Cardiology

Lecture 1
Introduction
Atherogenesis. Atherosclerosis.
Dislipidemias.
Chronic ischemic heart disease. Stable angina pectoris
 Senior medical student
No more a teenager !
Still young and happy, but
Responsible
Motivated

Your profession
Science
Art
Complex intelectual chalenge
 No more space for mediocrity !

The reward for a Penalty for a bad

good work work

In 3 months A good mark Failing the internal

medicine exam

In 3 years A longer and better life Early death or

for your patient invalidity for your
patient
Moral problems
Legal issues
 Dose it worth to study cardiology?

Huge clinical impact: cardiovascular diseases

are the most frequent cause of death all over the
world What is atherosclerosis? Can it be
prevented/ slowed down to prolong our life?

Big and rewording space to work

As a non-cardiologist doctor, you need basic

cardiology knowledge

As a mature, informed person - to make up your

own opinion about general debated issues, or
family/friends health problems
 Huge clinical impact
Cardiovascular disease mainly atherosclerotic
= leading cause of death all over the world (30% of deaths)
Coronary artery disease: myocardial infarction
Cerebrovascular disease: stroke
 Cardiology offers a big and rewording
space to work

Clinical practice
emergency cases,
spectacular solutions

Basic and clinical research

Health politics, prevention

correct measures and little
money can save more lives
than treating acute
conditions
 If you do not work directly as a cardiologist

You will need basic cardiology knowledge, as a

Family doctor avoid treating the syndrome of dyspnea,
cough and thoracic pain with antibiotics, because it might
not be pneumonia, but an acute MI
Anesthesiologist, Emergency doctor
Surgeon, gynecologist the most important number of
malpractice imputable deaths are due to cardiovascular
complications after unnecessary surgery
Oncologist effective chemotherapies can kill by cardiac
adverse effects
Forensic medicine specialist
 Make up your opinion in general issues,
or family / friends health problems

Is it true that US cardiologists abusively perform angioplasties, and if

so, what are the medical risks, beyond unnecessary costs?
Are the doctors guilty for sudden cardiac deaths of sportsmen? Are
these dramatic events preventable?
What are the signs of acute MI, acute pulmonary edema, pulmonary
embolism, cardiac arrest? and what can you do to help? Its great to
perform resuscitation, but if you dont call for specialized help, very
little chance for patient survival
If a patient was implanted with a cardiac defibrillator to prevent
sudden cardiac death, will he/she be immortal?
How long can a person live with a ventricular assisting device (a
mechanic pump that replaces the heart function) ?
Can stem cell transplantation help heart recovery after MI ?
Is flu vaccination indicated for a patient with ischemic heart disease?

 Further reading

Harrison Manual of Internal Medicine

Davidson's Principles and Practice of Medicine
Mercks Manual for Health Professionals
Mercks Manual for Patients and Caregivers (minimal
general knowledge)
www.escardio.org (free)
www.medscape.org (free)
www.uptodate.com
Atherogenesis. Atherosclerosis.
Atherosclerosis location and clinical impact

Coronary arteries coronary heart disease (angina, MI)

Carotid, subclavian, vertebral arteries TIA, stroke
Abdominal aorta aneurysms
Mesenteric arteries chronic mesenteric ischemia
(abdominal angina) or acute mesenteric ischemia
Renal arteries secondary hypertension
Lower limbs arteries chronic (claudication) or acute
limb ischemia
Spared arteries radial, mammary, external carotid
 Normal artery structure

Intimal layer
Endothelium
Basal membrane
Tunica media elastic and muscular
fibers
Tunica externa (adventicial layer)

Vascular endothelium = complex structure, a big endocrine, paracrine and

immune organ. 700 g and 5000 square meters Role in
Hemostasis and thrombosis One of the very few surfaces than can maintain the blood as a liquid
antithrombotic, fibrinolytic substances
Vascular tone: vasodilators (nitric oxyde, prostacyclin)
Immunity and tissue repair: directs the immune cells to the tissue injury
 Atherosclerosis (ATS) - pathology

= artery obliteration by fatty-

fibrous deposits
(atherosclerotic plaques)
in the arterial wall

Artery involvement is
segmental and focal
 Atherogenesis (I)

Incompletely elucidated
Complex pathogenesis
Hystorical explanations
Unavoidable, degenerative aging process of arteries
Proliferation
Vicious thrombi healing
Cholesterol deposits
Present:
Atherogenesis = chronic, low grade, aberrant
inflammation of the arterial wall, as a response to
prolonged aggresions
 Atherogenesis (II)

Atherogenesis = chronic inflammatory reaction of the arterial wall

Initial lesion = endothelium disfunction
Endothelial disfunction is caused by a variety of aggressors:
Hypertension by shear stress
Hypercolesterolemia by oxydative stress
Cigarette smoke
Diabetes, ..
The consequences of endothelial disfunction:
->increased endothelial permeability, with lipid entry
->Monocyte and lymphocyte adhesion, and penetrance into the arterial wall
->Monocyte transformation into macrophages, that incorporate oxydized LDL
particles
->Macrophages transform into foam cells, increase the ATS plaque (lesion
progresion)

Uncomplicated ATS plaque has

a lipid core (1) and 2
a fibrous cap (2) 1
Unstable plaque: cholesterol-rich core, thin fibrous cap
 Atherogenesis (III)

Complicated ATS plaque

Erosion/ulceration of the fibrous cap
Collagen exposure to circulating blood
Thrombus formation
Vessel oclusion

This is the mechanism for

acute atherothrombotic events
(AMI, stroke)
 Atherosclerosis risk factors
Risk factors = characteristics that are associated with
an increased probability of disease

