Table of Contents
iv
CHAPTER SIX: CARDIAC MARKERS ................................................................71

Total Cardiac Markers Market Size and Growth ........................................................ 73
CHAPTER SEVEN: CARDIAC DIAGNOSTIC CONTRAST

AGENTS AND RADIOPHARMACEUTICALS ...................................................77
Contrast Agents .............................................................................................................. 77
Radiopharmaceuticals ..................................................................................................... 80
Total Cardiac Diagnostic Contrast Agents and Radiopharmaceuticals Market Size
and Growth ........................................................................................................................ 81
CHAPTER EIGHT: MARKET PARTICIPANTS.................................................87

Summary ............................................................................................................................ 87
Abbott Diagnostics ............................................................................................................ 90
Company Overview .................................................................................................... 90
Products ..................................................................................................................... 90
Acusphere .......................................................................................................................... 92
Alere, Inc ............................................................................................................................ 94
Company Overview ................................................................................................... 94
Products ..................................................................................................................... 94
Locations .................................................................................................................... 96
Analogic Corp.................................................................................................................... 97
Bayer Healthcare .............................................................................................................. 99
Company Overview .................................................................................................... 99
Products ..................................................................................................................... 99
Bracco SpA ...................................................................................................................... 101
Cardinal Health ............................................................................................................... 102
CardioDX, Inc ................................................................................................................. 103
Company Overview .................................................................................................. 103
Products ................................................................................................................... 103
C.R. Bard ......................................................................................................................... 104
Danaher Corporation ..................................................................................................... 105
Products ................................................................................................................... 105
dpiX, LLC ........................................................................................................................ 107
FluoroPharma Medical................................................................................................... 109
GE Healthcare ................................................................................................................. 111
Products and Services .............................................................................................. 112
Locations .................................................................................................................. 112
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v
Hitachi Medical Systems America, Inc. ......................................................................... 113
Johnson & Johnson ......................................................................................................... 114
Products .................................................................................................................... 115
King Pharmaceuticals ..................................................................................................... 116
Lantheus Medical Imaging ............................................................................................. 117
LipoScience, Inc ............................................................................................................... 119
Products .................................................................................................................... 119
Medison America, Inc. .................................................................................................... 120
Molecular Insight Pharmaceuticals, Inc. ....................................................................... 122
Nanosphere, Inc. .............................................................................................................. 124
Products .................................................................................................................... 124
PerkinElmer ..................................................................................................................... 125
Philips Healthcare ........................................................................................................... 126
Products and Services ............................................................................................... 127
Locations................................................................................................................... 128
Roche Diagnostics US (Div of Roche) ............................................................................ 129
Products .................................................................................................................... 129
Locations................................................................................................................... 130
Shimadzu Corp ................................................................................................................ 131
Siemens Medical Solutions.............................................................................................. 132
St. Jude Medical .............................................................................................................. 134
Products .................................................................................................................... 135
Terumo Medical Corporation ........................................................................................ 136
TomTec Imaging Systems GmbH .................................................................................. 137
Toshiba America Medical Systems, Inc ......................................................................... 139
Trixell ............................................................................................................................... 142
Vascular Solutions ........................................................................................................... 144
Vermillion, Inc ................................................................................................................. 146
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vi
Products ................................................................................................................... 146
Volcano Corp ................................................................................................................... 147
Products ................................................................................................................... 147
Locations .................................................................................................................. 148
CHAPTER NINE: MARKET TRENDS AND SUMMARY ...............................149

Market Overview ............................................................................................................ 149
Market Revenues by Product Type ............................................................................... 152
Global Cardiac Diagnostic Market Analysis by Region ............................................... 155
United States ............................................................................................................ 155
Europe ...................................................................................................................... 156
Japan ........................................................................................................................ 156
Rest of World ............................................................................................................ 156
Competitive Analysis.................................................................................................... 161
CHAPTER TEN: INDUSTRY DEVELOPMENTS

AND TECHNOLOGIES ........................................................................................165
Demographics .................................................................................................................. 165
Cardiovascular Disease Worldwide .............................................................................. 167
European Cardiovascular Disease Statistics ................................................................. 168
US-Specific Population Demographics ........................................................................ 169
Population Over Age 65 ........................................................................................... 170
Life Expectancy ........................................................................................................ 172
Increasing Incidence of Disease............................................................................... 174
New Cardiac CT Device ................................................................................................. 175
CT Spots Seeds of Heart Disease in Healthy Patients .................................................. 176
Contrast Agent Toxicity ................................................................................................. 177
Contrast Agents Generic Competition .......................................................................... 177
MRI Catheter Guidance ................................................................................................. 178
Healthcare Reform.......................................................................................................... 179
CHAPTER ELEVEN: CONCLUSIONS ...............................................................183

LIST OF COMPANIES ..........................................................................................185

CHAPTER ONE:EXECUTIVE SUMMARY

Summary Table ................................................................................................................... 4
Global Cardiac Diagnostics Market Analysis, 2010-2017 ............................................... 4
Summary Figure ................................................................................................................. 5
Global Cardiac Diagnostics Market Analysis: 2010-2017 ............................................... 5
CHAPTER THREE: ELECTROCARDIOGRAPHY

Table 3-1 ............................................................................................................................ 40
Total Electrocardiography Testing Market Analysis, 2010-2017................................... 40
Figure 3-1 ........................................................................................................................... 41
Total Electrocardiography Testing Market Analysis, 2010-2017................................... 41
CHAPTER FOUR: IMAGING MARKET

Table 4-1 ............................................................................................................................ 62
Non-Invasive Cardiac Imaging Market Analysis, 2010-2017 ........................................ 62
Table 4-2 ............................................................................................................................ 68
Invasive Transcatheter Cardiac Imaging Market Analysis, 2010-2017 ......................... 68
Table 4-3 ............................................................................................................................ 70
Total Cardiac Diagnostic Imaging Market Analysis, 2010-2017 ................................... 70
Figure 4-1 ........................................................................................................................... 71
Total Cardiac Diagnostic Imaging Market Analysis, 2010-2017 ................................... 71
CHAPTER FIVE: CARDIAC POINT OF CARE TESTING

Table 5-1 ............................................................................................................................ 75
Cardiac Coagulation Testing Market Analysis, 2010-2017 ............................................ 75
Table 5-2 ............................................................................................................................ 77
Cardiac Cholesterol Testing Market Analysis, 2010-2017 ............................................. 77
Table 5-3 ............................................................................................................................ 78
Total Cardiac Diagnostic POC Testing Market Analysis, 2010-2017 ........................... 78
Figure 5-1 ........................................................................................................................... 79
Total Cardiac Diagnostic POC Testing Market Analysis, 2010-2017 ........................... 79
viiiCopyright 2013 Kalorama Information

List of Exhibits
ix
CHAPTER SIX: CARDIAC MARKERS

Table 6-1 ............................................................................................................................. 84
Total Cardiac Markers Market Analysis, 2010-2017 ...................................................... 84
Figure 6-1 ........................................................................................................................... 85
Total Cardiac Markers Market Analysis, 2010-2017 ...................................................... 85
CHAPTER SEVEN: CARDIAC CONTRAST AGENTS ......................................87

Table 7-1 ............................................................................................................................. 95
Total Cardiac Diagnostic Contrast Agent and Radiopharmaceuticals Market Analysis,
2010-2017 ....................................................................................................................... 95
Figure 7-1 ........................................................................................................................... 96
Total Cardiac Diagnostic Contrast Agent and Radiopharmaceuticals Market Analysis,
2010-2017 ....................................................................................................................... 96
CHAPTER NINE: MARKET TRENDS AND SUMMARY

Table 9-1 ........................................................................................................................... 150
Global Cardiac Diagnostics Market Analysis, 2010-2017 ............................................ 150
Figure 9-1 ......................................................................................................................... 151
Global Cardiac Diagnostics Market Analysis: 2010-2017 ............................................ 151
Table 9-2 ........................................................................................................................... 153
Global Cardiac Diagnostics by Type Revenues and Percent of Market 2012 (in
millions of dollars at the manufacturers level)............................................................. 153
Figure 9-2 ......................................................................................................................... 153
Global Cardiac Diagnostics by Type Revenues and Percent of Market 2012............... 153
Table 9.3 ........................................................................................................................... 154
Global Cardiac Diagnostic by Type Revenues and Percent of Market 2017 (in millions
of dollars at the manufacturers level)........................................................................... 154
Figure 9-3 ......................................................................................................................... 154
Global Cardiac Diagnostics by Type Revenues and Percent of Market 2016............... 154
Table 9-4 ........................................................................................................................... 158
Global Cardiac Diagnostics Market Revenues by Region 2012 ($millions) ................ 158
Figure 9-4 ......................................................................................................................... 158
Figure 9-5 ......................................................................................................................... 159
Global Cardiac Diagnostics by Region Percent 2012 (%) ............................................ 159
Table 9-5 ........................................................................................................................... 159

List of Exhibits
x
Figure 9-6 ......................................................................................................................... 160
Figure 9-7 ......................................................................................................................... 161
Global Cardiac Diagnostics by Region Percent 2017 (%) ............................................ 161
Table 9-6 .......................................................................................................................... 162
Estimated Global Cardiac Diagnostics Manufacturer Market Share 2012 .................. 162
Figure 9-8 ......................................................................................................................... 163
Estimated Global Cardiac Diagnostics Revenues and Market Share 2012 .................. 163
CHAPTER TEN: INDUSTRY DEVELOPMENTS AND TECHNOLOGIES..165

Table 10-1 ........................................................................................................................ 166
Total Global Population by Selected Geographical Region, 2000 - 2050 .................... 166
Table 10-2 ........................................................................................................................ 168
Cardiovascular Deaths by World Region 2008 ............................................................ 168
Table 10-3 ........................................................................................................................ 169
The U.S. Population, 1980-2020 .................................................................................. 169
Figure 10-1 ....................................................................................................................... 170
The US Population, 1980-2020 (in millions)................................................................ 170
Table 10-4 ........................................................................................................................ 171
Percent U.S. Population Over Age 65 by Year............................................................. 171
Figure 10-2 ....................................................................................................................... 172
Estimated Population by Age Group, 2000 and 2050................................................... 172
Table 10-5 ........................................................................................................................ 173
Average U.S. Life Expectancy in Years 1980, 2004, 2006, 2010, 2011 (years) .......... 173
Figure 10-3 ....................................................................................................................... 174
Average U.S. Life Expectancy in Years 1980, 2004, 2006, 2010, 2011 ...................... 174
APPENDIX ...............................................................................................................185

Executive Summary
INDUSTRY AT A GLANCE
Economic conditions in several markets within the global cardiac
diagnostics market remained challenging in 2012. Demand for cardiovascular
diagnostics slowed during the historical period due to a weakened global economy,
cost cutting measures and healthcare reform issues. However, demographics
worldwide and an aging world society remain primary factors in growth. By 2020,
16 percent of the US population will be over the age of 65, up from 13% in 2010.
People are also living longer, needing more health care, further fueling the market.
In 1980, the US life expectancy at birth was 74 years, today the average American
lives to be 78 years old.
Advancing technologies have also led to increased use of less invasive and
more sophisticated cardiac diagnostics. A trend toward preventive care involving
risk factor knowledge and earlier treatment of cardiovascular disease has been a
driving factor.
There are five categories of cardiac diagnostics that Kalorama assessed in
this market. These include:
x
ECG
Cardiac Diagnostic Imaging
Cardiac Diagnostic Point-of-Care

1Copyright 2013 Kalorama Information
One: Executive Summary

2
Cardiac Markers
Cardiac Diagnostic Contrast Agents and Radiopharmaceuticals
Cardiac diagnostic imaging is the largest category within the global cardiac
diagnostic market with 50.5% of the total revenues.
Cardiac contrast agents and radiopharmaceuticals accounted for 20.8% of
revenues in 2012 and cardiac markers accounted for 14.3% of revenues. Growth in
these two areas has been growing.
ECG equipment accounted for 8.4% of revenues in 2012 and is expected to
continue to increase as the elderly population grows and the incidence of heart
disease continues to increase.
Overall, increasing incidence of heart disease and an aging population,
which typically require more diagnostic procedures, will continue to fuel growth for
cardiac diagnostics throughout the forecast period.
The economic recession had a significant impact on the cardiac diagnostics
market, which experienced falling sales in key geographies. The difficulties were
mostly felt on the high-end imaging equipment segment after many health care
institutions delayed or outright cancelled equipment purchases. There also was a
concurrent decline in patient numbers as people skipped or deferred scans because
they lost jobs and health insurance coverage, or because of the high out-of-pocket
costs associated with cardiac imaging. Some growth in the market is attributed to
the continuous improvements in image quality, and to newer techniques for imaging
specific portions of the heart.
Growth rates in the United States, Europe and Japan have moderated due to
budgetary constraints, changes in reimbursement and a global economic slowdown.
However, in Rest of World markets spending on healthcare is increasing and there
is an increasing demand for medical technologies. This is especially apparent for
China, India, Latin America, the Middle East, and Brazil.


3
SCOPE AND METHODOLOGY

This report provides the reader with an overview of the global cardiac
diagnostics industry and the trends driving growth. Segments within the cardiac
diagnostic market include:
x
Electrocardiography including ECG testing, stress testing, Holter

monitoring, event monitoring and implantable loop.
Cardiac imaging including non-invasive X-Ray, MRI, CT,

ultrasound, and nuclear cardiography; and invasive /cardiac
catheterization/angiography, intravascular ultrasound, optical
coherence technology and electrophysiology.
Cardiac point-of-care including cholesterol testing and coagulation

testing
Cardiac markers
Cardiac contrast agents and radiopharmaceuticals
Included in the report are statistics influencing the industry, incidence of

cardiac and related diseases worldwide, demographics, life expectancy, and
company strategies. Information is presented as a global market. A market summary
includes a total market analysis. Also included is a competitive analysis of leading
cardiac diagnostic providers.
The information for this report was gathered using both primary and
secondary research including comprehensive research of secondary sources such as
company literature, databases, investment reports, and medical and business
journals. Telephone interviews and email correspondence were the primary method
of gathering information. For the purpose of this study, Kalorama Information
conducted interviews with more than 21 key industry officials, consultants, health
care providers, and government personnel. These sources were the primary basis in
gathering information specifically relating to revenue and market share data
presented in this report. Additional interviews were completed with relevant
company representatives including marketing directors, division managers, and
product representatives.


4
All market data pertains to the world market at the manufacturers level.
Revenues represent sales of diagnostics that pertain to the cardiovascular arena.
The base year for data was 2012. Historical data was provided for the years 2010
and 2011, with forecast data provided for 2012 through 2017. Compound annual
growth rates (CAGRs) are provided for the 2010-2012 and 2012-2017 periods for
each region and/or segment covered. Competitive analysis is provided for the year
2012. The forecasted market analysis for 2012-2017 was largely based on
demographic trends, new developments, company performance trends, merger and
acquisitions, and national expansion.
SIZE AND GROWTH OF THE MARKET

The global cardiac diagnostics market totaled approximately $13.2 billion
in 2012, increasing at a rate of 3.1% from $12.4 billion in 2010. There are several
trends which continue to influence growth in this market. The market is expected to
increase to approximately $16.6 billion in 2017, growing at a rate of 4.8%
throughout the forecast period. New technologies in testing will likely continue to
fuel growth in combination with an aging population, increasing cardiovascular
disease incidence and prevalence, and increasing life expectancy.
Summary Table
Global Cardiac Diagnostics Market Analysis, 2010-2017

Year
2010
2011
2012
2013
2014
2015
2016
2017
Revenues (millions$)
12,392.0
12,736.0
13,176.0
13,701.0
14,298.5
14,987.3
15,762.0
16,632.0
Percent Change
2.8%
335%
4.0%
4.4%
4.8%
5.2%
5.5%


5
Compound Annual Growth Rate
2010-2012
2010-2017
2010-2017
3.1%
4.8%
4.3%
Source: Kalorama Information
Summary Figure
Global Cardiac Diagnostics Market Analysis: 2010-2017
$18,000
$16,000
$14,000
$12,000
$10,000
$8,000
$6,000
$4,000
$2,000
$0
2010
2011
2012
2013
2014
2015
Calendar Year

2016

6
KEY ISSUES AND TRENDS AFFECTING THE MARKET

There are several primary issues and trends affecting the global cardiac
diagnostics market. Demographics, disease prevalence, and increasing life
expectancy will continue to fuel growth in the future. New developments will also
positively influence growth. Some of these issues are discussed in this study.
Issues and trends explored in this study include:
x
World Demographics
Aging Population
Increasing Life Expectancy
Increasing Incidence of Disease
New Cardiac CT Device
CT Spots Seeds of Heart Disease in Healthy Patients
Contrast Agent Toxicity
Contrast Agent Generic Competition
LEADING MARKET PARTICIPANTS

The global cardiac diagnostics market is competitive with a number of
providers. Companies remain competitive by offering a good selection of cardiac
diagnostic devices. Four companies, GE Healthcare, Siemens, Philips and Toshiba
dominate the industry with combined revenues of approximately $ 10.5 billion in
2012.
Several leading and unique market participants are discussed in this report
including:
Abbott Diagnostics
Acusphere
Analogic Corp
Bayer Healthcare

7
Bracco SpA
Cardinal Health
CardioDX
C.R. Bard
Danaher Corporation
dpiX
FluoroPharma Medical
GE Healthcare
Hitachi Medical Systems
Johnson & Johnson
King Pharmaceuticals
Lantheus Medical Imaging
LipoScience
Medison America
Molecular Insight Pharmaceuticals
Nanosphere
PerkinElmer
Philips Healthcare
Roche Diagnostics
Shimadzu
Siemens
St Jude Medical
Terumo Medical
TomTec Imaging Systems
Toshiba
Trixell
Vascular Solutions
Vermillion
Volcano

Industry Overview
INTRODUCTION
The primary function of the heart is to propel blood through the vessels of
the circulatory system. Along with the lungs, the heart works to distribute
oxygenated blood and nutrients to tissues and organs of the body.
Cardiovascular Anatomy
Heart
The heart is located in the mediastinum, suspended between the lungs,
behind the sternum, and in front of the vertebral column, thoracic aorta, and
esophagus. When seen from the front, the heart appears to be rotated to the left, so
that the right atrium and right ventricle are most anterior. The base of the heart
protrudes somewhat into the right side of the chest and is relatively fixed in place
by its attachments to the great vessels. The apex of the heart lies primarily in the left
anterior chest wall. With each heartbeat, a characteristic thrust, or point of maximal
impulse (PMI), is generated and can be palpated where the apex strikes against the
chest. The PMI is normally located on the left side of the chest where the fifth
intercostal space and midclavicular line intersect. Variations in heart size and
position within the chest may be related to age, body size, shape, weight, or
pathologic conditions of the heart and other nearby structures.

Two: Industry Overview

10
Functionally important cardiac tissues include connective tissues, which

form the fibrous skeleton and valves; cardiac muscle, which produces the
contractile force; and epithelial tissue, which lines the cardiac chambers and covers
the outer surfaces of the heart. The fibrous skeleton consists of four rings that
provide a firm scaffold for attachment of cardiac muscle and the cardiac valves.
Four cardiac valves control the direction of blood flow through the heart. The
mitral valve (bicuspid) directs blood flow from the left atrium to the left ventricle,
while the tricuspid valve directs blood from the right atrium to the right ventricle.
The edges of these atrioventricular (AV) valves are attached to rings formed by the
fibrous skeleton. Valve leaflets are tethered to papillary muscles of the ventricular
chambers by connective tissues called chordae tendineae. Papillary muscles attach
to ventricular walls and help prevent the valves leaflets from bending backward into
the atria during ventricular contraction. The AV valves open passively during
diastole when pressure of blood in the atria exceeds that in the ventricles.
Ventricular contraction reverses the pressure gradient and causes AV valves to snap
shut, preventing blood from flowing backward into the atria.
Two semilunar valves are located in the ventricular outflow tracts. The
pulmonic valve lies between the right ventricle and pulmonary artery and the aortic
valve lies between the left ventricle and aortic artery. Compared to the AV valves,
the semilunar valves are thicker and are not supported by fibrous cords. They open
and close passively according to pressure gradients, just as the AV valves do. When
intraventricular pressures exceed pulmonary and aortic artery pressures, the
semilunar valves remain open and then close when ventricular pressures fall below
aortic and pulmonary artery pressures.
The cardiac muscle layer (myocardium) produces the contractile force that
pushes blood through the circulatory system. Heart muscle is organized into four
separate chambers of varying muscular wall thickness, reflecting the degree of
pressure each chamber must generate to pump blood. Atria serve primarily as
conduits and have a thinner layer of muscle than the ventricles. The left ventricular
muscle is 2 to 3 times thicker than that of the right ventricle because higher
pressures are required to eject blood into the systemic circulation then into the
pulmonic system. Alterations in chamber pressures may reflect pathologic


11
cardiovascular changes such as valvular disorders, blood volume abnormalities, and

heart failure.
Cardiac chambers and valves are lined by a layer of squamous epithelial
cells called endocardium. The endocardial layer provides a smooth surface on
which blood can slide, which prevents clotting and minimizes trauma to read cells.
The endocardium is continuous with endothelium of the vascular system. Outer
surfaces of the heart are also covered by a layer of epithelial cells, called
epicardium, which is part of a protective covering called the pericardium. The
pericardium is actually composed of two layers that enveloped the heart like a sack.
The inner layer (visceral pericardium) is attached directly to the hearts outer
surface, while an outer layer (parietal pericardium) forms a sack around the heart.
Visceral and parietal layers are separated by a thin, fluid-filled pericardial
space that usually contains 10 to 30 mL of serous fluid. This fluid lubricates
pericardial surfaces and reduces friction as the layers slide against one another
during cardiac contraction. Accumulations of fluid in the pericardial space or
inflammation of the pericardial sac can restrict cardiac billing and impair cardiac
output.
Circulatory System
The left-sided heart chambers produce the force to propel blood through the
vessels of the body. The left atrium receives oxygenated blood from the lungs by
way of the pulmonary veins and delivers it to the left ventricle. This oxygenated
blood is pumped by the left ventricle into the aorta, which supplies the arteries of
the systemic circulation. Venous blood is collected from capillary networks of the
body and return to the right atrium by way of the vena cava. Blood from the head
returns to the right atrium through the superior vena cava, and blood from the body
returns by the interior vena cava.
The right side of the heart receives deoxygenated blood from the systemic
circulation and pumps it through the lungs by way of the pulmonary artery. The
pulmonary artery divides into left and right branches, which subdivide to supply
blood to pulmonary capillary beds. Exchange of respiratory gases occurs at the
pulmonary capillaries so that blood delivered to the left atrium by the pulmonary
veins is well oxygenated.

12
Left and right circulations are connected in series such that the output of one
becomes the input of the other. Thus, the functions of the right and left sides of the
heart are interdependent. Failure of one side of the heart pump efficiently will soon
lead to dysfunction of the other side.
Characteristic changes in the anatomy and physiology of the heart and
circulatory systems occur with aging. In general, these changes result in a decreased
cardiac reserve and it greater predisposition to cardiac muscle ischemia.
Cardiac Cycle
Each heartbeat is composed of a period of ventricular contraction (systole)
followed by a period of relaxation (diastole). The interval from one heartbeat to the
next is called the cardiac cycle and includes ventricular, atrial, and aortic events.
Each of these events is associated with characteristic pressure changes within the
cardiac chambers. Pressure changes result in valvular opening and closing and
unidirectional movement of blood through the heart. Abnormalities in these
waveforms may occur with valvular disease, changes in blood volume, or pumping
capacity of the heart. These waveforms are commonly monitored with specialized
cardiac catheters in patients with cardiac or hemodynamic disorders.
The cardiac cycle can be described sequentially, beginning with the
ventricular filling. During diastole the ventricles are relaxed and blood flows in
from the atria through open AV valves. Initially, ventricular filling occurs passively
because of a pressure gradient between the atria and ventricles. Toward the end of
ventricular diastole, the atria contract squeezing more blood through the AV valves
into the ventricles. Atrial contraction increases the ventricular blood volume by
20% to 30%. This atrial kick is particularly important during fast heart rates, when
the time for ventricular filling is shortened. Ventricular events include isovolumic
contraction, ejection, and isovolumic relaxation.
Atrial pressure waves have three characteristic curves, the a, c, and v
waves. The a wave corresponds to atrial contraction, which immediately precedes
AV valve closure. The c wave occurs early in ventricular systole and is thought to
represent bulging of AV valves into the atrial chambers. The v waves have a
gradual incline, which represents filling of the atrium as blood returns from the

13
circulation. The V wave drops rapidly as atrial pressure is relieved by AV valve

opening. A large V wave is often associated with an adequate closure of the AV
valve, resulting in regurgitation of ventricular blood back into the atrium during
ventricular systole.
Aortic and pulmonary artery pressures rise and fall in relation to the cardiac
cycle. Arterial pressures fall to their lowest value just prior to semi lunar valve
opening. This lowest pressure is called diastolic blood pressure. Arterial pressure
ejection and is called systolic blood pressure.
The difference in aortic pressure between systole and diastolic is partially
dependent on the aortas elastic characteristics. During systole, the aorta stretches to
accommodate blood ejected by the ventricle. The stretched aorta has stored or
potential energy that is released during diastole to maintain driving pressure and to
keep blood flowing continuously through the circulation. Aortic stiffening, as
occurs with aging or arteriosclerosis, may result in higher systolic and lower
diastolic blood pressure due to loss of aortic elastic properties.
Coronary Circulation
The blood supply to heart muscle is provided by the coronary arteries. Right
and left coronary artery openings are located within the sinuses of Valsalva, in the
aortic root, just beyond the aortic valve. The right coronary artery (RCA) originates
near the aortic valves anterior cusp and passes diagonally toward the right ventricle
in the AV groove. In approximately 80% of the population, the RCA gives rise to a
posterior descending vessel that supplies blood to the hearts posterior aspect. The
left main coronary artery arises near the aortic posterior cost and travels to a short
distance anteriorly before dividing into the left anterior descending and circumflex
branches. The anterior descending branch supplies septal, anterior, and apical areas
of the left ventricle, whereas the circumflex artery supplies the lateral and posterior
left ventricle. The three major coronary arteries give rise to a number of smaller
branches that penetrate the myocardium and branch into small arterials and
capillaries. Regular exercise and stable atherosclerotic plaques in the coronary
arteries are thought to stimulate the development of more extensive collateral
circulation in the heart. Collateral vessels may help limit infarct size in patients


14
suffering acute coronary occlusions. Most of the hearts capillary beds drain into the
coronary veins, which then empty into the right atrium through the coronary sinus.
Blood flow through coronary vessels is determined by the same physical
principles that govern flow to other vessels of the body, namely, driving pressure
and vascular resistance to flow. Driving pressure through the coronary arteries is
determined by aortic blood pressure and right atrial pressure.
Coronary vascular resistance has two major determinants: (1) coronary
artery diameter and (2) the degree of extra compression due to myocardial
contraction. Coronary artery diameter is continuously adjusted to maintain blood
flow at a level adequate for myocardial demands. Autoregulation is the term used to
describe the intrinsic ability of the arteries to adjust blood flow according to tissue
needs. Vasodilation occurs in response to increased tissue metabolism, whereas
decreased metabolic activity results in a decreased vessel diameter.
The mechanism of autoregulation can be explained by the metabolic
hypothesis, which proposes that increase metabolism results in a buildup of
vasodilatory chemicals in the vessel. Smooth muscle circling the vessel relaxes in
response to the presence of the chemicals increasing vessel diameter. Several
vasodilation substances have been proposed, including potassium ions, hydrogen
ions, carbon dioxide, nitric oxide, prostaglandins, and adenosine. The endothelial
cells that line vessels are known to secrete a variety of relaxing and constricting
factors, many of which have not yet been identified. An increase in the level of
adenosine is currently believed to be the chief vasodilatory chemicals. Low level of
oxygen in the blood also may cause vasodilation. Whatever their identity the
vasodilatory substances are washed away as blood flow increases in response to
increased vessel diameter. A declining level of vasodilatory chemicals results in
vasoconstriction. Thus, vessel diameter is continuously adjusted according to
concentrations of vasodilatory chemicals, which are directly related to the tissues
metabolic activity.
An ATP-sensitive potassium channel has been implicated in the regulation
of coronary blood flow. Concentration of ATP in vascular smooth muscle regulates
a specific K+ channel. As ATP levels rise in response to increase coronary flow, the
channel closes, making it easier to depolarize the cell and contract vascular smooth

15
muscle. Contraction of vascular smooth muscle reduces the diameter of the

coronary arteries and reduces blood flow. The opposite also occurs: a reduction in
ATP, due to low flow or increase metabolism, opens the K+ channels. Potassium
than leaks out of the vascular smooth muscle and short-circuits that the polarizing
influences. This inhibits vascular contraction, leading to vasodilation and increased
coronary blood flow. Substances other than ATP are believed to open and close
these channels and may contribute to coronary regulation during periods of
ischemia or increased metabolic demand.
Vessel diameter also is regulated by the autonomic nervous system. The
coronary arteries are primarily innervated by sympathetic nerves, but they also
receive a small amount of parasympathetic innervation. Sympathetic nervous
activity results in vasoconstriction; parasympathetic activity results in vasodilation.
Vessel diameter is, therefore, the result of an interplay between nervous system and
auto regulatory influences.
In addition to vessel diameter, coronary resistance is affected by myocardial
contraction. During systole, cardiac muscle compression creates a marked rise in
coronary resistance that reduces coronary blood flow. Blood flow to the left
ventricle is greatly decreased during systole because of the pressure generated by
the thick muscular layer. Blood vessels that penetrate the myocardium to supply the
innermost endocardial areas are more compressed during contraction than our outer
epicardial vessels. Even though coronary artery driving pressure is greatest during
ventricular systole, little blood flow reaches the ventricles because of the high
external pressure applied to the coronary vessels as the myocardium contracts.
Therefore, most myocardial blood flow occurs during the diastolic interval between
ventricular contractions. The time the heart spends in diastolic is directly related to
heart rate. Faster heart rates reduce diastolic time and decrease coronary artery
blood flow.
Cardiac muscle needs a continuous supply of oxygen and nutrients to
perform its pumping functions. A disruption in cardiac blood flow (ischemia)
generally results in some degree of pump failure and damaged cardiac tissues.
Myocardial ischemia may be caused by conditions that reduce coronary blood flow
or increase myocardial demands for oxygen.

