Cardiology 1 Introduction

Structure of the heart:

Size varies with body size; ave 14cm by 9 cm

Within mediastinum, bordered by lungs, vertebral column, sternum; rests on
the diaphragm

Right-sided structures lie mostly anterior to their left-sided

counterparts
Atrial chambers are located mostly to the right of their
corresponding ventricles
o Apex formed by tip of LV; points inferiorly, anteriorly and
to the left; this is where palpate for PMI
o Base/posterior surface formed by atria, esp. LA
o Anterior surface RA and RV
o Inferior/diaphragmatic surface ventricles, esp. LV

4 borders of the heart:

Right RA
Left LV, portion of LA

Inferior RV, a portion of LV near apex

Superior LA and RA

Pericardium - connected to diaphragm and right and left pleura

Outer fibrous layer

Inner serous pericardium:

o
o

Parietal layer inner, lines outer fibrous layer

Visceral layer epicardium, lines surface of the heart

Pericardial cavity between visceral and parietal layers; has small amt of serous
fluid; reduces friction between pericardial membranes as heart moves

Layers of heart wall:

Epicardium - visceral layer of serous pericardium

Myocardium - cardiac muscle layer; bulk of the heart
Endocardium - chamber lining and valves

Heart chambers and valves:

AV valves mitral and tricuspid; for one-way blood flow between atria and
ventricles; prevent backflow by closing passively when ventricle contracts
Semilunar valves aortic and pulmonic

Valves are attached to cardiac skeleton rings of dense CT

around pulmonary trunk and aorta at proximal ends
o

Cardiac skeleton provides firm attachments for valves and

muscle fibers

Coronary circulation:

Left main coronary artery betw. LA & pulm. trunk to AV groove

o LAD in interventricular groove towards apex

Septal perforators to anterior 2/3 of IV

septum and to apical portion of ant. papillary
muscle

Diagonal branches to ant. surface of LV

o Left circumflex in left AV groove (posterior)

Gives off obtuse marginals to lateral and

posterior LV wall
Right coronary artery in right AV groove
o Acute marginal branches supply RV
o AV nodal artery and SA nodal artery usually come off RCA (85%)
o Posterior descending artery comes off RCA in 85% of ppl right-dominant system

PDA supplies inferior and posterior wall of ventricles and posterior 1/3 of IV septum

If PDA comes off left circumflex left-dominant system

If PDA is supplied by both RCA and LCX codominant system

CARDIAC PHYSIOLOGY
Cardiac cycle:

Aortic valve closes as Paorta > Pventricle S2

LV undergoes relaxation eventually Pventricle < Patrium mitral

valve opens
Rapid ventricular filling (80%)
Atrial contraction - atrial kick (20%)

Pventricle > Patrium mitral valve closes

Isovolumetric contraction pressure in ventricle increases

Pventricle > Paorta aortic valve opens ejection

Cardiac output: CO = SV x HR

Stroke volume also depends on contractility, preload (EDV) and

afterload

Starlings law the greater the EDV, the greater the SV

CARDIAC CONDUCTING SYSTEM

SA node in RA near the opening of SVC; fibers continuous w/

atrial syncytium (stimulates RA and LA)
o Pacemaker rhythmic activity; initiates electrical impulse for contraction
AV node in inferoposterior portion of interatrial septum
o Gatekeeper slows conduction to ventricles allowing time for ventr. filling
His-Purkinje system distal to AV node; perforates IV septum posteriorly
o Right bundle branch
o Left bundle branch = left anterior fascicle and left posterior fascicle

CARDIAC INNERVATION

Autonomic fibers alter activity of SA node and AV node

o
PSNS arise from neurons in medulla oblongata and branch to SA and AV nodes; secrete ACh; heart rate decreases
o
SNS secrete norepi; increase heart rate and myocardial contractility

ELECTROPHYSIOLOGY OF THE HEART:

Ventricular cell AP:

Phase
Phase
Phase
Phase
Phase

0=
1=
2=
3=
4=

rapid Na influx rapid upstroke of AP

stop Na influx, K efflux, Cl influx
Ca influx, minimal K efflux - plateau
stop Ca influx, K efflux, Na efflux (actively pumped out of cell)
resting membrane potential state: - 90mV

Pacemaker cell AP self-generated (automaticity), no external stimulation

needed:

Resting voltage -60mV

Phase 4 spontaneous depolarization (If slow Na current) until threshold is reached
Phase 0 slow depolarization due to Ca influx
Repolarization due to K efflux

Relative refractory period - cell will respond to a second AP but it must be stronger than usual
Absolute refractory period - cell will not respond to repeated AP regardless of how strong it is
Pacemaker sites of the heart and intrinsic firing rates:

SA node 60-100bpm
AV jxn 40-60bpm
Ventricles 20-40bpm

P-wave atrial depolarization

QRS ventricular depolarization
T-wave ventricular repolarization

Cardiac Testing Methods

Non-invasive - chest X-ray, stress tests (exercise ECG, stress myocardial perfusion imaging thallium test, stress
echocardiography), echocardiocardiography, holter monitoring
CXR PA view
Invasive right heart catheterization, left heart cath and angiography
Emerging cardiac CT, cardiac MRI

Chest X-ray

Cardiac silhouette on CXR:

o Left border left ventricle
o Right border RA; RV is not border-forming on PA CXR
PA view useful for assessing size of LV, left atrial appendage,
pulmonary artery, aorta, SVC
Lateral view good for RV size, posterior border of LA and LV, AP
diameter of thorax
Usually in frontal view, heart occupies < 50% of max width of thorax

Lateral view

Exercise ECG (treadmill test):

Primary test for coronary disease easy and cheap, and not risky
There are protocols for changing speed and slope every few minutes
o Bruce protocol is most common (3-minute stages)
While pt is exercising, continually monitor EKG and BP
Besides diagnosing CAD, can be used for risk assessment and prognosis
False positives 10%, sensitivity 70%
Mainly look whether ST segment depression occurs (it occurs with
myocardial ischemia):
o
o
o
o
o

whether it occurs at low or high HR

degree of depression
number of leads where see change
duration of ST depression/ how long it takes to correct after test stopped
associated symptoms angina, hypoTN, arrhythmia

Bayes theorem predictive accuracy of a non-perfect test depends on:

Sensitivity and specificity of test

Prevalence of disease in those tested

Lower usefulness if disease is rare in a certain group low pretest probability

o Test most useful in the mid-range of pretest probability; least helpful at the extremes

Echocardiography ultrasound of the heart; best for viewing

internal structures of the heart

M-mode echo provides data from one US beam

o Good for measurement of wall thickness,
chamber diameters and for accurate timing of
valve mvts

2D-echo multiple US beams are transmitted through

wide arc; signals integrated to produce 2-D picture
chamber view
o Good for anatomic relationships, valve and wall motion and intracardiac
masses
o Parasternal long axis view transducer in 3rd or 4th ICS to L of sternum

LA, mitral valve, LV outflow tract (aortic valve and IV septum)

Parasternal short axis view transducer rotated 90 from parasternal long

axis view

See transverse planes of the heart

Aortic valve, mitral valve, LV wall motion

Doppler echo evaluates blood flow direction, its velocity and turbulence
o Allows estimation of pressure gradients within heart and great vessels
o Use color mapping to see direction of blood flow can see stenotic and regurgitant valves and abnormal
communication within the heart and great vessels

Alternalte tests for ischemia are indicated when:

Exercise ECG not interpretable:

o
ECG is abnormal at rest due to LBBB, resting ST abnormalities or old infarct
o
Use of digoxin
o
Inadequate heart rate achieved to make testing an adequate stress
Patient cant perform exercise ECG
Exercise ECG not applicable
Doubt remains after exercise ECG

Stress myocardial perfusion imaging (thallium test)

With exercise or pharmacologic stress:

o Normally perfused myocardium see evenly dense wall imaging
throughout LV
o Abnormally perfused myocardium relatively less wall density in
affected (ischemic) LV region

Better than exercise EKG to see which coronary artery is involved

However, radioactivity exposure thus only do this if necessary; besides,
its rather expensive

Stress echocardiography:

With exercise or pharmacologic stimulation:

Normally perfused myocardium - wall motion, wall thickening
Abnormally perfused myocardium - demonstrates hypokinesis, akineses, or
dyskinesis

Holter monitoring:

Ambulatory ECG monitoring

Invasive cardiac testing methods:

Right heart catheterization

o Use Swan-Ganz catheter - measures pressure; balloon on the end
helps advance it though bloodstream
o Go from femoral vein or brachial vein to right heart
o Can also measure pulmonary wedge pressure (indirectly measuring
LA pressure) as inflated balloon occludes pulm blood flow
o Can monitor blood flow inject fluid and calculate downstream
temperature change
Left heart catheterization and angiography
o Go through femoral artery or brachial/radial arteries
o Tip goes into LV or origins of coronaries
o Can open a blockage with stent

Emerging testing methods:

Cardiac computed tomography (cardiac CT)

Cardiac magnetic resonance imaging (cardiac MRI)

Exercise EKG missing non-risky disease

Specificity is similar for all 3 tests (least
for exercise EKG)

Heart Sounds
First feel the heart during physical exam with the palm of the hand, not the fingers

In normal heart, should not feel anything under the sternum

If feel a lift usually from right ventricular hypertrophy

At the apex, feel for PMI midclavicular and quarter-sized

Where to listen?

Start with diaphragm will give you high frequency sounds

o Right of sternum 2nd -3rd interspace aortic
o Left of sternum pulmonic
o Left sternal borde tricuspid
o Midclavicular line 5th interspace mitral
S1 and S2:

Caused by valvular closure

o S1 AV valves closure

Specifically mitral valve b/c pressure in left ventricle is much much

higher than in the right ventricle

Right ventricular hypertrophy/pulmonary hypertension will make T1

more audible and will cause S1 split
S2 semilunar valves closure

Aortic valve is louder than pulmonic

Physiologic splitting
o If confused which sound is S1 and which is S2 during rapid
heartbeat check for carotid pulse; S1 at the beginning, S2
is at the end.
o

S2 splits on inspiration (A2 comes before P2)

B/c on inspiration, more blood comes into RV, and it takes
more time to eject the blood, leading to later closure of
pulmonic valve

When listening, dont have the patient take a

deep breath because then chest wall moves
away from the heart and it will be hard to hear
anything
Pathological splitting
o Widened split will be caused by anything that causes
longer time for pulmonic valve to close

Pulmonic stenosis

Right bundle branch block

o Fixed splitting with ASD (due to shunt)

ASD equalized filling of both ventricles on

inspiration
o Paradoxical splitting on inspiration, lose the split

Caused by anything that causes prolonged leftsided ejection

Usually P2 here comes before A2; on inspiration P2 is brought closer to A2 and thus lose the split
o
o

Systolic murmurs:

Most murmurs are systolic murmurs; will hear them at the

same time as feeling carotid pulse
Ejection type starts with beginning of systole, increases, then
decreases
o Due to stenosis aortic or pulmonic
o Due to turbulence; also depends on how much flow there is

Thus may get this one in anemia even with normal valve
because try very hard to get the blood out

Also depends on blood viscosity

o Can hear both S1 and S2 very important that hear S1

S1 can be heard b/c when mitral valve closer there is

not flow yet b/c pressure gradient is still high

Thus should be a small space between S1 and beginning of murmur

The greater the pressure difference, the louder the murmur

With more severe aortic stenosis, the later does the peak of the
murmur come

With severe AS, get a single 2nd sound valve is calcified and barely opens, but it also does
not snap closed lose A2

With moderate AS, hear high-pitch murmur (seagull murmur)

Pansystolic/holosystolic
o Mitral regurgitation, tricuspid regurgitation, VSD
o Starts as soon as LV pressure > LA pressure

Thus murmur starts early and continues throughout systole

There is no space between S1 and beginning of the murmur (unlike stenosis)

Hear best at the apex, but sometimes her at the base (b/c of direction of blood flow)
Late systolic mitral valve prolapse
o This one is actually uncommon
o

Diastolic murmurs:

Early decrescendo
o Aortic regurgitation

High-pitched murumur (best

heard with the diaphragm along
LSB while sitting, leaning
forward and exhaling)
o Pulmonic regurgitation
Prolonged mid-to-late decrescendo
o Severe mitral or tricuspid stenosis

If resulting from stenosis,

murmur begins after S2 and is
preceded by opening snap

Murmur is at its loudest after

the opening snap

Length of murmur indicates severity of stenosis

Mitral stenosis best heard with the bell at the apex in left lateral decubitus position

Key points:

Listen at 4 areas
Timing of S1-S2 can be determined by palpating carotid pulse

Ejection systolic murmurs have preserved S1

Severity of AS defined by lateness of murmur, absence of A2

MR murmur obliterates S1

EKG REVIEW
EKG paper speed = 25 mm/sec

Small boxes 1 mm x 1 mm

Large boxes = 5 mm x 5 mm

Horizontal axis:

1 small box = 0.04 sec

1 large box = 0.2 sec

Vertical axis:

1 small box = 0.1 mV

1 large box = 0.5 mV

Normal intervals/waves:

P-wave - < 0.12 sec; < 0.25mV

PR interval 0.12 - 0.20 sec (3-5 mm)

QRS duration - < 0.12 sec (less than 3 mm)

o
If wide, look for RBBB or LBBB

QT interval - based on HR
o
Corrected QT < 0.44 sec (QT/ square root of RR) corrected QT interval

Physiologic Q-wave < 0.04 sec (1 box)

Normal sinus rhythm

Each QRS is after P wave; every P-wave followed by QRS

P waves upright in I, II, III, AVF

If P wave is inverted - ectopic focus

Frontal axis leads:

I L left arm to right arm

II LL right arm to left leg

III left arm to left leg

aVL, aVF, aVR

Precordial leads:

V1 - 4th ICS R of sternum

V2 4th ICS L of sternum

V3 - between V2 and V4

V4 5th ICS in midclavicular line

V5 between V4 and V6

V6 5th ICS in midaxillary line

V1 and V2 over RV
V3 and V4 - over IV septum
V5 and V6 over LV
V1-V4 anterior leads
V5, V6 left lateral leads

Inferior leads II, III, aVF

Inferior wall of the heart (LV)

An easy way to determine mean
Left lateral leads I, aVL, V5, V6
QRS axis is to find the most

See lateral wall of LV (supplied by left

isoelectric QRS complex mean
circumflex)
axis is perpendicular to it
o
I and aVL = high lateral wall
Anterior leads V1, V2, V3, V4
Posterior wall of the heart does not have any leads directly to it
The more parallel the electrical force is to the lead, the greater the magnitude of
deflection
Electrical force perpendicular to the lead no activity in the lead

Left axis deviation:

left anterior hemiblock

inferior myocardial infarction

artificial cardiac pacing

emphysema

Wolff-Parkinson-White syndrome - right sided accessory

pathway

tricuspid atresia

ostium primum ASD

Right axis deviation:

RVH

Vertical heart

Chronic lung disease

Pulmonary embolus

Left posterior fascicular block

Lateral wall MI

Ostium secundum ASD

Dextrocardia

Limb lead reversal

P wave amplitude < 0.25 mV (2.5 mm = 2.5 boxes)

First RA depolarizes, then LA thus depolarization vector points R L and slightly

inferiorly
Leads I, II, aVF, aVL, V5 and V6 will record positive deflection (current moving
towards them)
Leads III and V1 biphasic P-wave b/c perpendicular to depolarization vector
aVR negative deflection (current moving away from it)
Leads V2-V4 are variable
P WAVE IS BEST VISUALIZED IN LEAD II

QRS complex 0.06 0.1 sec (1.5 - 2.5 mm)

Septal depolarization gives a tiny Q-wave

o
Seen in aVL, I, V5 and V6 left
lateral leads; sometimes in inferior

L R septal depol. is
moving away negative
deflection
o
Sometimes seen in V3 and V4 leads
LV is much bulkier than RV depolarization
vector goes to the left (0 to 90 )
o
Lateral and inferior leads large
positive deflection (R-wave)
o
aVR, V1, V2 deep negative
deflection (S-wave)
Ventricular depolarization as seen in leads
o
V3 and V4 are transition zone
I, II, and AVR. Lead I records small Q wave
record nearly
due to septal depolarization and tall R
biphasic R and S
wave. Lead II also records a tall R wave
and, less often, small Q wave. QRS
waves
complex in AVR is also deeply negative.

R-wave progression
pattern of progressively
increasing R-wave amplitude R L in the precordial leads
o
R-wave smallest in V1; largest in V5

T wave:

It is typical to find a positive T-wave in the same leads that have tall
R-waves (lateral and inferior leads)
Normally T-wave is 2/3 of amplitude of corresponding R-wave

The normal P wave axis lies

approximately between 0 and 70 in
adults (between 0 and 90 in children).
The T wave axis is variable, but it should
lie within 50 to 60 of QRS axis.

HYPERTROPHY AND ENLARGEMENT OF THE HEART

Atrial enlargement look at P-wave in leads II (largest P-wave) and

V1 (biphasic):

II, III, AVF rule of threes

o
P wave 0.12 sec (3 boxes) - LA
o
P wave 3 mm tall - RA
Lead V1 (normal = biphasic P wave)
o
RA increased positive
deviation (RA component)
o
LA increased negative
deviation (LA component)

In normal heart, QRS axis is between -30

and +90, reflecting electrical dominance
of much larger LV over RV

LV hypertrophy L axis deviation.

RV hypertrophy R axis deviation.

RA

LA

RA enlargement:

II - P wave 3 mm tall and peaked

V1 - tall positive component (> 1x1)

Duration of P-wave is unchanged

LA enlargement:

II - P wave 0.12 sec wide and notched

V1 - deep negative component (>1x1)

No significant axis deviation (LA already dominant)

RV hypertrophy pulmonary dz, CHF

LV hypertrophy systemic HTN, valvular dz

Ventricular hypertrophy look at QRS complex

RV

Normally, see deep S wave in the right leads and tall R wave in
left leads
Thicker heart muscle produces taller R waves
o
Mean axis toward the thickest myocardial mass
ST-T abnormalities - in leads over hypertrophied chambers
Associated atrial enlargement

RV hypertrophy:

Usually RV is electrically submissive; becomes more dominant in

hypertrophy R axis deviation
o
In lead V1, R wave > S wave; S absent or small
o
In lead V6, S wave > R wave
Limb leads right axis deviation
Sokolow-Lyon criteria:
o
R in V1 + S in V5 or V6 11 mm

LV hypertrophy:

R-wave amplitude in leads over LV

S-wave amplitude in leads over RV
Generally, precordial leads are more sensitive than limb leads for LV hypertrophy

Sokolow and Lyon - voltage criteria

o
R in V5 or V6 + S in V1 or V2 35 mm
o
R in V5 or V6 26 mm
Cornell voltage criteria
o
Female - R in AVL + S in V3 > 20 mm
o
Male - R in AVL + S in V3 > 28 mm
Other criteria
o
R in AVL 11 mm
o
R wave in lead aVF >20 mm
o
S wave in lead aVR >14 mm

Secondary repolarization abnormalities of ventricular hypertrophy ST segment and T-wave affected:

Down-sloping ST segment depression (gradual downward slope, abrupt upward slope)

T-wave inversion no longer aligned with QRS axis (a.k.a. strain)

These changes most evident in leads with tall R-waves

o
RV V1, V2
o
LV I, aVL, V5, V6; more common

Usually accompany severe hypertrophy often right before ventricular failure

CONDUCTION BLOCKS
Due to the block, affected ventricle must rely on slow myocyte-tomyocyte depolarization spread; QRS widens as a result:

0.10 0.12 sec (2.5 3 mm) incomplete block

> 0.12 sec (> 3 mm) complete block

Right bundle branch block look at V1 and V6

Initially, sequence of depolarization proceeds as normal b/c

septal depolarization is unaffected and LV forces normally
outweight right forces anyway
When LV is (almost) fully depolarized, RV depolarization begins
forces go to the right and away from the left
o
This results in R wave in V1 (over RV) RSR
o
S-wave in V6 (over LV) RS
QRS complex is widened > 0.12 sec
Repolarization St depression and T-wave inversion in
right precordial leads (V1, V2)

Left bundle branch block look at V1 and V6:

See even greater QRS abnormalities

Normal initial depolarization of left septum does not occur
right septum is first to depolarize
o
Thus initial depolarization forces directed to LV
instead of LV

V1 initial downward deflection

I, V5, V6 normal small Q-wave is absent

RV depolarization happens first, then LV depolarization
begins widened QRS in leads over LV (V5, V6)
See widened or notched R-waves in V6, I, aVL (lateral leads)
In V1 reciprocal deep S-waves
Repolarization ST depression and T-wave inversion in left
lateral leads
o
Discordant ST segments (elevated in right sided
leads, depressed in laterals)

Problems in BBB:

Remember: BBBs do
NOT change axis

Diagnosis of ventricular hypertrophy

o
If RBBB, can dx LVH, but often masked
o
If LBBB + LAE, almost always LVH
Diagnosis of myocardial infarction
o
If RBBB, can dx MI
o
If LBBB, need to meet special criteria

RBBB is rather common in normal hearts

LBBB rarely occurs in normal hearts, and almost
always reflects significant underlying cardiac
disease (degenerative disease of conduction
system or ischemic coronary artery disease)

In some cases, BBB only becomes apparent when a certain heart rate is reached critical rate

Criteria for Right Bundle Branch Block

QRS complex widened to > 0.12 seconds

RSR' in V1 and V2 (rabbit ears) with ST segment

depression and T wave inversion

Reciprocal changes in V5, V6, I, and AVL.

Criteria for Left Bundle Branch Block

QRS complex widened to > 0.12 seconds

Broad or notched R wave with prolonged upstroke in leads V5, V6,

I, and AVL, with ST segment depression and T wave inversion

Reciprocal changes in V1 and V2

Left axis deviation may be present.

MYOCARDIAL ISCHEMIA AND INFARCTION

3 stages of EKG in acute MI:

T wave peaking, then

T wave inversion

ST segment elevation

Appearance of new Q
waves

T-wave peaking:

T-waves become tall and narrow with the onset of infarction hyperacute
T-waves
o
Few hours later, T-waves invert
These changes reflect myocardial ischemia, which is potentially reversible; fix it and T-waves
will go back to normal
o
After true MI (actual cell death) T-wave inversion persists for months or yrs
T-wave inversion is indicative of ischemia, NOT MI
T-wave inversion is a non-specific finding; it can be caused by many things including BBB and
LV hypertrophy with repolarization obnormalities
o
In ischemia. T-wave inversion is symmetrical
o
Otherwise, T-wave inversion is asymmetrical gentle down-slope and rapid up-slope
o
Pseudonormalization when already inverted T-wave is reverted back to normal

ST segment elevation (compare to TP segment,

NOT PR):

ST segment elevation in acute MI:

(A) Without T wave inversion
(B) With T wave inversion.

Appearance of new Q-waves = irreversible myocardial cell death

diagnostic of MI (transmural MI)
o
B/c when myocardium dies, there is no more electrical
conduction

Usually occurs several hrs after infarction, but may take a few days
o
Usually appear when ST segment already returned to baseline
o
Tend to persist for lifetime of patient
Usually small Q-waves are seen in left lateral leads (I, aVL, V5, V6) and sometimes in inferior
leads (II or III) caused by L R early septal depolarization

(A) Symmetric T wave inversion in

patient with ischemia.
(B) Asymmetric T wave inversion in
apatient with LV hypertrophy and
repolarization abnormalities.