Traditional risk factors of atherosclerosis (ATS) :

Unmodifiable
Age over 45 for male sex; over 55 for female sex
Male sex ( women risk gradually increses after menopause )
Family history of early ATS events
Modifiable
Smoking the most powerful risk factor for coronary and peripheral
ischemia
Dyslipidemia ( especially
specially high LDL-ch
LDL-chol ; high HDL-ch
HDL-chol is protective)
protective)
Hypertension
Diabetes melitus

Other, less well documented: diet, lack of exertion, obesity, psychosocial factors,
chronic inflammatory diseases

Recently described risk factors: inflammation markers (C reactive protein), homocystein,

lipoprotein (a), thrombogenic factors
Risk factors are additive
 General measures
for cardiovascular risk reduction

Eat various food, avoid excesive calories

intake, maintain optimal body weight
Prefere: fruit, vegetables, olive oil, nuts, whole
grain products, oily fish, poultry, low-fat diary
Avoid: saturated fat - pork, bacon, butter, sour
cream, full-fat yogurt and milk
Salt intake: less than 5 g/day (without salt on
the table, reduced quantity for cooking, avoid
salt-preserved foods, pickles, chips, salted
peanuts)
Alcohol intake: maximum 10-20 g pure
alcohol /day (women) and 20-30 g (men);
hypertriglyceridemic patient will completelly
avoid alcohol
Reduce food and beverages with added sugar
Exercise minimum 30 min/day
Quit smoking; second hand smoking can harm
Dyslipidemia
 Dyslipidemia - Definition and clinical impact
Definition: any of:
serum total cholesterol, LDL-
cholesterol, triglyceride
concentrations above the normal;
HDL-cholesterol concentrations
below the normal

Triglycerides, mg/dl (mmol/l)

<150 (<1,7) Optimal
150-200 (1,7-2,2) Borderline high
200-400 (2,2-5,6) High
> 400 (>5,6) Very high
 Dyslipidemia - Causes
Majority of cases: combination of factors
age
sedentarism, obesity, bad dietary habits
genetic predisposition (polygenic)

Familial hypercholesterolemia: monogenic

Secondary dyslipidemia
METABOLIC: Diabetes
RENAL: chronic renal failure, nephrotic syndrome
HEPATIC: Cholestasis
HORMONAL: Hypothyroidism
DRUGS:
Corticosteroids and immunosuppressants
Antiretrovirals (HIV-infection treatment)
Thiazides and betablockers (weak effect, mainly on triglycerides and
HDL-chol)
Dyslipidemia who and when to test?

Symptomatic cardiovascular disease (coronary, cerebral,

peripheral) once or twice a year
Other atherosclerosis risk factors present - yearly
Diabetes
Hypertension
Smoking
Obesity; overweight: BMI=25-29; obesity: IMC=30; abdominal
obesity: waist circumference over 94 cm (male) or over 80 cm
(female)
Age over 45
Family history of early atherosclerotic event or familial
dyslipidemia
Chronic inflammatory rheumatic disease (rheumatoid arthritis,
systemic lupus erithematosus, psoriatic arthritis ) - yearly
Chronic renal disease (cr cl below 60 ml/min) - yearly
Any person over 20 years - every 5 years
 Dyslipidemia as a c.v. risk factor

Bad guy
C.v. risk factors
Increased total cholesterol
Decreased HDL-cholesterol
Increased triglycerides

Worst guy

Most important c.v. risk factor

= Increased LDL-cholesterol
 Dyslipidemia treatment principles

Main target: decrease LDL-

cholesterol
Hyper TG needs to be specially
adressed only when severe
More aggressive therapeutic
targets for patients at (very) high
cardiovascular risk
Symptomatic cardiovascular
disease (coronary, cerebral,
peripheral)
Diabetes mellitus
Chronic renal disease
Very high risk individual factors
(familial dyslipidemia)
Multiple risk factors, generating
a death risk at 10 years of more
than 5-10%
 Dyslipidemia Therapeutic targets

Patient category Target LDL- Target total

chol chol.
Very high risk: Below 70 mg/dl or Below 155 mg/dl
Symptomatic cardiovascular decrease with
disease more than 50%
Diabetes
Chronic renal disease
Death risk at 10 years over 10%

High risk Below 100 mg/d

Multiple or Severe individual
risk factors
Death risk at 10 years 5-9%
Moderate risk (1-4%) Below 115 mg/dl Below 190 mg/dl
No special risk (<1%) Below 160 mg/dl Below 300 mg/dl
 Dyslipidemia drug classes
Statins
Best studied, most used
Inhibit a key enzyme in cholesterol synthesis:
HMG-CoA reductase ( hydroxy-methyl-glutaryl-CoA reductase)
Atorvastatin, rosuvastatin, simvastatin
Slower atherosclerosis progression, possibly induce atherosclerosis regression
ATS plaque stabilization - acute rupture less likely to occur (pleiotropic effect)
Decrease ATS events (MI, death) by one third
Cholesterol absorbtion inhibitors (ezetimib) well tolerated, used together
with statins (if statin alone not enough to achieve therapeutic goal)
Fibrates and omega 3 fatty acids used mainly for severe
hypertriglyceridemia - (TG800 mg/dl = acute pancreatitis risk)
Bile acid sequestrants (cholestyramine, colestipol, colesevelam) rarely used, frequent digestive
upset
Nicotinic acid cheap, effective, but poorly tolerated

PCSK9 inhibitors new, very potent, injections, yet expensive and not enough studied on long
term
 Statins - Adverse effects

Myalgia (no CK increase) - 5-10% of users; no need to

stop therapy, if bearable
Myopathy (less than 0,1%): muscle pain/ weakness and
CK increase
Increases of less than 5 X upper normal are acceptable
Increases of more than 5 X upper normal: stop therapy,
rhabdomyolysis and renal failure risk

Aminotransferases (liver enzyme) increase

More than 3 X upper normal value decrease dose or change
treatment
Heart anatomy and physiology (I)
The heart is little larger than the
size of the fist (200 - 425 g)

The heart beats 100.000 times a

day, pumping 7.500 liters of blood.