16
Cardiac Myocytes
Cardiac muscle cells are divided into two general types: working cells,
which have primarily mechanical pumping functions, and electrical cells, which
primarily transmit electrical impulses. Both types are excitable: they are able to
produce and transmit action potentials. Working myocardial cells are packed with
contractile filaments and make up the bulk of the arterial and ventricle muscle.
Electrical cells function to initiate and coordinate contraction of the working cells.
Microscopic inspection of the cardiac myocytes reveals a typical pattern of
banding called striation. This striated appearance is due to an organized structure of
the proteins of the contractile apparatus. The contractile proteins, actin and myosin,
are called filaments because they are long and narrow. Myosin filaments are larger
and referred to as thick filaments. Thin filaments are actually composed of three
different types of protein bundled together. Actin is the primary constituent of thin
filaments, with smaller amounts of the proteins tropomyosin and troponin bound to
it.
The thick and thin filaments are specifically arranged in contractile units
called sarcomeres. Sarcomeres are defined by dark bands called Z disks, which lie
perpendicular to actin and myosin filaments.
Molecular Contraction
The hearts pumping action is accomplished by the contractions of the many
myocytes that form the cardiac chambers. Because each myocyte contributes only a
small amount to overall muscle shortening, all cells of the chamber must shorten
simultaneously to produce a forceful contraction. The specialized cells of the
conduction system function to stimulate myocardial contraction in a coordinated
way. An action potential traveling down the conduction system is the usual trigger
for contraction. Cardiac myocyte depolarization causes ion channels in the plasma
membrane and T tubules to open, permitting sodium and calcium entry and release
of calcium from the sarcoplasmic reticulum. The presence of free calcium in the
sarcoplasmic reticulum results in contraction. These events describe the process of
excitation-contraction coupling.


17
DISEASES OF THE HEART

Ischemic Heart Disease
Ischemic heart disease is characterized by insufficient delivery of
oxygenated blood to the myocardium. When metabolic demand for oxygen exceeds
supply, the myocardium becomes ischemic, which leads to a dysfunction in cardiac
pumping and predisposes to abnormal heart rhythms. If the ischemic episode is
severe or prolonged, irreversible damage to myocardial cells may result in
myocardial infarction.
Etiology
The most common cause of ischemic heart disease is coronary artery
atherosclerosis-sometimes called coronary artery disease or coronary heart disease.
Atherosclerosis causes progressive narrowing of the atrial lumen and predisposes to
a number of processes that can precipitate myocardial ischemia, including thrombus
formation, coronary vasospasm, and endothelial cell dysfunction. Less common
causes of ischemic heart disease include abnormalities of blood oxygen content and
poor perfusion pressure through the coronary arteries. Sometimes, patients
experience the signs and symptoms of cardiac ischemia but show no evidence of
coronary artery atherosclerosis when evaluated by an angiogram. These patients are
thought to have abnormalities of the microcirculation. Abnormal vascular regulation
by endothelial cells in small vessels of the heart has been suggested as a probable
mechanism. Endothelial cells secrete variable quantities of vascular relaxing and
contracting factors and play a key role in controlling myocardial blood flow.
Abnormalities of the microcirculation are more difficult to detect than coronary
artery plaque, which is evident on coronary angiography. As evaluation methods
improve, disorders of the microcirculation are likely to be more frequently
recognized as factors contributing to ischemic heart disease.
Pathophysiology
Ischemia of cardiac cells occurs when oxygen supply is insufficient to meet
metabolic demands. Myocardial cells are able to store much energy in the form of
adenosine triphosphate (ATP) and must therefore continuously receive a supply of
oxygen for aerobics synthesis of ATP. ATP is essential for powering myocardial
contraction, as well as for cell maintenance. Because the heart is unable to stop and

18
rest when ATP supplies dwindle, it is essential that a steady flow of oxygen be
provided.
Factors that decreased myocardial oxygen supply or increased myocardial
oxygen demand can upset the balance and result in cellular ischemia. Thats the
critical factors in meeting cellular demands for oxygen are (1) the rate of coronary
perfusion and (2) myocardial workload. Coronary perfusion can be impaired in
several ways, including (1) large, stable atherosclerotic plaque, (2) acute platelet
aggregation and thrombosis, (3) vasospasm, (4) failure of autoregulation by the
microcirculation, and (5) poor perfusion pressure.
Myocardial workload depends on heart rate, preload, after load, and an
increase in any of these variables increases myocardial oxygen requirements and
may precipitate ischemia. However, even conditions resulting in very high
myocardial oxygen consumption will seldom lead to ischemia unless some
underlying impairment in coronary perfusion is present.
One or more of the aforementioned mechanisms are operative in producing
clinically significant myocardial ischemia resulting in the syndromes of MI,
ischemic cardiomyopathy, and sudden cardiac death.
Atherosclerosis
Knowledge about mechanisms of plaque formation in the coronary arteries
has rapidly accumulated in recent years. Epidemiologic studies reported in the
1960s suggested associations among certain traits and habits and the development
of coronary heart disease. More recent studies have confirmed and expanded upon
these risk factors which now include age, family history, hyperlipidemia, cigarette
smoking, hypertension, diabetes, and obesity. Although males and females succumb
to heart disease in equal numbers, male gender is a risk factor for earlier
development of heart disease (on average about 10 years earlier). The risk factors
for coronary heart disease are the same as those for atherosclerosis in other arteries.
The observation that atherosclerotic plaque is composed primarily of lipid
prompted the idea that abnormal lipid metabolism was a probable culprit in the
development of coronary heart disease. Lipids may accumulate in the arterial wall
for many reasons, including vessel trauma, inflammation, and infection. A great
deal of evidence supports the idea that hyperlipidemia is a major factor promoting

19
the development of coronary atherosclerosis. The risk of coronary heart disease

increases proportionately as the serum lipid level increases.
Lipids are transported through the bloodstream in combination with specific
proteins (apoproteins). Certain liquid-protein molecules (lipoproteins) are
associated with a greater risk of atherosclerosis. High levels of low-density
lipoproteins (LDLs), which are high in cholesterol, have been associated with the
highest risk. Very-low-density lipoproteins, have been correlated with a decreased
risk of atherosclerosis.
High-density lipoproteins are thought to transport cholesterol from the
vessel back to the liver for excretion, thus clearing away atheromatous plaque. The
role of low-density and indirectly very-low-density lipoproteins is to bring
cholesterol to the peripheral tissues. Cholesterol uptake by peripheral cells is
mediated by receptors (LDL receptors) on cell surfaces that bind and promote
endocytosis of cholesterol. The liver normally binds and internalizes about 75% of
the circulating LDL cholesterol.
Extreme cases of hyperlipidemia occur in individuals who have genetic
derangements in lipid metabolism. These disorders run in families and are
associated with the development of severe coronary atherosclerosis at a young age
unless aggressively treated. The most common form of genetic hyperlipidemia is
due to a defect in the LDL receptor on liver cells. It is associated with the inability
of the liver to effectively remove cholesterol from the bloodstream, which results in
hyperlipidemia. Even when lipid metabolism is normal, a high-fat diet can
overwhelm the livers ability to clear LDL cholesterol from the circulation and
result in hyperlipidemia. Dietary fat restriction may be beneficial in reducing
cholesterol in this case.
Atherosclerotic lesions generally increase in size over many years and
progressively occlude the lumen of the vessels. A significant reduction in blood
flow can result when plaque occupies 75% or more of the arterial lumen. Clinically
significant atherosclerotic plaque may be located anywhere within the three major
coronary arteries or major secondary branches. All three coronary arteries are often
simultaneously affected, although some individuals have only one or two diseased


20
vessels. Surprisingly, the extent and severity of atherosclerotic lesions are not good
predictors of the severity of ischemia.
The American Heart Association system for classification of coronary
lesions is helpful in understanding the types of coronary lesions that have been
characterized and attempts made to correlate the anatomic descriptions with plaque
development and behavior. In general, plaque is thought to progress sequentially
from type I through type VI, although the more advanced stages may not develop in
some individuals. Types IV, V, and VI are considered to be advanced lesions and
may cause the clinical syndromes of ischemia, including angina, infarction,
ischemic cardiomyopathy and sudden cardiac death.
Type I, II, and III lesions are silent precursors to the deadly processes of
advanced plaque formation. Type I and II lesions are present in childhood. Type I
lesions are characterized by the accumulation of lipids within macrophages located
in the intimal layer of the coronary artery. These lipid-laden macrophages are called
foam cells. In childhood, foam cells tend to reside in the areas of adaptive arterial
thickening-such as occurs at arterial branch points. In persons with hyperlipidemia,
foam cells may accumulate in other arterial regions. Type I lesions are present in
about 50% of infants at eight months of age. Foam cells are few and scattered in
type I lesions and are not visible to the unaided eye.
Type II lesions are also composed primarily of macrophage foam cells, but
they are more numerous and begin to coalesce. In addition, intimal smooth muscle
cells also begin to accumulate intracellular lipids. Nearly all the lipid in the arterial
wall at this stage is still confined to the intracellular compartment. Type II lesions
are visible on gross inspection and appear as yellowish fatty streaks or spots. In the
early 1900s when early childhood mentality was high, autopsy studies revealed that
type II lesions were initiated at early stages. Type II lesions were not seen before
age 9 years and became prevalent at puberty. The incidence of type II lesions was
noted to increase with age, being present in 30% of nine-year-olds, 60% of 10-to
14-year-olds and 75% of 15-to 19-year-olds.
Type III lesions are considered to be links between the nearly universal and
asymptomatic type I and II lesions and the pathologic forms of advanced lesions.
The main histologic difference between type II and III lesions is that extracellular

21
lipid droplets begin to accumulate in the matrix. However, the lipids have not yet
formed a pocket as occurs in type IV lesions. Type III lesions, like types I and II,
are asymptomatic.
Advanced lesions include types IV, V, and VI and carry a significant risk of
producing disruptions in coronary blood flow. Type IV lesions contain a large
amount of free lipid that forms a pocket in the intima just under the layer of
macrophage foam cells. Lipids forming the core are derived primarily from plasma,
and elevated serum cholesterol is a major factor in lesion progression from type III
to Type IV. Lesions do not protrude into the arterial lumen, but they are prone to
rupture and precipitate thrombus formation at the site. Acute thrombus formation
can suddenly occlude the artery resulting in cardiac ischemia. If the thrombus is
small, it may not occlude the artery lumen but may instead become incorporated
into the lesion and cause it to enlarge into a more advanced type. Type IV lesions
are of special interest because they may be more responsive to lipid-lowering
strategies than are the more dense lesions.
Type V lesions are characterized by the inclusion of fibrous connective
tissue within the plaque. The fibrous tissue forms a cap on the plaque that may
make it more stable and less prone to rupture than type for lesions the appearance of
type V morphology heralds the onset of progressive narrowing of the arterial lumen.
Over time, smooth muscle cells in the intima proliferate and fibrous connective
tissue expands into the lumen. Type V lesions are also prone to disruptions in the
plaque surface leading to intraplaque hemorrhage and thrombus formation.
When a type IV or type V lesion is complicated by plaque disruption and
thrombus formation, it is then classified as a type VI lesion. Type IV, V, and VI
lesions are responsible for the clinical syndromes of ischemia associated with
coronary heart disease.
Angina Pectoris
Angina pectoris is characterized by chest pain associated with intermittent
myocardial ischemia. The link in the severity of the myocardial ischemia is
insufficient to result in the death of cells. Bouts of chest pain and associated
symptoms are generally recurrent and may be precipitated by conditions that
increase myocardial oxygen demand such as exercise, stress, sympathetic nervous

22
system activation, and increase preload, after load, heart rate, or muscle mass.
Ischemic pain receptors from the myocardium travel to the central nervous system
with the eighth cervical and the first through fourth thoracic dorsal root ganglia.
Sensory neurons from the jaw, neck, and arm also travel in these nerve trunks, so
heart pain may be perceived as emanating from these body parts. This phenomenon
is called referred pain. Anginal pain may be described as burning, crushing,
squeezing, or choking. Pain is sometimes represented by expressions such as an
elephant is sitting on my chest or by the patient placing a tight fist on the chest.
Anginal pain may be mistakenly attributed to indigestion or dental pain.
Anginal ischemia, although temporary, may result in insufficient cardiac
pumping with resultant pulmonary congestion and shortness of breath. Three
patterns of angina pectoris have been described: stable or typical angina, Prinsmetal
or variant angina, and unstable or crescendo angina. All these patterns are
associated with underlying coronary vessel disease and may be exhibited in a
particular individual at different times and under different conditions.
Acute Ischemia and Myocardial Infarction Chronic
Unstable angina and MI are difficult to distinguish on the basis of clinical
manifestations. Both are characterized by chest pain that may be more severe and
last longer than the patients typical angina. In both cases, plaque rupture with
subsequent acute thrombus development is thought to occur. In unstable angina, the
occlusion is partial when the clot is broken down before the death of the myocardial
tissue. In MI, the occlusion is complete and the thrombus persists long enough for
development of irreversible damage to myocardial cells. In the past, differentiation
of unstable angina and MI was based on laboratory evaluation of serum enzyme
levels such as MB band of creatine kinase (CK-MB), lactate dehydrogenase (LDH).
If cardiac enzymes were elevated which is indicative of necrosis, a diagnosis of MI
was made; if not a diagnosis of unstable angina was appropriate.
Two types of MI have been described, each having different morphology
and clinical significance. A transmural infarct involves the entire thickness of the
ventricular wall and is the more serious of the two types. It is also more common. A
nonQ wave infarct affects only the inner third to half of the ventricular wall and
is generally associated with less severe symptoms. These lesions are not exclusive:

23
a non--Q wave MI can extend across the ventricular wall to become a transmural
MI under certain circumstances.
Chronic Ischemic Cardiomyopathy
Chronic ischemic cardiomyopathy refers to a disorder in which heart failure
develops insidiously as a consequence of progressive ischemic myocardial damage.
In most cases, individuals affected have a history of angina or MI, often many years
before the onset of heart failure. Heart failure appears to be a consequence of slow,
progressive atrophy or death of myocytes from chronic ischemia. The disease is
usually found in elderly individuals. Atrophic and dead cells are scattered
throughout the myocardium rather than being localized, as occurs with MI. The
prognosis for patients with chronic ischemic cardiomyopathy is quite poor, with
death from congestive heart failure the common outcome.
Sudden Cardiac Death
Sudden cardiac death is usually defined as unexpected death from cardiac
causes within one hour of the onset of symptoms. Ischemic heart disease is at the
root of the vast majority of cases of sudden cardiac death. Rarely, sudden cardiac
death may be a complication of hereditary or required structural or electrical
abnormalities. It is estimated that 300,000 to 400,000 individuals die each year in
the United States of sudden cardiac death. It is most often associated with coronary
atherosclerosis and may be the initial manifestation of the disease. MI occurs in
only a small subset of cases of sudden cardiac death. A lethal dysrhythmia such as
asystole or ventricular fibrillation is usually the primary cause of death. Ischemia
from multi-vessel atherosclerosis, diffuse myocardial atrophy, scarring and fibrous
of old MI tissue, and electrolyte imbalances are factors that may predispose the
heart to the electrical abnormalities that lead to sudden cardiac death
Diagnostic Tests
The diagnosis of ischemic heart disease is frequently made on the basis of
the patients history. Diagnosis of angina may also be facilitated by ECG, Holter
monitor, coronary angiography, and stress testing.


24
Valvular and Endocardial Diseases

Endocardial and valvular structures may be damaged by inflammation and
scarring, calcification, or congenital malformations. These processes interfere with
the normal valvular property of unimpeded, unidirectional flow. Although
congenital bowel formations may affect any valve, acquired valvular disorders
generally involve the mitral or aortic valves. Abnormalities in valvular function
cause altered hemodynamics in the heart and generally result in increased
myocardial workload. Ultimately, heart failure may result from significant valvular
dysfunction.
Normally heart valves open completely, so blood flows through with little or
no pressure difference across the valve. Failure of the valve to open completely is
termed stenosis. Significant hemodynamic consequences generally begin to occur
when the valve opening is reduced to half normal. The severity of stenosis can be
estimated by the degree of pressure gradient across the valve. Stenosis results in
extra pressure work for the heart because blood must be forced through the high
resistance of a narrow valve opening. Stenosis generally progresses slowly over
years to decades, which allows time for affected heart chambers to compensate
through myocardial cell hypertrophy.
Regurgitation or insufficiency refers to the inability of a valve to close
completely thereby allowing blood to flow in the reverse direction. Regurgitation
may develop suddenly from valvular infection or rupture of a supporting papillary
muscle. Sudden regurgitation is poorly tolerated inasmuch as little compensation is
possible. Regurgitation results in increased work for the heart because more blood
must be pumped to maintain adequate workflow.
Diseased valves may exhibit elements of both stenosis and regurgitation,
although one problem usually predominates. Post inflammatory scarring from
rheumatic heart disease and valvular calcification with aging of the primary causes
of stenosis. A wide variety of diseases of the endocardium may lead to valvular
regurgitation. Damaged cells are susceptible to infection, and antibiotic prophylaxis
is therefore indicated for dental, surgical, and diagnostic procedures.


25
Mitral Valve Disorders

Three important disorders of the mitral valve are stenosis, regurgitation, and
mitral valve prolapse. In mitral stenosis the flow of blood from the left atrium into
the left ventricle is impaired. Mitral stenosis is, therefore, characterized by an
abnormal left atrial-left ventricle pressure gradient during ventricular diastole.
Normally the pressure in the atrium and ventricle are nearly equal during ventricular
diastole when the mitral valve is opened. As stenosis worsens, the pressure gradient
often increases. Increased pressure work of the left atrium leads to atrial chamber
enlargement and hypertrophy. Progressive narrowing of the mitral valve may lead
to markedly elevated left atrial pressures and subsequent increased pulmonary
vascular pressure. If uncorrected, mitral stenosis may result in chronic pulmonary
hypertension, right ventricular hypertrophy, and right-sided heart failure.
Mitral regurgitation is characterized by back flow of blood from the left
ventricle into the left atrium during ventricular systole. Elevation of left atrial
volume and pressure by regurgitating flow leads to characteristic giant V waves on
the arterial pressure monitor. The left ventricle must pump a greater volume to
compensate for the regurgitating flow and maintain an effective stroke volume.
Both the left atrium and the left ventricle generally dilate and hypertrophy to
compensate for the extra volume that they are required to pump. If severe and
uncorrected, mitral regurgitation may lead to left heart failure.
Approximately 1% of the population has mitral valves that balloon up into
the left atrium during ventricular systole; this condition is called mitral valve
prolapse. Women between the ages of twenty and forty years are most often
affected. In the great majority of cases the disorder is asymptomatic and diagnosed
only incidentally on routine physical exam. In some cases the prolapse is sufficient
to cause a degree of mitral regurgitation. The cause of this valvular abnormality is
uncertain, although it is commonly associated with other connective tissue disorders
such as Marfan syndrome or scoliosis.
Aortic Valve Disorders
The primary disorders of the aortic valve are stenosis and regurgitation.
With the decline in incidents of rheumatic fever, the predominant cause of aortic
stenosis is age-related calcification. The hallmark of this disorder is calcium
deposits on the aortic cusps. Calcification is particularly common in patients with a

26
congenital bicuspid aortic valve. Aortic calcifications build up over several decades
and generally become clinically apparent in individuals 70 to 90 years old.
Rheumatic heart disease on the other hand, occurs primarily in children and young
adults and now accounts for only a small percentage of cases of aortic stenosis.
Causes of aortic regurgitation are similar to those of mitral regurgitation
Rheumatic Heart Disease
Rheumatic heart disease is an uncommon but serious consequence of
rheumatic fever. The incidence of rheumatic fever has steadily declined in the
United States, but the disease still affects an estimated 15,000,000 to 20,000,000
people a year worldwide. Rheumatic fever is an acute inflammatory disease that
follows infection with group A B-hemolytic streptococci. Damages are due to
immune attack on the individuals own tissues. For poorly understood reasons,
antibodies against the streptococcal androgens are also directed against self-tissues,
possibly because of autoimmune phenomena or cross-reactivity between
streptococcal androgens and certain tissue molecules. It is unknown why some
individuals experience progressive tissue damage and others suffer no lasting
consequences. The genetic predisposition to heightened immune responsiveness has
been suggested.
The acute infection occurs primarily in children and is accompanied by
fever and sore throat. In only 3% of children with pharyngeal streptococcal
infection does rheumatic fever eventually develop. Rheumatic heart disease
develops in 50% to 75% of children and 35% of adults with rheumatic fever.
Endocarditis
Infective endocarditis is caused by invasion and colonization of endocardial
structures of microorganisms with resulting inflammation. A variety of organisms
are known to have an affinity for the endocardium and for the cardiac valves in
particular. Valvular lesions include growth of microorganisms enmeshed in fibrin
deposits. These growths are called vegetations and may become quite large and
interfere with valvular function and are predisposed to embolus formation. The
most common bacterial culprits are several strains of streptococci and
Staphylococcus aureus.


27
Diagnostic Tests
Four major diagnostic tests are used to determine the presence of valvular
heart disease: chest x-ray, ECG, echocardiogram and cardiac catheterization
Pericardial Diseases
Pericardial disorders are rarely isolated processes of primary etiology;
rather, they are sequelae of other disorders such as systemic infection, trauma,
metabolic derangement, or neoplasia. Despite the diversity of cognitive factors,
pericardial involvement is generally manifested as an accumulation of fluid in the
pericardial sac or inflammation of pericardial structures.
Pericardial Effusion
An accumulation of noninflammatory fluid in the pericardial sac is called
pericardial effusion. Normally the pericardial space contains only 30 to 50 mL of
sand, clear fluid. Under pathologic conditions, as much as 500 mL may accumulate.
The accumulation of the pericardial fluid is generally without clinical significance
except as an indicator of underlying disease processes. However if the fluid
accumulation is large or occurs suddenly, the life-threatening condition of cardiac
tamponade may develop. Tamponade refers to external compression of the heart
chambers such that feeling is impaired. Signs and symptoms of cardiac tamponade
include reduced stroke volume and compensatory increases in heart rate. Systemic
venous congestion occurs because blood is prevented from entering the compressed
heart by way of the superior and inferior vena cava.
Pericarditis
Inflammation of the pericardium originates from a variety of causes. Rarely
is the pericardium the primary site of disease. Pericarditis is often categorized into
acute and chronic forms; however, these forms are morphologically and
etiologically similar. Chronic pericarditis refers to a healed stage of the acute form
which results in chronic pericardial dysfunction.
Myocardial Diseases
Myocardial diseases consist of myocarditis and cardiomyopathy.
Myocarditis is an inflammatory disorder of the heart muscle characterized by
necrosis and degeneration of heart muscle cells. Cardiomyopathy includes several

28
disorders of the heart muscle that may be genetic or acquired but are
noninflammatory.
Myocarditis
Myocarditis is characterized by inflammation, leukocyte infiltration and
necrosis of cardiac muscle cells. Causes of myocarditis are many and include
microbial agents, several forms of immune-mediated disease, and several physical
agents. The true incidence of myocarditis is unknown because the diagnosis relies
largely on circumstantial evidence.
Cardiomyopathy
Cardiomyopathy is variously defined by different groups. The World Health
Organization simply defines cardiomyopathy as a disease of the myocardium
associated with cardiac dysfunction. Others have adopted the terms primary
cardiomyopathy for dysfunction of unknown etiology and secondary
cardiomyopathy for myocardial dysfunction of known etiology. Most definitions of
primary cardiomyopathy exclude hypertensive, ischemic, congenital, valvular,
pericardial, and inflammatory myocardial disorders.
Diagnostic Tests
Although the clinical picture of severe crushing chest pain, diaphoresis, and
apprehension or a sense of impending doom is the classic description of a person
having a myocardial infarction, it by no means describes all infarction patients.
About 15% of myocardial infarctions occur without the characteristic signs and
symptoms and individual variation in the symptoms is to be expected. A variety of
diagnostic tests are used to verify the diagnosis. These tests include blood tests to
detect both nonspecific and specific changes caused by the infarction, ECG and
other procedures such as radionuclide imaging.
Congenital Heart Diseases
Congenital heart diseases are abnormality of the heart that is present from
birth. A wide variety of defects have been identified. Development of the heart
involves a complex orchestration of formation and resorption of structures.
Abnormalities in the development of four important heart structures are at the root
of most of the common heart defects: (1) development of the atrial septum, (2)

29
development of the ventricular septum, (3) division of the main outflow tract into
the pulmonary and aortic arteries, and (4) development of the valves.
Atrial Septal Defect
During the third to fifth week of fetal development, the right and left atria
are separated by flaps of tissue that become the atrial septum. The foramen ovale
remains patent during intrauterine life such as blood may pass from the right to the
left atrium and bypass the uninflated and nonfunctional lungs. With birth, however,
the pressure gradient reverses as the lungs inflate and greatly reduce pulmonary
vascular resistance. The higher left-sided pressure forces the flaps shut, and fusion
of the foramen ovale membrane normally occurs. Approximately 90% of atrial
septal defects occur at the location of the foramen ovale. The abnormal septal
opening may be a variable size. Small defects less than 1 cm are well tolerated.
Even larger atrial septal defects may be asymptomatic for many years as long as the
shunt flow is left to right and therefore acyanotic. The long-term increase in
pulmonary blood flow may eventually lead to pulmonary hypertension, right
ventricular hypertrophy, and a reversal of the shunt to the right-to-left pattern.
Ventral Septal Defect
The ventricular septal defect is the most common congenital cardiac
anomaly. It is frequently associated with other cardiac defects such as tetralogy of
Fallot, transposition of the great arteries, and arterial septal defects. The ventricular
septum develops between the fifth and sixth weeks of fetal life as the membrane
derived from the endocardial cushion fuses with the muscular septum.
Approximately 90% of ventricular septal defects are located within the membrane S
septum, very close to the bundle of HIS. As with atrial septal defects, the functional
significance depends largely on the size of the defect. The shunt is initially left to
right because left heart pressures are higher. With the increase in pulmonary blood
flow, pulmonary hypertension and right ventricular hypertrophy may result and
cause a reversal of the shunt. Large ventricular septal defects may be apparent at
birth because of rapidly developing right heart failure and loud systolic murmur.
Large, symptomatic defects in infants or moderate defects in older children are
repaired surgically to avoid progression to pulmonary vascular disease. Small
ventricular septal defects in infants are generally not immediately repaired because
of the tendency to close spontaneously.