2nd change in acute MI

ST elevation signifies myocardial injury but still
With myocardial disease,
may be reversible
elevated ST segment is bowed
Still return to baseline after a few hrs
upward and tends to merge
o
If persist, suggest ventricular aneurysm
imperceptibly with T wave
weakening and bulging of ventricle wall
ST elevation can be seen in conditions other than
myocardial injury, and even in normal heart (J point elevation)

Pathologic Q-waves:

Pathologic Q waves wider and deeper

o
> 0.04 sec in duration
o
At least 25% of R-wave in same QRS complex
In posterior wall infarct, instead of pathologic Q-waves
see the inverse in V1 and V2 taller than normal R-waves
(w/o R axis deviation like in RV hypertrophy)
If Q-wave appears only in a single lead, it is NOT
diagnostic of infarction
Also not helpful in the setting of LBBB

aVR should not be considered

when assessing possible
infarction because it normally
has a very deep Q wave

The only EKG changes seen with nonQ wave infarctions are T wave
inversion and ST segment depression.

Lead III =
pathologic Q-waves

II

V3

Reciprocal changes in an inferior

infarction. The acute ST elevation
and T wave peaking in lead II is
echoed by the ST depression and
T wave inversion in lead V3.

Ischemia symmetrical T-wave

inversion
Injury elevated ST segments
Infarct pathological Q-waves

Reciprocal changes:

Opposing changes seen by distal leads

For Q waves, T waves and ST segment

o
Ex: lead distant from site of infarct may record ST
depression or tall R-wave

Inferior infarcts - reciprocal changes can be seen in anterior

and left lateral leads
Lateral infarcts - reciprocal changes seen in inferior leads
Anterior infarcts - reciprocal changes seen in inferior leads
Posterior infarcts - reciprocal changes in anterior leads,
o
Especially V1 (ST depression and tall R waves)
o
Remember - R ventricular hypertrophy will also give
you tall R-waves, but you will not see ST depression
in this case

LOCALIZING THE INFARCT

RCA:

RV

Inferior wall of LV

Posterior wall of LV (75%)

SA node (60%)

AV node (>80%)

LCA:

LAD

o
Septal wall of LV
o
Anterior wall of LV
Left circumflex
o
Lateral wall of LV
o
Posterior wall of LV (10%)

The characteristic electrocardiographic changes of infarction occur only in leads overlying or

near the site of infarction
Inferior

infarct diaphragmatic surface of the heart

Often caused by occlusion of RCA or its descending branch
Changes seen in II, III, aVF
Reciprocal changes may be seen in anterior and left lateral leads
Significant Q-waves in anterior infarcts may not persist for lifetime

Lateral infarct left lateral wall of heart

Occlusion of left circumflex artery

Changes in I, aVL, V5, V6 (lateral leads)

Reciprocal changes in inferior leads

Anterior

infarct anterior surface of LV

Usually caused by occlusion of LAD
Changes in precordial leads (V1 V6) especially V3 and V4
May see Q wave formation or decreased normal R wave progression in precordial leads (V1 V5)
o
But poor R wave progression is NOT diagnostic of anterior infarction (also happens in RV hypertrophy)

Posterior infarct posterior surface of the heart

Usually occlusion of RCA

Look for reciprocal changes in anterior leads (esp V1)

o
ST segment depression and tall R waves

Tall R-waves are also found in RV hypertrophy but in posterior infarct we will not see right axis deviation

Posterior infarcts are usually accompanied by inferior infarcts b/c they have the same blood supply (RCA)
Septal wall V1 and V2
If left main is occluded, may see anterolateral infarct changes in precordial leads and I and aVL

Reciprocal changes in inferior leads

Congestive Heart Failure

Left ventricle posterior behind RV; longer and more conical in shape; 3-5x thicker than RV; mitral valve supported by 2 papillary muscles;
fibrous continuity between mitral and aortic valve

Perfusion branches from LAD in most cases

Right ventricle anterior; lies immediately behind sternum; 3 parts (inlet, apical, outlet); 3 prominent muscle bands (esp. moderator band near
apex attaches to anterior papillary muscle); septal leaflet of tricuspid valve supported through chords attached to IV septum

Much thinner does not handle pressure very well

Cardiac physiology:

Isometric

Preload - in isometric contrxn (fix ends, then contract), total tension

depends on length of muscle fiber at time of contrxn

o
Stretching muscle before contrxn - actin/myosin overlap
cross-bridge formation force of contrxn
o
Muscle fiber stretching also optimizes response of muscle to
Ca
o
Frank-Starling Law muscle stretch in diastole (preload)
stronger contrxn in systole ( EDV SV)

In CHF, see flattening of Frank-Starling curve

(do not get more squeeze with volume change)
Afterload in isotonic muscle contrxn (allow to shorten, then
contract), final length at end of contrxn is dependent on load
(afterload)
o
Independent of muscle length before contrxn
Contractility (inotropic state) increased force of contrxn w/o
changes in preload or afterload
o
Increased by catecholamines

Isotonic

Contractility
Increased
contractility
Normal
Heart
failure

Cardiac performance can be modified by changing 4 components

HR, preload, afterload and contractility
Heart rate controlled by ANS

HR O2 consumption, diastolic filling times, perfusion down coronaries

Stroke volume amount of blood ejected from ventricles during systole

SV = EDV ESV
SV influenced by preload, afterload and contractility

Preload - amount of myocardial stretch at the end of diastole

Strongly depends on compliance of ventricle how much volume ventricle accepts w/o
increasing pressure ( compliance pressure)
o
Affected by anemia, dehydration, volume overload, restriction to filling.

CO = HR x SV
In sick ppl, see tachycardia
since their stroke volume is
reduced, they need to increase
HR in order to maintain CO
thus dont decrease their HR!

Afterload - resistance or impedance to flow; clinically afterload = systemic vascular resistance or pulmonary

vascular resistance

Resistance has an inverse relationship to ventricular function

In myocardial dysfunction, if afterload increases, SV decreases and the body cannot compensate
Contractility (inotropism) - shortening of myocardial fiber w/o altering fiber length or preload or afterload

Mainly affected by SNS, meds and local envt; can be enhanced w/ drug therapy or hindered w/ acidosis or infarct, etc

Pressure-volume loop:

Preload

Afterload

Contractility

Congestive heart failure - inability of the heart to pump blood forward at sufficient

rate to meet metabolic demands of body or ability to do so only if cardiac filling pressures
are abnormally high or both

May be final and most severe manifestation of almost every form of heart disease

Systolic dysfunction (50%) diminished capacity to eject blood

b/c of contractility due to destruction of myocytes or

fibrosis/scarring or b/c of afterload

ESV is higher decreased SV thus try to fill it more to

compensate eventually fails

Diastolic dysfunction (50%) LV walls

become stiff and cant relax very well, and thus diastolic
filling of ventricle happens at higher pressure high
pressure can lead to pulmonary vascular congestion

See LV hypertrophy

Initial adaptation mechanism used to counteract low CO in

pts w/ heart failure - SNS activity to increase HR

Compensatory mechanisms - to fix decreasing cardiac output

Frank-Starling alterations EDV by retaining fluids and

consuming more fluids (to SV)
however, Frank-Starling curve is
nearly flat in severe heart failure
o
EDP (pressure at end
of diastole)
transmitted across
mitral valve to LA and
lungs leads to
pulmonary congestion

Neurohormal alterations

Decreased Cardiac Output

Decreased Baroreceptor Stimulus
Reflex Medullary Stimulation
Increased Central Sympathetic Outflow

SNS, renin-AT-aldo, ADH

Incr. Heart Rate
Venoconstriction
Arterial Vasoconstriction
o
All of these try to
Incr. Contractility
Incr Venous Return
Splanchnic Constriction
Increased Preload
Incr. Flow to Heart, Brain, MM
systemic vascular
resistance to maintain
perfusion to critical organs (brain, heart)
o
Although initially beneficial, these measures lead to overall harm.

volume vascular congestion

SVR afterload (HTN)

HR metabolic demand

Continuous SNS stimulation downregulation of betareceptors inotropic response

A-II & aldo fibrosis, inflammation and adverse remodeling

Ventricular hypertrophy and remodeling - attempt to reduce wall stress

o
LaPlaces law wall stress = (P x r) / 2h

Patterns

Thus ventricle needs to thicken to reduce wall stress

Thickening leads to stiffness impaired relaxation filling pressures pressure across mitral valve
of remodeling depend on stimulus
Chronic volume overload elongation of myocytes, ventricular enlargement
Chronic pressure overload hypertrophy of myocytes

In attempt to reduce wall stress, sacrifice LV fxn

Myocyte loss through apoptosis/ cellular necrosis

Apoptosis result of SNS, AT-II and mechanical strain

Even viable myocardium is abnormal in heart failure - ability to maintain Ca homeostasis, changes in use of high energy phosphates

Patient presentation:

Dyspnea, DOE, PND, fatigue, cough, wt gain, LE edema, urine output, tachypnea (Cheyne-Stokes breathing), tachycardia

Examples of conditions that cause right-sided heart failure:

Cardiac causes left heart failure, pulmonic valve stenosis, RV infarction

Parenchymal pulmonary dz COPD, interstitial lung dz, ARDS, chronic lung infx or bronchiectasis
Pulmonary vascular dz PE, primary pulmonary HTN

Cardiomyopathy, Left and Right

Sided Failure
Cardiomyopathies major structural abnormality is
limited to myocardium; often result in symptoms of
heart failure

Dilated cardiomyopathy:

DILATED CARDIOMYOPATHY:

Incidence of heart failure - > 5 mln

ppl in the US; 550,000 new cases
annually (projected 1.5 mln annually
by 2040); 300,000 deaths annually in
the US; leading cost of admission to
most US hospitals; $30-40 bln spent
annually

3 categories of cardiomyopathy:
1. Dilated
2. Hypertrophic
3. Restrictive

See caridiac enlargement by dilation, not

hypertrophy
Involves LV; also can cause atrial enlargement
Leads to right-sided heart failure

Marked enlargement of all 4 chambers

Myocyte degeneration on microscopy
Myofiber atrophy
Interstitial and perivascular fibrosis
are extensive

Myocyte damage results from wide spectrum of genetic, inflammatory, toxic and metabolic causes; most = idiopathic
o

Acute viral myocarditis Coxackievirus, adenovirus, enterovirus

o
o
o
o

Usually affects younger ppl; see viral prodrome 204 wks before
Thought to be triggered by immune-mediated injury (b/c body attacks the virus and ends up attacking heart, too)
Most people recover w/o long-lasting sequelae but some will have irreversible dilated cardiomyopathy
S1, S2, S3 gallop (hard to pick up if tachycardia); S4 (if stiff); see elevated JVD, hear rales/crackles in lung, see edema

Alcohol use really in excess

o

(1) Ischemic, (2) alcohol, (3) drugs (methamphetamines), viral syndrome, valve disease, hypertension, peripartum, burnt out
hypertrophic, previous OTC meds, vitamin deficiency, toxin-mediated, congenital, connective tissue disorders (SLE, RA)

Damage b/c impair cellular fxn at level of mitochondrial oxidative phosphorylation and fatty acid oxidation

o
Reversible w/ cessation of drinking
Several familial forms of DCM have been identified

Pathophysiology:

Ventricular dilatation with decreased contractile function

Regardless of the cause, see CO and pulmonary pressures

As body senses underperfusion, it activates neurohormonal pathways:

o

SNS HR and contractility

However, catecholamines aggravate ischemia, potentiate arrhythmias,

promote cardiac remodeling and are directly toxic to cardiomyocytes
Arteriolar vasoconstriction in non-essential vascular beds
Renin release renin-AT-aldo system active

Salt and water retention (Frank-Starling preload)

Endothelial dysfunction

Organ fibrosis

o
o

With continuous neurohormonal stimulation, LV remodeling (LV dilation & hypertrophy)

o
Causes wall tension
o
Furthers subendocardial ischemia
o
Separates mitral valve leaflets causing mitral regurgitation & pulmonary congestion

Atrial enlargement (excessive volume and pressure transmitted to atria), SV (blood goes into LA, less blood goes
into aorta), volume loading of ventricle (b/c regurgitant volume returns to LV in each diastole)

Enhanced neurohormonal stimulation of LV leads to fibrosis, apoptosis and eventual death

o
Downward spiral if not diagnosed and treated.
Prevention of sudden death b/c
Clinical manifestations of DCM those of congestive heart failure:
atrial and ventricular arrhythmias are