The heart has 4 chambers (2 atria

and 2 ventricles)

The left ventricle is the largest and

strongest chamber; its walls are 1
cm thick, and have enough force to
push blood through the aortic valve
into whole body

Arteries emerge from heart

ventricles; veins come back to atria
 Heart anatomy and physiology (II)
Four valves regulate blood flow
Cardiac cycle:
During systole the ventricles contract
and eject the blood in circulation
During diastole ventricles relax and are
filled with blood from atria (initially passive,
and in the last part of diastole, activelly, by
atrial contraction)
through the heart:
The tricuspid valve: between the
right atrium and right ventricle.
The pulmonary valve: between
right ventricle and pulmonary
artery
The mitral valve: between the
left atrium and left ventricle
The aortic valve: between the
left ventricle and the aorta
Mitral and tricuspid valves are
opened during diastole and
closed during systole; aortic and
pulmonic valves are opened
during systole and closed during
diastole
Heart anatomy and physiology (III)
Systemic circulation: oxygen rich blood
from left atrium goes by the mitral valve
into the left ventricle and is than ejected
by the aortic valve into aorta and
distributed to the whole body; after the
tissues have extracted oxygen from
capillaries, blood collected in the veins is
coming back to the heart (superior and
inferior vena cava are flowing into right
atrium)

Pulmonary circulation: oxygen

depleted blood from right atrium flows by
the tricuspid valve into the right ventricle
and is ejected by the pulmonary valve
into the pulmonary artery; in the
pulmonary capilaries, blood is enriched
with oxygen and cleared of carbon
dioxide; than the pulmonary veins collect
this blood and bring it into the left atrium
 Ischemic heart disease
(coronary artery disease, coronary heart disease)

Condition resulted from insufficient

blood and oxygen supply (= ischemia)
to the myocardium

(imbalance between oxygen demand

and supply)

Due to atherosclerotic narrowing of the

coronary arteries (usually)
Coronary arteries supply blood and oxygen
to the myocardium

Coronary arteries arise from the initial

portion of aorta
Aorta
Right coronary artery
Left coronary artery (left main coronary
artery - LM) with two important
branches
Left anterior descending coronary
artery (LAD)
Circumflex coronary artery (Cx)

Because of early bifurcation of LM, we

discuss about 3 coronary arteries
Pathogenesis of coronary heart disease

Most frequent cause for

insufficient blood/ oxygen
supply to the myocardium
= partial/ total occlusion of the
coronary arteries due to
atherosclerotic plaques
 Other causes for coronary ischemia
Coronary spasm
Prinzmetal (variant) angina typical coronary spasm, usually on a preexisting ATS
lesion
In variable degrees, coronary spasm is involved in about half of the cases of
coronary ischemia
Thrombosis
Associated to ulcerated athersclerotic plaque
causes the acute coronary syndromes (unstable angina, MI)
Isolated, on normal coronary arteries -
rarely, in thrombofilic syndromes (abnormal tendency to thrombosis)
can cause MI in young persons
Microvascular dysfunction
Coronary malformation coronary ischemia in infants, children, young
persons
Coronaritis syphilis, Takayasu
Coronary embolism (intracardiac thrombi, vegetation)
Aortic/ coronary dissection

Coronary ischemia with normal coronary arteries: severe aortic valve

disease, hypertrophic cardiomyopathy, extreme rhythm disorders (tachy,
brady), severe anemia or hypoxia
Clinical pictures of coronary heart disease

With angina
Stable angina
Acute coronary syndrome
Unstable angina
Myocardial infarction
Without angina
Rhythm disturbances, sudden death
Cardiac failure
Silent ischemia (demonstrable on ST segment
monitoring, stress test, scintigraphy)
 Chronic ischemic heart disease
Stable angina pectoris - clinical picture -
Thoracic discomfort
Location: typical retrosternal; possibly main
location and/or radiation anywhere on the
thorax, shoulders, arms, mandibula,
epigastrium
Character: pressure, constriction, squeezing,
burning, tearing; large area, shown with
palm, not one finger
Duration: less than 10 min
Induced by effort, emotion, cold exposure,
heavy meal; especially in the first morning
hours
Relieved by rest and sublingual nitroglycerin
(NTG); if no response to rest and NTG:
acute coronary syndrome or non-anginal
pain

stable angina is essentially

a diagnosis based on history
 Any chest discomfort, even non-anginal chest pain,
and no other obvious explanation for the pain
still consider possible coronary heart disease,
especially in high risk patients (e.g. elderly, complicated diabetes)
Features that suggest non-anginal pain

Small area of pain location; sub-mammary location

Pain augmentation/ reproduction by palpation, breathing,
cough, thoracic movement - parietal, pleural; pericardial pain
relief in sitting position
Associated with fever, purulent cough pulmonary disease
Long duration (beyond 12-24 hours) of continuous pain, with
no ECG and myocardial necrosis markers change pneumonia
Relief with fluids/ food ingestion or antiacid; associated with
heartburn, eructation, dysphagia, digestive bleeding
gastroesophageal reflux, ulcer;
esophageal spasm may respond to NTG
Intercostal radiation zona zoster (pre-eruptive phase),
vertebral pathology (fracture, tumor)
Abdominal component of pain that extends bellow umbilicus;
associated major digestive symptoms (repeated vomits, Intercostal
diarrhea, lack of bowel movements, abdominal pain or rigidity zona zoster
on palpation) abdominal pathology: billiary or renal colic,
pancreatitis, phrenic abscess
 Chest pain/ disconfort
associated with effort dyspnea/ fatigue
Coronary heart disease complicated by left heart failure (usually after known or unknown previous
myocardial infarction)