30
Pulmonary Stenosis
Isolated pulmonary stenosis or atresia is included in the category of
acyanotic defects because they do not themselves result in cyanosis. However, they
often occur in conjunction with other anomalies that allow survival into the neonatal
period. The other defects may allow shunting of blood and resultant cyanosis. In
pulmonary atresia, no communication is found between the right ventricle and the
lungs, so blood must enter the lungs by first traveling through a septal opening and
then through a patent ductus arteriosus. The right ventricle is typically
underdeveloped and the atrial septal defect is large. Pulmonary stenosis can be mild
to severe, depending on the extent of narrowing of the pulmonic valve. Pulmonary
stenosis is usually due to abnormal fusion of the valvular cusps. Right ventricular
hypertrophy occurs secondary to the high ventricular afterload caused by the
narrowed outflow opening. Isolated pulmonary stenosis is easily corrected by
surgery; however, the prognosis depends largely on the help of the right ventricle.
Aortic Stenosis
Congenital aortic atresia is rare and not compatible with survival.
Depending on its severity, aortic stenosis is correctable and associated with a good
prognosis. Aortic stenosis may involve the valvular cusps or the subvalvular fibrous
ring just below the cusps. The narrowed aortic outflow tract results in a high left
ventricular afterload, which causes the left ventricle to hypertrophy. A prominent
systolic murmur is usually apparent. Surgical replacement is the definitive treatment
of the stenosis is severe, progresses, or becomes symptomatic.
Coarctation of the Aorta
Coarctation refers to the narrowing or stricture that may impede blood flow.
Coarctation of the aorta is a common heart defect that affects males 3 to 4 times
more frequently than females. Narrowing of the aorta may occur anywhere along its
length; however, in most cases the coarctation is located just before or just after the
ductus arteriosus.
Patent Ductus Arteriosus
The ductus arteriosus is a normal channel between the pulmonary artery and
the aorta that remains open during intrauterine life. Within one to two days after
birth, the ductus arteriosus closes functionally, and within a few weeks it closes

31
permanently. The ductus arteriosus allows blood to flow from the pulmonary artery
into the aorta, thus bypassing the lungs. Low oxygen tension and local production
of prostaglandins appear to be important in maintaining patency of the channel
during fetal life. After birth, flow through the ductus arteriosus switches to left to
right because of the higher pressure in the aorta. This change in flow direction
brings oxygenated blood through the ductus arteriosus and stimulates it to close.
Truncus Arteriosus
Truncus arteriosus is a congenital malformation in which failure of the
pulmonary artery and aorta to separate results in the formation of one large vessel that
receives blood from both the right and left ventricles. A large ventricular septal defect
in a single valvular structure is present and lead to the single large artery. Mixing of
blood from the right and left sides of the heart results in systemic cyanosis. The
amount when entering the systemic versus the pulmonary circulation depends on the
degree of valvular resistance in the two systems. Abnormally high pulmonary blood
flow may progress to pulmonary hypertension and right ventricular hypertrophy.
Increased pulmonary resistance causes the cyanosis to become more severe as more
blood enters the systemic circulation.
Transposition of the Great Arteries
In the most common form of transposition of the great arteries, the aorta
arises from the right ventricle and the pulmonary artery arises from the left ventricle
this anomaly results in the formation of two separate, not communicating
circulations. The right heart receives blood from the systemic circulation and is
recirculated through the body by way of the aorta. Blood reaching the body has not
passed through the lungs and is therefore not oxygenated. The left heart receives
oxygenated blood from the lungs and is recirculated through the lungs again by way
of the pulmonary artery. Unless some mixing of these separate circulations takes
place through other heart defects such as septal defects, transposition is not
compatible with life
Tricuspid Atresia
Absence of the tricuspid valve is almost always associated with
underdevelopment of the right ventricle and an atrial septal defect. Circulation is
maintained by the defect, which allows blood to bypass the right ventricle. The

32
patent ductus arteriosus is required to perfused the lungs. In some cases a

concomitant ventricular septal defect is present and may allow some but the passion
to the right ventricle and enter the pulmonary circulation. Cyanosis is present from
birth, and the mortality rate is high.
Congestive Heart Failure
Heart failure is defined as insufficient cardiac output due to cardiac
dysfunction. Ineffectiveness of the cardiac pump results in congestion of blood flow
in the systemic or pulmonary circulation, leading to congestive heart failure (CHF)).
CHF is an increasingly common disorder, more than 400,000 new cases diagnosed
in the United States each year. Heart failure is the most common reason for
hospitalization in patients older than sixty-five years. The increasing incidence of
CHF reflects an improved survival rate after myocardial infarction as well as greater
longevity of the population in general.
Etiology
A number of disorders can contribute to the development of CHF. These
include ischemic cardiomyopathies and non-ischemic cardiomyopathies. The
majority of cases of CHF are associated with ischemic cardiomyopathy due to
coronary artery disease and hypertension. Other less common causes of CHF
include dilated cardiomyopathy, congenital heart defects, valvular disorders,
respiratory diseases, anemia, and hyperthyroidism.
Regardless of specific etiology, the pathophysiologic state of heart failure
results from impaired ability of myocardial fibers to contract, relax, or both. Until
the late 1980s, systolic dysfunction was thought to be the primary problem of all
forms of CHF. Now it is evident that a large subset of patients with CHF has
preserved systolic function, but impaired diastolic function. Systolic failure occurs
as the primary dysfunction in 60% to 70% of cases of CHF. Impaired diastolic
function is the primary problem in the remaining 30% to 40% of cases overall, but it
is more common in the elderly.
Diagnostic Tests
Heart failure is typically diagnosed based on the clinical signs and
symptoms and the presence of a precipitating cause. An electrocardiogram is

33
usually done to determine the presence or absence of an acute myocardial

infarction, to assess for arrhythmias, and to identify compensatory responses such
as ventricular hypertrophy. Chest x-ray films are done to assess pulmonary
congestion and cardiac enlargement. Actual cardiac output may be determined by a
variety of techniques, but this assessment is usually reserved for more critically ill
patients. A number of other tests devised to provide data about cardiac functioning
include echocardiograms, gated pool imaging and pulmonary artery catheterization.
Cardiac Dysrhythmias
Dysrhythmia refers to an abnormality of the heartbeat. A normal heartbeat is
initiated in the sinoatrial (SA) node and follows a consistent pathway of
depolarization through the atria, atrioventricular (AV) node, His-Purkinje system,
and the ventricular myocardium. Electrical depolarization of the heart is normally
followed by atrial and then ventricular muscular contraction. A number of factors
may lead to disturbances in heartbeat, including hypoxia, electrolyte imbalance,
trauma, inflammation, and drugs. Dysrhythmias are significant for two reasons: (1)
they indicate an underlying pathophysiologic disorder, and (2) they can disrupt
normal cardiac output. Dysrhythmias can be categorized into three major types:
abnormal rates of sinus rhythm, abnormal sites of impulse initiation, abnormal
disturbances in conduction pathways.
Diagnostic Tests
Electrocardiographic recording paper is specifically designed to allow easy
measurement of waveform amplitude and duration. Each small box on the ECG
paper represents an amplitude of 0.1 mV and the duration of 0.04 second. Larger
boxes are also marked on the paper and correspond to 0.5 mV in amplitude and 0.2
second in duration. These markings allow measurement of waveform amplitude,
duration, and heart rate.
Hypertension
Hypertension is defined in adults as blood pressure persistently elevated
above 140 mm Hg systolic, 90 mm Hg diastolic, or both. In the United States, more
than 50 million people have or are being treated for high blood pressure. A
classification scheme for blood pressure has been developed and is based on the

34
knowledge that as blood pressure, both systolic and diastolic, increases, so does the
risk of cardiovascular complications. If the systolic and diastolic values fall in
different stages, the higher stage is used for identifying appropriate treatment
Risk Factors
Age
Blood pressure rises consistently with age, beginning at levels as low as
50/40 mm Hg in newborns and increasing to over 200 mm Hg in some elderly
subjects. High blood pressure in children is classified as significant when it is
greater than or equal to the 95th percentile for age and as severe when it is greater
than or equal to the 99th percentile for age. High blood pressure in childhood is a
predictor of hypertension in adult life, especially in association with obesity.
Many vascular changes occur with aging. Vessel lumina narrow, and vessel
walls become stiff and less compliant with age. The resulting increase in SVR
contributes to increase blood pressure, primarily systolic blood pressure and
accounts for the isolated systolic high blood pressure seen most often in the elderly.
Race
High blood pressure occurs 2 to 3 times more frequently in AfricanAmericans than in Caucasians, especially at diastolic levels above 105 mm Hg.
Elevated blood pressure appears earlier in African-Americans, and target organ
damage is more severe than in Americans of European, Hispanic, or Native
American descent. The reason for this difference in African-Americans is not
known, although African-Americans with high blood pressure often have lower
renin levels than do other Americans with high blood pressure. Possibly because of
these lower renin levels, antihypertensive drugs that work primarily through altering
renin mechanisms, such as B-andrenergic blocking agents and ACE inhibitors, are
less effective in this population when used alone. When used in combination
therapy these drugs are equally effective across ethnic groups.
Obesity
Excess weight is associated with elevated levels of blood pressure. Obesity
in childhood is a predictor of high blood pressure in adulthood. Body mass index
has been found to be closely correlated with diastolic blood pressure. As BMI
increases, so does diastolic blood pressure. The mechanism by which excess weight

35
contributes to high blood pressure is not known; however, a relationship between

hyperinsulinemia, obesity, and hypertension has been noted. Weight reduction in
overweight individuals is known to reduce blood pressure.
Effects of High Blood Pressure
Cardiac
Elevated systemic blood pressure requires that the left ventricle work harder
to overcome the resistance to ejection of blood. In response, the left ventricle
muscle hypertrophies which increases myocardial oxygen demand. The workload of
the left ventricle increases as blood pressure increases. The myocardial oxygen
demand exceeds the supply, ischemia develops and heart failure may ensue.
Vascular
Sustained high blood pressure causes changes in the walls of arteries and
arterioles. High blood pressure accelerates the development of atherosclerosis in the
aorta and in medium-to large-sized arteries. The resultant decrease in caliber of
these arteries results in isolated systolic high blood pressure in the elderly.
Atherosclerosis also contributes to cerebral infarction.
Arterial sclerosis in the smaller arteries and arterioles contributes to cerebral
vascular disease and peripheral vascular disease. Fibrinoid necrosis occurs in the
small arteries and produces lesions in the kidneys and in the retina of the eyes.

Electrocardiography
INTRODUCTION
In addition to history, laboratory, and physical assessment, a number of
diagnostic tests may be employed to evaluate cardiac function. The
electrocardiogram is routinely obtained and provides information about the hearts
conduction patterns. The electrocardiogram graphically records electrical currents
generated by cardiac cells. The current is registered by skin electrodes placed in
particular positions on the body. The standard ECG has twelve different leads that
are obtained through ten skin electrodes: three standard bipolar limb leads, three
augmented unipolar limb leads, and six unipolar chest leads. Bipolar leads represent
a difference in electrical potential between two electrodes, one positive and one
negative. Augmented unipolar limb leads represent a difference in potential
between one electrode and the average of the other two limb electrodes. Unipolar
chest leads represent a difference in potential between the chest electrode and a
location at the center of the heart. Each lead provides a different ECG recording
because of its particular view of current flow through the heart.
Three standard bipolar limb leads are lead I, lead II, and lead III: lead I
measures the current between the right arm and the left arm, lead II measures the
current between the right arm and the left leg, and lead III measures the current
between the left arm and left leg.

Three: Electrocardiography
38
Unipolar limb lead electrodes provide the positive pole: lead aVr is recorded
from the right arm, lead aVl is recorded from the left arm, and lead aVf is recorded
from the left leg. In the leads, a stance for augmented V stands for voltage; and R,
L, and F indicate the location of the unipolar lead.
Precordial unipolar chest leads are obtained from electrodes placed in six
positions over the heart on the anterior chest. Chest leads are designated as
V1,V2,V3,V4, V5 and V6. Twelve-lead ECGs are usually recorded for a short
period of time when the patient is resting. Sequential ECGs are useful for
determining changes over time. In some cases it is necessary to monitor the ECG
for an extended period of time to capture rhythm problems that occur infrequently
or with particular activities. This is accomplished by continuous ambulatory
monitoring such as Holter monitoring over a 24 to 48 hour. ECG can also be
recorded during exercise to monitor the effects of exercise stress on cardiovascular
function. The stress test is usually performed while the subject progressively
increases his or her effort on a treadmill or stationary bike. The exercise ECG is
particularly useful for assessing the adequacy of coronary circulation and
myocardial workload is increased.
The vector cardiogram is a special kind of ECG that differs substantially
from the standard twelve-lead ECG. The vector cardiogram detects heart
depolarization in two planes simultaneously and displays it as two-dimensional
vector loops. Seven electrodes are placed on the body surface, including five chest
points, one left leg position and one forehead or neck position. The polarizations are
measured in each of three planes of the body: horizontal, frontal, and sagittal. Thus,
a vector cardiogram provides 83-dimensional view of the heart, whereas a standard
ECG provides only a two-dimensional view. The vector cardiogram may be more
sensitive than the standard twelve-lead ECG in picking up changes due to
Stress testing reveals how a patients heart and blood pressure respond to
physical exertion. During the test, the patient exercises on a treadmill or pedals a
stationary bicycle while the physician monitors the hearts electrical activity. Test
results can indicate possible blockage of an artery and where the blockage is
occurring. In addition, results are useful in determining whether the patient should
39
undergo a cardiac catheterization. For patients who are unable to exercise, several
different types of stress testing that use medication to mimic the effect of physical
activity on the heart can be utilized.
Holter monitoring and cardiac event monitoring are ECGs that are
performed over a long period of time. The patient receiving Holter monitoring
wears electrodes attached to a portable monitor, about the size of a small cassette
player, for 24 hours. The test can be done at home. Cardiac event monitoring is
performed the same way as Holter monitoring, although cardiac event monitoring
can take as long as a month.
An implantable Loop recorder is a medical device that is placed beneath the
skin in the chest to record data about heart events over a long period of time-up to
two years. This type of monitoring can help diagnose someone who has infrequent
symptoms.
GE healthcare offers the ECG Mac series offering the Mac 800, 1200, 1600,
3500, and 5500 HD. The Mac 800 ECG is a portable device that is lightweight,
currently available in hospitals and clinics in Asia and Europe. The company also
offers the MARS Holter analysis system and the CardiMem CardioDay Holter
system.
Phillips Healthcare offers the PageWriter TC series, which is easy to use and
provides superior workflow. The company also offers the ST 80i stress test system.
Philips DigiTrak XT is one of the lightest Holter recorders on the market with a
large onboard display.
Schiller Healthcare offers the Cardiovit series of single, three, and twelvechannel ECG equipment under its range of resting ECG. It offers Spandon,
Cardiovit AT-10 Plus, Cardiovit CS-200, and Cardiovit CS-20 stress test systems. It
also offers Medilog AR12Plus, Medilog FD12, Microvit MT-101 Holter monitoring
systems.
Aerotel Medical Systems offers the HeartView series of ECG products. It
also offers the Heart 2005A and the Heart 2006 ECG with event recorders. The
HeartOne is a pocket-sized trans-telephonic ECG event recorder.

40
BPL offers the Cardiart ECG with new models of three- and six-channel. It
also offers products for six-channel, twelve-channel, and Holter with some unique
features focused on clinical productivity and network connectivity. The TRAK48 is
BPLs Holter monitor.
L&T Medical offers the Orion, which is a three-channel ECG machine
which can indirectly be used like a twelve-channel machine. The product can
capture samples at a high 1,000 samples per second.
MARKET SIZE AND GROWTH

The total electrocardiography market reached revenues of $1.1 billion in
2012. The market is comprised of revenues for ECG machines, Holter monitoring,
event monitoring and implantable loop. As wireless technology proliferates and
opens possibilities for more ECG testing systems, market demand can only be
expected to increase. An aging population combined with advancements in
technology is fueling this growth as health care providers seek ways to meet the
demand for high levels of service in a more cost effective manner.
Revenues are expected to reach $1.4 billion in 2017, growing at 4.4% over
the forecast period of 2012-2017.
Table 3-1
Total Electrocardiography Testing Market Analysis, 2010-2017

Year
2010
2011
2012
2013
2014
2015
2016
2017
1,069.0
1,089.0
1,112.0
1,152.6
1,200.0
1,250.0
1,310.0
1,380.0
Percent Change
1.9%
2.1%
3.7%
4.1%
4.2%
4.8%
5.3%

41
2010-2012
2012-2017
2010-2017
2.0%
4.4%
3.7%
Figure 3-1
Total Electrocardiography Testing Market Analysis, 2010-2017
$1,400
Revenues (in millions)
$1,200
$1,000
$800
$600
$400
$200
$0
2010
2011
2012
2013
2014
2015
2016
2017
Calendar Year

NON-INVASIVE CARDIAC IMAGING

X-Ray
One of the most common non-invasive tests for cardiac issues is a
conventional chest x-ray. Chest x-rays are the most commonly performed
diagnostic x-ray examination. A chest x-ray can help determine if problems exist in
the organs and structures in the chest. However, a chest x-ray can sometimes be
difficult even for experts to interpret and may not provide all the information
needed to determine the cause of a problem. If a chest x-ray is abnormal, more
specific x-rays or other tests such as a CT scan, an ultrasound or a magnetic
resonance imaging (MRI) scan may be needed.
About half of all radiographic exams are chest x-rays. More than 150
million chest x-rays are performed yearly in the US at a cost of more than $11
billion. Digital x-ray imaging can eliminate the time-consuming step of
conventional film processing. It eliminates the need for chemicals used for
developing the film, which are potentially hazardous and require special storage
conditions. As the images created by digital systems surpass those produced by film
in terms of quality, and because digital imaging vastly improves the efficiency of
storage and transmission of image data. The advantages of converting to digital xray technology are obvious.

Four: Cardiac Diagnostic Imaging

44
X-rays can be valuable in initially evaluating the size of the heart and the
contour of the heart. Enlargement of a particular chamber or blood vessel may
suggest heart failure or other abnormal functioning. It can also visualize the size of
the large blood vessels of the lungs. Enlarged blood vessels may suggest any of
several heart defects or diseases - and indicate the need for more sophisticated tests.
The use of x-rays to image moving blood is a challenge to system
manufacturers. The heart and blood vessels are in constant motion, and the image in
many applications involves motion, rather than a static image. Digital technology
products have evolved that image at sufficient speed to meet required specifications,
although the memory required to store such images is extremely high.
Conventional x-ray angiography has a lead role in the detection, diagnosis
and treatment of heart disease, heart attacks, acute stroke and vascular disease that
can lead to stroke. The market remains somewhat mature, with little growth
expected. Often, sales are made to replace aging systems. Angiographic x-ray
imaging has grown into its own specialty of x-ray imaging. Originally, angiograms
were obtained using conventional film. However, the development of more
powerful processors made it possible to digitally record images, obtaining the image
from an image intensifier and digitizing the output. With the arrival of digital x-ray
detectors, it became possible for the image intensifier and video camera to be
replaced by a more direct system of acquisition. Consequently, there was an
improvement in the quality of images produced and lower radiation doses to the
patient.
Compared with analog systems, digital images can also be manipulated in
various ways. One technique -- digital subtraction angiography -- acquires an image
of the patients tissue and skeletal structure before the contrast is injected. This
image -- the subtraction mask --- is digitally subtracted from the later images that
contain contrast. This creates an image in which the underlying body structures
virtually disappear, leaving only a picture of the injected contrast.
A traditional angiography suite includes an x-ray tube and an image
intensifier, which consists of a vacuum tube device that is placed near the patient.
The x-rays form an image on the face of the device. This image is amplified by a
photomultiplier tube and subsequently the image is viewed by a video camera, the

45
output of which is digitized and analyzed in a computer system. The dose to the
patient is significantly greater than in standard fluoroscopy because the patient is
being imaged for longer periods of time. The detectors must be sensitive and
operate at high speed in order to minimize the x-ray dosage.
The sensitivity of digital flat-panel systems and their ability to work at high
speeds can help decrease x-ray exposure and increase the definition of the image.
Also, digital flat-panel systems can replace the large image intensifiers, as well as
the pick-up apparatus and camera systems. This can allow developers to design
compact systems that cut down on required space and which give the care giver and
patient more room to maneuver during imaging.
Consumers lifestyle choices and the resulting increase in obesity rates and
incidences of heart disease are major drivers for cardiovascular x-ray systems,
which are used for cardiac catheterization and angiography. To view the heart and
blood vessels, the radiologist inserts a catheter into a blood vessel using
fluoroscopic guidance, and releases a contrast agent when the catheter reaches the
target. Images of the heart and blood vessels are obtained using digital subtraction
technology or similar methods. X-ray angiography is undertaken to specifically
image and diagnose diseases of the blood vessels of the body, including the brain
and heart. Traditionally, angiography was used to diagnose the pathology of these
vessels, such as blockage caused by plaque buildup. However, radiologists,
cardiologists and vascular surgeons now use x-ray angiography to guide minimally
invasive surgery of the blood vessels and arteries of the heart. Angiography to
diagnose an occluded artery may be performed using fluoroscopy or CT.
MRI
MRI can help physicians closely examine the structures and function of the
heart and major vessels quickly and thoroughly, without the risks associated with
traditional, more invasive procedures. Using MRI, physicians can examine the size
and thickness of the chambers of the heart, and determine the extent of damage
caused by a heart attack or progressive heart disease.
As a flexible tool, cardiac MRI has been harnessed for a variety of specific
applications, such as the detection and management of congenital heart disease and

46
cardiac masses, the assessment of valvular and ventricular function and myocardial
perfusion. Many cardiac MRI exams have been done on 1.5T systems but facilities
with the economic, technical, and staff resources have been converting to 3T systems.
In addition, developments in high-field technology and the advent of fast imaging
sequences have helped cardiac MRI become the reference modality for making
assessments of myocardial function, perfusion and viability imaging in ischemic and
nonischemic cardiomyopathies; for assessing cardiac tumors; and evaluating complex
congenital heart disease prior to and after surgery.
Non-contrast MRI is about five times more sensitive than and twice as
accurate as non-contrast CT when it comes to diagnosing ischemic stroke. MRI
appears to be a more sensitive test in detecting the most common form of stroke as
well as for diagnosing hemorrhagic strokes. MRI and CT are equally effective in
detecting acute intracranial hemorrhage. CT does have an advantage over MR for
coronary artery imaging. A 64 slice CT scan, although of lower resolution than a 3T
MRI, is relatively inexpensive and more popular. The image quality of cardiac CT
can also improve with the advent of the 128-slice CT, and this may be a threat for
cardiac MRI. However, concerns over the high radiation dose of the multi-slice CT
systems can increase the popularity of MRI once again.
Cardiac MRI gives physicians comprehensive data related to cardiovascular
function and disease. The images generated by MRI are complete, detailed and
precise, more so than other cardiac imaging tests. In certain groups of patients, the
modality is an alternative to competing modalities, such as stress tests,
electrocardiography, cardiac CT, and SPECT imaging. Makers of cardiovascular MRI
systems should develop automated coil-changing systems, and focus on enhancing
image-reconstruction technology. Cardiac MRI, because of its complexity, has largely
been limited to university hospitals where there is a strong research interest. Much of
the work with cardiac MRI has been done in the research setting.
New MRI systems featuring sophisticated 32-coil designs, low signal-to-noise
ratio and improved image acquisition have driven the cardiac area. MRI is giving
doctors a noninvasive way to gather data related to cardiovascular function and
disease. Cardiac MRI exams also offer rapid analysis and increased accuracy. The
modality has proven useful diagnosing various unusual cardiovascular problems. The

47
speed of MRI systems has earned them a place as an important research tool for
studying ischemia and cardiomyopathy.
Cardiac MRI can provide more information about atherosclerotic plaque than
does catheter angiography. MRI contrast agents under development will identify
vulnerable plaques work by targeting mediators of neovascularization or
macrophages in inflamed plaques. MRI probably will not replace any of the existing
cardiac imaging modalities but will become an integral part of a patients diagnostic
workup.
Ultrasound
Echocardiography uses reflected sound waves to provide an image of
cardiac structure and motion within the chest. The cardiac echo is obtained by
placing a blunt probe on the chest surface that transmits and receives highfrequency sound waves. Sound waves traveling to chest and heart structures are
reflected back to the receiving probe. The time between sound wave and
transmission and detection of reflected waves is used to calculate distances between
the probe and the reflecting tissue. The sound waves are not heard or felt by the
subject and have no known detrimental effects on tissues. The probe is moved
across the chest to assess cardiac structures of interest, and recordings are
videotaped for later viewing.
Echocardiograms are particularly useful for diagnosis of heart enlargement,
valvular disorders, collections of fluid in the pericardial space, cardiac tumors, and
abnormalities in the left ventricular motion.
Computed Tomography
Computed tomography or CT scanning of the heart (CT coronary
angiogram) is a procedure used to assess the extent of occlusion in the coronary
arteries, usually in order to diagnose coronary artery disease. The patient is injected
with an intravenous dye (iodine) and then the heart is scanned using a high speed
CT scanner, allowing radiographers to assess the blood flow to their heart muscle.
Computed tomography of the heart is not yet routinely used in clinical
practice. It may be useful in the diagnosis of suspected coronary heart disease, for

48
follow-up of a coronary artery bypass, for the evaluation of valvular heart disease
and for the evaluation of cardiac masses. More than just a diagnostic tool to
determine whether or not a patient has coronary artery disease, coronary CT
angiography (CCTA) can help physicians predict a patients risk of future cardiac
problems, according to a 2011 study published online in the Journal of the
American College of Cardiology. The study, led by Fabian Bamberg, MD, MPH, of
Ludwig-Maximilians University, Massachusetts General Hospital and Harvard
Medical School, is a meta-analysis of 11 articles involving 7,335 participants
(average age 59.1 years, 62.8% male) from studies published in PubMed, Embase
and the Cochrane Library through January 2010. The studies involved patients with
suspected heart disease, followed up with more than 100 subjects for more than a
year, and reported elevated risk of subsequent heart issues in areas of interest to the
researchers.
The researchers found that one or more CCTA-spotted stenoses of 50% or
greater led to a more than 10-fold higher risk of subsequent events in studies that
included data on revascularization. In studies excluding revascularization, patients
with similar stenosis had a more than six-fold risk of subsequent events. The study
found that CCTAs predictive value was solid even when adjusting for coronary
calcification. Patients with arterial plaque were 4.5 times more likely to have had a
future coronary event, the data showed. The presence and extent of coronary artery
disease on CCTA are strong, independent predictors of cardiovascular events
despite heterogeneity in endpoints, categorization of computed tomography
findings, and study population, the authors conclude.
It is uncertain whether this modality will replace invasive coronary
catheterization. At present, it appears that the greatest utility of cardiac CT lies in
ruling out coronary artery disease rather than ruling it in. This is because the test is
highly sensitive (over 90% detection rate), so a negative test result largely rules out
coronary artery disease. The test is not very specific, however, so a positive result is
less conclusive and will need to be confirmed by subsequent invasive angiography.
Electron Beam Computed Tomography
Electron beam computed tomography (EBCT) is a specific form of
computed tomography in which the X-ray tube is not mechanically spun in order to

49
rotate the source of X-ray photons. This different design was explicitly developed to
better image heart structures which never stop moving, performing a complete cycle
of movement with each heartbeat.
As in conventional CT technology, the X-ray source-point moves along a
circle in space around an object to be imaged. In EBT, however, the X-ray tube
itself is large and stationary, and partially surrounds the imaging circle. Rather than
moving the tube itself, electron-beam focal point is swept electronically along a
tungsten anode in the tube, tracing a large circular arc on its inner surface. This
motion can be very fast.
GE offers the eSpeed EBCT scanner which detects and measures calcium in
the coronary arteries. The test is non-invasive with no pain, using no injections,
chemicals or incisions.
Dual Source Computed Tomography
Dual source computed tomography(DSCT) is also available. With its 2X-ray
sources and to sixty-four-row detectors, it is twice as fast as previous high-end CT
scanners. It provides brilliant images of the heart and coronary vessels. DSCT
provides high-resolution images of the coronary vessels at an incredible speed,
which makes it possible to take perfect images even of a rapidly or irregularly
beating heart.
Nuclear Cardiography
Reactive substances injected into the bloodstream can be used to trace the
patterns of blood flow in the heart. Radiation exposure is minimal, as very small
amounts of radioactive substances are used. The most common nuclear imaging
tests are technetium pyrophosphate scanning, thallium imaging, and gated bloodpool scanning.
Technetium scanning is used to visualize infarcted areas of cardiac muscle
that accumulate the radioisotope. The radioactive technetium is injected into the
bloodstream and then allowed to clear from the system for two hours. Infarcted
cardiac tissues appear as hotspots when scanned with a gamma scintillation camera,
which measures radioactive disintegrations of the 99mTc radioisotope.


50
Thallium imaging is used to assess the adequacy of blood flow to cardiac

tissues. After injection of radioactive thallium, the heart is quickly scanned to
visualize the amount of radioactivity taken up by cardiac tissues. Healthy cardiac
tissues that receive adequate blood supply actively accumulate the isotope. Areas of
inadequate blood flow or infarcted tissue do not accumulate the isotope and appear
as cold spots on the skin.
Gated pool scanning is used primarily to assess the left ventricular motion
and ejection fraction. Before it is injected intravenously, radioactive technetium is
attached to albumin or red cells, and therefore it remains in the bloodstream and is
not taken up by the cells. Computer imaging is used to analyze blood flow through
the chambers of the heart over many cardiac cycles. The dynamics of ventricular
motion, such as hyper contractility or hypo contractility, may be visualized.
Single photon emission computed tomography (SPECT) is a nuclear
medicine tomographic imaging technique that involves the use of gamma rays.
SPECT is very similar to conventional nuclear medicine planar imaging that uses a
gamma camera. However, it is able to provide true three-dimensional (3-D)
information. This information is typically presented as cross-sectional slices
through the patient, and can be freely reformatted or manipulated as required. In the
same way that a plain x-ray is a 2-dimensional (2-D) view of a three-dimensional
structure, the image obtained by a gamma camera image is a 2-D view of the 3-D
distribution of a radionuclide.
In SPECT imaging, a gamma camera acquires several 2-D images
from a variety of angles. Software applies a tomographic reconstruction algorithm
to the projections, yielding a 3-D dataset. This dataset may then be manipulated to
show thin slices along any chosen axis of the body, similar to those obtained from
other tomographic techniques, such as MRI, CT and PET. Because SPECT
acquisition is very similar to planar gamma camera imaging, the same
radiopharmaceuticals may be used.
To acquire SPECT images, the gamma camera is rotated around the
patient. Cardiac gated acquisitions are possible with SPECT. These are triggered by
an EKG which guides the acquisition of information to obtain data about the heart
in various parts of its cycle. Gated myocardial SPECT can be used to obtain

51
quantitative information about the perfusion, thickness and contractility of the

myocardium during various parts of the cardiac cycle. The technique also makes it
possible to calculate left ventricular ejection fraction, stroke volume, and cardiac
output. SPECT can complement any gamma imaging study, in which a true 3-D
representation can be helpful, such as in tumor imaging, infection (leukocyte)
imaging, thyroid imaging or bone imaging. Because SPECT permits accurate
localization in 3-D space, it can provide information about the functioning of
internal organs, such as the heart and the brain.
SPECT cardiac imaging, as used in nuclear cardiac stress testing, is
performed using several cameras, which are slowly turned in a circle, on a single
axis of rotation, around the target. Multi-headed gamma cameras can also be used
for PET scanning, provided that their hardware and software can be configured to
detect near simultaneous events on two different heads. Gamma cameras will be
helped by the creation of novel imaging agents that allow small molecules or
peptides that target tumor cells to be bound to technetium-99. Such agents would
allow gamma cameras to image the metabolic activity of tumors, much like PET
does today. Nuclear cardiology exams are estimated to account for more than 50%
of total nuclear exams performed by gamma cameras, and the number continues to
grow
Myocardial perfusion imaging (MPI) is a form of functional cardiac
imaging, and is used for the diagnosis of ischemic heart disease. SPECT imaging
performed after stress can indicate the distribution of the radiopharmaceutical, and
the relative blood flow to the different regions of the myocardium. Diagnosis of a
problem is made by comparing these stress images to a set of images obtained with
the patient at rest. The radionuclide redistributes slowly throughout the system, so it
is not usually possible to perform both sets of images on the same day, so a second
attendance is required a few days later. In some cases, if stress imaging is normal, it
may be unnecessary to perform rest imaging, as it too will be normal. For this
reason, stress imaging is usually performed first.