Fatigue, lightheadedness, exertional dyspnea due to tissue perfusion

common; 40% deaths b/c v-tach & v-fib

Dyspnea, orthopnea, paroxysmal nocturnal dyspnea due to pulmonary congestion

- Defibrillators - since meds to Tx

Ascites, peripheral edema due to chronic systemic venous congestion

arrhythmias are not always that

Cool extremities (peripheral vasoconstriction), arterial pressure and tachycardia ( CO)

effective and are limited to Amiodarone

Crackles in lungs/rales (pulmonary venous congestion), basilar chest dullness to percussion

- Thus use cardiac defibrillator (ICD)
(pleural effusions)
for pts w/ LV ejection fraction < 35%
- Still only 50% 5-yr survival

Displaced PMI due to enlarged heart; S3 on auscultation due to poor systolic fxn
- Also anti-thrombotic Tx & transplant

Mitral regurgitation due to LV dilatation (may also see tricuspid regurgitation)

Diagnostic studies:

History and physical (most important); CXR; EKG (may show atrial and ventricular enlargement, cardiac arrhythmias, BBBs);
echocardiogram (very helpful regurgitation, chamber size); cardiac catheterization (coronary artery disease)

Treatment - alleviate pathologic conditions causing heart failure; diurese to remove volume; control BP and reduce systemic vascular

resistance (vasodilators ACE inhibitors, AT-receptor blockers); slow down HR and block SNS (beta-blockers); oral inotropic agents? (digoxin)

HYPERTROPHIC CARDIOMYOPATHY:

Incidence = 1/500; see sudden death in athletes and young ppl

Genetic disorder that leads to myocardial fiber disarray, scarring and fatal arrhythmias.
o
Autosomal dominant w/ variable penetrance; abnormal proteins related to sarcomere complex
o
Age of onset varies depending on genetics
o
Certain genetic profiles lead to risk of sudden death (-MHC myosin heavy chain)

Pathophysiology:

Asymmetric ventricular hypertrophy that is not due to chronic pressure overload

o
Myocardial fibers in extensive disarray short wide hypertrophied myocardial fibers are oriented
in chaotic directions and surrounded by numerous fibroblasts and ECM
LV outflow tract obstruction in systole due to abnormal thickening of ventricular muscle, esp. IV septum
o
Prone to mov-t of anterior leaflet of mitral valve in
systole towards LV outflow tract (which is narrowed
due to septal hypertrophy) + pressure gradient between
LV and outflow tract blood flow to aorta/brain syncope
o
Significant mitral valve regurgitation (b/c ant. leaflet moves towards septum)
o
HCM w/ obstruction is worsened by dehydration, tachycardia and positive
inotropic drugs (b/c more contractility)
o
HCM w/ obstruction is made better by reducing heart rate (beta-blockers),
avoidance of dehydration, and avoidance of nitrates (b/c vasodilation HR)
LV thickness leads to impaired relaxation (diastolic dysfunction)
impaired ventricular filling
o
This leads to LA, pulmonary venous and pulmonary capillary
pressures dyspnea, esp. w/ exertion
Angina is a common complaint b/c muscle mass leads to O2 demand,
and small coronary vessels get squished in thickened LV
o
Syncope can occur (arrhythmias) bad prognostic sign

Poor prognostic indicators thickened IV septum (> 30 mm), syncope, family Hx of

sudden death, BP w/ exercise; v-tach on holter monitor; certain genetic mutations

Examination depends on degree of hypertrophy; need defibrillator:

May hear S4 due to thickness

Loud systolic murmur if obstruction is present (softer when squats b/c

mitral and septum further apart due to increased venous return, louder when standing b/c of decreased venous return opposite to
what happens in aortic stenosis) crescendo-decrescendo, best heard at LLSB (where outflow tract is)
May hear murmur of mitral regurgitation at apex (holosystolic, radiates to axilla)

Diagnostic studies:

ECG - shows hypertrophy (large Q-waves in inferior andlateral leads due to increased septal size), LA enlargement (leads II, V1),
possible diffuse T- wave inversions
Echo - most helpful initial study (hypertrophy, SAM (systolic anterior motion?), gradients w/ Valsalva (brings mitral valve and IV
septum closer due to decreased venous return), atrial size, degree of mitral regurgitation)
Cardiac catheterization if uncertain Dx or if plan septal ablation

Treatment:

Avoid dehydration, digoxin and diuretic therapy

o
Anything that reduces intravascular volume will bring mitral valve closer to septum BAD!
o
Positive inotropic drugs also force mitral valve and IV septum closer together
Use beta blockers or calcium channel blockers
o
Negative inotropic drugs will keep mitral valve away from the septum and will reduce HR and contractility; Ca channel
blockers may help resuce ventricular stiffness and improve exercise capacity if little response to beta-blockers
Treat a-fib (Amiodarone or Disopyramide); treat mitral regurgitation; consider surgical myomectomy, consider septal ablation
For high-risk patients, consider AICD
Counsel to avoid strenuous activity
Antibiotic prophylaxis is NO LONGER INDICATED!
Screen first degree relatives with an echo

Prognosis:

Sudden death - 2-4% per year in adults (due to v-fib or v-tach; especially during strenuous physical activity)
Children - 4-6% per year
Life expectancy can be normal if high risk features are absent

RESTRICTIVE CARDIOMYOPATHY

Much less common than HCM and DCM

Very rigid myocardium (but not necessarily thickened) due to either fibrosis/scarring or
infiltration of myocardium by abnormal substance

See diastolic dysfunction but usually normal or near-normal systolic fxn

Causes amyloidosis (most common), scleroderma, sarcoidosis, hemochromatosis, glycogen
storage disease, endomyocardial fibrosis, metastatic tumors, and radiation therapy

Amyloidosis:

Insoluble misfolded amyloid fibrils deposit in tissues, including between myocardial fibers in
atria and ventricles, in coronary arteries and veins, and in heart valves
o
Congo Red stain green birefringence under polarized light
Primary amyloidosis deposition of Ig light chains AL fragments secreted by plasma cell tumors
Secondary amyloidosis - AA amyloid deposition, chronic systemic inflammatory conditions (RA)

Clinical manifestations of amyloidosis:

Heart failure will ensue

Diastolic dysfunction dominates

Orthostatic hypotension ANS invasion by amyloid

Conduction system disease arrhythmias; leads to tachycardia then bradycardia and recurrent syncope; sudden death can happen

On EKG, see small QRS complexes b/c proteins do not conduct electricity well

Clinical signs of RCM:

Reduced ventricular compliance leads to:

o
diastolic ventricular pressure venous congestion
JVD (may worsen w/ inspiration = Kussmaul sign),
hepatomegaly and ascites, and peripheral edema
o
ventricular filling CO weakness and fatigue
Arrhythmias are common
Signs of congestive heart failure (left- and right-sided) pulmonary rales, distended neck veins, ascites, peripheral edema

Diagnostic studies:

CXR - usually normal heart w/ signs of pulmonary congestion

RCM shares similarities to constrictive pericarditis
o
Distinguish these 2 by transvenous endomyocardial biopsy, CT and MRI

Treatment:

Treat any underlying disease (see causes)

Salt restriction and diuretic use to
improve symptoms of pulmonary
congestion
Vasodilators and inotropic drugs not
helpful b/c systolic fxn usually preserved
Prognosis is very poor

Takotsubo Cardiomyopathy:

A.k.a. stress cardiomyopathy, broken heart syndrome, octopus pot cardiomyopathy (tako tsubo =
octopus trap in Japanese), and apical ballooning cardiomyopathy
See sudden temporary weakening of myocardium (non-ischemic) can be triggered by emotional
stress (thus broken heart syndrome)
Often see bulging of LV apex (akinesis or dyskinesis) in systole w/ hypercontratile base of LV
o
Assume its due to high circulating levels of catecholamines
On EKG, see typical pattern of ST-segment elevations and T-wave inversions in right precordial leads
o
Look like acute anterior wall MI

RIGHT VENTRICULAR FAILURE:

Unlike LV, RV has little difficulty accepting increased preload (b/c of high compliance due to thin walls) but is very susceptible to

sudden increase in afterload (b/c used to 25/10 mmHg pressures)

Usually systolic dysfunction

Causes - left-sided failure, acute pulmonary embolism, arrhythmogenic RV dysplasia, left-to-right shunts (ASD, VSD), or RV infarct

Acute pulmonary embolism:

Abrupt onset of pressure in pulmonary arteries afterload in RV pressures may be doubled

RV cannot compensate -> will fail to contract will become hypokinetic and falls off Frank-Starling curve
Treatment - pressure in pulmonary arteries, embolectomy (in certain centers), thrombolytic therapy after pulmonary consultation,
ICU admission, possible dobutamine w/ dopamine support
o
Dobutamine - sympathomimetic drug for treatment of heart failure and cardiogenic shock

Primary mechanism stimulation of beta-1 receptors in the SNS

Pulmonary hypertension

WHO classification idiopathic, pulmonary venous (associated w/ respiratory illness) and embolic/thrombotic (associated w/
pulmonary vasculature)
Treatment ID cause w/ CXR, echo, CT and history; then treat any underlying disease; right heart cath before therapy
o
Pharm therapy oral, inhaled and subcutaneous modulators

Arrhythmogenic RV dysplasia (ARVD) - rare form of

cardiomyopathy

Fatty infiltration of RV; usually involves free wall, but

can involve septum; LV involvement is uncommon

Genetic disorder (desmosomes) w/ variable penetrance;

usually Dx < 40 yo based on Hx/physical

Characterized by hypokinetic areas involving free wall

of RV, with fatty or fibro-fatty replacement of RV
myocardium, w/ associated arrhythmias

originating in RV
Can present with sudden death, arrhythmias or heart failure symptoms (SOB).
Diagnostic studies echo, CT, MRI (best)
No known curative treatment usually just prevent
arrhythmias, treat heart failure and placing AICD if needed

RV infarction:

Depending on the data source, RV infarction complicates

inferior wall MI in 40-50% of cases.
This is usually due to proximal occlusion of the right
coronary artery, but it can be due to circumflex occlusion as
well depending on the blood supply and the patients
anatomy.

Treatment of CHF
Overall goals of therapy ID and treat underlying conditions, correct/reverse

precipitating causes, modulate neurohormonal activation, treat acute symptoms and

eliminate their cause, and improve quality of life and long-term survival

At bedside, we can manipulate preload, afterload, contractility, volume, etc

We want to achieve better perfusion as well as lose extra volume:

o
Improve congestion Tx pulmonary and systemic vascular congestion
o
Improve perfusion increase forward CO and peripheral/organ
perfusion (basically cold warm)

Systolic dysfunction
(poor contractility)
common causes are
coronary heart
disease, hypertensive
heart disease, valvular
heart disease, and
cardiomyopathy

General non-pharm Tx guidelines Na restriction, fluid restriction (if congestion persists despite

diuretics), rest acutely (b/c recumbency can renal perfusion and improve response to diuresis) & education

Diastolic dysfunction
(poor relaxation)
common causes are
age, hypertensive
cardiomyopathy, RCM,
HCM and
ischemic/coronary
heart disease
CHF and gender:

Coronary - male

Valvular - female

HTN - female =male

General pharm Tx guidelines diuretics, ACE inhibitors/vasodilators, inotropic agents, beta-blockers and Ca-channels blockers

Diuretics:

In heart failure, see ECV (peripheral edema and pulmonary congestion) due to EffCV
retention of Na and water by kidneys
Indications:
o
Signs or symptoms of pulmonary and peripheral congestion (rales, edema)
o
Systolic and diastolic dysfunction
Mechanism of action:
o
renal excretion of sodium and water
o
intravascular volume and venous return ( LV EDP, preload, pulmonary
congestion, lower extremity edema)
o
CO is not significantly reduced (despite what wed think) b/c heart operates on
flat portion of Frank-Starling curve

But if diurese too hard may reduce SV (BAD!)