Recent onset dyspnea in a patient with high coronary risk (old, diabetic) may be the only symptom of
coronary heart disease (angina equivalent)

Aortic valve disease or hypertrophic cardiomyopathy

Pulmonary hypertension (rare)

Especially if new onset chest disconfort and effort dyspnea

Pericarditis

Pulmonary embolism (may associate cough, hemoptysis)

Acute pneumopathy (associated with fever, cough, sputum)

Canadian classification of angina severity

Class I: angina during very high effort

Class II: angina during effort higher than usual activity
(brisk walking up the hill, or on cold climate, or after
heavy meal); slight limitation of usual activity
Class III: angina during usual effort (walking 100-200 m,
climbing 1 level of stairs in basic conditions); marked
limitation of usual activity
Class IV: angina during minimal effort (dressing,
speaking, arranging the bed) or on rest; incapacity to
perform any effort without discomfort
 Evaluation of stable angina pectoris (I)

Anamnesis (History):
Character of the pain, inducing and relieving factors
ATS risk factors
Symptoms of complications or other ATS disease: cardiac failure
symptoms, claudication, history of stroke/TIA
Clinical exam: hypertension, cardiac murmurs, cardiac
failure signs, peripheral arterial pulsation, vascular bruits
(carotid, femoral)
Lab tests: blood count, glucose and glycated
haemoglobin, creatinin and creatinin clearance
estimation , aminotransferases, lipid profile (total chol,
LDL-chol, HDL-chol, triglycerides); TSH if suspicion of
thyroid disease; creatin-kinase (CK) to be checked
before statin initiation
Evaluation of stable angina pectoris (II)

Electrocardiogram (ECG)
X ray especially if cardiac failure or pulmonary
disease suspicion
Ischemia provocation tests
Echocardiography

Coronary arteriography (Coronarography) -

selected cases
Multidetector computed tomography (MDCT) of the coronary arteries
to exclude coronary lesion in patients with intermediate suspicion
(ex: atipical pain, inconclusive stress test)
 Electrocardiogram (ECG)
Usually normal between pain episodes; sometimes even during pain
Possible permanent changes (not correlated with pain): old MI, left
bundle branch block, left ventricular hypertrophy, rhythm disturbances
Transient changes during pain:
ST depression
ST elevation (rarelly)
T wave inversion (not so specific)
 Non-invasive tests for coronary ischemia
(Ischemia provocation tests)
principle of the method

Ischemia is induced (provoked) by:

Effort or, for patients who cannot exercise:
I.v. administration of tachycardia generating substances (adenosine,
dobutamine, dipyridamole)
Ischemia is demonstrated with :
ECG ST segment shift
Myocardial scintigraphy perfusion defects (cold areas)
Echocardiography segmental contraction defects
Myocardial MRI
Contraindicated in
Acute coronary syndromes
Severe aortic valve disease, severe obstructive cardiomyopathy
Advanced cardiac failure
Ventricular arrhythmias
 Non-invasive tests for coronary ischemia
ECG stress test:
ST changes induced by effort demonstrate coronary ischemia
Cannot be used in patients with highly abnormal rest ECG: left bundle branch block,
cardiostimulation, preexcitation, severe left ventricular hypertrophy

Myocardial scintigraphy (radionuclide myocardial perfusion imaging) +

effort
Perfusion deffects demonstrate ischemia
Used
instead of ECG stress test in cases with highly abnormal rest ECG, or
After ECG stress test, if inconclusive

Pharmacologic stress tests

Examples: dipyridamole scintigraphy or MRI
dobutamin echocardiography
Used
In patients who cannot exercise
In case of inconclusive ECG stress test
 ECG stres test
Indication
Diagnostic: to confirm the
ischemic origin of thoracic
pain
Prognostic: to asses disease
severity
Severe ST changes =
marker for high risk of MI
and cardiac death

Sensibility and specificity:

aprox 75% (false negative
and false positive results are
possible)
 Normal effort ECG
(negative test for ischemia)

Sinus tahicardia

Upsloping ST
depression
Pathologic ECG stress test
(positive test for ischemia)

Horizontal or downsloping ST
depression, at least 1 mm (in
comparison with resting ECG aspect)

ST elevation, at least 1 mm (in

comparison with resting ECG aspect)
 Myocardial scintigraphy

A radioactive substance
with myocardial tropism is
injected i.v. (technetium)
A radiation detector
registrates the scintillation
emitted from the normally
perfused myocardium, that
has fixed the radiotrasor
Cold areas have impared
perfusion (ischemia)

Effort induced perfusion deffects demonstrate reversible ischemia

Permanent perfusion deffects suggest irreversible myocardial necrosis
Multiple and extensive perfusion deffects are a high risk marker
 Rest echocardiography

Can exclude alternative causes of

thoracic pain
Percarditis
Aortic dissection
Pulmonary embolism
Can exclude alternative causes of
angina
Cardiomyopathies
Valvular disease
Can disclose ischemia
complications and comorbidities
Systolic ventricular disfunction
Old myocardial infarction
Mitral regurgitation
Left ventricular hypertrophy
 Coronarography (coronary arteriography)