52
Table 4-1
Non-Invasive Cardiac Imaging Market Analysis, 2010-2017

Year
2010
2011
2012
2013
2014
2015
2016
2017
3,800.0
3,910.3
4,050.0
4,223.0
4,421.5
4,642.3
4,900.0
5,200.0
Percent Change
2.9%
3.6%
4.3%
4.7%
5.0%
5.6%
6.1%

2010-2012
2012
2012-2017
2010-2017
3.2%
5.1%
4.6%
INVASIVE TRANSCATHETER CARDIAC IMAGING

Cardiac Catheterization/Angiography Products
Of the many available diagnostic tools for cardiac evaluation, cardiac
catheterization provides the most definitive information. Cardiac catheterization
may be used to determine important structural and hemodynamic characteristics as
it affords direct measurement of pressure within cardiac chambers; visualization of
chamber size, shape, and movement; sampling for blood oxygen content in various
heart regions; measurement cardiac output and ejection fraction; and visualization
and treatment of coronary artery obstructions.
Cardiovascular catheterization is technically a minimally invasive procedure
in which a catheter is guided into the heart, usually through a blood vessel in the leg
or arm. Once inside the heart, it can be used for diagnosing or treating a condition.
By gaining access to the beating heart, cardiac catheters allow a physician to check
the internal blood pressure of the heart, assess blood supply, view the coronary

53
arteries on the surface of the heart and the aorta, and check the level of oxygen in
the blood.
Cardiovascular catheters can also be used to evaluate the ability of the
pumping chambers to contract, as well as to assess the function of heart valves.
Cardiac catheterization is one of the most accurate tests in the diagnosis of coronary
artery disease, and more than one million of them are performed each year. During
cardiac catheterization, the catheter is inserted through a very small cut made by the
physician (in the groin, arm or wrist), then guided up through the blood vessel to the
heart. The physician tracks the course of the catheter by watching it on a
fluoroscope. A variety of measurements may be performed when the catheter is in
place, and then the catheter is removed. After some recovery time, most patients are
free to go home after about six hours. Results are available to the physician
immediately. Cardiac catheterization angiography is associated with several serious
risks, including bleeding, dysrhythmias, heart perforation, and coronary ischemia.
However, the value of information supplied is generally believed to far outweigh
the risks. Catheterization is frequently used to evaluate suspected or confirmed
coronary artery disease, valvular dysfunction, congenital defects, left ventricular
dysfunction, and coronary bypass graft patency.
Assessment of the left side of the heart, including the coronary arteries is
achieved by passing a catheter through a femoral or brachial artery into the aorta.
The catheter is then manipulated into the left ventricle or left atrium to assess
chamber pressures, and a ventriculogram is obtained. Contrast dye injected into the
ventricular chamber is monitored by fluoroscopy to assess ventricular function. The
catheter is usually pulled back into the aorta and advanced into one or more of the
coronary arteries. The patency of the coronary arteries can be visualized by
injecting contrast dye into them and monitoring by fluoroscopy. If contrast dye is in
the coronary artery, a period of cardiac ischemia is produced during which the
patient may experience angina, dysrhythmias, and coronary spasms.
Right-sided heart catheterization is done to evaluate right-sided heart
structures. The catheter is introduced into a vein, usually femoral or antecubital,
then threaded through the inferior vena cava and into the heart. Pressures and blood
samples are obtained as the catheter is advanced into the right atrium, ventricle, and

54
pulmonary artery. Right heart catheterization is useful in assessing tricuspid and

pulmonary valve disorders, pulmonary hypertension, septal defects, and right
ventricular function.
In the last 20 years, coronary angiography has moved from method of
assessment only to a method of treatment for coronary occlusion. The coronary
catheter can be used to direct thrombolytic agents to the site of coronary thrombosis
and rapidly restore blood flow to ischemic areas. Laser therapy, coronary balloon
angioplasty, and stent placement can also be performed during angiography. Nearly
80% of angiography laboratories in the US have made the transition to filmless
imaging. Digital technology enables cardiologists to control all movements and
interventional tools in order to provide support for diagnosing and treating
congenital heart disease and performing vascular examinations. One of the major
advantages of digital technology is that treatment can also be carried out at the same
time. Closed or impeded blood vessels can be opened by inflating a balloon catheter
and if necessary, a stent can be placed to keep the vessel open.
Catheters also are used in an ablation electrophysiology study. This is a
procedure in which the catheter is inserted into a vein or artery, such as in the groin,
and guided to the heart, where it can perform highly specific measurements of the
hearts electrical activity and pathways. These measurements are particularly helpful
in the diagnosis of abnormally fast heart rhythms tachycardias -- or abnormally
slow heart rhythms -- bradycardias. This study is usually performed only after other
noninvasive tests, such as an electrocardiogram (EKG), have been performed.
Another type of cardiovascular catheter is also used when a cardiac or
coronary angiography is performed to detect obstruction in the coronary arteries of
the heart. During the procedure a catheter is inserted into an artery in the arm or groin
and threaded carefully into the heart. The blood vessels of the heart are studied by
injection of contrast media through the catheter. Fluoroscopy is used to view the flow
of blood. Peripheral angiograms are most commonly done to test the arteries which
supply the blood to the head and neck or the abdomen and legs. Because arteries do
not show up on ordinary x-rays, arteriograms utilize a contrast agent containing
iodine, which is injected into the arteries to make them visible on radiographs.

55
Problems with the arteries may lead to a variety of complications such as stroke, high
blood pressure or leg pain. In a peripheral angiography, the groin will be numbed
with a local anesthetic which burns or stings a bit before it takes effect. A catheter is
placed into the artery in the groin and manipulated by the doctor into the artery
requiring study. As the catheter is being moved, there is slight pressure in the groin.
Once the catheter is in place, contrast material is injected through the catheter into the
arteries and a series of x-rays will be taken very quickly.
Vascular imaging is changing dramatically. It is no longer enough simply to
find that a patient has an arterial stenosis. Now, physicians want to visualize the
circulation to the region, evaluate the vessel wall, and determine the composition of
plaques so they can better select and monitor treatment. There also is a growing
push to screen for vascular diseases beyond the heart in order to prevent myocardial
infarction and stroke.
Intravascular Ultrasound
Intravascular ultrasound (IVUS) is a medical imaging methodology using a
specially designed catheter with a miniaturized ultrasound probe attached to the
distal end of the catheter. The proximal end of the catheter is attached to
computerized ultrasound equipment. It allows the application of ultrasound
technology to see from inside blood vessels out through the surrounding blood
column, visualizing the endothelium (inner wall) of blood vessels in living
individuals.
The coronary arteries are the most frequent imaging target for IVUS. IVUS
is used in the coronary arteries to determine the amount of atheromatous plaque
built up at any particular point in the epicardial coronary artery. The progressive
accumulation of plaque within the artery wall over decades is the setup for
vulnerable plaque which, in turn, leads to heart attack and stenosis of the artery.
IVUS is of use to determine both plaque volume within the wall of the artery and/or
the degree of stenosis of the artery lumen. It can be especially useful in situations in
which angiographic imaging is considered unreliable; such as for the lumen of ostial
lesions or where angiographic images do not visualize lumen segments adequately,
such as regions with multiple overlapping arterial segments. It is also used to assess

56
the effects of treatments of stenosis such as with hydraulic angioplasty expansion of

the artery, with or without stents, and the results of medical therapy over time.
Cardiovascular imaging may also include other important imaging
techniques. InfraReDx, Burlington, MA, is marketing the LipiScan IVUS Coronary
Imaging System that combines co-registered grayscale intravascular ultrasound with
the companys proprietary near infrared lipid core plaque detection technology/NIR
spectroscopy to help physicians optimize their stenting strategy when dealing with
plaque in the coronary artery walls. VP is plaque that does not show up in a normal
angiography but is far, far more likely to be lethal than the usual clogged arteries.
The TVC Imaging System is a IVUS system that provides information that
is critical for evaluating vessel structure and composition, also known as true vessel
characterization. The TVC Imaging System helps interventional cardiologists
identify which patients are prone to complications during stenting. The device
enables cardiologists to predict peri-procedural heart attacks by assessing not only
the degree of stenosis, but also the presence and extent of lipid core plaques. The
device is the only multimodality imaging system to combine both intravascular
ultrasound and near-infrared spectroscopy (NIRS).
Other groups, such as the University of Arizona, Tucson, AZ, are trying
optical coherence tomography, RAMAN and fluorescence to locate areas of disease
from within.
Players in this market include Boston Scientific, St. Jude, and Volcano.
Optical Coherence Tomography
Optical coherence tomography (OCT) is a next-generation coronary imaging
technology platform that aids physicians in the diagnosis and treatment of
cardiovascular disease, and is used by interventional cardiologists to assist with
stent selection and provide post-stenting information.
OCT technology utilizes near-infrared light to create images that go beyond
older coronary imaging technologies - such as fluoroscopy and intravascular
ultrasound (IVUS) - offering cardiologists an assessment method with enhanced
clarity for their patients with coronary artery disease. With the technology,
physicians can visualize and measure important vessel characteristics that are

57
otherwise not visible or difficult to assess with the older imaging technology.
Additionally, images are created with 10 times the resolution of intravascular
ultrasound technology.
The C7-XR System with the C7 Dragonfly Imaging Catheter was launched
in Europe in May 2009 and follows the M3 OCT Imaging System. St. Jude Medical
offers the only commercially available intracoronary OCT imaging device in the
world. The C7-XR Coronary Imaging System is commercially available in the U.S,
Europe and Australia.
Electrophysiology
Catheters also are used in an ablation electrophysiology study. This is a
procedure in which the catheter is inserted into a vein or artery, such as in the groin,
and guided to the heart, where it can perform highly specific measurements of the
hearts electrical activity and pathways. These measurements are particularly
helpful in the diagnosis of abnormally fast heart rhythms tachycardias -- or
abnormally slow heart rhythms -- bradycardias. This study is usually performed
only after other noninvasive tests, such as an electrocardiogram (EKG), have been
performed.
Many abnormal rhythms are the result of areas of abnormal tissue which
cause the hearts electrical system to short circuit. Once a doctor determines exactly
where abnormal tissue in the heart is located, it can be ablated. By ablating, or
destroying, abnormal tissue areas in the heart, its electrical system can be repaired
and the heart will return to a normal rhythm. A physician will position the ablation
catheter so that it lies on or very close to the abnormal tissue. High-frequency
electrical energy is then sent through the ablation catheter into this abnormal tissue.
The small area of heart tissue under the tip of the ablation catheter is heated by this
high-frequency energy, creating a lesion or tiny scar. As a result, this tissue is no
longer capable of conducting or sustaining the arrhythmia.


58
Table 4-2
Invasive Transcatheter Cardiac Imaging Market Analysis,

2010-2017
Year
2010
2011
2012
2013
2014
2015
2016
2017
2,468.0
2,520.0
2,598.0
2,688.0
2,790.0
2,912.0
3,040.0
3,180.0
Percent Change
2.1%
3.1%
3.5%
3.8%
4.4%
4.4%
4.6%

2010-2012
2012
2012-2017
2010-2017
2.6%
4.1%
3.7%
MARKET SIZE AND GROWTH

The total cardiac diagnostic imaging market reached revenues of $6.6 billion
in 2012. The market is comprised of revenues for noninvasive imaging modalities
and invasive transcatheter imaging. These two segments vary in total revenues and
growth rates. Since cost is a predominate factor, we will likely see continued
growth in less expensive modalities such as ultrasound and general x-ray. Revenues
are expected to reach $8.4 billion in 2017, growing at a healthy 4.7% over the
forecast period of 2012-2017.
Noninvasive Imaging
The cardiology market for noninvasive imaging will continue to grow
coming out of the recession in the 4% to 5% range annually. MRI could

59
complement several cardiac tests, including the echocardiogram, the MUGA scan,
the thallium scan and diagnostic cardiac catheterization. MRI has the potential of
detecting changes in the blood vessels of the heart the microvascular circulation
that are completely missed by cardiac catheterization. Detecting such changes seem
to be useful in predicting the outcome of patients after a heart attack, and may prove
to be useful in assessing patients with cardiac syndrome X, diabetes, and certain
other conditions. Facilitating growth would be any software that helps acquire better
images. New contrast agents could also improve the diagnosis of heart-related
disease.
The cylindrical 3T MRI market is set for global revenue growth. This will
likely be due to increased market penetration of wide aperture and short bore systems.
Demand for 64-slice and above CT systems will continue to drive CT revenues as the
demand for greater image quality, particularly in CT angiography (CTA) is realized.
In addition, the release of dynamic flat panel detectors for angiography, cardiology
and fluoroscopy X-ray should help to increase revenues as well.
Invasive Transcatheter Imaging
Spurring the use of cardiac angiography catheters is the improved
predictability of the procedure itself. In addition, the angiography procedure is
becoming more popular in lesser developed countries as the incidence of
cardiovascular disease has grown in such places as Asia, sub-Saharan Africa and
Latin America. Whereas in the past, communicable disease and infant mortality due
to malnutrition were the primary causes of death in these regions, the gradual
improvement in the standard of living has reduced deaths due to those causes. As
the economies in those regions develop, dietary fat consumption increases, the level
of physical exercise drops and smoking tends to increase -- all leading to an
increased risk of cardiovascular disease.
Also, certain populations are genetically predisposed to cardiovascular
disease, particularly in lesser developed countries. That is explained by the selection
process that occurs in times of famine, when individuals who are genetically
predisposed to minimize calorie use tend to have a survival advantage. As food
becomes more available, such individuals' risk of cardiovascular disease increases

60
dramatically. Other causes of cardiovascular disease in developing countries include

parasitic infections, such as Chagas' disease and rheumatic fever, infectious diseases
that can cause destruction of heart muscle and eventually lead to heart failure.
Table 4-3
Total Cardiac Diagnostic Imaging Market Analysis, 2010-2017

Year
2010
2011
2012
2013
2014
2015
2016
2017
6,268.0
6,430.3
6,648.0
6,911.0
7,211.5
7,554.3
7,940.0
8,380.0
Percent Change
2.6%
3.4%
4.0%
4.3%
4.8%
5.1%
5.5%

2010-2012
2012-2017
2010-2017

3.0%
4.7%
4.2%

61
Figure 4-1
Total Cardiac Diagnostic Imaging Market Analysis, 2010-2017
$9,000
$8,000
$7,000
$6,000
$5,000
$4,000
$3,000
$2,000
$1,000
$0
2010
2011
2012
2013
2014
2015
2016
2017
Calendar Year

Cardiac Diagnostic Point of

Care Testing
Cardiac point-of-care (POC) diagnostics encompasses tests performed both

in and out of the hospital setting. Professionals administer cardiac POC tests in the
hospitals, physicians offices, clinics, and other patient care sites. The hospital arena
is by far the largest user of cardiac POC testing, but there is a growing trend to offer
cardiac POC tests in other professional settings as well. Physicians offices and
clinics use cardiac POC testing to increase patient satisfaction with the visit and
improve diagnostic, therapeutic, and monitoring practices. The growth of cardiac
POC testing in physicians offices, clinics, and other patient care sites has
preliminarily resulted from continual pressure by payers to treat patients outside the
acute-care facility setting in order to reduce costs.
Cardiac POC tests fall under the category of laboratory testing though they
are performed at the bedside, office, or clinic. This deems it necessary for cardiac
POC tests to be regulated by the Clinical Laboratory Improvement
Amendments(CLIA). The FDA is responsible for categorizing medical diagnostic
tests based on order of difficulty-wave testing being the least difficult; moderate
complexity; and high complexity.

Five: Cardiac Diagnostic Point of Care Testing

64
Kaloramas market for cardiac POC testing consists of two areas:

x
Coagulation
Cholesterol
Coagulation Testing
The hospital market for cardiac POC coagulation tests is made up primarily
of activated coagulation time (ACT) test run on patients receiving heparin during
cardiovascular and other surgeries. Prothrombin time test (PTT) measures the
activity of clotting factors. Deficiency of any of these clotting factors can lead to a
prolongation of one-stage prothrombin times, as will circulating anticoagulants that
are active against these factors. The test is considered basic to any study of the
cardiac coagulation process and is also widely used for guidance in establishing and
maintaining anticoagulant therapy.
In prothrombin time self-testing for patients taking Coumadin the market for
POC PT testing is still evolving. Roche diagnostics pioneered the coagulation selftest market since the mid-1990s and has had some success in Europe, especially in
Germany. The US market for home PT testing has been developing slowly. Several
companies have developed home PT devices that were cleared by the FDA.
International Technidyne Corporation offers the Prothrombin Time Test
System and the ProTime Microcoagulation System for home and professional use.
The system consists of a portable battery-operated instrument and disposable
determination of prothrombin time from finger-stick whole blood or anti-coagulantfree venous whole blood. The system measures prothrombin time using fibrin clot
formation and detection. International Technidyne Corporation also offers the
Hemochron Signature Elite. International Technidyne Corporation is the market
leader in ACT testing but Siemens, Roche Diagnostics and Abbott are making
inroads into the area as well
Alere/HemoSense offers INRatio Prothrombin Time Monitoring System.
This product uses a modified version of the one-stage PTT and provides a
quantitative prothrombin time result that is intended for use by healthcare
professionals in monitoring patients who are on warfare and anticoagulant therapy.


65
Roche diagnostics offers the PTS test strip intended for quantitative
prothrombin time testing to be used with the CoaguChek system. The system uses
whole blood for testing and is designed for on-the-spot testing of prothrombin time
and aPTT. CoaguChek is a diagnostic system that is to be used by the attending
physician and by the patient for monitoring of oral anticoagulant therapy. The result
is directly displayed as INR, %Quick, SEC, or Ratio.
Table 5-1
Cardiac Coagulation Testing Market Analysis, 2010-2017

Year
2010
2011
2012
2013
2014
2015
2016
2017
445.0
460.0
480.0
502.0
526.0
553.0
582.0
612.0
Percent Change
3.4%
4.3%
4.6%
4.8%
5.1%
5.2%
5.2%

2010-2012
2012
2012-2017
2010-2017
3.9%
5.0%
4.7%
Cholesterol Testing
Cholesterol test give an indication of lipid levels in the blood. An elevated
serum lipid level is one of the foremost firmly established risk factors for
cardiovascular disease. More specifically the risk of cardiovascular disease is
associated with a serum cholesterol level of more than 200 mg/dL or a fasting
triglyceride level of more than 150 mg per d>. The liver is capable of producing
cholesterol from saturated fats, even when the dietary intake of fats is severely
limited. High correlation between cholesterol and triglyceride levels has been


66
found. Elevated triglyceride levels are correlated with obesity, a sedentary lifestyle,
and high alcohol intake.
For lipids to be transported by the body, they need to be soluble in the blood
by combining with proteins. Lipids combined with proteins to form
macromolecules called lipoproteins. Glycoproteins are vehicles for fat mobilization
and transport. The different types of lipoprotein very in composition and are
classified as high-density lipoproteins (HDL), low-density lipoproteins (LDL), and
very low-density lipoproteins (VLDL).
HDLs contain more protein weight and fewer lipids than any other
lipoprotein. HDLs carry lipids away from arteries and to the liver for metabolism.
Therefore, high serum HDL levels are desirable. This process of HDL transport
prevents lipid accumulation within the arterial walls. The higher the HDL levels in
the blood, the lower risk for heart disease. HDL levels are generally higher in
women than in men and are increased by physical exercise and estrogen.
LDLs contain more cholesterol than any of the other lipoproteins and have
an affinity for arterial walls. Elevated LDL levels correlate most closely with an
increased incidence of atherosclerosis. Cholesterol testing identifies the LDL level.
Alere/Cholestech offers LDX system, which measures the levels of total
cholesterol (TC), high-density lipoprotein, and triglycerides; calculates TC/HDL
ratio; and estimates levels of low-density lipoprotein and very-low-density
lipoprotein.
Roche offers the AccuCheck InstantPlus and the Reflotron cholesterol
testing products. The AccuCheck InstantPlus cholesterol test uses reflectance
photometers for the quantitative determination of cholesterol and triglycerides, with
data output ports or data management functions. The Reflotron is a self-calibrating
desktop system for near-patient-testing in the physicians office. The product
provides quantitative determination of seventeen basic clinical parameters for the
most common indicators, with results obtained in 2 to 3 minutes.
CholesTrak was FDA-cleared for professional use in 1991 and was
introduced to the over-the-counter market for consumer use in 1994. CholesTrak
was formally known as Advanced Care and originally promoted by Johnson &

67
Johnson. AccuTech acquired cholesterol in 1999 from a failed company called

ChemTrak who used to manufacture the product for Johnson & Johnson. AccuTech
then reintroduced the product to the POC market in its current form, a palm size,
non-instrumented cassette cholesterol test system called the CholesTrak.
Polymer Technology Systems offers the PTS Lipid Panel Test Strips for use
with the CardioChek device. The lipid panel test strips are dry phase test strips that
are constructed from a plastic strip holder that holds chemically treated membranes.
The lipid panel test strips are for in vitro diagnostic use with the CardioChek
reflectance photometers. Lipid measurements are used to measure cholesterol, HDL
cholesterol, and triglycerides in whole blood.
The self-test market is struggling to make inroads. This is mainly due to the
fact that market penetration has been hampered by patient reluctance to prick their
fingers for a test that is not considered lifesaving such as glucose testing. As the
industry continues to evolve, this may be an area for expansion and needle-free
mechanisms may be an answer. There are numerous needle-free innovations that are
presenting on the market. Please see Kaloramas new report Injectable and Needlefree Drug Delivery published earlier this year.
Most professional cholesterol testing takes place outside the hospital
inpatient care sites such as physicians offices, clinics, and wellness fairs. The
market leaders are Roche and Alere/Cholestech.
Table 5-2
Cardiac Cholesterol Testing Market Analysis, 2010-2017

Year
2010
2011
2012
2013
2014
2015
2016
2017
290.0
302.0
315.0
330.0
347.0
366.0
387.0
410.0
Percent Change
4.1%
4.3%
4.8%
5.2%
5.5%
5.7%
5.9%


68
2010-2012
2012-2017
2010-2017
4.2%
5.4%
5.1%
TOTAL CARDIAC DIAGNOSTIC POINT-OF- CARE MARKET

SIZE AND GROWTH
The total cardiac diagnostics point-of-care market reached revenues of $795
million in 2012. The market is comprised of revenues for coagulation testing and
cholesterol testing. These two segments vary in total revenues and growth rates.
Since cost is a predominate factor, it is anticipated that cardiac point-of-care testing
will continue to demonstrate healthy growth. Revenues are expected to reach $1.0
billion in 2017, growing at a healthy 5.2% over the forecast period of 2012-2017
Table 5-3
Total Cardiac Diagnostic POC Testing Market Analysis,

2010-2017
Year
2010
2011
2012
2013
2014
2015
2016
2017
735.0
762.0
795.0
832.0
873.0
919.0
969.0
1,022.0
2010-2012
2012-2017
2010-2017
Percent Change
3.7%
4.3%
4.7%
4.9%
5.3%
5.4%
5.5%
4.0%
5.2%
4.8%


69
Figure 5-1
Total Cardiac Diagnostic POC Testing Market Analysis,

2010-2017
$1,200
$1,000
$800
$600
$400
$200
$0
2010
2011
2012
2013
2014
2015
2016
2017
Calendar Year

Cardiac Markers
Cardiac markers are biomarkers measured to evaluate heart function. Most

of the early markers were identified as enzymes. However, not all of the markers
currently used are enzymes. Physicians use cardiac markers in two ways-to
diagnose a cardiac event in the hospital emergency room or to evaluate the risk of a
cardiovascular event occurring. The traditional markers are CK-MB, troponin, and
myglobin. There cardiac biomarkers are one of the fastest growing markets
involving clinical immunoassay testing. Cardiac biomarkers have been the new
frontier in cardiovascular and metabolic disease diagnosis. By coupling cardiac
biomarkers with cholesterol testing and patient histories, physicians have been
moving toward the prevention of disease such as coronary thrombosis and stroke by
accurately assessing risks.
To date, cardiac markers that are available on the market assist physicians in
the diagnosis, prognosis and risk management of cardiovascular diseases such as
heart failure and myocardial infarction. However, there is a concerted effort to
identify other cardiac markers that will assist in the detection of earlier events in the
MI disease process that will improve treatment and save lives.
CK-MB stands for Creatine Kinase. CK-AMB resides in the cytosol and
facilitates movement of high-energy phosphates into and out of mitochondria. It is
distributed in a large number of tissues even in the skeletal muscle. Since it has a
short duration, it cannot be used for late diagnosis of acute MI but can be used to
Six: Cardiac Markers

72
suggest infarct extension if levels rise again. This is usually returns to normal within
2 to 3 days.
Troponin is released during MI from the cytosolic pool of the myocytes. Its
subsequent release is prolonged with degradation of actin and myosin filaments.
Differential diagnosis of troponin elevation includes acute infarction, severe
pulmonary embolism causing acute right heart overload, heart failure, and
myocarditis. Proponents can also calculate infarct size but the peak must be
measured in the third day. After MI injury, troponin is released up to four hours and
persists for up to seven days.
Myoglobin is used less than the other markers. Myoglobin is the primary
oxygen-carrying pigment of muscle tissue. It is high when muscle tissue is damaged
but it lacks specificity. It has the advantage of responding very rapidly, rising and
falling earlier than CK-MB or troponin. It also has been used in assessing
reperfusion after thrombolysis.
Additional cardiac markers are being used which include tests such as mild
low peroxidase (MPO), brain natriuretic peptide (BNP), pro-BNP, C-reactive
protein (hsCRP), homocysteine, fatty acid binding protein (FABP), glycogen
phosphorylate isoenzyme BB GPBB), urinary albumin, and S-100 protein and
hemoglobin A-1 c (hbA1c) .
Rapid, quantitative results for multiple cardiac markers elicited from the
point-of-care generally have a positive effect on misdiagnosed myocardial
infarctions, and provide cost-savings benefits to hospitals, clinics, and patients.
Selected companies that participate in the cardiac marker POC test kit arena
include:
Ani Biotech Oy offers the Biocard Troponin I test which is a one-step
immunochromatographic assay for the rapid detection of cardiac specific troponin I
from patient whole blood samples. The company also offers myoglobin, MPO,
hsCRP, quantitative reader, and CRP cardiac marker tests.
Alere offers the CardioProfilER panel as an aid in the diagnosis of
myocardial infarction, the diagnosis and assessment of severity of congestive heart
failure and the risk stratification of patients with acute coronary syndromes. The

73
panel combines troponin I, CK-MB, myoglobin, BNP and D-dimer to provide

accurate results in whole blood and plasma.
Siemens offers the Stratus CS analyzer for near-patient care quantitative
cardiac marker testing from a whole blood sample in 14 minutes. The company also
offers myoglobulin, CK-MB, and cardiac troponin I tests.
Nexus Dx offers the cardiac STATus test.
Other companies offering cardiac markers include A/C Diagnostics, Critical
Diagnostics, Gold Standard Diagnostics, Athera Biotechnologies, B. R. A. H. M. S
/Fisher, China Sky One Medical, Rennesens GmbH, and Roche Diagnostics.
TOTAL CARDIAC MARKERS MARKET SIZE
AND GROWTH
The total cardiac markers market reached revenues of $1.9 billion in 2012.
The market is comprised of revenues for troponin, CK-MB, BNP, myoglobin
testing, which account for approximately 75% of cardiac marker testing. Since cost
is a predominate factor, it is anticipated that cardiac marker testing will continue to
demonstrate healthy growth. An aging population combined with advancements in
A number of new and developing markers are in development. It
anticipated that new cardiac panels will emerge, which combine markers
inflammation, ischemia, plaque instability and necrosis. Revenues are expected
reach $2.6 billion in 2017, growing at a healthy 6.3% over the forecast period
2012-2017

is
of
to
of

74
Table 6-1
Total Cardiac Markers Market Analysis, 2010-2017

Year
2010
2011
2012
2013
2014
2015
2016
2017
1,750.0
1,795.0
1,880.0
1,976.0
2,086.0
2,223.0
2,375.0
2,550.0
2010-2012
2012-2017
2010-2017
Percent Change
3.8%
4.7%
5.1%
5.6%
5.6%
6.8%
7.4%
4.2%
6.3%
5.7%


75
Figure 6-1
Total Cardiac Markers Market Analysis, 2010-2017
$3,000
$2,500
$2,000
$1,500
$1,000
$500
$0
2010
2011
2012
2013
2014
2015
2016
2017
Calendar Year

Cardiac Diagnostic Contrast

Agents and
Radiopharmaceuticals
A contrast medium, or contrast agent, is a substance that enhances the visual

information contained in an image generated by medical diagnostic equipment,
including such modalities as x-ray, computed tomography (CT), magnetic
resonance (MR), and ultrasound. A radiopharmaceutical is an image-enhancing
agent, or drug, used for imaging purposes with nuclear medicine modalities -- single
photon emission computed tomography (SPECT) and positron emission
tomography (PET). Contrast media and radiopharmaceuticals can either be
swallowed or injected intravenously to enhance the contrast and distinction among
anatomical structures in the image itself.
Contrast Agents
Ultrasound images can be improved by using contrast agents. In ultrasound,
a contrast agent's purpose is to increase the refraction and reflection of the
ultrasonic waves. One way of doing this is to use a contrast agent that consists of
millions of ultra-small air bubbles, each of which will reflect the sound wave. Tiny
gas bubbles with a size of less than 10 m are stabilized within a biodegradable
shell. Without this shell, the bubbles would be stable only for a matter of seconds,
and the unstabilized bubbles would soon merge into larger bubbles. Besides being
Seven: Cardiac Diagnostic Contrast Agents and Radiopharmaceuticals

78
potentially hazardous to the patient, large bubbles have different, and less suitable,
reflective properties. By filling the blood stream with the ultrasound contrast agent,
it is possible to significantly increase the reflections from the blood-filled chambers
of the heart, so that the chambers image on the monitor will be clearly
differentiated from those of the heart muscle itself.
One area of intense interest involves the development of an ultrasound
contrast medium for cardiac perfusion, which would enable cardiologists to
measure how well the heart muscle is being perfused by its local blood supply and
to assess heart function. This will enable ultrasound to be used for diagnosing
myocardial infarction. Industry and academic experts see much of ultrasounds
future as a tool to image for cardiac disease and malfunctions. The sensitivity and
flexibility of ultrasound makes it the most sensitive method of imaging
microbubbles, since it deliberately disrupts the pattern and produces a very strong
and highly characteristic transient effect. Schering AG and other companies have
investigated several types of in vivo molecular imaging using ultrasound bubbles.
The agent and technique fulfill the requirements of an ideal molecular imaging
agent due to high specificity, fast target access (allowing examination shortly after
administration), safety, and high signal-to-noise ratio.
The commercial availability of ultrasound contrast agents poses some
challenges. There continuously is a need to identify the most relevant clinical
applications for which the agents are indicated, as well as ways in which to use
existing ultrasound technology with contrast to give the greatest detail. Some of the
limitations of ultrasound imaging can be reduced by applying contrast agents that
consist of fluid with a high concentration of air bubbles.
A number of ultrasound contrast agents have been approved by regulatory
authorities, including Levovist (Bayer Schering Pharma), Optison (GE Healthcare),
Definity (Lantheus Medical Imaging) and SonoVue (Bracco Diagnostics). The
latest generation of microbubbles use a more solid stabilizing shell, such as a
phospholipid and perfluorocarbon gasses. These products are more echogenic and
have a long life in the bloodstream that allows them to pass many times through the
heart and accumulate in different organs in the body. They can be used for
perfusion studies and to image myocardium. It is also possible to look at an organ,

79
destroy using ultrasound the accumulated microbubbles and see how circulating
microbubbles overrun in the organ.
A New Drug Application for Imagify was submitted to the FDA in April
2008 by Acusphere. Acusphere is working with the FDA on a Special Protocol
Assessment (SPA) that will define the remaining requirements for approval in the
US. Acusphere has reached agreement with FDA on the overall design of a placebo
trial, comparing ultrasound with Imagify to ultrasound without Imagify. In February
2009 the company sent a Complete Response Letter to the agency. Approval in
Europe also is pending.
Dyes are used in x-rays and CT to optimize the ability of imaging specialists
to see internal structures. The common dyes that are used are either barium
containing materials (barium sulphate) or iodine containing materials. A barium
sulphate suspension in water is the universal contrast medium for radiography.
Some patients may be allergic to iodine and should not receive this agent. Iodine
containing agents can be monomeric salts of tri-iodinated benzoic acid with
substituted ionic or non-ionic side-chains.
Iodinated contrast agents are utilized in many cardiac catheterization
procedures. Ionic contrast media have higher osmolarity and more side-effects.
Non-ionic contrast media have lower osmolarity and tend to have fewer side effects,
such as Omnipaque, Ultravist and Visipaque. Both types are used most commonly
in radiology.
The primary agents used in cardiovascular imaging in the past consisted of
diatrizoate sodium or a combination of diatrizoate sodium and various meglumine
salts. These agents are ionic or high osmolar agents with osmolarities exceeding
1,500 mOsm per kg. In recent years, several nonionic or low osmolar agents have
been introduced and widely marketed. These include iohexol, iopamidol and
ioversol. An additional agent, ioxaglate, is best described as an ionic, but low
osmolar contrast agent. All four of these agents have osmolarities in the range of
about 600 to 700 mOsm/kg. Data suggest that the low osmolar agents are better
tolerated than the high osmolar agents. They are potentially safer in
hemodynamically compromised patients, but the low osmolar agents are much more
expensive.