Loop diuretics (ascending limb of Loop of Henle)- most potent

Furosemide (short-acting), torsemide (more bioavailability),

bumetanide (greater potency and bioavailability, less ototoxicity)
Effective in the setting of impaired renal fxn
Also may induce venous vasodilatation via prostaglandins and NO (good
for reducing venous return and pulmonary congestion)
Side effects intravascular volume depletion, hypokalemia (aldo +
high urine flow), metabolic alkalosis ( H+ secretion in distal tubule
due to 2ry hyperaldosteronism + contraction alkalosis leading to
increased proximal Na and HCO3 reabsorption)
May see hypomagnesimia, ototoxicity

Thiazide diuretics (distal convoluted tubule), less potent than loop diuretics, but have longer duration of action; generally not effective when
GFR < 25

ml/min (reduced renal function)

HCTZ, metolazone
Have anti-hypertensive effect (reduced intravascular volume initially, then vasodilatation) but may take up to 12 wks
Not very effective w/ reduced renal fxn (unlike loop diuretics); metolazone is somewhat an exception to that (sometimes effective)
May be combined w/ loop diuretics
Side effects hypokalemia, metabolic alkalosis, hyponatremia, hyperuricemia (possible precipitation of gout), hyperglycemia, transiet
alteration in serum lipids, weakness/fatigability/paresthesias in long-term use due to volume depletion and hypokalemia

K-sparing diuretics in distal tubule/cortical collecting duct

Aldosterone antagonists spironolactone, eplerenone; Na-channels inhibitors triamterene, amiloride

Improved survival by combined diuretic and aldosterone receptor blocker effects
o
Class III/IV CHF; 27% decrease in mortality; 25% decrease in sudden death; decreased fibrosis and scarring
Weak diuretics, often combined w/ other diuretics when need to preserve K
Side effects hyperkalemia, gynecomastia (spironolactone)

Side effects of diuretics:

CO in over-diuresis (fatigue, dizziness, hypoTN), electrolyte disturbances ( K, Mg); arrhythmias, hyperuricemia (HCTZ),
ototoxixity (high dose loop diuretics), gynecomastia (spironolactone)
Careful if use these in diastolic dysfxn

VASODILATORS:

CHF activates SNS and renin-AT-aldo system

o
As a result, afterload/aortic pressure
Sequelae of activation of neurohormonal compensatory mechanisms:
o
Excessive vasoconstriction, volume retention, SNS activation,
tachycardia

ACE inhibitors captopril, enalapril, lisinopril

Balanced vasodilators dilate both veins and arteries (due to inhibition

of AT-II formation vasoconstrictor)
o
Thus, decrease preload AND afterload, and increase CO
Facilitate natriuresis (b/c aldosterone inhibition) intravascular
volume and systemic and pulmonary vascular congestion
Augment circulating levels of bradykinin (vasodilator)
o
Increased bradykinin may cause cough
o
Vasodilation less than with AT-II blockers
Basically limit maladaptive ventricular remodeling
Clinical effects improve quality of life, decrease hospitalizations,
prevent progression to more severe CHF, limit pathological remodeling
of LV, and improve survival
Standard first-line chronic therapy for pts w/ LV systolic dysfxn

ARBs Angiotensin-II receptor blockers hydralazine, minoxidil,

nitroprusside, fenoldopam, diazoxide

Provide more complete inhibition of AT-II effects (since it can be made

by pathways other than ACE) but NOT superior to ACEIs

Effects are vasodilation, natriuresis, NO rise in serum bradykinin (less cough)

Also lower BP in HTN

Clinical effects are similar to ACE inhibitors (see above)

o
Used primarily when ACEIs not tolerated, sometimes w/ ACEIs

Isordil (isosorbide dinitrate venous dilator) and Hydralazine (arterial dilator) - BiDil

Can be used for afterload reduction

Usually used in pts w/ renal insufficiency in which ACE or ARBs are contraindicated (renal insufficiency, hyperkalemia)
May reduce mortality in African American pts already on good medical therapy
TID to QID medications - very difficult for pts to take
o
Used inpatient when want to decrease BP and improve CO

Nitrates:

Mechanism of action:
o
Venodilation decrease preload due to decreased venous return
o
NO activates cGMP - acts on VSMC vasodilation
o
At high doses, see arterial dilation body gets used to it fast (tachyphylaxis)
o
Can serve as coronary vasodilators for ppl w/ ischemic chest pain as cause of heart
failure symptoms
o
Not used as first line vasodilation

Nitroprusside - both arterial and venous vasodilation; use IV to Tx HTN emergencies and for BP control in ICU; for afterload and
preload modulation in SEVERE CHF
o
Fast onset (30 sec, peak in 2 min), short duration (minutes)

Beta-blockers:

Can improve CO by HR (slow SA node), blunting chronic SNS activation, anti-ischemic properties
Historically were contraindicated in heart failure pts (thought that CO) now mainstay of Tx
Improved survival these 3 reduce mortality by ~ 35%
o
Bisoprolol (beta-1 selective antagonist) class III/IV; 32% decreased mortality
o
Metoprolol (beta-1 selective antagonist class II/III; 35% decreased mortality
o
Carvediol (alpha-blocker, beta-1/2 antagonist) class II/III; 35% decreased mortality
Work in clinically stable heart failure

Inotropic agents - beta-adrenergic agonists, digitalis glycosides, phosphodiesterase inhibitors

Mechanism of action:
o
contractility (when systolic function is impaired)
o
force of contraction (b/c intracellular Ca)
o
Shift Frank-Starling curve upwards = SV for given LV EDP CO
Useful for systolic dysfxn only, NOT for diastolic dysfxn
o
Digoxin
o
Dopamine alpha AND beta increase BP to keep from decreasing too much from
dobutamine
o
Dobutamine - mixed beta-agonist and vasodilator
o
Milrinone - PDE inhibitor
Beta-adrenergic agonists (dobutamine, dopamine) IV for temporary
hemodynamic support in acutely ill hospitalized pts
o
IV only; rapid tolerance
PDE inhibitors (amrinone, milrinone) IV Tx of CHF in acutely ill pts

Digoxin acts on Na/K ATPase; contractility, cardiac enlargement, CO,

baroreceptor sensitivity (blunts compensatory SNS drive); slows AV nodal

conduction (reduces rate of ventricular contrxns)

Clinical effects improved CHF symptoms, decreased hospitalization

rate, DOES NOT improve CHF mortality

Systolic dysfxn only!

Calcium channel blockers verapamil, diltiazem, dihydropyridines (end in -dipine)

Clinical effects - exacerbate CHF symptoms; increase mortality (exception = Amlodipine); DIASTOLIC DYSFXN only
o
May be appropriate to use in pts w/ CHF and a-fib/atrial arrhythmias (slow ventricular response associated w/ atrial rate)

Amlodipine

Improved survival in CHF; low negative inotropic effect (decreased contractility)

Especially helpful in non-ischemic cardiomyopathies and CHF in hypertensives

Guidelines for pharmacologic treatment

of CHF due to systolic dysfxn:

Guidelines for pharm treatment of CHF due to

diastolic dysfxn:

Diuretics if volume overloaded

ACE or ARB for afterload reduction
Isordil and Hydralazine if needed
Beta-blockers - only the big 3
Spironolactone/Eplerenone
Digoxin

Avoid calcium channel

blockers!

Beta blockers - slow HR

Calcium channel blockers - slow HR
Spironolactone aldosterone antagonist
Diuretics - NOT first b/c BP will decrease too
much
ACE +/- ARB
Avoid beta-blockers for pts who are initially
unstable, mainstay in outpatient setting along
with ACE inhibitors and diuretics

NO digoxin - contraction by blocking Na/K ATPase (blocks relaxation)

Management of end-stage heart failure:

Cardiac transplantation/replacement therapy

Cardiac resynchronization therapy (intraventricular conduction abnormalities leading to uncoordinated RV and LV contraction)
3 lead defibrilator
Mechanical devices
o
Left ventricular assist device (LVAD)
o
Temporary artificial heart
Stem cell therapy?

Q: Which cannot reduce mortality in pts with CHF?

o
BB
o
ACEI
o
Aldactone
o
Isordial and Hydralazine
o
Loop diuretics - not been shown to change mortality

Coronary Artery Disease Pathophysiology and Stable Angina

Atherosclerosis - chronic inflammatory condition, involving lipids, thrombosis, elements of
the vascular wall, and immune cells
o
Atherosclerosis incubates over decades

Atherosclerotic inflammatory process: (1) endothelial dysfunction, (2)

accumulation of lipids within intima, (3) recruitment of leukocytes and smooth
muscle cells to vessel wall, (4) formation of foam cells, and (5) deposition of
extracellular matrix
o
Begins as fatty streaks in children, depends on diet, exercise, genetics

Lipid-laden plaque is inflammatory - can ulcerate, fissure, rupture where

cap is broken and contents go into circulating blood as thrombus (white
platelet clot as opposed to red coagulation cascade clot); can lead to MI
death
o
Most acute coronary syndromes (MI or unstable angina pectoris)
result when the fibrous cap of atherosclerotic plaque ruptures and
prothrombotic molecules within the lipid core are exposed,
precipitating an acute thrombus that suddenly occludes arterial
lumen

70% narrowing lumen diameter causes symptoms of ischemia

Atherosclerotic plaques do not distribute homogeneously throughout vasculature

First develop in dorsal abdominal aorta, then popliteal arteries, descending
thoracic aorta, internal carotids and renal arteries
Complications of atherosclerotic plaques calcification (results in rigidity and
fragility), rupture or ulceration (results in thrombus formation), hemorrhage into the
plaque, embolization of fragments, and weakening of vessel wall
3 major manifestations of CAD - angina pectoris (least frequent initial manifestation
of CAD), MI (irreversible damage to cardiac muscle), and sudden death

ISCHEMIC HEART DISEASE

Ischemic heart disease - when imbalance between
myocardial oxygen supply and demand results in
myocardial hypoxia and accumulation of waste
metabolites; most often caused by coronary artery
disease (atherosclerosis)

Angina is most common manifestation

o
Stable angina - no symptoms AT
REST; only w/activity; no permanent
myocardial damage
o
Sx at rest - unstable angina or MI

Permanent myocardial damage does not result from

angina (since angina is transient <5 min)

Ischemic imbalance events occur rapidly - minutes

1.
2.
3.
4.
5.
6.

Supply-demand imbalance (perfusion defect)

LV compliance stiff ventricle (higher
pressure at any volume)
LV EDP (b/c stiff ventricle)
contractility wall motion abnormalities (b/c regional ischemia) hypokinesis, akinesis, dyskinesis
ECG changes
Angina/symptoms (dyspnea, fatigue)

Mechanisms of myocardial ischemia:

Only about 25% of ischemic

episodes have chest pain

Demand ischemia - myocardial O2 demand increases but O2 supply cannot meet demand

Low (or no) flow ischemia - primary reduction in myocardial O2 supply in absence of alteration in O2 demand

o
o

See stable angina during exercise when increase in blood flow is inadequate to meet increased demand
Occlusion of coronary artery by thrombus limits coronary BF w/ no change in O2 demand; rarely coronary artery spasm

When myocardial O2 supply =/= O2 demand ischemia

Wall stress

Reduce ischemia by reducing O2 demand , or increasing O2 supply (bypass narrowing,

open artery with stent)
SUPPLY:
Most of coronary perfusion takes place during diastole
o
Conditions that decrease aortic diastolic pressure (such as hypotension or
aortic valve regurgitation) decrease coronary artery perfusion pressure and
may impair myocardial oxygen supply.
o
Coronary vascular resistance - another determinant of coronary blood flow

In normal artery, determined by (1) forces that externally compress coronary arteries and (2) factors that alter intrinsic
coronary tone

External compression on coronary vessels during cardiac cycle due to contrxn of surrounding myocardium;
greatest in systole (esp. subendocardium thus most vulnerable to ischemic damage)

Intrinsic coronary tone altered by autoregulation due to accumulation of local metabolites (adenosine),
endothelium-derived substances (prostacyclins dilation, endothelin constriction) and neural innervation (SNS)

Oxygen supply to myocardium depends on oxygen content of blood and rate of coronary blood flow

The only way heart can get more nutrients is by increasing flow (autoregulation)

Cannot increase oxygen extraction unlike skeletal muscle thus cannot tolerate transient ischemia
DEMAND:
Ventricular wall stress (tension) = (P x r) / 2h (by law of LaPlace)

Increase systolic ventricular pressure increase wall stress (aortic stenosis, HTN)

Anything that decreases LV filling and size (nitrate therapy) will reduce wall stress and
myocardial O2 consumption

Anything that increases LV filling will increase wall stress and O2 consumption
(mitral or aortic regurgitation)

Slowing heart rate (beta-blockers) decreases oxygen consumption

Decreasing contractility with negative inotropic effectors (beta-blockers)

Major determinants of
myocardial O2 demand:
Ventricular wall stress
(LV volume x pressure)
Heart rate
Contractility
Notice CO is not one of them

Coronary arteries and regulation of coronary blood flow:

Conductance arteries (proximal 3-5 cm of vessels) - bypassed in CABG

o
Major site of atherosclerosis
o
Diameter 0.1-4.0 mm, relatively little muscle, little vasomotion, little capacity for dynamic resistance (normally)

Can confer major resistance when severely narrowed by atherosclerosis or by vasospasm

Resistance arteries (distal, intramyocardial)
o
Diameter < 0.1 mm, relatively abundant smooth muscle b/c rapid lumen diameter regulation

Regulate coronary artery resistance by vasomotion (normal) - AUTOREGULATION

o

Increasingly dilated at rest when conductance arteries narrowed by atherosclerosis.