Shows the anatomy of coronary arteries and

possibilities for revascularization
Indicated when revascularization is
considered
Angina on small effort, angina refractory to
medical treatment
Important ECG changes during pain
Positive stress test, with high risk features
Left ventricle systolic dysfunction
Malignant ventricular arrhythmia
Risks
Serious events (death, MI, stroke, major
bleeding): 1%
Death: 0,01%
Contrast induced nephropathy (mainly in
patients with previously renal impairment)
Image: critical stenosis of
right coronary artery
Coronarography principle of the method -

Radiology image of the

coronary arteries
Contrast substance is injected
in the ostium of each coronary
artery (the origin from the
aortic root)
The catheter is introduced
through a large peripheral
artery femoral or radial
 Coronarography images -

Normal left coronary artery

Stenosis of the circumflex artery

Stenoses in the left trunk and

circumflex coronary artery
Pt also has aortic valve prosthesis
 Particular cases of angina pectoris

Angina with permeable epicardial coronary arteries (coronary X syndrome,

microvascular angina) reduced risk of major ATS events (MI, sudden
cardiac death)
Prinzmetal (vasospastic) angina transient ST elevation during pain
Coronary spasm appears usually superposed on an ATS coronary
lesion
Treatment: calcium inhibitors, nitrates, myocardial revascularization if
important ATS lesion

Changes reverse
in a few minutes in
Prinzmetal angina;
persistent ST
elevation for more
than 20-30 min is
a sign of acute MI
 Prognosis of stable angina pectoris

Mortality: 1-2% / year

Patients with higher risk are those with
Multiple coronary risk factors
Severe angina (low effort treshold, frequent attacks)
Chronic ECG changes (left bundle branch block, left
ventricle hypertrophy, old MI, atrial fibrillation)
High risk results on ischemia provocation tests
Depressed left ventricle contractility
Malignant ventricular arrhythmia (VT, VFib)
Multiple and complex coronary lesions
 Treatment of stable angina pectoris

Objectives:
To improve prognosis = to reduce frequency of
ATS events (MI, sudden cardiac death)
To improve symptoms

Therapeutic measures:
1. Life style changes
2. Medical treatment
3. Myocardial revascularization techniques
selected patients
 1. Life style changes

Exercising at least 30 min daily, in the limit of patients

own tollerance
Smoking cessation
Moderate alcohol consumption (1 glass of wine daily)
may help; alcohol abuse is clearly deleterious
Mediteranean diet (vegetables, olive oil, nuts, fish, sea
food, whole grain pastry)
Body weight reduction in obese

Sexual intercourse is permitted, if it does not induce angina; prophylactic

NTG can be used
In erectile dysfunction, phosphodiesterase inhibitors (sildenafil Viagra) are
allowed,
but NOT ASSOCIATED TO NITRATES
 Immediate patient attitude
in angina pectoris attack

Stop the causatory effort

Administer NTG under the tongue (tablet
or spray); be aware of possible secondary
headache, hypotension, mainly at the first
doses
If pain continues more than 20 min, call
112
NTG can be used prophylactically, before
an effort that usually induces angina
NTG bottle must not be opened for more
than a month before
2. Medical treatment in stable angina pectoris
To reduce the risk of ATS events
Antiaggregants:
Low dose aspirin (75-150 mg/ day)
Clopidogrel 75 mg/day in aspirin intolerance
Statins - simvastatin, atorvastatin, rosuvastatin
target: LDL-cholesterol lower than 70 mg/dl
Beta-blockers in patients with previous MI and/or left ventricle systolic
dysfunction metoprolol 50-200 mg/day, bisoprolol 1,25-10 mg/day
target: cardiac beat 50-70/min
Angiotensin converting enzyme inhibitors (ACEI)* - captopril, enalapril,
ramipril 5-10 mg/day, perindopril 5-10 mg/day
target: gradually increase to the biggest tolerated dose (that does not induce
hypotension)

Antianginal medication: reduces the myocardial oxygen demands and/or

increases the coronary flow
Beta-blockers (metoprolol, bisoprolol, nebivolol)
Calcium channel inhibitors : amlodipin, verapamil, diltiazem
Nitrates: nytroglicerine, isosorbiddinitrate
 Beta-blockers in stable angina pectoris

Bisoprolol (2,5-10 mg/day), metoprolol (25-200 mg/day)

Antianginal drugs by reducing myocardial oxygen
demand (decrease blood pressure, cardiac beat and
contractility)
Contraindicated in
Arterial hypotension (lower than 90-100 mmHg)
Bradycardia (lower than 60/min)
Advanced atrioventricular block (II-III degree)
Important bronchospasm (asthma, severe COPD)
Adverse effects
Hypotension, bradycardia, atrioventricular block; bronchospasm
Headache, nightmares, fatigue, cold extremities
Impotence (2/1000 need treatment stop)
Long acting nitrates in stable angina pectoris

Isosorbid-dinitrate, isosorbid-mononitrate (20-240 mg/day)

Antianginal effect by
Arterial vasodilation, including coronary arteries
Venous dilation preload reduction (the heart works easier)
No effect on coronary ATS events
A free interval is necessary in 24 hours to avoid
tachyphylaxis (decreasing effect)
Adverse effects: frequent but not dangerous headache,
flush
 Calcium channel blockers
in stable angina pectoris
Unselective, non-dihydropiridines, (heart rate-lowering calcium
channel blockers): verapamil (120-480 mg/day) diltiazem effects
Systemic and coronary vasodilation
Reduce cardiac beat (negative chronotropic action)
Reduce myocardial contraction (negative inotropic action)
Reduce atrio-ventricular conduction (negative dromotropic action)
Selective, dihyropiridines (DHP): amlodipin (2,5-10 mg/day)
mainly vasodilator effect
Adverse effects
Due to vasodilation: headache, flush, edema more pronounced for
DHP
Cardiodepressing: bradycardia, hypotension, blocks, cardiac failure
aggravation - more important for non-DHP
Constipation - verapamil
Contraindication: non-DHP in patients with left ventricle decreased
systolic function
 Other antianginal drugs