80
The low osmolar agents cost hospital pharmacies approximately

$100/100 ml. This represents approximately 10 times the cost of conventional ionic
agents. Despite the high cost, the use of these types of agents is increasing. The
conversion to the newer low osmolar agents for cardiac catheterization represents a
substantial cost to hospitals, insurers and patients.
Contrast agents play a significant role in improving the quality of MRI
diagnostic images by increasing the contrast between different internal structures or
types of tissues in various disease states. Most contrast agents that have been
approved for human use are extracellular, gadolinium (Gd)-based agents that have a
relatively short residence time in the vascular system. In addition, intracellular
agents have been introduced that have longer residence times and which allow make
possible extended imaging procedures without the need for repeated injections of
the agent. Many MRI contrast agents that are on the market are applied, for the
most part, to image the central nervous system, but they also are used to check for
cancer, inflammation or to evaluate blood vessels. These agents improve the
resolution of MRI images by increasing the brightness in various parts of the body
where the agent resides
Radiopharmaceuticals are used in nuclear medicine as tracers in the
diagnosis and treatment of many illnesses. Many radiopharmaceuticals use
technetium (Tc-99m). Radiopharmaceuticals are biologically active chemicals that
emit radiation and have a short half-life. Radiopharmaceutical isotopes sometimes
are bonded to biological carriers that concentrate preferentially in particular organs
or tissues. The emitted gamma radiation is projected, and three-dimensional (3D)
images are generated.
The design of these compounds is based solely upon the
physiological function of the target organ. The increasing awareness of nuclear
medicine by specialists in oncology, neurology and cardiology is furthering a focus
on PET, SPECT and dual modality equipment, such as PET-CT and SPECT-CT.
These technologies provide enhanced information on the functional aspects of the
organ rather than on the anatomical aspects. The most commonly used PET
radiopharmaceutical is FDG (2-fluoro-2deoxy-D-glucose).

81
Of the diagnostic radiopharmaceuticals injected into patients in the US in

2008, nearly two-thirds were for cardiac exams, with the remaining for oncology,
neurology and other applications. Diagnostic radiopharmaceuticals offer a detailed
description of the morphology and dynamic functioning of various internal organs
of the body. The radiopharmaceutical accumulated in an organ of interest emits
gamma radiation which is used to image organs with the help of an external
imaging device called gamma camera. The following are some cardiac
radiopharmaceutical compounds, which have found applications worldwide for
various diagnostic purposes:
Heart diseaseAmmonia N 13, Fludeoxyglucose F 18, Rubidium Rb 82,
Sodium Pertechnetate Tc 99m, Technetium Tc 99m Albumin, Technetium Tc 99m
Sestamibi, Technetium Tc 99m Teboroxime, Technetium Tc 99m Tetrofosmin,
Thallous Chloride Tl 201.
Heart muscle damage (infarct)Ammonia N 13, Fludeoxyglucose F 18,
Rubidium Rb 82, Technetium Tc 99m Pyrophosphate, Technetium Tc 99m (Pyroand trimeta-) Phosphates, Technetium Tc 99m Sestamibi, Technetium Tc 99m
Teboroxime, Technetium Tc 99m Tetrofosmin, Thallous Chloride Tl 201.
TOTAL CARDIAC DIAGNOSTIC CONTRAST AGENTS AND

RADIOPHARMACEUTICALS MARKET SIZE AND GROWTH
The ongoing development of new contrast agents and radiopharmaceuticals
indicates the vast market potential for these compounds in medical imaging. The
imaging market is being driven by an aging population, and an increasing
prevalence of inactive lifestyle. The aging population has almost guaranteed there
will be more cardiovascular, neurological and oncological disorders. This has
transformed into increased procedural volumes for magnetic resonance angiography
(MRA) as well as cardiac ultrasound, which require the use of contrast agents. This
volume growth has prompted most of the global radiopharmaceutical manufacturing
companies to work closely with nuclear physicians and oncologists to harness the
potential of radiopharmaceuticals, although shortage issues have been a concern.
With the new generation of products emerging, especially for studying the heart and
cardiac perfusion, nuclear imaging is attaining a good market.

82
The market for radiopharmaceuticals, used in PET and SPECT diagnostic

imaging is expected to be stronger growing markets in an annual range of over 5%
through 2017. The ability of these drugs to detect metabolic changes at the
molecular level has significant potential for improving visualization and quality of
care. They can yield succinct images by exploiting specific molecular targets,
pathways or cellular processes of disease. These are just as important as system
hardware in terms of influencing patient outcomes as well as institutional bottom
lines.
Most of the growth has been occurring in the US, which has garnered the
greatest share of the PET and SPECT radiopharmaceutical market in the 60%
range -- probably because many of the related advancements in science and
technology have occurred in the US, although reimbursement and utilization issues
may soften growth in the market place. In addition, in Europe and elsewhere
difficult reimbursement situations and limited state funding have impeded
development of the commercial market, although BRIC nations represent growth
opportunities.
Helping to grow the business for radiopharmaceuticals, PET-CT
imaging has added precision to anatomic localization, which is not available with
PET imaging alone. Several hospitals and imaging centers have been transitioning
to PET-CT units from solely PET. Although the hybrid system is more expensive, it
provides both functions in one device. One issue slowing the greater acceptance of
PET-CT is the difficulty and cost of producing and transporting
the radiopharmaceuticals, which usually have short half-lives.
Then there is
PET-MRI. Unlike PET-CT, in which sequential scanning facilitates image
co-registration that correlates structural and functional information. PET-MRI
reduces study acquisition time and allows for scanning under the same
physiological conditions. High-field MRI generates high-resolution anatomical and
structural images that create better soft-tissue contrast resolution and a wide variety
of tissue contrast. The system enables functional MRI imaging, and can assess flow,
diffusion, perfusion and cardiac motion in one examination. MRI does not use any
ionizing radiation.


83
Bayer HealthCare has formed a new business unit through the integration of
its subsidiary Medrad Inc. and Bayer HealthCare Pharmaceuticals contrast media
business. The new unit is operating under the name of Radiology and
Interventional. The name Medrad will transition to become a Bayer product brand.
With this move, Bayer HealthCare aligns its portfolio to focus investments on
critical strategic growth drivers. The new unit operates within Bayer HealthCares
Medical Care Division.
The former Medrad business has improved patient outcomes by being a
manufacturer and distributor of high tech medical devices that enable or enhance
diagnostic and therapeutic medical procedures for CT, MRI, and cardiovascular
applications. The Contrast Media business has facilitated advances in the field of
diagnostic imaging in X-ray, CT and MRI.
Although the long recession may have caused hospitals, physician offices
and other institutions to delay or cancel the purchase of imaging equipment, it has
not had a significant negative impact on the use of contrast agents with the
equipment already on hand. Growth in the contrast market will continue as cost
effective products and new technologies are commercialized by suppliers. As new
targeted imaging techniques evolve, there will be a greater need for targeted
contrast agents to optimize visualization of images. And, the diagnosis and
treatment of age-related illnesses, as the older population grows in numbers, also
will expand the market for contrast agents.
In addition, there are challenges facing diagnostic imaging tests in
developing countries, which in a sense can act as drivers of the market. According
to WHO, there is a severe lack of, and therefore need for, safe and appropriate
diagnostic imaging services -- basic x-ray and ultrasound -- in many parts of the
world. In several countries, a large number of images are of poor quality and are of
no diagnostic use. Many are also misread. In other areas, imaging facilities are
simply not available, or not functioning. There is a lack of adequately trained
medical specialists, including radiographers and technologists. To solve these issues
will require greater use of contrast agents, in part.
As new applications as cardiac evolve for MRI, the modality will grow into
a highly sophisticated medical imaging tool. New contrast agents could also

84
improve the diagnosis of heart-related disease. As 3T and more powerful scanners

account for more of the clinical MR market, the increased magnetic field strengths
are helping to open applications for contrast reagents, because, as the field strength
increases, the detection threshold decreases.
Also, the demand for CT contrast agents has been driven by advances in
multislice systems, which have been pushing the envelope in terms of speed, patient
comfort and resolution. Examinations are faster and more patient-friendly, as more
anatomy can be scanned in less time.
One problem facing the marketers of branded contrast agents, though, has
been the introduction of generic contrast media as the patent coverage for some
more branded products expires. Generic players, both suppliers of the end product
contrast agent and of pharmaceutical ingredients used by the end product
manufacturers, are playing a greater force in the market as more branded products
loose patent protection. The most important competitive advantage that these
generic vendors may offer involves a lower product cost as compared to higher
priced branded agents. Generic manufacturers compete for market share by
competing on price with branded contrast agents. The biggest target market for
generic MRI contrast agents are the low end hospitals and imaging centers segment,
especially in Europe. Agfa entered the generic contrast agent market with its
purchase of Insight Agents GmbH and has long term plans for its portfolio.
The total cardiac diagnostic contrast agents and radiopharmaceuticals
market reached revenues of $2.7 billion in 2012. The market is comprised of
revenues for cardiac diagnostic contrast agents and cardiac diagnostic
radiopharmaceuticals. As imaging technology proliferates and opens possibilities
for more non-interventional procedures, market demand can only be expected to
increase. Imaging has become increasingly pervasive in health care, and it is no
exaggeration to say that virtually nothing of consequence takes place in medicine
today without a picture. An aging population combined with advancements in
The recent recession has not had an extensive negative impact on the use of
contrast agents with the equipment already on hand. Annual growth for cardiac

85
diagnostic contrast media during the next five years appears to be holding its own,
despite the recession slowing capital equipment purchases. Imaging exams are still
needed for making many diagnoses, and contrast enhancement facilitates diagnosis
in many cases. Revenues are expected to reach $3.3 billion in 2017, growing at
3.8% over the forecast period of 2012-2017.
Table 7-1
Total Cardiac Diagnostic Contrast Agent and Radiopharmaceuticals Market

Analysis, 2010-2017
Year
2010
2011
2012
2013
2014
2015
2016
2017
2,590.0
2,660.0
2,741.0
2,830.0
2,928.0
3,041.0
3,168.0
3,300.0
2010-2012
2012-2017
2010-2017
Percent Change
2.7%
3.0%
3.2%
3.5%
3.9%
4.2%
4.2%
2.9%
3.8%
3.5%


86
Figure 7-1
Total Cardiac Diagnostic Contrast Agent and Radiopharmaceuticals Market

Analysis, 2010-2017
$3,500
$3,000
$2,500
$2,000
$1,500
$1,000
$500
$0
2010
2011
2012
2013
2014
2015
2016
2017
Calendar Year

Market Participants
SUMMARY
The global cardiac diagnostic industry is a diverse and highly competitive
market. It is anticipated that provider demand for cardiac diagnostic products and
services will continue to rise providing opportunities for both existing market
participants and emerging market participants. Manufacturers should look for ways
to distinguish themselves in the marketplace by keeping abreast of key market
drivers, restraints, and trends that are affecting the market and the economy as a
whole. More than ever before, manufacturers are facing survival challenges in
todays marketplace while the need for innovative and safe products continues to
grow.
Companies outlined in this chapter include:
x
Abbott Diagnostics
Acusphere
Alere
Analogic Corp
Bayer Healthcare
Bracco SpA
Cardinal Health
Eight: Market Participants

88
CardioDX
C.R. Bard
Danaher Corporation
dpiX
GE Healthcare
Hitachi Medical Systems
Johnson & Johnson
LipScience
Medison America
Molecular Insight Pharmaceuticals
Nanosphere
PerkinElmer
Philips Healthcare
Roche Diagnostics
Shimadzu Corp
Siemens Medical Solutions
St Jude Medical
Terumo Medical
TomTec Imaging Systems
Toshiba
Trixell
Vascular Solutions

89
Vermillion
Volcano
Some of these companies are high stakes players in the market and control
considerable market share while others are small or niche players that provide a
valuable product to the global cardiac diagnostic arena. All are equally important to
the market as a whole.


90
ABBOTT DIAGNOSTICS
Company: Abbott Diagnostics
Address: : 675 N. Field Dr
Abbott Park, IL 60064
Phone: 847-937-6100
WebSite: www.international.abbottdiagnostics.com
Employees: 90,000
Recent Revenue History (in millions): 2011 $ 4,126 2012 $4,292
Company Overview
Abbott Diagnostics is part of Abbott Laboratories located in Abbott Park,
Illinois. The company as a whole is involved in the manufacture, discovery and
sales of pharmaceuticals, nutritionals, devices and diagnostics. The company has a
presence worldwide in more than 130 countries with many distribution channels,
from consumer outlets to clinical laboratories.
Products
The company offers several key diagnostic testing systems for molecular
testing, immunoassays, hematology, clinical chemistry and blood glucose
monitoring. Within the cardiac diagnostic arena, Abbott Diagnostics offers its
ARCHITECT series. In 2011, Abbott developed the ARCHITECT STAT High
Sensitive Troponin I tests to improve screening for heart attack in patients
presenting at the hospital with chest pain. Products for cardiac diagnostics include:
ARCHITECT c16000
ARCHITECT c4000
ARCHITECT c8000
ARCHITECT ci16200 Integrated System


91

ARCHITECT i1000SR
ARCHITECT i2000SR
ARCHITECT i4000SR


92
ACUSPHERE
Company:
Acusphere
Phone: 617-648-8800
Address: : 99 Hayden Ave., Suite 385

Lexington, MA 02421
WebSite: www.acusphere.com
Acusphere is a specialty pharmaceutical company, primarily focused on the

development of Imagify (perflubutane polymer microspheres) injectable
suspension, a cardiovascular drug used with ultrasound to detect coronary artery
disease. Acusphere is in the process of seeking regulatory approval of Imagify in
the US and Europe. In the US, it is the subject of an NDA, and in Europe, an MAA
-- a marketing authorization application.
The niche for Imagify would be that it would enable cardiologists to
measure how well the heart muscle is being perfused by its local blood supply.
Perfusion is a key marker of cardio disease. Imagify was created using Acuspheres
proprietary porous microparticle technology, which has the potential to create a
wide variety of new drugs by reformulating hydrophobic drugs and creating
sustained release formulations of existing drugs. The companys technology enables
it to control the size and porosity of microspheres, so that they can be customized to
deliver a variety of drugs. The porous microspheres are smaller than red blood cells.
Small microspheres are important for delivering drugs intravenously so that they
can pass through the body's smallest blood vessels, for increasing the surface area
of a drug so that the drug will dissolve more rapidly, and for delivering drugs to the
lung via inhalation. Porosity is important for entrapping gases in microspheres, for
controlling the release rate of the drug from a microsphere, and for targeting inhaled
drugs to specific regions of the lung.
Imagify will find use in evaluating myocardial perfusion, an
important marker of coronary artery disease. Imagify is radiation-free. Two Phase
III trials demonstrated that myocardial perfusion assessment with Imagify

93
(perflubutane polymer microspheres) injectable suspension is equivalent to nuclear

stress testing. Strong patent position with global rights owned by Acusphere.
Acusphere management believes the potential market opportunity for
Imagify is more than $2 billion in the US and $600 million in Europe. In the US,
approximately 10 million patients undergo non-invasive cardiac stress testing each
year, and 3 million do so in Europe. Imagify can be used in such testing.


94
ALERE, INC
Company:
Address:
Alere, Inc
51 Sawyer Rd Suite 200
Waltham, MA 02453
Phone: 781-647-3900
WebSite: www.alere.com
Employees: 17,400
Recent Revenue History (in thousands):
2011 $2,790
2012 $ 2,363
Company Overview
Alere offers professional diagnostics, health information solutions, and
consumer diagnostics for a variety of disorders. The company is located in
Waltham, MA. In July 2010, the company changed its name from Inverness
Medical Innovations. The company has been very active with acquisitions to boost
its market share in an increasingly competitive market.
Aleres previous acquisitions include: Abbott Diagnostics Determine line,
Acon laboratories, British Biocell International Limited, Biosite, Cholestek
Corporation, Clondiag GmbH, First Check Diagnostics, Ischemia Technologies,
HemoSense. Instant Technologies, Matritech, Orgenix Limited, Panbio Ltd, Quality
Assured Services, Spectral Diagnostics, TechLab and Thermo Biostar.
Products
The company offers the Alere Triage, Cholestech LDX, and INRatio
products. The Alere Triage system consists of a portable fluorometer that interprets
consumable test devices for cardiovascular conditions. These tests include:
Alere Triage BNP Test- an immunoassay that measures B-type Natriuretic
Peptide (BNP) in whole blood or plasma, used as an aid in the diagnosis and
assessment of severity of congestive heart failure.


95
Alere Triage NT-proBNP - an immunoassay for the rapid quantitative

Determination of N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) in
anticoagulated whole blood and plasma specimens the test is used as an aid in the
diagnosis of congestive heart failure.
Alere Triage Cardiac Panel - and immunoassay for the quantitative
determination of creatine kinase-MB (CK-MB), myoglobin and troponin I in whole
blood or plasma, used as an aid in the diagnosis of acute myocardial infarction.
Alere Triage ProfilER Panel - an immunoassay for use as an aid in the
diagnosis of acute myocardial infarction, the diagnosis and assessment of severity
of congestive heart failure and the risk stratification of patients with acute coronary
syndromes and heart failure.
Alere Triage Cardio3 Panel - an immunoassay for the rapid quantitative
determination of CK-MB, troponin I and BNP in whole blood and plasma
specimens. CE Mark only
Alere Triage Cardio2 Panel - an immunoassay for the rapid quantitative
determination of troponin one and BNP in whole blood and plasma used in the
diagnosis of myocardial infarction. CE Mark only
Alere Triage Troponin I - an immunoassay for the quantitative
determination of troponin I in whole blood and plasma to aid in the diagnosis of
The company also offers the Cholestek LDX system, a point-of-care
monitor of blood cholesterol which is used to test patients at risk for suffering from
heart disease. The test provides a complete lipid profile with test for total
cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein
cholesterol, triglycerides, and glucose.
In 2010, the company launched the Alere Heart Check System in Europe. This
provides a quantitative reading of BNP in less than fifteen minutes using a fingerstick sample. The product is being marketed as a point-of-care device but will
ultimately be designed for home use and is intended to enable doctors to remotely
monitor BNP levels of congestive heart failure patients and adjust their therapy
accordingly.

96
The cardiology portion of professional diagnostics totaled $503,504 in 2012

compared to $518,746 in 2011 demonstrating a 3% decrease in revenues as a result
of the FDA recall of certain Triage meter-based products.
Locations
The company has locations in over 25 countries including North America,
Europe, Middle East, Asia-Pacific, Latin America, and Africa.


97
ANALOGIC CORP
Company: Analogic Corp
Address: : 8 Centennial Dr
Peabody, MA 01906
Phone: 978-326-4000
WebSite: www.analogic.com
Analogic is a designer and manufacturer of health and security systems and

subsystems sold primarily to original equipment manufacturers (OEMs). The
company is involved in CT, digital radiography, ultrasound, MRI, patient
monitoring and advanced signal processing technology. Analogic supplies CT
systems for a growing number of niche applications, including large-bore systems
for radiotherapy. The company designs and produces complete digital radiography
systems, while its Anrad subsidiary develops and manufactures amorphous
selenium-based flat-panel detectors for digital radiography. Analogic also develops
advanced subsystems for medical imaging. It is a developer of complex data
acquisition systems for CT.
Analogic has pursued digital radiography from two perspectives. The
company acquired proprietary selenium technology necessary for the development
of direct digital radiography detector plates, and established its Anrad subsidiary to
develop and manufacture flat panel x-ray detectors using selenium technology.
Anrad develops, manufactures, and integrates a broad series of direct conversion, xray detectors and their associated electronics subsystems for digital radiography
systems. Amorphous selenium deposition technologies, combined with very high
speed, low level, precise, signal processing electronics, all covered by Anrad
patents, provide solutions to digital detectors use in angiography and cardiac
applications. Analogic also focuses on direct digital radiography.
The companys custom ultrasound subsystems include spectral Doppler,
color flow mapping, and proprietary front-end electronics. In 2010, the company
introduced two new systems to the Flex Focus family: the Flex Focus 400

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Anesthesia, for guiding the placement of nerve blocks prior to surgical procedures
and the Flex Focus 700 for the surgical environment. Analogics direct ultrasound
systems business saw a 7% increase in revenues in 2011, driven by the success of
the Flex Focus family of ultrasound systems.
Capitalizing on its application-specific integrated circuit technology,
Analogics scalable digital beam formers are designed for multi-beam capability
and can support mid-tier to high-performance systems (64 to 128 or more channels).
Analogic also develops and supplies custom multi-element phased and linear array
ultrasound transducers that support frequencies up to 10 MHz, as well as specialty
probes, including transesophageal probes that provide improved images of the heart.
The companys compact Pro Focus UltraView is a fully-featured ultrasound system,
offering contrast imaging, HistoScanning capabilities, and a complete range of
specialized transducers.


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BAYER HEALTHCARE
Company:
Address:
Bayer Healthcare
Phone: +49 30 468 1111
Mllerstrasse 178
13353 Berlin, Germany
Employees: 55,300
WebSite: www.helathcare.bayer.com
Recent Revenue History (in millions): 2011 $22,742 2012 $ 24,654
Company Overview
Bayer HealthCare markets its products in more than 100 countries, and in
2012 generated sales of more than $24 billion. Bayer HealthCare had a global
workforce of 55,300 employees, as of Dec. 31, 2012. The company focuses on four
business areas: Diagnostic Imaging, General Medicine, Specialty Medicine and
Womens Health care.
In March 2012, Bayer HealthCare formed a new business unit by integrating
its subsidiary Medrad Inc. and Bayer HealthCare Pharmaceuticals contrast media
business. The new unit operates under the name of Radiology and Interventional.
The name Medrad will transition to become a Bayer product brand. With this move,
Bayer HealthCare aligns its portfolio to focus investments on critical strategic
growth drivers.
Products
Bayer acquired Schering AG in July 2006. Schering offered a broad
spectrum of x-ray contrast media, including Ultravist and Iopamiron. Both are
suitable for all common x-ray and CT examinations and can also be used to provide
answers to a wide range of diagnostic questions. There are a number of clinical
benefits from the combination of Ultravist with novel CT methods, such as the
ultra-fast Dual Source CT system developed by Siemens. These benefits include CT
examinations of the heart as well as CT applications in acute medical care. Schering
and Siemens Medical Solutions are collaborating in this field.

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Schering helped Bayer attain a leading global position in the x-ray

contrast media market. Ultravist has been a top-selling product. It is a non-ionic
product with a broad spectrum of indications in the area of CT such as the diagnosis
of kidney diseases, strokes, and cardiac diseases. Ultravist is approved for all
common x-ray examinations, including CT. It is used extensively, for example, in
the diagnosis of liver diseases, strokes and cardiac diseases and in diagnosing
cancer using CT. Ultravist is applied over 10 million times a year. Schering also
markets Iopamiron under a license from Bracco, mainly in Japan, France and Latin
America.


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BRACCO SPA
Company:
Bracco SpA
Address: :
Via E. Folli 50
20134 Milan, Italy
Phone: +39 02 2177.1
WebSite: www.bracco.com
Bracco started as a pharmaceuticals trading company in the 1970s. Bracco's

researchers discovered and developed the iopamidol molecule, the first non-ionic
contrast medium. Bracco is active in the health care sector through Bracco Imaging
(diagnostic imaging), Pharma (prescription and over the counter drugs), Acist
Medical Systems (advanced injection systems) and the Centro Diagnostico Italiano
diagnostic clinic in Milan, Italy. The company has 2,800 employees and annual
total consolidated revenues of approximately $1.4 billion, of which 65% is from
international sales. The company is present in 80 countries.
Bracco's diagnostic imaging products are complemented by advanced
contrast imaging system technology in the fields of cardiology and radiology
developed by its Acist Medical Systems, Eden Prairie, MN, a manufacturer of
advanced contrast media injection systems. In September 2011, Bracco acquired
Swiss Medical Care, Lausanne, Switzerland, which is focused on the research,
production, and marketing of automated systems for the administration of contrast
agents for diagnostic imaging.
Bracco also has a line of cardio radiopharmaceuticals including CardioGen82, a generator-based PET agent for the evaluation of coronary artery disease.


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CARDINAL HEALTH
Company:
Cardinal Health
Address: :
7000 Cardinal Place

Dublin, OH 43017
Phone: 614-757-5000
WebSite: www.cardinalhealth.com
Cardinal Health is a $103 billion health care services company, providing

pharmaceuticals and medical products to more than 60,000 locations each day. The
company is also a leading manufacturer of medical and surgical products, including
gloves, surgical apparel and fluid management products. In addition, the company
operates the US' largest network of radiopharmacies. Ranked #19 on the Fortune
500, Cardinal Health employs more than 30,000 people worldwide.
The combination of Cardinal Health's national network of nuclear
pharmacies and its expertise in the manufacturing and distribution of PET agents
enables the company to support clinical trials conducted by pharmaceutical
researchers and academic organizations. Cardinal Health's Pharmaceutical segment
operates nuclear pharmacies and cyclotron facilities that prepare and deliver
radiopharmaceuticals for use in nuclear imaging and other procedures in hospitals
and clinics. The company operates the largest network of nuclear pharmacies in the
US, delivering 12 million doses of radiopharmaceuticals every year to hospitals and
outpatient care centers. The company also serves the PET market with
manufacturing of PET agents used in diagnostics, therapies and clinical trial studies
in the areas of cardiology, neurology, oncology and general nuclear medicine.


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CARDIODX, INC
Company:
CardioDX, Inc
Phone: 650-475-2788
Address: : 2500 Faber Pl

Palo Alto, CA 94303
WebSite: www.cardiodx.com
Recent Revenue History (in millions): Private
Company Overview
CardioDX was founded in 2004 and is located in Palo Alto, California. The
company focuses on genomic diagnostics for coronary artery disease, cardiac
arrhythmia, and heart failure. The company is held by a group of private investors.
Products
The company offers the Corus CAD test which is a blood test to assess
symptoms that are consistent with CAD and to provide assessment to identify
patients by sex-specific results.
The company has other products in research and development for
arrhythmia and heart failure.


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C.R. BARD
Company:
C.R. Bard
Phone: 801 522-5000
Address:
605 N. 5600 W.
Salt Lake City, UT 84116
WebSite: www.crbard.com
C. R. Bard, Inc. is engaged in the design, manufacture, packaging,

distribution and sale of medical, surgical, diagnostic and patient care devices. The
company was founded in 1907, and incorporated as C. R. Bard, Inc. in 1923. The
company participates in the markets for vascular, urology, oncology and surgical
specialty products to hospitals, individual healthcare professionals, extended care
facilities and alternate site facilities on a global basis. Its products are intended to be
for single use or implantation. Sales of vascular access and urological products
contribute more than 50% of total company revenues.
Vascular products contributed 29% of total revenues in 2012. Bards
vascular products are minimally invasive devices for the treatment of peripheral
vascular disease and heart arrhythmias. These products include: percutaneous
transluminal angioplasty catheters, chronic total occlusion catheters, guidewires,
fabrics, meshes, introducers and accessories; peripheral vascular stents, covered
stents and vascular grafts; vena cava filters; biopsy devices; and electrophysiology
products, including electrophysiology laboratory systems and diagnostic,
therapeutic and temporary pacing electrode catheters.


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DANAHER CORPORATION
Company: Danaher Corporation
Phone: 202-828-0850
Address: : 2200 Pennsylvania Ave NW Suite 800 W
Washington, DC 20037
WebSite: www.danaher.com
Employees: 63,000
Recent Revenue History (in millions): 2011 $16,090.5
2012 $ 18,260.4
Company Overview
Danaher Corporation was founded in 1969 as Danaher Business Systems.
The company designs, manufactures, and markets professional, medical, industrial,
and commercial products and services. The companys businesses are divided into
five segments: test and measurement; environmental; life sciences and diagnostics;
dental and industrial technologies. Sales in 2012 by geographic destination were:
United States 43%; Europe, 26%; Asia/Australia, 21% and all other regions, 7%.
Danahers diagnostic business was established in 2004 with the acquisition
of Radiometer. The diagnostic business has expanded through numerous subsequent
acquisitions including the acquisitions of Leica Microsystems in 2005, Vision
Systems in 2006, Genetix in 2009, and Beckman Coulter in 2011. The companys
diagnostic businesses offer a broad range of products including analytical
instruments, reagents, consumables, software and services for use in hospitals,
physicians offices, reference laboratories and other critical care settings.
Products
The acquisition of Beckman Coulter in June 2011 has provided additional
sales and deeper involvement in cardiac diagnostics. Beckman Coulter is a leader in
protein analysis and has more than sixty tests for cancer detection, cardiac disease
thyroid function, and many others. Beckman Coulter offers the Access family of


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immunoassay analyzers including the Access 2 Immunoassay System, Synchron

Systems, and the Unit Cell DXI 600 Access Immunoassay System.