Thus, coronary flow reserve is decreased (if already dilated at rest cant dilate more when demand increases)

Vasoactive mediators:

Coronary arterioles are normally in a relatively dilated state

Vasodilators - endothelium-derived hyperpolarizing factor (EDHF), NO, prostacyclin
Vasoconstrictors endothelin-1
Normally, healthy endothelium promotes vasodilatation (VSM relaxation) due to
release of NO and prostacyclin > endothelial vasoconstrictors
o
Dysfxnal endothelium (e.g. atherosclerosis) secrete reduced amt of
vasodilators and balance shifts toward vasoconstriction

Coronary arterioles become increasingly dilated to maximum as resting flow

falls flow reserve is thereby decreased

In all organs, flow reserve is not impaired until 70% narrowing

o
Reserve = microcirculation dilation capacity
At 85%, resting flow is compromised and microcirculation is constantly dilated
o
With increasing dilation, flow reserve is compromised
Flow follows demand in the normal state (due to autoregulation)
o
If flow reserve is limited in at least one artery, demand > supply; lasting ischemia may follow if demand is sustained
Spasm is primary reduction in flow with no increase in demand

Stable angina syndromes

Stable exertional angina

Chronic, predictable transient angina during exertion or emotional stress

Generally caused by > 70% stenosis in conductance coronary arteries; in 99% of pts etiology is atherosclerosis
o

Syndrome X rare and often is overdiagnosed

See typical or atypical Sx of stable exertional angina

No significant coronary stenosis (normal angiogram)

Thought to be due to impaired coronary microvascular dilation

Coronary vasospasm very rare

Diagnosis of stable angina:

History is most important quality of pain

(pressure, constriction), location (retrosternal),
radiation (arms L > R, neck, jaw)
Provoked by physical or emotional stress
o
Due to increased myocardial demand
(BP, HR, contractility)
o
Usually predictable caused by same
activity or stress
o
Remits within 3-5 min of rest transient
Response to therapy - remits within ~2-3 min
post-NTG (sublingual nitroglycerin)
Symptoms more atypical in women & elderly
o
Dyspnea, dizziness, dysphagia

Unstable angina/MI have similar Sx to stable angina

in quality/location/radiation except they are more
severe, occur at rest or w/ little provocation, and
are unremitting (last 30 min - several hrs)

Pathophysiology of physical signs during acute MI

Can have transient heart failure with pulmonary edema and rales

compliance can cause S4 (hard for atria to get blood into stiff ventricle)
Papillary muscles can become ischemic
SNS due to the pain of angina

Common transient EKG abnormalities in

ischemia

Ischemia indicated by repolarization

abnormalities
o
ST depression > 1 mm
suggestive of ischemia
o
T wave inversion
Remember that there may be multiple etiologies for these thus need to interpret EKG
results in the context of clinical findings

Diagnostic tests:

Stress EKG cheap and good screening test (esp. when also look at labs and Hx)

Angiogram necessary to make a definite Dx of CAD

CT angiography but can be overused; plus lots of radiation and dye

Summary:

Myocardial ischemia results from a disparity between myocardial oxygen supply and demand (increased demand or reduced supply)
W/o significant stenoses of conductance coronary arteries, coronary flow reserve is determined by vasomotion of coronary
resistance arterioles which dilate and constrict to provide appropriate flow
With significant stenoses ( 70%) of conductance coronary arteries, resistance arterioles become increasingly dilated at rest and
coronary flow reserve is compromised, resulting in demand ischemia and stable angina
If coronary stenoses are > 85%, resting coronary flow falls resulting in low flow ischemia and angina at rest (unstable angina)
Myocardial ischemia see transient alterations in cardiac function and EKG (ST depression, T-wave inversion)
Multiple etiologies can cause chest pain similar to angina but careful history helps distinguish
Definitive test for CAD is coronary angiography

Chronic stable angina:

Quality of pain generally not described as pain but as pressure, discomfort, tightness, burning or heaviness in chest

Not sharp or stabbing, does not vary significantly with inspiration/mvt of chest wall

Steady discomfort, lasts more than a few seconds (unlike musculoskeletal pain); lasts a few minutes but rarely more
than 5-10 min; may describe with clenched fist over sternum
Usually diffuse rather than localized to a single point; most often retrosternal or in left pericardium but can be anywhere in chest,
back, arms, neck, lower face, or upper abdomen; often radiates to shoulders and inner aspect of arms, especially left

Accompanying symptoms tachycardia, diaphoresis, nausea; often dyspnea (due to elevation of LV diastolic pressure that is
transmitted to pulmonary vasculature); commonly see transient fatigue and weakness, esp. in the elderly

Precipitants unless caused by vasospasm, precipitated by conditions that increase myocardial oxygen demand (increased HR, wall
stress, and contractility) physical exertion, anger, other emotional excitement; also can be precipitated by large meal or cold
weather (due to peripheral vasoconstriction)

Angina usually relieved within minutes of cessation of the activity; quicker with sublingual nitroglycerin (3-5 min) unlike other
causes of chest discomfort

Often results in reduction of daily activities since people try to avoid precipitating events

Risk factors for atherosclerosis and CAD smoking, hyperlipidemia, HTN, diabetes, family Hx of premature CAD

DDx GERD, esophageal spasm, biliary pain, pericarditis, musculoskeletal conditions (chest wall pain, spinal osteoarthritis, cervical
radiculitis)

Physical exam increased HR and BP (due to increased SNS response); mitral regurgitation (if papillary muscle dysfxn in MI),
ischemia-induced regional ventricular contractile abnormalities (abnormal bulging impulse on palpation of left chest); may have S4
(stiff ventricle) but all of these may not be present w/o abnormal cardiac physical findings

Treatment - cease physical activity; sublingual nitroglycerin (relieves ischemia through vasodilation and augmentation of coronary
blood flow)

Acute Coronary Syndromes (ACS)

Despite what the book says, most common presentation of
CAD is not angina but MI and sudden death

Pathogenesis of ACS:

More than 90% of ACS result from disruption of

atherosclerotic plaque w/ subsequent platelet
aggregation and formation of intracoronary thrombus
o
Thrombus can lead to severe or complete
occlusion of the artery
o
Most of ACS symptoms are at the sites of
plaques that are 30-50% stenotic prior to
rupture (thus no angina before MI)
Partially occlusive thrombus typically causes unstable angina and NSTEMI (non-ST elevation MI)
Completely occlusive thrombus more severe ischemia, more necrosis STEMI (Q-wave MI); determine if infarct by serum
markers; however do not wait for labs before starting therapy if typical Sx + ST elevation (15-20% of ppl will actually be ok)

If taken to cath lab with ST elevation and symptoms 15-20% will have normal
coronary arteries and ST elevation from something else
Majority of acute coronary symptoms are at the site of plaques that are 30-50%
stenotic prior to their rupture (explains why never had angina before the MI)

Vulnerable plaques have large lumen (but not always), thin fibrous cap and large
lipid pool w/ many inflammatory cells and thin layer of activated intimal smooth
muscle cells
Inflammation due to HTN, oxidized LDL, smoking
o
Inflammatory substances compromise integrity of fibrous cap
Plaques can go back and forth between stable and unstable, depending on
risk factor profile
o
However, changing risk factor profile will have little effect on
opening up stenotic lumen

Stable plaque less inflammation, smaller lipid pool, thick fibrous cap
5 systems that balance intravascular coagulation and anti-coagulation:
Antithrombin III/ heparan sulfate inactivate thrombin
Thrombomodulin activates protein S and C inactivate clotting factors
Tissue factor stimulates clotting cascade, exposed when plaque ruptures
o
TFPI opposes actions of tissue factors
tPA (tissue plasminogen activator) activates plasmin clot lysis
Prostacyclin and EDRF-NO vasodilators (augments blood flow and thus guards
against thrombosis) and anti-thrombotic agents (prostacyclin inhibits platelet
activation and aggregation)
Balance shifts to clotting in
atherosclerosis
Due to plaque rupture
exposes circulating
blood elements to
thrombogenic
substances
Endothelial dysfxn w/ loss of normal protective antithrombotic and
vasodilatory properties

Nonatherosclerotic causes of ACS (suspect when young ppl or no coronary risk

factors):
Coronary emboli, inflammation from acute vasculitis, intense transient
coronary spasm, cocaine abuse (increases SNS tone by blocking presyn
uptake of NE and enhancing release of adrenal catecolamines vasospasm)

Continuum of ASC:

1. Unstable angina no evidence of necrosis

Comes with less activity, may come at rest (low flow/no flow
ischemia), does not respond well to nitroglycerin
2. NSTEMI necrosis + injury markers

Injury markers most sensitive and specific are troponin-I and

troponin-C; they take ~3 hrs to come back
3. STEMI necrosis + injury markers

MI results when myocardial ischemia is sufficiently severe to

cause myocyte necrosis
Transmural infarcts result from total prolonged
occlusion of epicardial coronary artery
Subendocardial infarcts exclusively involve innermost
layers of myocardium
o
Subendocardium particularly susceptible to
ischemia b/c here there is highest pressure
in ventricle and has few collaterals (think
of vessels squished)

Early changes in infarction can happen within 2 min

following occlusive thrombosis:

Rapid shift to anaerobic metabolism lactic acid
accumulation decreased pH
Na/K ATPase slows down (low ATP) Na and K
gradients collapse cellular edema due to increased
intracellular Na and arrhythmias due to increased
extracellular K
Intracellular Ca accumulates in damaged myocytes
activate degradative lipases and proteases
Irreversible cell injury w/o intervention happens in 20 min
marked by development of membrane defects
Edema of myocardium develops within 4 12 hrs

Late changes in infarction:

Clearance of necrotic myocardium

Deposition of collagen to form scar tissue

Functional alterations:

Impaired contractility and compliance

o
Systolic dysfunction due to myocardial cells destruction
o
Compromised CO b/c lose synchronous contraction of myocytes
Wall motion abnormalities
o
Hypokinesis, akinesis, dyskinesis (ventricular aneurysm bulges outward)
Diastolic dysfunction in LV since relaxation is impaired as well
o
Results in reduced ventricular compliance and contributes to elevated ventricular filling pressures

Stunned myocardium prolonged but gradually reversible period of contractile dysfxn after a discrete episode of severe ischemia despite
restoration of adequate blood flow
Ventricular remodeling:
Infarct expansion in early post-MI period thinning and dilatation of necrotic
zone increases ventricular size and thus augments wall stress, impairs systolic
contractile fxn, and increases likelihood of aneurysm formation
Dilatation of over-worked non-infarcted segments