Potassium channel activators nicorandil

Action similar to nitrates
Sinus node inhibitors ivabradine
In patients intolerant to beta-blockers
Metabolic agents trimetazidine
- in patients intolerant to other drugs
- can aggravate Parkinson disease
 Angiotensin converting enzyme inhibitors
(ACEI) in stable angina pectoris

Ramipril (2,5 -5 mg twice daily), perindopril

Do not directly influence angina, but reduce MI and
sudden cardiac death
Indicated in patients with confirmed coronary disease,
especially if they associate:
Previous MI
Left ventricle decreased systolic function
Diabetes
Hypertension
Adverse effects
Frequent but not dangerous dry cough
Potentially dangerous hypotension, hyperpotassemia
Angioedema indicate intolerance to the whole ACEI class
Therapeutic strategy in stable angina pectoris
Lifestyle changes to minimize coronary risk factors
Sublingual NTG to treat the attack
Aspirin 75-150 mg (clopidogrel 75 mg in case of intolerance)
Statin (target LDL-chol: bellow 70 mg/dl)
ACEI (confirmed coronary disease)
Beta blocker
In patients with previous MI and/or left ventricle decreased systolic function
In patients without previous MI and left ventricle decreased systolic function; for
intolerants calcium channel inhibitors or ivabradine may be used instead
If after dosage optimization, angina persists, alternatives are:
1. Change the antianginal class
2. Combine two classes of antianginal drugs
3. Consider myocardial revascularization
Coronarography (if indicated- see slide 55) and revascularization if needed
(see next slide)

In yellow: measures that reduce the ATS events (MI and sudden cardiac death)

Lifestyle changes and medical therapy should be the mainstay for

most patients with stable ischemic heart disease
 3. Myocardial revascularization techniques
in stable angina pectoris
= blood flow restoration in the ischemic myocardial area

Indications:
For prognostic reason: significant stenosis of
left main coronary artery or
proxymal left anterior descending coronary artery
2 - 3 major coronary vessels and depressed LV function
For symptoms: patients with angina refractory to optimal medical
therapy (OMT), with significant coronary stenosis
Methods
Percutaneous transluminal coronary angioplasty (PTCA)
Coronary artery by-pass graft surgery (CABG)
Significant stenosis = more than 50-70% (more than 50% for left main coronary artery)
 Percutaneous transluminal coronary
angioplasty (PTCA)
Interventional procedure, realized in the
cath lab, with local anesthesia
May be performed during the same intervention,
together with coronarography, or as a second,
planned intervention

The catheter is introduced into a

big peripheral artery (femoral,
radial) and advanced to the aortic
root and than into the affected
coronary artery
A baloon that is initially collapsed,
is inflated to reopen the narrowed
artery
Usually a stent is implanted during
the procedure, to ensue a longer
time the permeability of the artery
PTCA is better used in short,
uncomplicated coronary artery
stenoses
 Percutaneous transluminal coronary
angioplasty (PTCA) schematic presentation

1. The cateter is
introduced into the
arterial lumen, at the
site of the stenosis;
the baloon is flat at
this moment

2. Inflation of the
baloon reopens the
artery lumen

3. The baloon is
deflated and
extracted; the artery
remains with a
larger diameter
Coronary stent

Is a mesh 'tube' inserted in the

coronary artery during the
angioplasty procedure
It maintains the artery opened for a
longer time, in comparison with
simple angioplasty; restenosis may
still appear in 20-30% of pts at 6-12
months, when simple bare metal
stents (BMS) are used
Better results are obtained with
drug eluting stents (DES)
more expensive than bare metal
stents
covered with an antiproliferative
substance (sirolimus, everolimus)
that reduces restenosis (only 6-
10% of pts at 6-12 months)
Impose longer dual antiaggregant
treatment after implantation
Percutaneous transluminal coronary
angioplasty with stent implantation
-schematic presentation-

The catheter is introduced at

the stenosis site; the baloon
is flat, the stent is not
expanded yet

Baloon inflation produces

stent expansion

Finally, the baloon is deflated

and extracted; the stent
remains inside the artery and
maintains the larger lumen,
opened for circulation
 Stents inside coronary arteries
- pathology image -

Transvers section
AS = ATS plaque

Longitudinal section
 Coronary artery by-pass graft surgery

Surgical procedure, performed

under general anesthesia and
extra-corporeal circulation, with a
mediosternal incision
a minimal invazive procedure is
under study, with an intercostal
incision, on beating heart (off-
pump surgery)
Arteries (or veins) from
elsewhere in the patient's body
are grafted to the coronary
arteries to
bypass atherosclerotic narrowing
and improve the blood supply to
the myocardium
Used in patients with multiple and
complex coronary stenoses
Coronary artery by-pass graft surgery

The coronary stenosis is by-passed

with a vascular graft

Usually used vessels are

Internal mammary artery is
dissected from the presternal
zone and the distal end is
anastomosed distal to the
coronary stenosis
Radial artery
Saphenous vein the distal
extremity is sutured in the aorta
Coronary arteries and the proxymal extremity is
anastomosed to the coronary
artery, distal to the stenosis
 Coronary artery by-pass graft surgery

Usually more grafts are performed during a surgical intervention

Aterial grafts are preferred due to better patency over time
 CABG versus PTCA
- as myocardial revascularization solutions -

Higher acute mortality (4-5% versus bellow 1%)