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DPIX, LLC
Company:
dpiX, LLC
Address: :
1635 Aeroplaza Dr
Colorado Springs, CO 80916
Phone: 719-457-7700
WebSite: www.dpix.com
dpiX produces semiconductors on large glass substrates for manufacturers

of x-ray systems. The companys technology is used to produce large area
amorphous silicon (a-Si) sensor arrays and displays. Flat panel x-ray detectors made
with dpiX technology have found use in medical, security, explosive detection and
non-destructive testing applications. The companys customers include Varian
Medical Systems, Thales Electron Devices and Trixell -- a consortium of Thales,
Philips and Siemens.
The companys a-Si sensor arrays can be used in a variety of digital
imaging applications. dpiXs amorphous-silicon thin-film transistor (TFT)
technology, combined with n-i-p photo detector technology, is backed by a large
intellectual property portfolio. The a-Si arrays are compatible with indirect
detection techniques, including scintillating materials, such as cesium-iodide, leadiodide and others, as well as direct detection techniques involving photoconductors.
Each dpiX image sensor contains an array of switching TFTs, one
for each pixel. These products are similar to very large integrated circuits, except
they are manufactured onto sheets of glass, instead of purified silicon wafers. In the
indirect detector, the pixel structure has an additional light-sensitive photodiode in
each pixel. The fabrication of the pixel-addressing matrix for a large-format image
sensor array is essentially the same as that used for the active matrix liquid crystal
display (AMLCD).As in an AMLCD, a matrix of TFTs is used to address each pixel
location. In the structure of a TFT-based large-format image sensor array, data
signals are readout from the array rather than written into it, creating a digital file

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that represents the two-dimensional image. Instead of using voltage levels to adjust
the light throughput in a display pixel, each sensor pixel senses a charge and
converts it to an electrical signal.
The medical market for the companys products include:
radiography/fluoroscopy; general x-ray; tomography; vascular studies; angiography;
urology; oncology; cardiology; and dental imaging.


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FLUOROPHARMA MEDICAL
Company:
Fluoropharma Medical
Phone: 617-456-0366
Address: : 500 Boylston Street, Suite 1600

Boston, MA 02116
WebSite: www.fluoropharma.com
FluoroPharma is a privately-held molecular imaging company. The

companys initial focus is the development of PET imaging agents for the detection
and assessment of acute and chronic forms of coronary artery disease (CAD). Other
products in development include agents for detection of amyloid plaque in
Alzheimers disease and agents for detecting certain types of cancer.
FluoroPharmas technology consists of molecular PET agents for the
cardiovascular, oncology and neurology arenas. The most advanced programs are in
the area of cardiology where the agents have been designed to rapidly target either
the myocardial cells within the heart or the vulnerable plaque within the coronary
arteries. The companys proprietary molecules are labeled with the radioactive
isotope of fluorine [18F] and combined with PET scanning. Currently, FDG, mainly
used in oncology, is the primary commercial [18F] labeled PET molecular imaging
agent. FluoroPharmas cardiovascular program targets nuclear cardiology.
The companys CardioPET, which has completed Phase I clinical trials, is
an F-18 labeled, modified fatty acid that provides insight into regions of metabolic
insufficiency in myocardium. CardioPET may be used to identify patients that will
benefit from percutaneous coronary intervention PCI or revascularization and guide
intervention, and to evaluate CAD in patients that cannot exercise. BFPET, which
also has completed Phase I trials, is a cardiovascular blood flow imaging agent that
concentrates in healthy myocardial cells. It is used for detection of presumptive


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CAD in combination with stress testing and for the improved detection of CAD
during multi-vessel disease.
VasoPET, which has completed preclinical studies, is an F-18 labeled agent
that accumulates in areas of inflammation. VasoPET may be used for the evaluation
of patients with acute coronary syndrome or risk of stroke, as well as therapy
following an acute cardiac event or stroke. The Azpet platform is in discovery and
involves multiple biomarkers for imaging and treatment of Alzheimer's disease.
In March 2012, FluoroPharma announced that it recruited SGS Life
Science Services as the contract research organization for its Phase II study of
CardioPET to assess myocardial perfusion and fatty acid uptake in coronary artery
disease patients.


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GE HEALTHCARE
Company: GE Healthcare
Address: : Amersham Place
Little Chalfont
Buckinghamshire HP7 0NA
England
Phone: +44 870 606 1921
WebSite: www.gehealthcare.com
Employees: 46,000
Recent Revenue History (in millions): 2011 $1,700.0 (e)
2012 $ 1,800.0(e)
Company Overview
GE Healthcare is a $18 billion unit of the General Electric Co. Worldwide,
GE Healthcare employs more than 46,000 people in more than 100 countries. In April
2004, GE acquired Amersham plc, involved in medical diagnostics and life sciences.
Products include diagnostic imaging agents used in medical scanning procedures,
protein separations products including chromatography purification systems used in
the manufacture of biopharmaceuticals, and high-throughput systems for applications
in genomics, proteomics and bioassays.
GE Healthcare is a worldwide provider of a variety of technologies and
products including medical imaging and information technologies, medical
diagnostics, patient monitoring systems, drug discovery, and biopharmaceutical
manufacturing technologies. The company is based in the United Kingdom and is a
wholly owned subsidiary of General Electric Company. The business manufactures
sells and services a wide range of medical equipment including magnetic resonance
(MR), computed tomography (CT), positron emission tomography (PET) imaging, xray, digital x-ray, patient monitoring, diagnostic cardiology, nuclear imaging, and
ultrasound systems, among other products.


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Products and Services

GE Healthcares MRI products include the Signa HD (High Definition)
Family, which provides broad clinical capability, and fast scanning capability. The
Signa family includes: the Signa HDxt 3.0T, Signa HDxt 1.5T, Signa HD 1.5T and
the Signa HDe 1.5T closed high field scanners. Signa HD technology makes it
possible to diagnose those challenging patients, providing a range of technologies
that improve clarity, detail and process.
GE also offers mobile MRI Systems that are complete MRI diagnostic suites.
Also on the market is the Applause, a portable in-office MRI. Designed to image
human extremities, Applause provides
ides detailed views that are optimized for the
evaluation of inflammatory diseases. Also available from GE is the Signa MR
Surgical Suite. GE, in collaboration with Maquet GmbH & Co. KG, created the next
generation MR guided intra-operative surgical suite. The suite can be used as a standalone MR imaging center, a stand-alone operating room, or a combined MR guided
suite. GE also offers its Discovery MR450 1.5T system with true real-time cardiac
imaging. The companys MR750 offers 3T imaging capability. Other GE MRI
systems on the market include the Signa OpenSpeed 0.7T, the open 0.35T Signa
Ovation and the open Signa Profile 0.2 T. Also on the market are 1.5T and 3T high
definition coils.
In April 2011, GE Healthcare received FDA clearance of the GEM Suite
(Geometry Embracing Method) of surface coils designed for use with the Optima
MR450w 1.5T wide bore MRI system.
GEs Logiq E9 has the ability to simultaneously display side-by-side-or
even one laid over the other in a 3D model-gray-scale or color ultrasound data and
CT, MR, or PET data. GE has designed new editions of its LOGIQ e compact and a
new edition of the LOGIQ Book XP Enhanced compact. CrossXBeam software
enhances image clarity by defining continuous boundaries of anatomy and
improving overall image resolution
Locations
The company is worldwide with locations in Spain, India, Italy, Canada,
United Kingdom, Germany, France, Japan, Denmark and the United States.


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HITACHI MEDICAL SYSTEMS AMERICA, INC.

Company:
Hitachi Medical Systems America, Inc
Address: :
1959 Summit Commerce Park

Twinsburg, OH 44087
Phone: 330-425-1313
WebSite: www.hitachimed.com
As a full-line supplier of medical imaging equipment in Japan, Hitachi

Medical founded Hitachi Medical Systems America to give itself a direct link to the
US medical market. The companies market diagnostic imaging products.
The Japanese company operates 33 research facilities worldwide, employing
more than 16,000 research and development specialists. Hitachi Medical Systems
America is responsible for the marketing and support of all Hitachi diagnostic
imaging products in the US.
Hitachi has sold more than 9,000 CT systems worldwide since 1975, and is
offering a family of multidetector CT systems. The ECLOS16 is a multi-slice noncardiac CT, suited for imaging centers and community hospitals and group
practices. It offers extended coverage with thin slice exams and routine multi-region
exams, such as chest-abdomen-pelvis. It has broad CT angiography, renal and
pulmonary applications. In November 2010, Hitachi introduced a 64-slice CT, the
Scenaria. The new CT features a 75 cm aperture gantry, which is large enough to
allow the patient table to shift laterally to center the heart exactly in the field-ofview.


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JOHNSON & JOHNSON

Company: Johnson & Johnson
Phone: 732-524-0400
Address: One Johnson & Johnson Plaza

New Brunswick, New Jersey 08933
WebSite: www.jnj.com
Employees: 127,600
Recent Revenue History (in millions): 2011 $ 2,288
Cardio Care
2012 $1,985
Company Overview
Johnson & Johnson has approximately 127,600 employees worldwide
engaged in the research and development, manufacture and sale of a broad range of
products in the health care field. Johnson & Johnson operates as a holding company,
which has more than 275 operating companies. Johnson & Johnson was incorporated
in the State of New Jersey in 1887.
The Company is organized into three business segments: Consumer,
Pharmaceutical and Medical Devices and Diagnostics. Each segment account for
approximately one-third of total revenues. The Medical Devices and Diagnostics
segment includes products to treat cardiovascular disease; orthopedic and
neurological products; blood glucose monitoring and insulin delivery products;
general surgery, biosurgical, and energy products; professional diagnostic products;
infection prevention products; and disposable contact lenses. These products are
distributed to wholesalers, hospitals and retailers both directly and through surgical
supply and other distributors.
The Medical Devices & Diagnostics segment is further divided into company
brands. Those that manufacture and market catheter products include Cardiovascular
Care, consisting of Cordis and Biosense Webster electrophysiology and circulatory

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disease management products; and Ethicon Endo-Surgerys minimally-invasive

lly-invasive
surgical products.
Products
Johnson & Johnson is the leading provider of diagnostic cardiac catheters.
The company offers the INFINITI 4F, 5F, and 6F line of diagnostic catheters, which
is ideal for coronary angioplasty. These catheters incorporate proprietary Vestan
Nylon to deliver exceptional responsiveness and flow rates, optimal torque, and
shape retention.
Other products in the cardio diagnostics arena include the RadialSource
Access Kit, the Emerald Diagnostic Guidewire, and the Avanti Sheath Introducer.
These products are offered through J&Js Cordis divison.
More products include the AcuNav catheter, PentaRay Nav catheter, Carto3
System and the Lasso Nave eco catheter offered through J&Js Biosense Webster
division.


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KING PHARMACEUTICALS
Company:
Address: :
501 Fifth St.

Bristol, TN 37620
Phone: 423-989-8000
WebSite: www.kingpharm.com
King Pharmaceuticals was a $2.1 billion vertically integrated branded

pharmaceutical company in the areas of cardiovascular-metabolics, neuroscience
and hospital-acute care. In February 2011, Pfizer acquired King through the merger
of its wholly owned subsidiary, Parker Tennessee Corp., with and into King.
Kings Adenoscan, marketed in the US by Astellas Pharma US,
contains the active ingredient adenosine. Intravenous Adenoscan (adenosine
injection) is a pharmacologic stress agent indicated as an adjunct to thallium-201
myocardial perfusion scintigraphy in patients unable to exercise adequately.
Adenoscan has shown consistency in producing maximal vasodilation of coronary
arteries relative to intracoronary papaverine. The short half-life of Adenoscan is
responsible for its short-acting pharmacological effects, making it useful for
diagnostic evaluation and risk stratification in coronary artery disease.
Adenosine works by opening up the heart's blood vessels to allow
blood to flow more freely. Adenoscan is used during radionuclide imaging of the
heart and is administered before the radionuclide.


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LANTHEUS MEDICAL IMAGING

Company:
Address: :
Building 200-2
331 Treble Cove Rd.
N. Billerica, MA 01862
Phone: 978-671-8001
WebSite: www.lantheus.com
Lantheus Medical Imaging, formerly BMS Medical Imaging, is a supplier of

radiopharmaceuticals and contrast agents for nuclear and ultrasound-based
cardiovascular diagnostic imaging procedures. Bristol-Myers Squibb completed the
sale of BMS Medical Imaging to Avista Capital Partners, a private equity firm, in
January 2008 for approximately $525 million. Lantheus Medical Imaging has
nearly 700 employees worldwide. The company has marketed products including
Cardiolite (Kit for the Preparation of Technetium Tc99m Sestamibi for Injection),
Definity Vial for (Perflutren Lipid Microsphere) Injectable Suspension and
TechneLite (Technetium Tc99m Generator) for imaging the heart and other organs.
In April 2009, Lantheus Medical Imaging acquired from EPIX
Pharmaceuticals, Inc., the US, Canadian, and Australian rights to MS-325 (formerly
marketed as Vasovist, gadofosveset trisodium, by Bayer Schering Pharma, a
magnetic resonance angiography (MRA) agent. In December 2008, EPIX received
FDA marketing approval for MS-325 to evaluate aortoiliac occlusive disease
(AIOD) in adults with known or suspected peripheral vascular disease. It is now on
the market as Vasovist (Ablavar in the US).
The company's clinical development efforts include a program to develop a
PET myocardial perfusion imaging agent, which has completed Phase II clinical
trials, as well as programs in the areas of heart failure and vulnerable plaque.
Flurpiridaz F 18 (formerly known as BMS747158) is the cardiac PET imaging
agent candidate and has completed Phase II clinical development. Data show that

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PET imaging with flurpiridaz F-18 provided better image quality than technetium99m sestamibi SPECT, the current standard for the non-invasive detection of
coronary artery disease. Meanwhile, LMI 1195 is a new cardiac neuronal PET
imaging agent that has completed Phase I clinical trials. LMI 1195 is a F-18 small
molecule tracer designed to use PET imaging technology to improve the evaluation
and management of patients with heart failure.
In addition, the company is exploring a non-invasive imaging agent
that may be useful in identifying patients at risk of sudden cardiac death due to
plaque rupture. Researchers have identified a method to view and assess the
coronary arterial vasculature using a compound that binds to elastin, a protein found
in artery walls. In animal models, the molecule enables visualization of the full
thickness of arterial walls in an MRI scan.
In February 2012, Lantheus and Beijing Double-Crane
Pharmaceutical Co., LTD., announced a strategic distribution arrangement for
Definity Vial for (Perflutren Lipid Microsphere) Injectable Suspension in the
Peoples Republic of China, including Hong Kong and Macau. The 15-year
agreement is for exclusive distribution and supply of Definity, which is currently
approved in North America, Europe, and a number of other countries.
In May 2009, Lantheus Medical Imaging signed an agreement with NTP
Radioisotopes (Pty) Ltd., a subsidiary of the South African Nuclear Energy Corp.,
to manufacture and supply Lantheus with an ongoing volume of molybdenum-99
(Mo-99), a key isotope used in medical imaging procedures.


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LIPOSCIENCE, INC
Company: LipoScience, Inc
Address:
Phone: 919-212-1979
2500 Sumner Blvd

Raleigh, NC 27616
WebSite: www.liposcience.com
Employees: 204
2011 $ 45,807
2012 $54,798
Company Overview
LipoScience is a diagnostic company featuring personalized diagnostics
based on nuclear magnetic resonance technology. The company employs
approximately 204 individuals and is located in Raleigh,North Carolina.
Products
In the cardio diagnostics arena, the company offers the and MR LipoProfile
test which provides direct quantification of the number of LDL particles, as well as
additional measurements related to a patients risk for developing cardiovascular
disease. The companys automated clinical analyzer, the Vantera system, was
cleared by the FDA in August 2012 and became commercially available in
December 2012. The Vantera system requires no previous knowledge of a NMR
technology to operate and has been designed to significantly simplify complex
technology.


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MEDISON AMERICA, INC.

Company:
Medison America, Inc.
Phone: 714-889-3000
Address:
11075 Knott Ave.
Cypress, CA 90630
WebSite: www.medisonamerica.com
Through its global network extending to more than 80 countries, Medison

has provided a range of ultrasound products from portable devices to multispecialty real-time 3D systems. In a deal that marked Samsung's first major push
into health care, in December 2010, Samsung purchased a majority stake of 43.5%
in Medison. The purchase indicates that Samsung may be on the acquisition trail to
take on rivals such as General Electric by diversifying away from its core
businesses of electronic components, mobile phone handsets and televisions.
Medisons products have included automatic volume data acquisition, multibeam technology, and Live 3D. Automatic acquisition enables users to acquire an
entire volume of data in a single, static action rather than in separate slices of
information in several movements. This results in more exact spatial relationships.
Samsung Medison offers a number of products for general imaging
applications, as well as black and white, color, portable, and Doppler systems.
These include the Accuvix XQ, a multi-specialty ultrasound system possessing
premium features and 2D image quality as well as 3D/4D capabilities. Medison also
offers the Sonace 9900, a multi-beam 3D ultrasound system. The Sonace 9900 has a
wide range of applications, including specialty cardiac functions. The Accuvix V20
contains 2D, 3D and 4D image technologies: Dynamic MR, Speckle Reduction
Filter, 3DXI, and VOCAL. In addition, the SonoAce X6 is a compact ultrasound


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system with a variety of advanced imaging functions. SonoAce X6 offers spectral,

color and power Doppler technology.


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MOLECULAR INSIGHT PHARMACEUTICALS, INC.

Company:
Molecular Insight Pharmaceuticals, Inc
Address: :
160 Second St.

Cambridge, MA 02142
Phone: 617-492-5554
WebSite: www.molecularinsight.com
Molecular Insight Pharmaceuticals specializes in molecular medicine. The

company is focused on discovering, developing and commercializing molecular
imaging radiopharmaceuticals and targeted molecular radiotherapeutics with initial
applications in the areas of cardiology and oncology.
Molecular Insight's lead molecular imaging radiopharmaceutical product
candidate, Zemiva, is being developed for the diagnosis of cardiac ischemia, or
insufficient blood flow to the heart. Zemiva is a radiolabeled fatty acid analog for
the diagnosis of insufficient blood flow to the heart, or cardiac ischemia.
Using its proprietary technologies, the company has identified potential
candidates that may be useful in the detection or treatment of prostate cancer, heart
failure and neurodegenerative disease, which is a disease characterized by the
gradual and progressive loss of nerve cells. Additionally, several other indications
relating to the future development for Zemiva have been identified, such as
diabetes, chronic kidney disease and heart failure.
The company has a Phase II clinical trial to develop its own Normals
database for Zemiva that will be used as part of its pivotal registration trials and in
the commercialization of Zemiva, if approved by the FDA and other regulatory
bodies. Upon validation of its Normals database against the completed Phase II trial
results, the company plans to begin a US multi-center pivotal registration clinical
trial with Zemiva.


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If the company achieves FDA approval, it would expect to license its

products outside of the US. The company plans to develop its own specialty sales
and marketing teams to market Zemiva in the US. It plans to establish one or more
strategic collaborations to market Zemiva for non-US markets.
The company wants to expand the indications for which Zemiva may be
used, beginning with indications in the non-acute settings. Zemiva may offer
significant benefits over the current standard of care in the non-acute setting for the
diagnosis of coronary disease. The companys plan is to initiate a US Phase II
clinical trial for Zemiva in non-acute settings in the future in order to demonstrate
significant throughput advantages of dual-isotope imaging with Zemiva. The
company is also exploring the use of Zemiva in other indications such as the
detection and monitoring of diabetes-related cardiac disease, microvascular cardiac
disease in women, chronic kidney disease, heart failure and cardiomyopathy.


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NANOSPHERE, INC.
Company: Nanosphere, Inc.
Address:
Phone: 847-400-9000
4088 Commercial Av
Northbrooke, IL 60062
WebSite: www.nansphere.com
Employees: 151
2011 $ 2,533
2012 $5,078
Company Overview
Nanosphere was founded in 2000 and is based on nanotechnology
discoveries at Northwestern University in Illinois. The company develops,
manufactures, and markets an advanced molecular diagnostic platform. This
platform, the Verigene System, provides simple, highly sensitive nucleic acid and
protein testing on a single platform. The Verigene system is easy to use, provides
rapid turnaround times, and has the ability to detect many targets on a single test.
Products
Within the cardiac diagnostic arena the company provides a
hypercoagulation test and the Warfarin metabolism test. In development, the
company has an ultra-sensitive protein test for cardiac troponin 14 diagnosis of
myocardial infarction, and identification of patients with acute coronary syndromes.
The company is exploring its potential to sell primary functional components of this
assay to commercial labs as a marker for cardiac risk.


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PERKINELMER
Company:
Address:
PerkinElmer
Phone: 781-663-6900
940 Winter St.

Waltham, MA 02451
WebSite: www.perkinelmer.com
PerkinElmer is a provider of technology, services and solutions to the

diagnostics, research, environmental and safety, industrial and laboratory services
markets. The company provides early detection for genetic disorders from preconception to early childhood, as well as digital x-ray flat panel detectors for the
diagnostics market.
The companys digital x-ray amorphous silicon flat panel detectors, the
XRD family, are used to make diagnoses of conditions ranging from broken bones
to reduced blood flow in vascular systems. In addition, its digital x-ray flat panel
detectors focus radiation directly at tumors. The amorphous silicon digital x-ray flat
panel detectors are used in applications such as radiography, cardiology,
angiography and cancer treatments.
In June 2011, PerkinElmer acquired London-based Dexela Ltd., a
provider of x-ray detection technologies and services. The acquisition will expand
PerkinElmers medical imaging portfolio in cardiology. Dexelas products include
hardware and software offerings for low-dose x-ray imaging.


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PHILIPS HEALTHCARE
Company: Philips Healthcare
Address:
Phone: 978-659-3000
3000 Minuteman Rd
Andover, MA 01810
WebSite: www.healthcare.philips.com
Employees: 37,000
2012 $13,070
Company Overview
Royal Philips Electronics of the Netherlands is one of the worlds biggest
electronics companies, as well as the largest in Europe. The US is a key market for
Philips, accounting for one-third of the companys worldwide sales. All five of
Philips product divisions have a presence in the US.
Philips is positioned in the x-ray, ultrasound, nuclear medicine, patient
monitoring and automated external defibrillator device markets. Its portfolio
includes patient monitoring and ultrasound systems, diagnostic cardiology devices,
resuscitation products, x-ray, magnetic resonance, computed tomography products,
nuclear medicine and PET, information management and medical information
technology. The division is represented in more than 60 countries and employs over
30,000 people.
Philips Healthcare accounts for about 25% of Philips overall sales, making
healthcare the companys second largest contributor to companywide sales, after the
Consumer Electronics division. Philips has introduced the concept of automating the
entire MR examination with automatic planning, scanning and processing. Its
ExamCards are standardized customizable examinations that start at a single touch
and can be exchanged among users. Philips SmartExam uses anatomy recognition
and localization software to plan the MR study. Then ExamCard software

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automatically carries out the study and finishes processing the image data.
SmartExams anatomy recognition algorithm extracts the soft tissue features from
each data set and uses these features to localize the anatomy based on position,
orientation and size. The tool is self-adjusting.

Among its MRI products, Philips also offers the Achieva family of MRI
systems -- including the Achieva 3.0T, Achieva 1.5T, Achieva CV for cardiovascular
applications and the Achieva I/T for interventional applications, as well as the
Panorama family of MR products. The companys Panorama high field open MRI
features a wide-open design, high image quality, large field of view and broad
coverage of clinical applications. The Panorama provides a 360-degree panoramic
viewing angle and a 160 cm-wide patient aperture. The company also is in the mobile
field with its Achieva Mobile MRI, which offers parallel imaging technology for
faster scanning times. The companys Ingenia MR system features digital signal
acquisition and processing in the RF receive coil.
In January 2011, Philips received the European CE Mark for its Ingenuity TF
PET/MR system. The two imaging modalities are physically separate in the system,
with a moving and rotating table passing the patient from one to the other. Philips
believes that this approach allows for greater overall resolution and provides the
benefit of using either modality independently as stand-alone machines. In November
2006, Philips Electronics acquired Intermagnetics General, adding the manufacturer
of MRI components and accessories to the Dutch electronics giants portfolio.
In the medical x-ray arena, Philips offers x-ray systems for radiography,
fluoroscopy, urology and mammography. The company is involved in both CR and
flat-panel products. Among its products, Philips is marketing its Allura Xper FD20,
a flexible flat detector system designed for the vascular and mixed cardiovascular
field for both diagnostic and interventional procedures. Some other product
highlights include the companys 256-slice Brilliance iCT scanner, Integrated cath
lab, Avalon FM 20 and FM 30 fetal monitors, and the Ambient Experience CT
system.


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Philips also is offering its Cardio/Vascular X-Ray system, the Allura

Xper FD20/10, which is a biplane flat detector x-ray system. The Allura features a
digital distortion-free imaging chain; a floor mounted C-arm in frontal plane; and a
novel double C-arc in lateral plane. Meanwhile, the Allura 3D-RA is suited for
general vascular as well as non-vascular interventions by providing extensive threedimensional insight into vascular pathologies from a single rotational angiographic
x-ray acquisition.
Philips also offers multislice CT, cardiovascular CT, CT angiography, thin
slice spiral CT, CT endoscopy, multislice cardiac imaging, and mobile radiography,
among other products. Advanced tools, such as 3D rotational angiography and 3D
mapping, have also been integrated, for detailed real-time information
Philips has ultrasound offerings for general imaging, cardiology, emergency
medicine, regional anesthesia, vascular and womens health care. The companys
new xMatrix ultrasound systems use a single transducer to deliver 2D and 3D
images, with uses in general and emergency medicine, cardiology, vascular and
other applications. In the area of ultrasound cardiology, the company offers the
iE33, a 3D quantitative echo system. The iE33 intelligent echo system offers 2D
and volumetric Live 3D imaging and quantification. These tools help find detailed
information related to cardiac disease management: structure, efficiency, size, flow
and function.
Locations
The company has locations in Australia/New Zealand, Brazil, China,
Canada, Europe, Hong Kong, India, Israel, Mexico, Pakistan, Greece, Poland, UK,
and the US.


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ROCHE DIAGNOSTICS US (DIV OF ROCHE)

Company: Roche Diagnostics (US)
Address:
Phone: 317-521-2000
9115 Hague Rd.

Indianapolis, IN 46250
WebSite: www.rochediagnostics.com
Employees: 3,500
2010 $10,900
Company Overview
Roche specializes in therapeutics and diagnostics. A major
jor focus for the
group is cancer therapies,
ies, but it also offers products in other areas such as influenza
and infection. Genentech, Chugai, and Roche Pharmaceuticals are part of the Roche
Group. The Roche Groups Pharmaceuticals Division consists of Roche
Pharmaceuticals, Genentech in the United States and Chugai in Japan. For 2007 and
beyond, a strategic focus has been in personalized
onalized healthcare. The company noted
that the benefits of personalized medicine can increase thee success rate of drugs in
development and bring clinically differentiated medicines to market.
The diagnostics division of Roche includes professional diagnostics, diabetes
care, molecular diagnostics,
stics, and applied science and tissue diagnostics. The
professional diagnostics segment is responsible for approximately 51% of Roche
Diagnostics 2012 revenue.
Products
Roche offers core lab offerings that include clinical chemistry,
immunoassays, hematology, coagulation and others. In March 2011, Roche
introduced a number of STAT immunoassays cardiac biomarker testing on the
cobas 6000 analyzer series. The nine minute STAT immunoassay tests include
troponin T, creatine kinase-AMB, myoglobin, and N-terminal pro-brain natriuretic


130
peptide and run on the cobras e- 601 analyzer, and integrated platform that offers
both clinical chemistry and immunoassay testing.
Another popular product is Roches CoaguChek. The CoaguChek XS Plus
System is the fifth generation of point-of-care anticoagulation monitoring devices
from Roche diagnostics. The system works with the RLS-plus information
management system and can hold up to 1,000 patient results and uses a sample size
of 8 mL. In October 2011, Roche expanded its coagulation testing product line in
North America beyond physician offices and outpatient clinics with the
development of a full line of coagulation analyzers for hospital and reference
laboratories. The new line
is expected to be introduced in 2014. The new
central coagulation lab, which will be marketed under
expected to include three platforms that address a range
low-volume testing to the high-throughput demands of
along with a complete menu of coagulation assays.
line of analyzers for the

Roches cobas brand, is
of consumer needs, from
commercial laboratories,
Locations
Roche has locations worldwide including North America, South America,
Latin America, Asia/Pacific and Japan.


131
SHIMADZU CORP
Company:
Address:
Shimadzu Corp
Phone: +81-75-823-1111
1, Nishinokyo-Kuwabara-cho
Nakagyo-ku
Kyoto 604-8511, Japan
WebSite: www.shimadzu.com
Shimadzu provides a broad range of diagnostic imaging equipment that

includes digital X-ray systems, PET systems, CT scanners and diagnostic ultrasound
systems.
Among its ultrasound products, the company offers the digital color SDU2200 Pro for clinical diagnostics. The SDU-1200 Pro delivers high spatial resolution
and realizes high frequencies and wide aperture imaging at up to 15 MHz. The Pro is
equipped with a digital beam former. The SDU-1100 platform offers dynamic clip
images with calculations and color Doppler. Exam data is stored in JPEG-compressed
DICOM format for fast access. The platform supports a full range of highperformance wide bandwidth imaging probes for a wide range of clinical
applications. Shimadzu also markets a compact SDU-350XL ultrasound system


132
SIEMENS MEDICAL SOLUTIONS

Company: Siemens Medical Solutions
Phone: +49 9131 84-0
Address: Henkestrae 127

91052 Erlangen
Postfach 32 60
91050 Erlangen, Germany
WebSite: www.siemens.com/medical
Employees: 48,000
2012 $17,800
Company Overview
The Siemens Healthcare unit of Siemens AG employs 48,000 worldwide. The
company markets ultrasound products for the following markets: cardiology,
OB/GYN and radiology, among other areas.