Clinical presentation:

Unstable angina (crescendo pattern, occurs at rest w/o provocation,

new onset of severe anginal episodes in ppl w/o previous Sx of CAD)
Acute MI
o
Up to 25% of pts w/ acute MI asymptomatic during an event,
esp. diabetics
o
Some ppl feel sharp pleuritic pain instead of typical MI Sx
o
o
o

Often there is S4 (still ventricle)

Sometimes S3 (volume overload)
Elevated biomarkers (esp. since 510% of MI pts have normal ECG)

ECG changes:
Unstable angina
or NSTEMI

STEMI
Cardiac troponins:

Cardiac troponin I and troponin T

o
Begin to rise 3-4 hrs after onset of MI, peak between 18 and 36 hrs, and then decline
slowly over 10-14 days
o
More sensitive than creatine kinase
Creatine kinase (CK-MB) starts to rise 3-8 hrs after MI, peaks after 24 hrs, returns to normal
within 48 72 hrs

A 60 yo man presents to the ED with 40 minutes of severe retrosternal pressure at rest. The ECG shows ST depression and T wave inversion.
(Best single choice):
These data confirm that he is having unstable angina
These data indicate that he has a totally occlusive coronary thrombus
These data indicate that he is having a non-ST elevation MI
Additional testing is needed to determine if he is having an MI

Complications of MI:

Complications of MI = complications of necrosis

o
If small amount of necrosis - uncomplicated MI (50%)
Contractility decreased b/c lost muscle promotes stasis
thrombosis can embolize, usually to head stroke
If 40% muscle lost cardiogenic shock (end-organ perfusion so low
that unless reversed 24 hours it is incompatible with life)
Any amount can cause electrical instability, but w/ greater amt
more likely to have fatal arrythmias
Necrosis can infarct/ rupture papillary muscles so blood not
separate from LA/LV and blood goes backwards
Can have septal defect shunt
If infarct very large muscle ruptures blood into pericardium = cardiac tamponade compressing ventricle and rapid death
Pericarditis due to inflammation of epicardium

Post-MI prognosis:

Varies widely; mortality <2% to >25%/yr; related to:

o
How much myocardium was destroyed
o
LV fxn measure clinically by ejection fraction (55-70% is normal)
o
Extent of CAD 1, 2, or 3-vessel disease
o
Electrical instability symptomatic or asymptomatic ventricular arrhythmias
o
Age, co-morbidities

Summary:

ACS - Continuum of pathologic, ECG, cardiac injury markers and clinical syndromes (Unstable angina, Non-STEMI, STEMI)
Typical cause of ACS Rupture of unstable plaque (plaque is usually 30-50% stenotic) = non-flow limiting and dont limit coronary
reserve) and coronary thrombosis (partially or totally occlusive)
Atherosclerotic mileu alters homeostatic vascular protective mechanisms and reduces their coronary vasodilating and antithrombotic
effects (dysfunctional endothelium)
Unstable angina severe ischemia, rest symptoms (or progressive from prior stable angina), no necrosis (negative injury markers)
Non-STE MI and STEMI myocardial necrosis (positive injury markers)
Non-STE ACS ECG Usually ST segment depression and/or T wave inversion
STEMI ECG Characteristic acute ST segment elevation (but other things can also do this)
Major complications of MI Systolic and diastolic LV dysfunction (heart failure), arrhythmias, mitral valve regurgitation, emboli,
cardiac rupture
Prognosis after ACS - Related to multiple factors
LV function (LV ejection fraction), extent of CAD, arrhythmias; Age; Co-morbidities

RE: DISCUSSION OF FREQUENTLY ASKED QUESTIONS CONCERNING CORONARY AUTOREGULATION, VASOMOTION, SPASM, SMALL
(RESISTANCE) CORONARY ARTERIES, LARGE CORONARY ARTERIES.
Normal coronary circulatory physiology: Because myocardial oxygen extraction from perfusing blood is near maximal at rest (in sharp contrast
to other organs in which extraction at rest is much lower), alteration of coronary blood flow (CBF) is the principal means by which myocardial
oxygen supply is regulated. This is achieved by moment-to-moment changes in coronary vascular resistance. This exquisitely sensitive
mechanism of adjusting CBF to meet myocardial oxygen needs is termed autoregulation and is under the control of the coronary resistance
vessels (<100 micra diam., precisely termed arterioles and characterized by a high ratio of smooth muscle to connective tissue). Autoregulation
is a property of the resistance arteries of all tissues and organs and enables the organism to differentially distribute a given cardiac output to
the appropriate organs to meet their physiologic requirements during different metabolic states, e.g., exercise, rest, digestion, etc. The
resistance vessels and capillaries comprise the microcirculation of all organs. Resistance in these vessels is modulated by a variety of mediators
(discussed in class and described in chapter 6, text) to provide appropriate oxygen supply to the tissues. The most important influence on
coronary vascular resistance is local metabolic factors, such as alterations in local oxygen tension. The large coronary arteries (diam. hundreds
of micra to 4 mm) have a relatively small proportion of muscle to connective tissue, have minimal vasomotion under normal conditions and play no
role in coronary autoregulation. These arteries are also referred to as conduit vessels because of their function as primarily passive channels
for conduction of large volumes of blood.
Coronary Pathophysiology: When frank atherosclerosis (or even fatty streaks or subintimal lipid deposition with no compromise of coronary
lumen) occurs, the normal physiology described above can be altered. Coronary spasm can occur spontaneously and produce total or subtotal
(>90%) stenosis. This pathologic event is a property of the large coronary arteries. It is rare, usually transient (seconds-minutes) and its
mechanism has not been clarified. The clinical syndrome associated with this phenomenon is variant angina (rare), a form of unstable angina.
Most patients with coronary spasm have significant atherosclerotic obstruction (>50% decrease in coronary lumen diameter) and the spasm is
usually superimposed on the site of the fixed stenosis. In a minority of patients (<20%), spasm occurs in arteries with no detectable
(angiographically) atherosclerosis. Lesser degrees of dynamic constriction can also occur in the large coronary arteries. These are referred to
as increases in coronary tone and may result in an additional 10-30% constriction at the site of an atherosclerotic lesion.
The term, spasm, does not apply to the small, resistance coronary arteries. In these vessels, in which frank atherosclerosis is rare, endothelial
dysfunction and subintimal deposition of lipid may occur and impair normal vasomotion in response to physiologic mediators. The vasodilating
ability of these vessels in response to normal stimuli is thereby compromised. Under experimental conditions, inappropriate increases in
resistance of these vessels due to endothelial dysfunction have been documented in some patients with elevated serum cholesterol levels,
suggesting that even in the absence of frank atherosclerosis of the small vessels, abnormal vasomotion may be related to elevated lipid levels
without anatomic lipid deposition. This functional abnormality is due to impairment of endothelium controlled vasodilation of the arterioles.
This dysfunction of the small vessels may produce myocardial ischemia. The degree to which this mechansim contributes to ischemi heart
disease is not clear.
Summary: The major points to understand in the above discussion are:
1) The importance and mechanisms of coronary autoregulation.
2) Physiologic vasomotion is a property of the resistance (small) arteries.
3) Frank coronary spasm and lesser degrees of dynamic coronary constriction occur in diseased (atherosclerotic) large coronary arteries
4) Frank spasm is a rare contributor to ischemic heart disease.
5) Normal vasomotion of the resistance vessels can be impaired in the presence of risk factors such as hypercholesterolemia (in the absence of
anatomic lipid depositions) causing endothelial dysfunction. The latter results in abnormal vasomotion which is related to endothelial
dysfunction.

CAD Treatment
Goals of therapy for stable angina - alleviate
symptoms, improve fxnal capacity for
occupation/recreation, and improve prognosis
(survival)

Anti-anginal therapy improve myocardial

oxygen supply-demand imbalance by O2
demand, O2 supply or both

O2 demand - lifestyle

changes (weight loss

and exercise) and pharmacological agents (acute
sublingual nitro and prophylactic Tx)

Organic nitrates O2 demand by

preload (venodilation)
o
In vasopasm actually O2
supply by coronary perfusion
and spasm
o
Also relieve esophageal spasm
o
Side effects due to vasidilatation
HA, hypoTN, reflex tachycardia (prevent by taking beta-blocker)
o
No evidence that they improve survival or prevent MI; only used for symptomatic relief
o

At low doses, nitrates cause venodilation but has less effect on arterioles except the coronaries, facial vessels, & meningeal arteries; high
doses cause venodilation and arterial dilation.

Low doses decrease CO; high doses increase CO (b/c reduce afterload)

Beta-blockers negative inotropic effect - contractility, HR (during exercise), BP

o

Side effects excessive bradycardia, LV contractile fxn (change systolic Ca levels; decrease myocardial sensitivity to Ca),
bronchoconstriction (antagonize beta-2 receptors avoid in COPD), may worsen diabetic control (overemphasized); fatigue
(due to bradycardia)

Beta-1 on cardiac cells; beta-2 in smooth muscle (blockers incr. contractility here beta-2 agonists cause vasodilation)

Reduce contractility by reducing the amount of Ca available to the myofibrils.

o
Decrease O2 demand by reducing crossbridge cycling.

-blockers slow HR by decreasing cAMP (cAMP increases IF faster depolarization)

Some of side effects b/c block beta-1 and beta-2 (even selective ones are not THAT selective)
Only use in stable pts w/ heart failure otherwise negative inotropic effect will further reduce LV fxn
o
Decrease rates of recurrent MI and improve survival after acute MI; reduce
likelihood of MI in pts w/ HTN
Ranolazine (Ranexa) anti
Ca-channel
blockers negative inotropic effect - wall stress ( BP), contractility, HR
anginal drug approved in 2006;
(verapamil and diltiazem); also dilate smooth muscle (dihydropyridines nifedipine and
rarely used; not first-line Tx
amlodipine - due to impaired Ca influx) thus preload and afterload
used as adjunct to Tx; not sure

Also O2 supply in vasospasm by coronary perfusion and spasm

how it relieves angina
o
Cant
give
to pts w/ CHF - systolic dysfxn (ok in diastolic) due to contractility

No effect on HR, BP,

o
Side
effects
HA, flushing, LV contractile fxn, marked bradycardia, edema (by
contractility, coronary
increasing peripheral capillary pressure), constipation
blood flow

Probably works by
inhibiting late phase of
Na current in myocytes

o
o

Vasodilation prevention of calmodulin activation prevents MLCK activation smooth muscle

relaxation/vasodilatation
At high enough concentrations all CCBs reduce contractility

At clinical conc. dihydropyridines (nifedipine & amlodipine) do not affect E-C coupling.

Non-DHPs (verapamil & diltiazem) do reduce E-C coupling

Aspirin - inhibits COX and TXA-2 platelet aggregation

o

Side effects - bleeding

After Tx, HR and BP are lower in submaximal exertion as compared to pre-Tx; onset of angina is delayed until greater
exertion achieved

But HR and BP at which angina occurs are unchanged (they just happen later)

Thus know that therapeutic mechanism is reduction in myocardial O2 demand to fit reduced capacity to increase blood flow
o
o

Pt can perform more work w/ less cardiac work work of heart at any workload is reduced
But coronary blood flow is NOT increased need CABG for this

A 60 yo man has reduced symptoms of stable exertional angina after receiving therapy that increases his coronary blood flow. This therapy is
likely to be which of the following:

A long-acting nitrate

None of the above none of these Tx increase blood flow; revascularization

A calcium channel blocker

does.