Better persistence of patency over time (arterial grafts -
90% at 3 years)
More complete revascularization
Is the best choice in
High risk coronary lesions: multiple, complex, left main or
proxymal LAD, angulated, calcified, chronic obstructions
Depressed left ventricle contractility, but viable myocardium
demonstrable on stress myocardial scintigraphy/ echography
Diabetes
 How to chose between CABG/ PTCA/
or just optimal medical therapy

The choice takes into account

Coronary anatomy
Global patients risk
Local availability and expertise
Patients preference
The decision involves a
Heart team (cardiologist,
interventionist, heart
surgeon)
Case presentation
 Clinical picture
46 years old male patient
Smoker (25 pack-years)
Mild hypertension
No personal or family history for c.v. disease; no
chronic treatments
For 2 months vague retrosternal disconfort for
1-2 min during morning ordinary activities,
accompanied by sweating and nausea, ceases
spontaneously even if continues activity; no
symptoms later during the day
Physical exam and routine tests
BP 145/90 mmHg; HR 78/min; BMI 26 (overweight)
Discrete apical systolic murmur; no pericardial friction
rub, no signs of heart failure, no vascular bruits
Palpable pulses in radial, femoral, tibial arteries
Resting ECG: sinus rhythm, normal morphology
Biology: normal blood count, glucose, creatinin, liver
function tests, ions, CK, urinalysis; increased total chol
(230 mg/dl) and LDL-chol (155 mg/dl)
Echocardiography: mild mitral regurgitation; normal sized
cavities, normal left ventricle contractility
 Working diagnosis
Atypical effort angina
Mild mitral regurgitation
Mild hypertension
Dyslipidemia
Overweight
Smoker
 First recommendations
Quit smoking
Healthy diet, reduce weight but do not engage in heavy efforts
before further testing
Aspirin 100 mg daily with food at main meal
Statin (ex: atorvastatin 40 mg) at bedtime; in 1-2 months to verify
LDL chol (target is below 70 mg/dl) and liver function tests (to be
normal or less than 3 times upper limit of normal)
Beta blocker (ex: bisoprolol 2,5-5 mg in the morning)
Sublingual nitroglycerin for the pain (to be seated)
Call emergency service if pain lasts for more than 15-20 min
Explain the small risk of bleeding during aspirin treatment and
advice to report dyspepsia, black stools or any abnormal bleeding
Explain the small risk of statin induced myopathy and advice to seek
medical attention if myalgia or muscle weakness
Stress test to be scheduled (effort ECG may be the first choice in a
patient that has no physical inability and has a normal rest ECG)
ECG stress test positive, high risk

ECG changes and pain persisted for about 15 minutes, than resolved
completely, with no troponin change (no stress induced myocardial infarction,
but high risk positive stress test); transient ST segment elevation suggests
coronary spasm and is called Prinzmetall angina
Coronarography