Acuson, acquired by Siemens in 2000, remains a dominant player in
ultrasound. In April, Siemens offered the 1.6 release of its Acuson SC2000 volume
imaging ultrasound system. The SC2000 delivers the same detail resolution across
the entire image without sacrificing frame rates. In order to harness the clinical
value that 4D imaging brings to patient care in echocardiography, Siemens has
integrated a number of technologies into the SC2000 real-time full-volume
ultrasound system. Acuson Sequoia has been a leader in the general radiology
market. The mid-market Aspen is cost effective for a variety of applications, and
the XP/10 has been Acuson's workhorse since the early 1980s. The Acuson Aspen
echocardiography system is a convergence of Acuson Sequoia and other advanced
Acuson technologies.
Among Siemens other ultrasound products is the Cypress echocardiography
system, an all-digital, phased array system. It provides 2D in fundamental and
harmonic modes, M-Mode, color flow, spectral Doppler, as well as digital image

133
storage, direct DICOM networking, stress echo, and contrast agent imaging. The
all-digital Sonoline G60 S ultrasound system is a portable, multi-specialty
ultrasound system providing comprehensive solutions in flexibility, workflow, and
performance in all applications.
Also within cardio diagnostics, Siemens offers the Dimension Vista System
Assay. The Dimension EXL system integrates chemistry and immunoassay testing
on a single instrument and includes a number of automated productivity-enhancing
features. In July 2011, Siemens expanded its cardiac marker menu by adding a DNP
assay to its Dimension Vista Intelligent Lab Systems. According to Siemens, the
company was the first clinical laboratory diagnostics company to offer customers
the choice of BNP or NT-pro-BNP testing on separate analyzers. This is designed to
promote greater flexibility and more options for cardiac care testing.
In the point-of-care arena the Stratus CS analyzer provides quantitative
assays de-dimmer PE exclusion, hsTroponin-I, CK-MB, myoglobin, NT-pro-BNP,
D-dimer, CardioPhase hsCRP and Bhcg.
Four coagulation testing, Siemens introduced the Innovance VWF Ac Assay
and the Sysmex CS-2000i/CS-2100 Automated Blood Coagulation Analyzer that
automatically performs pre-analytical sample quality checks.
Since its introduction in 1992, the Immulight family of systems has grown
to be a premier brand and immunoassay testing. The newest addition to the product
line is the Immulite 2000 XPi Immunoassy System that received FDA clearance in
May 2011. The analyzer offers the largest automated immunoassay test menus
available and features several innovative hardware and software solutions to
enhance productivity and efficiency.


134
ST. JUDE MEDICAL

Company:
St Jude Medical
Phone: 651-756-2000
Address: : One St. Jude Medical Drive

St. Paul, Minnesota 55117
WebSite: www.sjm.com
Employees: 16,000
2012 $ 5,503
Company Overview
St. Jude Medical, Inc. develops, manufactures and distributes cardiovascular
medical devices for the global cardiac rhythm management, cardiovascular and atrial
fibrillation therapy areas and neurostimulation medical devices for the management
of chronic pain. St. Jude Medical is headquartered in St. Paul, Minnesota and has four
major focus areas that include: cardiac rhythm management, atrial fibrillation,
cardiovascular and neuromodulation. The St. Jude Medical product portfolio includes
implantable cardioverter defibrillators (ICDs), cardiac resynchronization therapy
(CRT) devices, pacemakers, electrophysiology catheters, mapping and visualization
systems, vascular closure devices, structural heart products, spinal cord stimulation
and deep brain stimulation devices. St. Jude Medical employs more than 16,000
people worldwide. The principal geographic markets for our products are the United
States, Europe, Japan and Asia Pacific. St. Jude Medical was incorporated in
Minnesota in 1976.
Its principal products are cardiovascular; vascular products, which include
vascular closure products, pressure measurement guidewires, optical coherence
tomography (OCT) imaging products, vascular plugs and other vascular accessories,
and structural heart products, which include heart valve replacement and repair

135
products and structural heart defect devices; Atrial Fibrillation electrophysiology

(EP) introducers and catheters, advanced cardiac mapping, navigation and recording
systems and ablation systems; and Neuromodulation neurostimulation products,
which include spinal cord and deep brain stimulation devices.
St. Jude provides a complete system of access, diagnostic, visualization and
ablation products for diagnosing and treating various irregular heart rhythms and
designed to be used in the electrophysiology (EP) lab.
Products
The DragonFly intravascular imaging catheter for the diagnosis and
treatment of coronary artery disease. Products for the transcatheter treatment of
structural heart defects are available including interventions for holes in the septum
between the right and left sides of the heart and device closure for patients with
PFO.


136
TERUMO MEDICAL CORPORATION

Company:
Address:
Terumo Medical Corp
Phone: 732-302-4900
2101 Cottontail Lane

Somerset, NJ 08873
WebSite: www.terumomedical.com
Terumo Medical Corporation develops, manufactures, markets, and

distributes medical devices and supplies. While many products and devices are still
produced in Japan, Terumo has invested in its Elkton, Maryland, plant. Founded in
1921, Terumo Corporation has expanded into blood-management systems and
endovascular therapy. Its products are sold in 160 countries and generate over $3
billion in global annual sales. Terumo Medical Corporation operates two business
divisions: Terumo Interventional Systems and Terumo Medical Products.
Terumo Interventional Systems markets a full line of guidewires, catheters,
introducer sheaths, guiding sheaths, and embolics for use in a interventional
procedures including radiology, neuroradiology, cardiology, and vascular surgery.
Terumo Medical Products manufactures medical devices including hypodermics,
infusion, and blood collection products.
Terumo Interventional Systems markets devices for endovascular
procedures, including peripheral embolization and transradial access including:
o Introducer sheaths
o Guiding sheaths
o Guidewires
o Angiographic catheters
o Coronary catheters
o Microcatheters
o Embolics

137
TOMTEC IMAGING SYSTEMS GMBH

Company:
TomTec Imaging Systems GmbH
Address:
Edisonstrasse 6
85716 Unterschleissheim
Munich, Germany
Phone: +49 (0) 89-32175-500
WebSite: www.tomtec.de
TomTec Imaging Systems manufactures and markets 2D, 3D and 4D tools

for clinical as well as research-oriented ultrasound applications. Its product line
encompasses 2D and 3D/4D technology and software for the acquisition, analysis,
and reconstruction of ultrasound data. The product line is applicable to the fields of
adult and pediatric cardiology as well as obstetrics and gynecology, radiology, and
vascular diagnostics.
Among its products, the company is offering dynamic 3D ultrasound
systems that allow the visualization and examination of cardiovascular structures as
they move in time and space. It is possible to analyze the spatial and temporal
relationships of heart valves, vessels, and chambers. In adult and pediatric
cardiology, a realistic representation of cardiovascular anatomy can be evaluated
and documented. Color flow techniques assist in evaluating pathological findings,
such as regurgitant flow and stenotic valves.
The company also has developed vendor independent software that can be
used to review cardiac ultrasound data. Image-Com makes echocardiographic
information available faster, provides additional clinical information and accelerates
reporting. It can be used for multimodal reviewing of 2D ultrasound data, coronary
and left ventricle (LV) angiograms and to measure and report cardiac 2D ultrasound
data. Another vendor independent software, 4D LV-Analysis, makes it possible to
analyze and visualize LV function and LV dyssynchrony in cardiac 3D ultrasound

138
data. 4D LV-Function assesses the LV including volumes, ejection fraction and

global longitudinal strain.


139
TOSHIBA AMERICA MEDICAL SYSTEMS, INC

Company: Toshiba America Medical Systems, Inc
Address:
Phone: 800-421-1968
2441 Michelle Rd
Tustin, CA 92780
WebSite: www.medical.toshiba.com
Employees: 210,000 total Toshiba
Recent Revenue History (in billions): 2011 $ 64.6
Toshiba)
2012 $61.5 (Includes all of
Company Overview
Toshiba America Medical Systems markets, distributes and services
diagnostic imaging systems, and coordinates clinical diagnostic imaging research in
the US. Toshiba Medicals products include CT, x-ray, ultrasound, nuclear
medicine, MRI and information systems.
In the MRI area, Toshiba markets the Vantage 1.5T Ultra-Short Bore MRI
system. The product is an ultra-short, ultra-wide-bore system. Its magnet offers more
homogeneity than other 1.5T systems. Vantage's ultra-short bore magnet and 65.5 cm
gantry opening provide a feeling of openness for the patient. Other Vantage products
include the Vantage Titan with a 71 cm aperture. It provides the largest clinical fieldof-view of any ultra-short, open bore system (55 x 55 x 50 cm). The Titan also is
available in 3T. Toshiba's Vantage systems are available with contrast-free magnetic
resonance angiographic techniques.
In October 2011, Toshiba unveiled enhancements to its Vantage Titan MR
product line, including a high-density 16-channel flexible coil system. The 16channel flexible coil system conforms closer to the anatomy, improving signal-tonoise ratio for more accurate images.


140
Toshiba also offers the Ultra with a gradient performance that facilitates
higher resolution imaging with thinner slices and smaller fields of view, better image
quality, and faster scanning capabilities. It features a 25 milli-T per meter amplitude;
100 T per meter per second slew rate; and high resolution imaging, among other
features. Ultra's 100 m/T/s allows the gradient speed to be nearly five times that of
current open systems, and 250% greater than higher Tesla open systems. Superior
gradient performance allows the application of high-field imaging techniques: single
shot EPI diffusion; true SSFP; superFASE (Fast Advanced Spin Echo); and black
blood MRA.
Toshiba also is marketing the Opart, a cryogen-free, superconducting, midfield (0.35T) MR system that offers an open design and high-field applications.
Toshiba offers fresh blood imaging, which is good for evaluating peripheral
vascular diseases of the lower extremities. Other techniques available include
contrast-free improved angiography, which adds systolic black blood imaging to
reduce ghosting and improve arterial and venous flow separation. In September 2011,
Toshibas advanced M-Power interface received FDA clearance. M-Power is a
customizable MR system user interface enabling technologists to streamline and
accelerate scanning processes and enhance diagnoses.
Toshiba has a number of products in the ultrasound area, including the Aplio
Artida cardiology ultrasound system for cardiac 4D. Toshibas 2D/3D wall motion
tracking features allow the user to obtain angle-independent, quantitative and regional
information about myocardial contraction. This ability to identify wall motion defects
and heart timing will greatly improve cardiac resynchronization therapy (CRT) using
pace makers by determining who will be a responder to CRT and who will probably
not.
In March 2006, Toshiba introduced a comprehensive cardio offering for its
Aplio CV, the companys all-digital ultrasound system for advanced cardiovascular
applications. The technology allows for improvements in a variety of cardiac
procedures including stress echo, contrast harmonics, and tissue Doppler imaging,
which quantifies CRT and biventricular pacing. The comprehensive cardio package
features dyssynchrony imaging (DI), a rapid visual assessment technique that
evaluates electrical timing events within the heart. Toshibas DI technique aids

141
cardiologists in the quantification of left ventricular mechanical dyssynchrony by

providing a color-coded display that demonstrates the timing of events within the
myocardium of the heart.
The Aplio XG is the next generation in a premium cardiology system
developed specifically for demanding ultrasound environments. Aplio XG expands
clinical performance and improves patient care by offering complex data processing
in real time and excellent image quality, sensitivity and artifact suppression. For
general radiology, it has volumetric imaging that provides the ability to view
multidimensional images in any plane similar to CT and MR. For its flagship cardiac
system, Aplio ArtidaTM, 3D Wall Motion Tracking and Tissue Enhancement
technologies are now available.


142
TRIXELL
Company:
Address:
Trixell
Phone: +33 (0) 4 76 57 41 00
460 rue du Pommarin ZI Centr'Alp

38430 Moirans, France
WebSite: www.trixell.com
Trixell is a joint-venture company that develops a family of x-ray flat panel

digital detectors for radiological imaging manufacturers. Trixells three parent
companies are Thales (51% ownership); Philips Medical Systems (24.5%
ownership); and Siemens Medical Solutions (24.5% ownership). Systems equipped
with Trixell detectors are already in use in close to 2,000 radiology departments
worldwide.
In the area of general radiography, Trixell offers the Pixium family,
including the Pixium 4600, designed to replace conventional film technology and
computed radiography. It can be used for all types of examinations, thanks to the
large square format, high resolution and wide dynamic range. The Pixium 4700 and
Pixium 4800 meet the requirements for high-resolution, wide-field radiography as
well as for real-time low dose fluoroscopy. Pixium 4700 features optimized
resolution (154 m pixel pitch) and numerous operating modes. It benefits from the
Trixell cesium iodide scintillator on an amorphous silicon matrix. The digital x-ray
detector, the Pixium 4800, uses the same technology as the Pixium 4600, combining
an amorphous silicon flat panel with a cesium iodide scintillator (CsI/TI).
The Pixium 4343F is a flat-panel radiography and fluoroscopy
digital detector with the largest coverage area in the market. It is designed for easy
installation in remote-controlled exam tables and allows manufacturers to offer
radiologists an all-digital real-time system. This product generates high-quality

143
images for both fluoroscopy (up to 30 images per second) and radiography
applications. The Pixium 3543pR is a wireless digital detector for radiographic Xray exams. The Pixium 4343R is a new technology digital radiographic imaging
flat-panel detector.
The Trixell flat-panel detectors are based on a cesium iodide
scintillator (CsI) and an active amorphous silicon array, controlled by ultra-low
noise electronics. The basic Trixell flat-panel x-ray detector consists of a matrix of
photodiodes, made from amorphous silicon, which is covered with a cesium iodide
scintillator. X-rays are absorbed in the CsI layer and are converted into visible
photons, which in turn generate electric charges in the photodiodes. Each pixel of
the matrix is connected to a row line for driving voltages and to a column line for
readout via an active switching element, which may be either a thin-film diode or a
thin-film transistor. The electric charges are read out in parallel for one row. The
signals are then multiplexed and converted to digital inside the detector housing.
The data are transmitted via a fiber-optic link to the acquisition system, where
digital processing is performed.


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VASCULAR SOLUTIONS
Company:
Address:
Vascular Solutions
Phone: 763-656-4300
6464 Sycamore Court North

Minneapolis, Minnesota 55369
WebSite: www.vasc.com
Vascular Solutions, Inc. (VS) designs and develops minimally invasive

medical devices for interventional cardiologists and interventional radiologists
worldwide. During 2012, 63% of sales were derived from catheter products. The
firm was founded in December 1996, and began operations in February 1997. In
2000 it completed an initial public offering following FDA clearance for the first
product, the Duett sealing device, used to seal the puncture site following
catheterization procedures. The firm now offers over 70 vascular products
developed and launched since 2002, including catheter products, hemostat products
and vein products and services.
In December 2011, it acquired exclusive 5-year rights to sell reprocessing
services for the ClosureFast catheter in the United States from Northeast Scientific,
Inc. In January 2012, VS acquired the Pronto catheter from Dr. Pedro Silva and his
affiliates. In August 2012, the company acquired the Venture Wire Control Catheter
assets from St. Jude Medical, Cardiology Division, Inc..
Catheter products represent the largest of the three product categories. The
products consist of a variety of devices used to access, diagnose and treat vascular
conditions during minimally invasive catheterization procedures. Examples include
the Pronto extraction catheters used in treating acute myocardial infarction and the
GuideLiner catheter used to access discrete regions of the coronary anatomy.


145
The best-selling catheter products are the Pronto catheters, consisting of a

catheter with a proprietary distal tip and large extraction lumen that can be
delivered into arteries to mechanically remove blood clots.


146
VERMILLION, INC
Company: Vermillion, Inc
Address:
Phone: 512-519-0400
12117 Bee Caves Rd

Austin, TX 78738
WebSite: www.vermillion.com
Employees: 20
2011 $ 1,923
2010 $2,094
Company Overview
Vermillion discovers, develops and commercializes diagnostic tests. The
companys concentration has been in the field of GYN oncology, which led to the
approval of OVA1. The company is located in Austin, Texas and employs 20
individuals.
Products
In the cardiac diagnostic arena, Vermillion is expanding its menus to include
cardiac markers. The company is developing B2m (Beta-2 microgloblin) and CRP as
biomarkers for peripheral artery disease. The company is also developing a test for
the diagnosis and clinical evaluation of thrombotic thrombocytopenic purpura (TTP),
a blood disorder that can directly affect cardiac function.


147
VOLCANO CORP
Company: Volcano Corp
Address:
Phone: 916-638-8008
3661 Valley Centre Dr Suite 200

San Diego, CA 92130
WebSite: www.volcanocorp.com
Employees: 1,565
2012 $381,866
Company Overview
Volcano develops catheter-based intravascular ultrasound systems (IVUS) and
related products for diagnosing heart disease, including atherosclerosis. Volcano's
IVUS allow physicians to acquire images of diseased vessels from inside the artery.
They give information about the condition of arteries as well as plaque and lesions.
The IVUS products consist of consoles, single-procedure disposable catheters and
advanced functionality options.
IVUS technology uses advanced spectral analysis techniques to simplify the
interpretation of ultrasound images and provide detailed information on the
composition of each patient's atherosclerotic plaques. IVUS provides detailed
measurements of lumen and vessel size, plaque area and volume, and the location of
key anatomical landmarks. The technology helps differentiate the four plaque types:
fibrous, fibro-fatty, necrotic core, and dense calcium.
Products
Volcanos IVUS imaging products include: the Eagle Eye Gold intravascular
ultrasound imaging catheter; the Visions PV .018 F/X intravascular ultrasound
imaging catheter; the Visions PV 8.2F intravascular ultrasound imaging catheter; and
the Revolution 45 MHz.

148
The company is developing OCT products to complement its existing product

offerings in imaging technology. The companys early model OCT systems have been
used in several clinical settings in Europe and South America. Volcano believes its
OCT products will be an important addition to its cardio product line, and will allow
the company
to expand its reach into clinical situations where extremely high
resolution imaging is paramount.

Locations
Volcano has direct sales capability in the US, Western Europe and Japan. In
addition to its direct sales efforts, the company has Japanese distribution
relationships with Goodman, Fukuda Denshi and Johnson & Johnsons Cordis
Division. Altogether, it has 50 distribution partnerships in 40 countries.

Market Trends and Summary
MARKET OVERVIEW
The global cardiac diagnostics market totaled approximately $13.2 billion
in 2012, increasing at a rate of 3.1% from $12.4 billion in 2010. There are several
trends which continue to influence growth in this market. Economic conditions in
several markets remained challenging in 2012. Demand for cardiovascular
diagnostics slowed during the historical period due to a weakened global economy,
cost cutting measures and healthcare reform issues. However, demographics
worldwide and an aging world society remain primary factors in growth. By 2020,
16 percent of the US population will be over the age of 65, up from 13 percent in
2010. People are also living longer, needing more health care, further fueling the
market. In 1980, the US life expectancy at birth was 74 years, today the average
American lives to be 78 years old.
Advancing technologies have also led to increased use less invasive and more
sophisticated cardiac diagnostics. A trend toward preventive care, education of
cardiovascular risk factors and earlier treatment of cardiovascular disease has been
driving factors.
The market is expected to increase to approximately $16.6 billion in 2017,
growing at a rate of 4.8% throughout the forecast period. New technologies in
testing will likely continue to fuel growth in combination with an aging population,

Nine: Market Trends and Summary

150
increasing cardiovascular disease incidence and prevalence, and increasing life

expectancy.
Table 9-1
Global Cardiac Diagnostics Market Analysis, 2010-2017

Year
2010
2011
2012
2013
2014
2015
2016
2017
12,392.0
12,736.0
13,176.0
13,701.0
14,298.5
14,987.3
15,762.0
16,632.0
Percent Change
2.8%
335%
4.0%
4.4%
4.8%
5.2%
5.5%

2010-2012
2010-2017
2010-2017

3.1%
4.8%
4.3%

151
Figure 9-1
Global Cardiac Diagnostics Market Analysis: 2010-2017
$18,000
$16,000
$14,000
$12,000
$10,000
$8,000
$6,000
$4,000
$2,000
$0
2010
2011
2012
2013
2014
2015
Calendar Year

2016

152
Market Revenues by Product Type

There are five categories of cardiac diagnostics that Kalorama assessed in this
market. These include:
x
ECG
Cardiac Diagnostic Point-of-Care
Cardiac Markers
Cardiac Diagnostic Contrast Agents and Radiopharmaceuticals
Cardiac diagnostic imaging is the largest category within the global cardiac
diagnostic market with 50.5% of the total revenues.
Cardiac contrast agents and radiopharmaceuticals accounted for 20.8% of
revenues in 2012 and cardiac markers accounted for 14.3% of revenues. Growth in
these two areas has been growing.
ECG equipment accounted for 8.4% of revenues in 2012 and is expected to
continue to increase as the elderly population grows and the incidence of heart
disease continues to increase.
Overall, increasing incidence of heart disease and an aging population,
which typically require more diagnostic procedures, will continue to fuel growth for
cardiac diagnostics throughout the forecast period.


153
Table 9-2
Global Cardiac Diagnostics by Type Revenues and Percent of Market 2012

(in millions of dollars at the manufacturers level)
CARDIAC
REVENUES 2012
DIAGNOSTIC TYPE
ECG
$ 1,112.0
Imaging
6,648.0
POC
795.0
Cardiac Markers
1,880.0
Contrast
Agents
and
2,741.0
TOTAL
$13,176.0
PERCENT OF
MARKET
8.4%
50.5%
6.0%
14.3%
20.8%
100.0%
Figure 9-2
CardiacDiagnosticType2012
20.8%
8.4%
ECG
Imaging
14.3%
50.5%
6.0%
POC
Markers
ContrastAgents


154
Table 9.3
Global Cardiac Diagnostic by Type Revenues and Percent of Market 2017

(in millions of dollars at the manufacturers level)
CARDIAC
REVENUES
DIAGNOSTIC TYPE
ECG
$1,380.0
Imaging
8,380.0
POC
1,022.0
Cardiac Markers
2,550.0
Contrast
Agents
and
3,330.0
TOTAL
$16,632.0
PERCENT OF
MARKET
8.3%
50.4%
6.1%
15.3%
19.8%
100.0%
Figure 9-3
CardiacDiagnosticTypes 2017
19.8%
8.3%
ECG
Imaging
15.3%
50.4%
6.1%
POC
Markers
ContrastAgents


155
Global Cardiac Diagnostic Market Analysis by Region

The global cardiac diagnostic market is divided into four geographic regions
x
United States
Europe
Japan
Rest of World
The economic recession had a significant impact on the cardiac diagnostics

market, which experienced falling sales in key geographies. The difficulties were
mostly felt on the high-end imaging equipment segment after many health care
institutions delayed or outright cancelled equipment purchases. There also was a
concurrent decline in patient numbers as people skipped or deferred scans because
they lost jobs and health insurance coverage, or because of the high out-of-pocket
costs associated with cardiac imaging. Some growth in the market is attributed to
the continuous improvements in image quality, and to newer techniques for imaging
specific portions of the heart.
Growth rates in the United States, Europe and Japan have moderated due to
budgetary constraints, changes in reimbursement and a global economic slowdown.
However, in Rest of World markets spending on healthcare is increasing and there
is an increasing demand for medical technologies. This is especially apparent for
China, India, Latin America, the Middle East, and Brazil.
United States
The United States is the largest market for cardiac diagnostics.
Demographically, the region is staged for growth due to an aging population, longer
life expectancies, increasing numbers of cardiovascular patients across all care
settings including hospitals, extended care facilities, and in the home. However,
negative factors such unsure health care reform issues, cost controls, shrinking
budgets, and an excise tax on medical devices are expected to slow the markets
growth.


156
Europe
Europe is experiencing similar issues as the United States. Demographically,
the population is aging, people are experiencing longer life expectancies which has
led to an increasing number of sicker patients across all care settings..
As in the US, European governments are facing rising health care costs, and
they have limited some health care related expenditures. Some cardiac diagnostic
equipment purchases have been affected.
Europe, particularly Western Europe,
benefits from high levels of healthcare coverage, but many of these countries face
challenges such as rising costs, increasing expectations and the impact on
government debt of the financial crisis. Europes primary risk to healthcare levels
comes from an aging population, which is putting upward pressure on costs as well
as reducing the viability of existing funding mechanisms.
But the market should recover somewhat, as there is a need for cardiac
diagnostics. Technological advancements in all areas of cardiac diagnostics are
increasing contrast image and resolution, improving workflow, increasing patient
throughput and reducing scan time and more. Much of the focus is on improving
patient comfort. A growing need for effective diagnosis is driving the demand for
cardiac diagnostic products. Europe ranks with the US as one of the most developed
cardiac diagnostic markets.
Japan
Japan has experienced similar demographic, economic and financial issues
as the United States and Europe. The earthquake in early 2011 created new demand
for medical equipment during the rebuilding period. This trend is expected to
continue for the next two years and then level off again. The countrys health care
institutions are early adopters of newer cardiac diagnostic equipment, making it a
prime market opportunity.
Rest of World
In Rest of World the cardiac diagnostic markets are continuing to flourish.
For example, India, whose population exceeds one billion people, has significantly
increased its healthcare expenditures over the past decade to more than $37 billion

157
or roughly 7% of GDP. The population of individuals at least 60 years of age is

projected to triple over the next 20 years to an estimated 190 million people.
With a population of nearly 1.4 billion, about 20% of the worlds total,
China has a growing need for advanced healthcare products, including cardiac
diagnostic systems. One of the key factors in Chinas population spurt, from slightly
more than 500 million in 1949 todays levels, is its declining mortality rate. This
increase in lifespan and the aging of China's population, with over 11% of the
population expected to be over the age of 65 in 2020, indicates the need for
improved diagnostics for cardiovascular disease.
Driven by a growing economy, although it may have slowed in recent years,
China still retains one of the fastest growing health care markets in the world,
exceeding 16% annual growth over the last decade. Demand for higher living
standards, an aging population, and increased healthcare awareness are a few
factors responsible.
Brazil is the largest and most populous country in South America, with a
population of more than 200 million. It is the fifth largest country worldwide in
terms of area and number of inhabitants. Because of Brazils health care system,
location and proximity to most of the Latin American countries, Brazil has evolved
into the main medical tourism destination in South America. Cardiac diagnostics are
less costly to the patient in Brazil than in the US, for example. Because the
Brazilian health care model has comprehensive coverage, anyone can have medical
assistance in any of the hospitals that are in the national health care network free of
charge. A large number of health care services are sponsored directly by the
Brazilian government at more than 1,000 hospitals, where non-citizens can receive
free treatment, according to the CIA Factbook.


158
Table 9-4
Global Cardiac Diagnostics Market Revenues by Region 2012 ($millions)

Region
Revenues
US
Europe
Japan
Rest of World
Total
$6,271.4
3,241.3
1,331.1
2,332.2
$13,176.0
% of
Global Market
47.6
24.6
10.1
17.7
100.0
Figure 9-4
2012
7000
6000
5000
4000
2012
3000
2000
1000
0
US
Europe
Japan
RestofWorld


159
Figure 9-5
Global Cardiac Diagnostics by Region Percent 2012 (%)
PercentofGlobalMarket
US
Europe
Japan
RestofWorld
Table 9-5
Global Cardiac Diagnostics Market Revenues by Region 2017

($millions)
Region
Revenues
US
Europe
Japan
Rest of World
Total
$7,733.9
3,825.4
1,812.9
3,259.8
$16,632.0
% of
Global Market
46.5
23.0
10.9
19.6
100.0


160
Figure 9-6
2017
9000
8000
7000
6000
5000
2017
4000
3000
2000
1000
0
US
Europe
Japan
RestofWorld


161
Figure 9-7
Global Cardiac Diagnostics by Region Percent 2017 (%)
PercentofGlobalMarket
US
Europe
Japan
RestofWorld
Competitive Analysis
The global cardiac diagnostic market is highly competitive with a large
number of providers. Companies remain competitive by offering high-quality
products for the healthcare community including patients, hospitals and clinics.
Four companies, GE, Siemens, Philips and Toshiba, dominate the industry with
combined cardiac diagnostics revenues of nearly $10.5 billion in 2012.
GE Healthcare is the leading cardiac diagnostics provider worldwide with a
28% market share for 2012. GE Healthcares cardiac diagnostic revenues were
estimated at $3,689.3 million for the year. GE Healthcare is a major participant in the
ECG testing market and cardiac diagnostic imaging markets (CT market, X-ray
market, ultrasound market, and MRI market).
Siemens secured the second market position in the cardiac diagnostics market
with 2012 estimated revenues of $2,898.7 million and a 22% market share. Siemens

162
is a major participant in the cardiac diagnostic imaging market (CT market, X-Ray
market, ultrasound market, and MRI market) and the cardiac markers market.
Philips Healthcare held the third position with 20% of the total market with
revenues estimated at $2,635.2 million. Philips is a major participant in the ECG
testing market and the cardiac imaging market (CT market, X-Ray market, ultrasound
market, and MRI market).
Toshiba secured the fourth market position with a 10% market share with
estimated revenues for cardiac diagnostics of $1,317.6 million. Toshiba is a major
participant in the cardiac imaging market.
The remaining 20% market share revenues of $2,635.2 million are divided
among a host of other companies including Alere , Roche Diagnostics, Response
Medical, Abbott Diagnostics, and many others.
Table 9-6
Estimated Global Cardiac Diagnostics Manufacturer Market Share

2012
Provider
GE Healthcare
Siemens
Philips
Toshiba
Others
Total
Revenues Estimates
(in millions)
3,689.3
2,898.7
2,635.2
1,317.6
2,635.2
13,176.0
Market Share
(%)
28.0%
22.0%
20.0%
10.0%
20.0%
100.0%


163
Figure 9-8
Estimated Global Cardiac Diagnostics Revenues and Market Share 2012
Philips
20.0%
Toshiba
10.0%
Siemens
22.0%
Others
20.0%
GE
28.0%

Industry Developments and

Technologies
DEMOGRAPHICS
There are approximately 7.1 billion people living in the world today with
more than 60% of these in Asia, 14% in Africa, 11% in Europe, 8% in North
America, 6% in South America, and less than 1% in the Oceania region. By 2050,
the world population is expected to grow by nearly 3 billion reaching 9.4 billion
worldwide. The U.S. Census Bureau estimates that nearly 130 million live births
take place each year worldwide and approximately 55 million people die each year,
which reflects growth of 1.13% over 2010.

Ten: Industry Developments and Technologies

166
Table 10-1
Total Global Population by Selected Geographical Region, 2000 - 2050

Year
Population by Region (in millions)

Africa Asia Europe North America Oceania South
America
2000 807.9
3,693.6 730.4
313.4
30.4
519.9
2010 1,027.8 4,164.4 738.1
344.5
36.6
590.1
2011 1,052.3 4,207.4 739.3
347.6
37.1
596.3
2020 1,288.5 4,543.0 734.1
373.4
39.3
653.9
2030 1,583.2 4.861.2 723.1
404.4
43.1
708.4
2040 1,912.8 5,078.2 704.7
434.4
46.1
748.7
2050 2,270.4 5,205.8 679.3
463.8
48.5
773.3
Percent Change
2000-2010 2.4% 1.1% 07%
.88%
1.2%
1.3%
2010-2011 2.4% 1.0% .01%
.88%
1.3%
1.1%
2011-2020 2.3% .92% -.02%
.87%
1.2%
1.0%
2020-2030 2.1% .68% -.15% .80%
.93%
.80%
2030-2040 1.9% .44% -.26% .71%
.68%
.55%
2040-2050 1.7% .25% -.37% .66%
.50%
.32%
World
6,090.7
6,895.9
6,974.0
7,632.2
8,323.4
8,924.6
9,441.1
1.2%
1.1%
1.1%
.87%
.70%
.56%
Source: U.S. Census Bureau, World Health Organization.
Because there is an increased cardiovascular diseases among the elderly

population, it is prudent to consider the number of elderly worldwide.
In 2009, the global population of the world age 60 and over was 680 million
people, representing 11 percent of the world's population. They have increased by
10.4 million just since 2007an average increase of 30,000 each day.
By 2050, the 60 and older population will increase from 680 million to 2
billionincreasing from 11 to 22 percent of the world's population. From 1950 to
2050, the world population will have increased by a factor of 3.6; those 60 and over
will have increased by a factor of 10; and those 80 and over by a factor of 27.
By 2050, Europe will continue to be the world's oldest region with its elder
population increasing more than five-foldfrom 40 million to 219 million.

167
Only 5 percent of Africa's population is projected to be 60 and older by

2050, with sub-Saharan Africa remaining the world's youngest region.
China and India have the largest older populations. By 2050, China will see
its number of elders grow 30% from 109 million to 350 millionIndia, from 62
million to 240 million.
Japan, with today's largest share of the world's old-age population, will see
its percentage of those 60 and over rise from 27 percent to 44 percent in 2050.
By 2050, more than 70 countries, representing about one third of the world's
population, will surpass Japan's present old-age share of 27 percent.
In the coming decades, all regions of the globe will experience population
aging. Today's 5-22 percent range will become an 11-34 percent range in 2050.
Cardiovascular Disease Worldwide
Cardiovascular diseases are the number one cause of death globally: more
people die annually from cardiovascular disease than any other cause. An estimated
17.3 million people died from cardiovascular disease in 2008, representing 30% of
all global deaths. Of these deaths, an estimated 7.3 million were due to coronary
heart disease and 6.2 million were due to stroke.
Low-and middle-income countries are disproportionately affected. Over
80% of cardiovascular desk take place in low-and middle-income countries and
occur almost equally in men and women.
Number of people who die from cardiovascular disease mainly from heart
disease and stroke will increase to reach 23.3 million by 2030. Cardiovascular
disease is projected to remain the single leading cause of death. Most cardiovascular
diseases can be prevented by addressing risk factors such as cigarette smoking,
unhealthy diet and obesity, physical inactivity, high blood pressure, diabetes and
raised lipids. Approximately 9.4 million deaths each year, or 16.5% of all deaths
can be attributed to high blood pressure. This includes 51% of deaths due to strokes
and 45% of deaths due to coronary heart disease.


168
Table 10-2
Cardiovascular Deaths by World Region 2008

Region
The Americas
Europe
East Mediterranean
Africa
South-East Asia
Western Pacific
All Regions Total
Number of CVD Deaths

1,944,000
4,584,000
1,195,000
1,254,000
3,616,000
4,737,000
17,327,000
Source: Word Heart Federation, WHO 2008 Summary Tables
European Cardiovascular Disease Statistics

There are approximately 4 million deaths in Europe and 1.9 million deaths
in the European Union attributed to cardiovascular disease. This equates to
approximately 47% of all deaths in Europe and 40% in the EU caused from
cardiovascular disease. Cardiovascular disease is the main cause of death in women
in all countries of Europe and is the main cause of death in men in all but six
countries. Death rates from coronary heart disease are higher in Central and Eastern
Europe than in northern, southern and western Europe.
Smoking remains the number one health issue in Europe. All of smoking has
declined in many European countries the rate of decline is now slow and rates
remained stable or increasing in some countries, particularly among women .
Women are now smoking nearly as much as men in many European countries and
girls often smoke more than boys.
Overall the European diet has remained much the same but fewer adults in
European countries are participating in adequate levels of physical exercise. Levels
of obesity are high across Europe in both adults and children, although rates vary
substantially between countries. The prevalence of diabetes in Europe is high and
has increased rapidly over the last ten years, increasing by more than 50% in many
countries.

169
The estimated cost of cardiovascular disease in the EU is approximately

196 billion per year.
US-Specific Population Demographics
The US population has shown steady growth since the year 1980 and is expected
to continue its growth at approximately the same rate of one percent through the year
2020. The US population in the year 1980 was estimated to be 228 million; this is
expected to reach 336 million by the year 2020. Between 2000 and 2010, the 45 to 64
population grew 31.5 percent to 81.5 million, and now makes up 26.4 percent of the total
U.S. population. This rapid growth is due to aging of the Baby Boom generation.
Approximately 82 million individuals in the US are affected with some form of
cardiovascular disease, causing about 2,200 deaths a day, averaging one death every 39
seconds. Almost one out of every three deaths results from cardiovascular disease.
Approximately 16 million US adults are diagnosed with coronary heart disease.
Another 76 million are diagnosed with hypertension and an estimated 98 million carry
the diagnosis of high cholesterol, and an estimated 18 million carry the diagnosis of
diabetes.
Cardiovascular disease is the number one killer of both women and men with
about one-third of cardiovascular disease deaths occurring prematurely before age 75.
Table 10-3
The U.S. Population, 1980-2020

Year
Population
(millions)
1980
1990
2000
2010
2020
228
250
282
309
336
% Growth
0.9%
1.2%
0.9%
0.8%
Source: U.S. Census Bureau.


170
Figure 10-1
The US Population, 1980-2020 (in millions)
Source: US Census Bureau.
Population Over Age 65

The US Administration on Aging reports that in 2009 the older population of
those 65 and older was 39.6 million, representing 12.9 percent of the U.S. population,
or about one in every eight Americans.
Back in 2000, people aged 65 and older represented 12.4 percent of the
population. By 2030, there will be about 72.1 million older persons, more than twice
their 2000 number.


171
The future will likely show an increase in the number of Americans over the age of
65, incredibly growing to 87 million in 2050 or 20.7% of the population.
Table 10-4
Percent U.S. Population Over Age 65 by Year

Year
Over 65 Population
(millions)
% of Total
U.S.
Population
2000
2010
2020
2030
2040
2050
35
40
55
72
80
87
12.4%
13.0%
16.3%
19.6%
20.4%
20.7%


172
Figure 10-2
Estimated Population by Age Group, 2000 and 2050
Life Expectancy
Life expectancy has been increasing around the world due to advances in
healthcare, medical research, sanitation, and nutrition. This provides a setting for
increasing incidence of disease and a focus on preventive care as the population
continues to add years to their life.
In the U.S. a child born in 1900 had roughly a 50 percent chance of living to
the age of 50. By 1980, the U.S. life expectancy at birth rose to 74 years of age (77
for female and 70 for male). By 2004 the average life expectancy in the U.S. had

173
risen to approximately 78 years of age. Life expectancy by gender is also a key factor
in aging disease as women often live longer, but they show higher incidence of the
disease over their lifetime.
Table 10-5
Average U.S. Life Expectancy in Years 1980, 2004, 2006, 2010, 2011 (years)
Gender
Women
Men
United States
Average
1980
2004
2006
2010
2011
77
70
74
81
75
78
81
75
78
81.0
76.2
78.7
81.1
76.3
78.7
Source: U.S. National Center for Health Statistics, Vital Statistics of the United States; Kalorama
Information


174
Figure 10-3
Average U.S. Life Expectancy in Years 1980, 2004, 2006, 2010, 2011
85
Women
Women
80
Men
Women
Men
Men
Years
75
70
65
60
55
1980
2004
2006
2010
2011
Source: U.S. National Center for Health Statistics, Vital Statistics of the United States; Kalorama
Information
Increasing Incidence of Disease

There is an increasing incidence of disease due to three factors:
x
An increase in the population
An increase in the elderly population
An increase in life expectancy


175
Cardiovascular disease (CVD), including heart disease and stroke, is the

number one killer of men and women in the U.S., accounting for 600,000 deaths in
2012. Coronary heart disease is the most common type of heart disease, killing
more than 385,000 people annually. Every year about 715,000 Americans have a
heart attack. Of these, 525,000 are a first heart attack and 190,000 happen in people
who have already had a heart attack.
CVD prevalence is higher among older Americans and, as baby boomers
age, deaths from heart disease and stroke are expected to increase. Research has
yielded breakthrough findings on CVD prevention and treatment, such as effective
medications, procedures and lifestyle changes, and annual death rates from CVD
have declined over the past few decades for the U.S. population, but there is still no
cure. A continued, robust research effort to better understand the development,
treatment and prevention of CVD, and its interaction with the aging process, is
needed. Such research findings could have enormous health and economic benefits
and allow older Americans to live more independent, productive and healthier lives
for longer.
NEW CARDIAC CT DEVICE

Researchers from Mount Sinai School of Medicine, New York, NY, have
developed a way to visualize coronary artery plaques vulnerable to rupture using
multi-color CT, an innovation that will lead to better and earlier diagnosis of
cardiovascular disease. The data are published in the September 2010 issue
of Radiology. Ruptures of atherosclerotic plaques are the cause of nearly 70% of
heart attacks. High density lipoproteins (HDL), the good cholesterol, are drawn to
plaques vulnerable to rupture and remove them from the arterial wall. The Mount
Sinai team harnessed HDL by encapsulating tiny gold particles within it and
injected them into mice.
By using a multi-color CT scanner, the researchers were able to see the gold
particles as the HDL was targeting macrophages, or the cells that cause
inflammation in the arterial wall, therefore illuminating the location of the
vulnerable plaques.


176
The use of multi-color CT and gold nanoparticles to visualize plaque will

revolutionize cardiac imaging, says the research team leader, Zahi A. Fayad, PhD,
Professor of Radiology and Medicine and the Director of the Translational and
Molecular Imaging Institute at Mount Sinai School of Medicine. Conventional CT
detectors provide a gray image of the artery being studied, and do not provide
contrast to differentiate types and density of tissue. In addition to showing the
impact of the gold particles, spectral CT can simultaneously distinguish calcium
deposits and contrast agents used such as iodine, which is often used to identify
stenoses, or the narrowing of arteries, informing the severity of atherosclerosis and
heart attack risk. Multi-color CT technology may also be beneficial in imaging
other biological process and diseases, including cancer, kidney disease, and bowel
diseases. The Mount Sinai team plans to continue studying the new scanner in
additional animal studies and in humans.
CT SPOTS SEEDS OF HEART DISEASE IN HEALTHY

PATIENTS
Even healthy patients with low cholesterol are at a greater risk of heart
attack or stroke if their CT scans show calcium buildup in their coronary arties, a
2011 study has found. The study, published in the July 19 edition of the Journal of
the American College of Cardiology, involved 3,714 patients in the MESA (MultiEthnic Study of Atherosclerosis) trial. Like all MESA participants, they were free of
cardiovascular disease, but those selected also had low-density lipoprotein
cholesterol (LDL-C) levels of less than 130 mg/dL without lipid-lowering therapies.
The CT scans were used to detect coronary artery calcium (CAC) and
carotid intima media thickness to see if abnormalities on these two fronts had
impacts beyond traditional cardiovascular risk factors. After adjusting for myriad
risk factors and variables including age, sex, hypertension, diabetes, high-density
lipoprotein cholesterol (HDL-C), and triglycerides, the presence of calcium in the
coronary arteries predicted a 4.23-fold risk stroke or heart attack at a median
follow-up of 5.4 years, lead author Khurram Nasir, MD, MPH, of Yale University
and colleagues reports. However, cost and radiation-dose concerns make systematic
CT screening impractical.

177
CONTRAST AGENT TOXICITY

With a number of contrast agents and radiopharmaceuticals already on the
market, developers of new contrast agents and radiopharmaceuticals are faced with
regulatory requirements to prove both the safety and efficacy of their products.
Companies are developing new agents that are based on novel chemistries, which
must be fully understood and shown to have excellent repeatability. One successful
approach has been the development of injected agents that increase the image
contrast during an MRI procedure. The catch is that heavy metals that have the
appropriate magnetic properties, like gadolinium (Gd), are toxic.
The solution to the toxicity problem is to wrap the Gd in a chelate, which
encloses it and protects the body from the toxicity. But gadolinium chelates are
small molecules that diffuse rapidly out of the circulatory system by osmotic
diffusion into the interstitial tissue, dissipating the image enhancement. Another
problem with chelates is they do not provide sufficient improvement in relativity to
visualize everything the physician wishes to observe. Because of difficulties with
experimental conditions, the altered physiology of the patient, or limitations of the
contrast, there are many settings in which the image isnt sufficient.
Depending on their chemical structure, different contrast agents may
alter the signal in specific regions of the image or in specific pathologies. What is
needed is a class of contrast agents that remains in the targeted tissue for a longer
period of time. Products must rely on new principles of enhancement for organspecific imaging and on novel physicochemical properties that boost the
concentration of gadolinium delivered. Blood pool agents are being developed for
MR angiography, which is emerging as a noninvasive means of assessing vessels.
Ablavar, the only commercially available blood pool MR contrast agent, highlights
blood vessels. Ablavar's albumin-binding properties allow the agent to remain in
circulation for an extended time, illustrating vascular anomalies in dynamic and
steady-state imaging.
CONTRAST AGENTS GENERIC COMPETITION

For the next generation of MR contrast agents, companies should place an
emphasis on prolonging intravascular retention, improving tissue targeting, and

178
using new contrast mechanisms. Macromolecular paramagnetic contrast agents are

being tested. Preclinical data show that these agents have promise for improving the
quality of MR angiography, and for quantificating myocardial perfusion, among
other targets.
Another concern: group purchasing organization (GPO) contracts may slow
the growth of total market revenues. Makers of contrast agents that are not included
in such agreements may face a slowdown in revenues. And, the commercialization
of generic contrast agents has begun to erode the share of some branded products,
some of which will lose patent coverage in the next few years. As a result, more
competitive pricing strategies may come about.
MRI CATHETER GUIDANCE

According to a pilot study released in September 2012, Heart catheter
procedures guided by magnetic resonance imaging (MRI) are as safe as X-ray-guided
procedures and take no more time National Institutes of Health. The results of the
study indicate that real-time MRI-guided catheterization could be a radiation-free
alternative to certain X-ray-guided procedures.
Clinical heart catheter procedures are possible without using radiation, of
greatest initial benefit in pediatric surgeries. MRI creates pictures of internal tissues
using magnetic fields, unlike X-ray which uses ionizing radiation. In general X-ray
fluoroscopy pictures have higher resolution but less detail than MRI pictures.
The research team performed transfemoral catheterization (guiding a catheter
from the large vein in the leg to the heart) in 16 patients to examine the right side of
the heart, including the attached veins and the pulmonary arteries. The study
volunteers all needed catheterization for heart and valve disease. The researchers
performed the procedure in the 16 patients using X-ray guidance, and then repeated it
twice using real-time MRI guidance of a balloon-tipped catheter filled with air or
with a contrast agent.
The average procedure time for the two approaches was about 20 minutes
despite initial concerns about the visibility of MRI catheters on the imaging systems.
The research group is still performing MRI catheterization on additional patients, and

179
is currently designing improved catheters and other tools that will be more visible
under MRI. The National Heart, Lung and Blood Institute also hopes to use MRI to
guide non-surgical catheter treatments in the future
HEALTHCARE REFORM
The U.S. healthcare system is the most expensive in the world, and costs are
continuing to climb. According to data from the Centers for Medicaid and
Medicare Services, healthcare expenditures in the United States in 2010 were $2.6
trillion, almost a ten-fold increase over the $256 billion spent in 1980 and almost a
100-fold increase over the $27.4 million spent in 1960.
To try to address this problem, the Patient Protection and Affordable Care
Act was signed into law by President Obama on March 23, 2010. This law affects
the cardiac diagnsotics market in many ways. It has a positive impact in that 33
million more people in the United States will be covered by health insurance.
However, there are also aspects of the law that are meant to try to control healthcare
costs. For example, for the clinical laboratory market, the act and a pending
package of additional changes include adjustments to the clinical laboratory fee
schedule, the technical component of certain pathology services, the date of service
demonstration project, prevention and wellness services, and more.
Most important is the attempt to base the use of tests and technologies on
patient outcome benefits as proven by medical evidence and research. Public and
private payers have always used this approach in their reimbursement policies, but
now there is expected to be a more standardized application of these principles. The
major objective is to provide safe products with an eye for cost effectiveness and
also to avoid redundancies as patients go from physician, to hospital, and then to
home.
One important part of the Affordable Care Act is the creation of
accountable-care organizations (ACOs), which are groups of healthcare providers
(hospitals, doctors, and other providers) that coordinate care to Medicare patients
that they serve. The goal is to ensure that patients receive the right care at the right


180
time while avoiding medical errors and unnecessary duplication of services,

resulting in savings for the Medicare program.
Another important part of the Affordable Healthcare Act is a focus on
preventive services. This is a major shift away from the current reactive system that
primarily responds to acute problems and urgent needs to an approach that helps
foster optimal health and wellbeing. The Affordable Healthcare Act addresses
preventive services for men and women of all ages, although women in particular
stand to benefit from additional preventive health services. The inclusion of
evidence-based screenings, counseling and procedures that address womens greater
need for services over the course of a lifetime may have a profound impact. The
emphasis on prevention and early detection is expected to grow.
For women, the Institute of Medicine was asked to recommend what
preventive services would be important to womens health and well-being. In July
2011, the Institute of Medicine published a report called Clinical Preventive
Services for Women: Closing the Gaps. In this report, the Institute of Medicine
recommends that womens preventive services include improved screening for
cardiovascular disease, cervical cancer, counseling and screening for HIV,
screening of pregnant women for gestational diabetes, and other preventive
services.
These are selected examples of some of the many ways the Patient
Protection and Affordable Care Act will affect the cardiac diagnostics industry.
Another important part of this act, comparative effectiveness, is discussed
separately below.
In general, the Affordable Care Act will have both positive and negative
impacts on this industry. With another 33 million people covered by health
insurance, the demand for healthcare services is expected to increase. Another
factor expected to drive growth of the diagnostic industry is the emphasis on
preventative services and screening. Also, diagnostic testing may have an important
role in improving the cost effective use of other types of healthcare such as
expensive therapies. However, there will also be increased pressure on reducing the
costs of all procedures, including diagnostic tests. In addition, the cost benefit


181
analysis of new cardiac diagnostic tests will be an even more important issue in the
future.

Conclusions
There are a number of factors affecting this market, which are slowing
growth. However, there are other factors that are poised to help propel the market
forward.
Conclusion 1: The aging world population will increase demand for cardiac
diagnostics.
The aging population worldwide coupled with longer life expectancies is
creating more demand for cardiac diagnostics both in the institutional settings and
in the home setting.
Conclusion 2: There is a growing desire in developed and developing countries
to invest in health care.
Growth rates in US, western and northern Europe and Japan have moderated
but in many other areas spending on healthcare is increasing leading to a demand
for cardiac diagnostics. New construction and hospital remodels are prompting the
need for new and updated cardiac diagnostic equipment especially in Asia, the
Middle East and Latin and South America.
Conclusion 3: Health care reform in the United States is creating stress in the
market
Healthcare reform in the United States is causing apprehension in the
medical beds market. Passage of the Patient Protection and Affordable Health Care
Eleven: Conclusions
184
Act and the Health Care and Education Reconciliation Act impose a 2.3 percent
excise tax on medical devices beginning in January 2013. This may affect pricing
and consequently sales of cardiac diagnostics in the future in the United States.
Conclusion 4: The rising incidence of cardiac diseases will contribute to growth
in the future.
There has been rising incidence of cardiac diseases due to obesity and
diabetes which complicate recovery. This has created a need for continued care. The
trend is to move the patient through the hospital stay faster and move them to a
lower acuity setting. This provides more demand for more sophisticated care of
patients in these alternative settings which require improved technologies.

List of Companies
Abbott Diagnostics
675 N Field Dr
Abbott Park, IL 60064
847-937-6100
Analogic Corporation
8 Centennial Dr
Peabody, MA 01906
978-326-4000
Acusphere
99 Hayden Ave Suite 385
Lexington, MA 02421
617-648-8800
Ani Biotech Oy
Tiiltie 3
FI-01720 VANTAA
Finland
358 (0) 10 155 7510
Aerotel Medical Systems

5 Hazoref St
Holon 58856
Israel
+972-3-559 3222
Agfa Healthcare GmbH
Konrad-Zuse-Platz 1-3
D-53227 Bonn
Germany
+49 (228) 26 68 000
Alere Inc
51 Sawyer Rd Suite 200
Waltham, MA 02453
781-647-3900
Athena Biotechnologies AB
Fogdevreten 2A
Stockholm 17177
Sweden
46 8 50 88 47 4 4
Bayer Healthcare
Mulerstrasse 178
133353
Berlin
Germany
+49 30 468 111

Appendix
186
bioMerieux SA
69280 Marcy lEtoile
France
+33 04 78 87 20 00
Biosense Webster, Ltd.
4 Hatnufa St POB 275
Yokneam 20692
972-4-813-2884
Boston Scientfic, Inc
One Boston Scientific Place
Natick, MA 01760
508-650-8000
Bracco SpA
Via E. Folli 50
20134
Milan
Italy
+39 02 21 77 1
BRAHMS/Fisher
Thermo Fisher Scientific
Clinical Diagnostics
Neuendorfstrasse 25
D-16761 Hennigsdorf
+49 3302 883 0
Cambridge Heart, Inc
100 Ames Pond Dr
Cambridge, MA
Cardinal Health
7000 Cardinal Place
Dublin, OH 43017
614-575-5000
CardioDX Inc
2500 Faber Place
Palo Alto, CA 94303
650-475-2788
China Sky One Medical, Inc

No 2158 North Xiang An Rd
Song Bei District
Harbin, 150028
China
86 451 8703 2617
C.R. Bard
605 N. 5600 W
Salt Lake City, UT 84116
801-522-5000
Critical Diagnostics
3030 Bunkerhill St Suite 117A
San Diego, CA 92109
877-700-1250
Danaher Corporation
2200 Pennsylvania Ave NW
Suite 800 W
Washington, DC 20037
202-828-0850
dpiX LLC
1635 Aeroplaza Dr
Colorado Springs, CO 80916
719-457-7700
500 Boylston St Suite 1600
Boston, MA 02116
617-456-0366
GE Healthcare
Amersham Place
Little Chalfont
Buckinghamshire
HP70NA
England
+44 870 6061921

Appendix
187
Gold Standard Diagnostics

2851 Spafford St
Davis, CA 95616
530-759-8000
LifeSign Medical
85 Orchard Rd
Skilman, NJ 08558
732-246-3366
Hitachi Medical Systems America

Inc
1959 Summit Commerce Park
Twinsburg, OH 44087
330-425-1313
LipoScience Inc
2500 Sumner Blvd
Raleigh, NC 27616
919-212-1979
Home Access Health Corp

2401 West Hassel Road Suite
1510
Hoffman Estates, IL 60159
847-781-2500
InfraReDx, Inc
34 Third Ave
Burlington, MA 01803
781-221-0053
International Technidyne
Corporation
20 Corporation Place S
Piscataway, NJ 08854
732-548-5700
Johnson & Johnson Inc
One Johnson & Johnson Plaza
New Brunswick, NJ 08933
732-524-0400
501 5th St
Bristol, TN 37620
423-989-8000
Building 200-2
331 Treble Cove Road
N. Billeriea, MA 01862
978-671-8001
Medison America, Inc

11075 Knott Ave
Cypress, CA 90630
714-889-3000
Medtronic, Inc
710 Medtronic Parkway
Minneapolis MN 55432
763-514-4000
Molecular Insight Pharmaceuticals,
Inc
160 Second St
Cambridge, MA 02142
617-492-5554
Nanosphere, Inc
4088 Commercial Ave
Northbrooke, IL 60062
847-400-9000
Nexus Dx, Inc
6859 Mes Ridge Rd Building
A Suite 100
San Diego, CA 92121
858-410-4600
PerkinElmer
940 Winter St
Waltham, MA 02451
881-663-6900

Appendix
188
Philips Healthcare
3000 Minuteman Rd
Andover, MA 01810
978-659-3000
Polymer Technology Systems, Inc
7736 Zionsville Rd
Indianapolis, IN 46268
317-870-5610
Rennesens GmbH
Hauptstr 30
Berlin
Germany 10827
+49-30-787-10911
Response Biomedical Corp
1781-75th Ave W
Vancouver, BC
Canada
604-456-6010
Siemens Medical Solutions

HenkestraBe 127
91052 Erlangen
Postfach 3260
91050 Erlangen
Germany
+49 9131 84-0
TomTec Imaging Systems GmbH
Edisonstrasse 6
85716 Unterschleissheim
Munich
Germany
+49 (0) 89-32175-500
Toshiba America Medical Systems,
Inc
2441 Michelle Rd
Tustin, CA 92780
800-421-1968
Trixell
Roche Diagnostics
9115 Hague Rd
Indianapolis, IN 46250317521-2000
Schiller Healthcare India Pvt Ltd
DC Mill Compound, A Wing
1st Floor, 5 Chunavala Estate
Kondivitta Lane,Anderi Kurla
Road, Andheri (E)
Mumbi-400059, Marharashtra
India
+91 22 56920520
Shimadzu Corporation
1, Nishinoko, Kuwabara-cho
Nakagyo-Ku
Kyoto 604-8511
Japan
+81-75-823-1111
460 rue du Pommarin ZI

CentrAlp
28420 Moirans
France
+33 (0) 4 76 574100
Vascular Solutions
6464 Sycamore Ct N
Minneapolis, MN 55369
763-656-4300
Vermillion, Inc
12117 Bees Cave Rd
Austin, TX 78738
512-519-0400
Volcano Corporation
3661 Valley Centre Dr Suite
200
San Diego, CA 92130
916-638-8008

Appendix
189
Skanray Healthcare Pvt Ltd

Hebbal Industrial Area
Mysore 570-016
India
+91 821 2415559
St Jude Medical
One St Jude Dr
St. Paul, MN 55717
651-756-2000
Terumo Medical Corporation
2101 Cottontail Lane
Somerset, NJ 08873
732-302-4900


The World Market For Cardiovascular Diagnostics

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The World Market For Cardiovascular Diagnostics

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Cardiovascular Diagnostics

(800) 298-5699 Outside the U.S. (212) 807-2657

Copyright 2013 Kalorama Information

CHAPTER ONE: EXECUTIVE SUMMARY ..........................................................1

CHAPTER TWO: INDUSTRY OVERVIEW ..........................................................9

CHAPTER THREE: ELECTROCARDIOGRAPHY ...........................................37

CHAPTER FOUR: CARDIAC DIAGNOSTIC IMAGING ..................................43

CHAPTER FIVE: CARDIAC DIAGNOSTIC POINT OF CARE TESTING ....63

Copyright 2013 Kalorama Information

CHAPTER SIX: CARDIAC MARKERS ................................................................71

CHAPTER SEVEN: CARDIAC DIAGNOSTIC CONTRAST

CHAPTER EIGHT: MARKET PARTICIPANTS.................................................87

CHAPTER NINE: MARKET TRENDS AND SUMMARY ...............................149

CHAPTER TEN: INDUSTRY DEVELOPMENTS

CHAPTER ELEVEN: CONCLUSIONS ...............................................................183

Copyright 2013 Kalorama Information

CHAPTER ONE:EXECUTIVE SUMMARY

CHAPTER THREE: ELECTROCARDIOGRAPHY

CHAPTER FOUR: IMAGING MARKET

CHAPTER FIVE: CARDIAC POINT OF CARE TESTING

viiiCopyright 2013 Kalorama Information

CHAPTER SIX: CARDIAC MARKERS

CHAPTER SEVEN: CARDIAC CONTRAST AGENTS ......................................87

CHAPTER NINE: MARKET TRENDS AND SUMMARY

Copyright 2013 Kalorama Information

CHAPTER TEN: INDUSTRY DEVELOPMENTS AND TECHNOLOGIES..165

Copyright 2013 Kalorama Information

Cardiac Diagnostic Imaging

Cardiac Diagnostic Point-of-Care

One: Executive Summary

Cardiac Diagnostic Contrast Agents and Radiopharmaceuticals

Copyright 2013 Kalorama Information

One: Executive Summary

SCOPE AND METHODOLOGY

Electrocardiography including ECG testing, stress testing, Holter

Cardiac imaging including non-invasive X-Ray, MRI, CT,

Cardiac point-of-care including cholesterol testing and coagulation

Cardiac contrast agents and radiopharmaceuticals

Included in the report are statistics influencing the industry, incidence of

Copyright 2013 Kalorama Information

One: Executive Summary

SIZE AND GROWTH OF THE MARKET

Global Cardiac Diagnostics Market Analysis, 2010-2017

Copyright 2013 Kalorama Information

One: Executive Summary

Compound Annual Growth Rate

Source: Kalorama Information

Global Cardiac Diagnostics Market Analysis: 2010-2017

Copyright 2013 Kalorama Information

One: Executive Summary

KEY ISSUES AND TRENDS AFFECTING THE MARKET

Increasing Life Expectancy

Increasing Incidence of Disease

New Cardiac CT Device

CT Spots Seeds of Heart Disease in Healthy Patients

Contrast Agent Toxicity

Contrast Agent Generic Competition

LEADING MARKET PARTICIPANTS

One: Executive Summary

Copyright 2013 Kalorama Information

9Copyright 2013 Kalorama Information

Two: Industry Overview