60% stenosis
proxymal anterior
descending artery
 Final diagnosis
Monovascular ischemic heart disease;
proxymal LAD artery stenosis
Prinzmetall angina
Mild mitral regurgitation
Mild hypertension
Dyslipidemia
Overweight
Smoker
 Treatment options
Medical treatment: same, but replace beta blocker with
calcium channel blocker (ex: verapamil 240 mg daily)
due to presumed coronary spasm (transient ST segment
elevation)
Patient declares himself satisfied with symptom relief
obtained with medical treatment
Revascularization is still indicated for prognostic
benefit: to reduce death and infarction rate (proxymal
LAD lesion)
Coronary by-pass graft surgery or coronary angioplasty;
consider local expertise and patient prefference; explain that
angioplasty has smaller acute risk, but increased risk to need
reintervention for restenosis after 6-12 months
Dual antiggregant treatment (aspirin plus clopidogrel) will
be indicated for 6-12 months after angioplasty
Multiple choice questions
What arteries are rarely involved in
atherosclerosis? (single correct)
A. Coronary arteries
B. Carotid arteries
C. Lower limb arteries
D. Radial artery
E. Abdominal aorta
Which of the following is not a risk factor for
atherosclerosis?
A. Smoking
B. Diabetes
C. Age lower than 45 years
D. High HDL-cholesterol level
E. Hypertension
Which of the following are not possible
causes for dyslipidemia?
A. Diabetes
B. Hyperthyroidism
C. Nephrotic syndrome
D. Corticosteroids
E. Statins
What is the main target of dyslipidemia
treatment in a patient with old myocardial
infarction and effort angina? (single
correct)
A. Triglyceride level below 200 mg/dl
B. HDL-cholesterol level below 70 mg/dl
C. Total cholesterol level below 260 mg/dl
D. LDL-cholesterol level above 40 mg/dl
E. LDL-cholesterol level below 70 mg/dl
Which of the following statement is false
about statins
A. Decrease cholesterol level
B. Main mechanism of action is inhibition of
cholesterol absorbtion from gut
C. Decrease cardiovascular events by
aproximatively one third
D. Can induce myopathy
E. Can induce dry cough
Which of the following can be the clinical
presentation of ischemic heart disease?
A. Effort angina
B. Acute myocardial infarction
C. Ventricular tachycardia
D. Claudication
E. Cardiac failure
Characters of stable angina pectoris include
the following
A. Retrosternal pain
B. Radiation on left arm
C. Relieved by effort
D. Constrictive character
E. Lasts for longer than 10 minutes
Transient ECG changes during pain in
patients with stable angina may include
A. Q waves
B. ST segment depression
C. ST segment elevation
D. Negative T waves
E. Left ventricle hypertrophy
Ischemia provocation tests are
contraindicated in patients with
A. Unstable angina
B. Stable angina
C. Diabetes
D. Acute myocardial infarction
E. Severe aortic valve disease
Which of the following are true about myocardial
scintigraphy?
A. Effort induced perfusion deffects demonstrate
irreversible myocardial necrosis
B. Permanent perfusion deffects suggest reversible
ischemia
C. Multiple and extensive perfusion deffects are a high risk
marker
D. A medicine than causes bradycardia may be used as an
efftort substitute to induce ischemia in patients who
cannot exercise
E. May be used instead of ECG stress test in cases with
highly abnormal rest ECG
The following can produce angina, with the
exception of:
A. Pericarditis
B. Coronary heart disease
C. Aortic valve disease
D. Pneumothorax
E. Hypertrophic cardiomyopathy
The following statement are false about the ECG stress test
A. Myocardial perfusion deffects are demonstrated as
cold areas
B. Horizontal ST segment depression induced by effort
suggests myocardial ischemia (positive test)
C. ST segment elevation induced by effort is a good
prognosis sign (negative test for ischemia)
D. False positive results can appear
E. A positive stress test excludes coronary ischemia
Rest echocardiography in ischemic heart
disease can demonstrate
A. Old myocardial infarction
B. Reduced left ventricle systolic function
C. Perfusion deffects as cold areas
D. ST segment displacement
E. The precise site of coronary occlusion
Which of the following statements about
coronarography are false?
A. Demonstrates the anatomy of coronary
arteries
B. Is indicated in all the patients with ischemic
heart disease
C. Can be rarely complicated by stroke
D. Is necessary in patients with positive stress
test, with high risk features
E. Is indicated especially in patients with normal
left ventricle systolic function
What is true about contrast induced nephropathy?
A. Can be a complication of ECG stress test
B. Can be a complication of myocardial
scintigraphy
C. Can be a complication of coronarography
D. Can be a complication of echocardiography
E. Is more frequent in patients with previous renal
impairment
Which of the following statements about
coronarography are false?
A. The catheter may be introduced through the
femoral artery
B. The catheter may be introduced through the
carotid artery
C. The catheter may be introduced through the
radial artery
D. Contrast substance is injected intravenously
E. Coronary artery by-pass graft can be
performed during the same procedure
Which of the following are negative
prognostic factors in patients with stable
angina pectoris?
A. Presence of left bundle branch block
B. History of old myocardial infarction
C. High risk results on ischemia provocation
tests
D. Increased left ventricle contractility
E. Multiple and complex coronary lesions
Which of the following associations is not
permitted? (single correct answer)
A. Nitrates and beta blockers
B. Nitrates and calcium channel antagonists
C. Nitrates and statins
D. Nitrates and sildenafil
E. Nitrates and angiotensin converting
enzyme inhibitors or angiotensin receptor
blockers
Which of the following statements are false about
nitroglycerin tablets use?
A. Are administered under the tongue
B. Can induce headache
C. Can induce hypertension
D. Can be used prophylactically, before an effort
that usually induces angina
E. The patients must be instructed to wait one
hour for the nitroglycerin tablet to take effect
Which of the following drugs do not directly
act as symptomatic antianginal
medication?
A. Nitrates
B. Aspirin
C. Angiotensin converting enzyme inhibitors
D. Beta blockers
E. Calcium channel blockers
Which of following statements about beta
blockers (metoprolol, bisoprolol) are
false?
A. Are vasodilators
B. Decrease heart beat
C. Increase myocardial contractility
D. Decrease blood pressure
E. Can induce bronchodilation
What is true about long acting nitrates in
stable angina?
A. Induce arterial vasodilation
B. Induce venous dilation
C. Reduce coronary atherosclerotic events
D. A free interval is necessary in 24 hours to
avoid tachyphylaxis
E. Adverse effects like headache are rare
What is false about unselective (non-
dihydropiridine) calcium channel inhibitors?
A. Induce systemic and coronary vasodilation
B. Reduce cardiac beat (negative chronotropic
action)
C. Are indicated in patients with reduced left
ventricle systolic function
D. Verapamil and diltiazem are non-
dihydropiridine calcium channel inhibitors
E. Amlodipin is a non-dihydropiridine calcium
channel inhibitor
Which of the following measures can reduce the incidence
of myocardial infarction and sudden cardiac death in
patients with ischemic heart disease?
A. Lifestyle changes to minimize coronary risk factors
B. Sublingual NTG for the anginal attack
C. Statin tretament
D. Beta blockers in patients with previous myocardial
infarction and/or left ventricle decreased systolic function
E. Calcium channel inhibitors
Coronary revascularization is indicated in patients
with stable angina who have
A. Significant stenosis of left main coronary artery
B. Hypertension and dyslipidemia
C. 2 - 3 major coronary vessel significant stenosis
and depressed LV function
D. Angina refractory to optimal medical therapy
and significant coronary lesion
E. Angina on small effort, hypertrophic
cardiomyopathy and normal epicardial
coronary vessels
Which of the following are correct about coronary
artery by-pass graft surgery, compared with
coronary angioplasty?
A. Has lower acute mortality
B. Has better persistence of patency over time
C. Allows less complete revascularization
D. Is the best choice in multiple, complex, high risk
coronary lesions
E. Usualy involves general anesthesia and extra-
corporeal circulation
 Short questions - examples
Why is it indicated to verify creatin-kinase (CK)
before statin treatment initiation?
A 75 old male, diabetic patient complains of jaw
pain during uphill walking; do you consider
angina as a possible diagnosis? What if the pain
is in the calf, induced by effort and relieved by
rest?
If a patient with effort angina is doing well with
aspirin, atorvastatin and bisoprolol, would you
still recommend a stress test? Motivate your
answer
A little tired?
Take a break!