A beta blocker

 O2 supply revascularization

- for significant CAD ( 70% stenosis) in appropriate pts:

Refractory angina
Left main disease ( 50% stenosis)
o

Left main supplies almost entire LV (except inferior wall) infarct is life-threatening thus do CABG

RCA disease is not life-threatening, so use medical therapy

3-vessel CAD with LV function (RCA, LAD, LCX)

High risk noninvasive stress test
o
o
o

Exercise test - marked ST depression (suggests left main or 3-vessel disease)

Nuclear - large perfusion defect
Echo - large ventricular wall motion abnormality

Balloon angioplasty + stent successful if reduce stenosis to < 20%:

CABG:

Usually use femoral, brachial or radial artery

Coronary perfusion and myocardial oxygen supply are increased as a result of dilation of stenosis
Risk of MI from angioplasty < 1.5%, mortality < 1%
Stents are thrombogenic need oral antiplatelet agents (aspirin and clopidogrel Plavix)
Also give anti-hypertensives and anti-hyperlipidemic agents

Saphenous vein aorta to RCA

Internal mammary artery better b/c dont need to attach to aorta, plus artery is always better than vein for CABG
o
Arteries 90% patent at 10 yrs, veins 50% (may need to stent)

B/c veins are more vulnerable to atherosclerosis use lipid-lowering Tx after CABG

Comprehensive management of stable angina

o
o

Diagnosis - history, physical exam, ECG, stress test

Treatment (reduce or eliminate angina at same level of activity)
o
Sublingual nitroglycerin for acute angina
o
Prophylaxis - -blocker ( survival), nitrates, Ca channel blockers, ranolozine
o
atherosclerotic risk factors - cholesterol (statin - ( survival), HTN, smoking ( survival), obesity, inactivity
o
Antithrombotic aspirin, clopidogrel - Plavix ( survival)
o
Revascularization medically refractory or high risk - left main disease ( survival)

Complications of MI CHF, arrhythmias, embolism,

cardiogenic shock, pericarditis, cardiac tamponade

Therapy of acute STEMI remember, the

artery is completely occluded (unlike NSTEMI)
o

o
o
o
o
o

Reperfusion angioplasty-stent (within 2-4 hrs) or

thrombolysis (if cannot send to cath lab)
o
Thrombolytics:

TNKase better than tPA b/c

can give as a bolus instead of
continuous infusion; but 0.5%
risk of cerebral hemorrhage

SK (streptokinase) binds to
plasminogen and together they
activate other plasminogens to plasmin but hardly used b/c of allergic rxns
Oxygen
Aspirin, clopidogrel, heparin - antithrombotic
Beta-blockers - anti-ischemic
Nitrate - anti-ischemic
ACE inhibitor vasodilator, anti-inflammatory

A patient with acute MI receives therapy to directly inhibit platelet aggregation. This therapy includes (1 or more may be correct):
o
Aspirin
o
ACE inhibitor
o
Nitrate
o
Clopidogrel this is Plavix
o
All of the above

PREVENTIVE CARDIOLOGY
Primary prevention - reduce incidence of cardiovascular disease in healthy population
Secondary prevention - to decrease morbidity and mortality in pts who already have overt disease
In 60-70% of pts w/ CAD, initial manifestation is MI (50%) or sudden death (10-20%).
Prevention is effective, safer than conventional medical therapy and far cheaper
CIGARETTE SMOKING - the most preventable risk factor for CAD
Risk of CAD is double in smokers vs. nonsmokers and cardiac mortality increases progressively with number of cigarettes smoked.
Nicotine and hydrocarbons in cigarette smoke directly damage vascular endothelium, which is an important initial step in atherogenesis
Smoking is also associated with a reduction in HDL-cholesterol, further enhancing ATH.
In addition to these long-term effects, nicotine and products of cigarette smoke can acutely induce coronary events:
o
Nicotine increases coronary vascular resistance, can displace oxygen from Hb by CO production and stimulates release of
catecholamines which increase myocardial oxygen demand (BP, HR, contractility).

All of these actions can promote ischemia and arrhythmias in pts with CAD.
o
Nicotine also increases platelet aggregability directly and through catecholamine release.
Cessation of smoking is associated with beneficial effects on cardiac morbidity and mortality in normal ppl and in CAD pts.
o
Benefits occur early; can be as high as 50% reduction in risk for coronary events within 6-12 months of smoking cessation
HYPERTENSION - believed to contribute to ATH by hemodynamic injury to vascular endothelium
Both systolic and diastolic BP elevations are associated with increased coronary and systemic vascular disease
Most hypertensives are in the mild category (diastolic <105) and many of them can be managed w/o drugs by altering factors that
increase BP.
o
Decreasing alcohol intake (0-2 drinks/d), reducing dietary NaCl and decreasing obesity
o
Aerobic exercise is effective and stress reduction shown to be effective in some pts.
BP reduction total CV mortality and morbidity - stroke, congestive heart failure, renal disease, peripheral vascular disease and CAD.
HYPERCHOLESTEROLEMIA - lowering serum cholesterol in pts with CAD can result in reduced progression and very modest regression of
coronary atherosclerotic lesions and major decreases in CAD mortality and morbidity
Mechanism - plaque stabilization rather than the minimal regression in coronary lesions.
Need LDL for atherosclerosis
Low TC (< 150 mg/dl) - associated with diets very low in animal and dairy fat.
LDL-C is the atherogenic particle and HDL-C has a protective role through reverse C transport.
Total serum C, HDL-C and the ratio of total C/HDL-C each independently predict risk of CAD.
o
This risk is directly related to level of serum C, is continuous and thus, there is no "normal"
o
In the elderly (>65 yo), C/HDL-C has better predictive power for CAD than C or LDL-C.

Intervention to lower C: (1) reduces CAD morbidity and mortality in healthy populations and in pts with CAD and (2) retards progression, causes
some regression of CAD lesions and appears to stabilize atherosclerotic plaques.
Current guidelines for desirable serum C:
Healthy adults - LDL <160 mg/dL (or < 130 mg/dL if there are > 2 other RFs) and HDL > 40mg/dL.
Pts with overt CAD or other significant atherosclerotic vascular disease: LDL <100 mg/dL (LDL < 70 in very high risk patients)
Currently the average C in the US is ~ 210 mg/dL; 250 mg/dL is the 75th percentile and 270 mg/dL is the 90th percentile.

Inflammation (sub clinical) has gained increasing recognition for its importance in atherogenesis and plaque rupture.

State produced by local concentration of inflammatory mediators, reflected by C- reactive protein, interleukin, and matrix
metalloproteinases.
o
Cause endothelial injury, promote plaque disruption, and are prothrombotic.
At this time, C-reactive protein is the most readily measured inflammatory marker.
Evidence of inflammation is decreased by treating cardiac risk factors.

EXERCISE - sedentary lifestyle correlates with increased risk of CAD but it is not clear whether this is related to selection
(i.e., healthy individuals are more likely to exercise) or the benefits of exercise.
Aerobic exercise training is associated with benefits on several CAD risk factors:
o
Decreases in obesity, BP, HR, catecholamines, triglycerides (little direct effect on LDL-C);
o
Increases in HDL-C (modest) and in activity threshold for ischemia.
Diet has a much greater effect on serum cholesterol than the modest influence of exercise.

DIABETES - now considered a "CAD equivalent" with the same targets for lipids as patients with overt CAD.
Current data strongly suggest that tight control of BP and lipids can reduce CAD risk.
Tight control of glycemia has not yet clearly been shown to reduce CAD events.
METABOLIC SYNDROME - abdominal obesity, insulin resistance (fasting glucose 110-125), HTN, high triglycerides (<150), and low HDL (< 40).
It is very high risk state for CAD and aggressive risk factor modification is indicated.
OBESITY - closely associated with other risk factors such as HTN, low HDL, inactivity and diabetes.
These factors are all decreased by reversal of obesity.
EMERGING RISK FACTORS
Homocystinemia; lipoprotein (a); small, dense LDL; triglycerides; fibrinogen and inflammatory factors (e.g., c-reactive proteins;
Chlamydia).

In vasospastic angina, spasm

usually occurs at the site of
mild to moderate anatomic
stenosis; <30% of pts with
vasospastic angina have "normal"
coronary arteries

Anti-Thrombotic Drugs
Components of normal hemostasis (overall goal is to form a stable hemostatic plug that is
limited to the site of vascular injury)

Normal vascular integrity

Platelets - primary hemostasis

Coagulation system - secondary hemostasis (initiated by Tissue Factor)

Fibrinolytic system (remodels clots) - tertiary hemostasis

HEPARINS anticoagulant drugs; inhibit thrombin activation by Xa

Antithrombin III binds to and inhibits all serine proteases but mostly Factor Xa and thrombin (IIa)

Heparin binds to AT-III and makes it 1000 10,000x more effective indirect anticoagulation

Unfractionated heparin (usually bovine):

Binds to AT inhibition of Xa and thrombin; also antiplatelet properties blocks action of vW factor

o
o

Needs to be given parenterally (acute give bolus and then continuous infusion)
Bioavailability varies between pts thus dose-effect relationship (pharmacokinetics and dynamics) may be unpredictable

Need to continuously monitor degree of anticoagulation by measuring aPTT

Indicated in unstable angina and NSTEMI, acute MI after fibrinolytic Tx or w/ extensive WMA, and PE or DVT

Sometimes give low doses of subcut UFH to prevent DVT in bed-ridden pts
Side effects bleeding (Tx by giving protamine sulfate forms a stable complex w/ UFH)

o
o

Heparin-induced thrombocytopenia (HIT) can be mild or severe (immune-mediated, can lead to life-

threatening bleeding and thrombosis Abs activate platelets;

Ag-Ab complexes bind to platelets at Fc receptor which activates platelets clotting

Abs can also cross-react with GAGs on endothelial surface vascular damage release TF clotting

Tx - stop heparin and give another anti-coagulation alternative e/g/ direct thrombin inhibitors

Low molecular wt heparins (LMW heparins) enoxaparin, dalteparin and tinzaparin

Made from UFH 1/3 of UFH molecules size

Preferentially inhibit Xa instead of thrombin (thrombin inhibition

requires larger molecules)
Less binding to plasma proteins and endothelial cells more
predictable bioavailability, longer half-life, lower bleeding
complications and lower incidence of immune-mediated HIT

Can give subcut once or twice per day in fixed doses w/o frequent
blood monitoring (if need to monitor look at Xa inhibition assay instead of thrombin)

However, unlike UHF, effects of LMW heparin are NOT completely reversed by protamine sulfate
Used for DVT prophylaxis, DVT treatment and management of ACS

Advantages of heparins:

Indications for heparin

Primary or secondary prevention of DVT

Treatment of ACS

During percutaneous coronary interventions

During dialysis and other extracorporeal circuits

To keep central venous catheters from clotting

Quick onset of action (hrs vs. days for oral Warfarin)

LMWH - predictable pharmacokinetics and dynamics no lab monitoring needed for most pts
Can be used in pregnancy (both LMWH and UFH do not
cross placenta unlike Warfarin)
Parenteral (good for ICU, hospital situation)

Disadvantages of heparins

Parenteral (difficult for long-term outpatient use)

LMWH is very expensive (in the US)
Impurities in UFH
No reversal agent for LMWH
Heparin-induced thrombocytopenia (HIT)
o
Incidence with LMWH is 0.1% vs. UFH 2-3%

Direct thrombin inhibitors lepirudin, bivalirudin, argatroban (parenteral) and ximelagatran (oral)

Bind to catalytic site of thrombin and are effective against both circulating and bound thrombin (unlike heparins)
Do not cause thrombocytopenia thus can be used in pts w/ HIT
All are potent anticoagulants thus bleeding is major side effect
Given parenterally or orally
o
Ximelagatran available orally but only approved for short-term use in Europe b/c of liver toxicity
Differ in half-lives and mode of clearance (renal vs. hepatic)

Fondaparinux synthetic analog of heparin (pentasaccharide); specifically inhibits Factor Xa reduces thrombin activation

Binds to AT-III like heparin but with very high affinity

Predictable PK and PD daily dosing, no monitoring; borad weight-based dosing (2.5 mg for prophylaxis; 5, 7.5 and 10 for therapy)

Can be given subcut daily (long half-life)

Can be used in patients w/ HIT; probably safe in pregnancy; no known reversal agents
Approved for DVT prevention in ppl undergoing orthopedic surgery and for DVT and PE treatment

Warfarin Vitamin K antagonist

Vitamin K is a cofactor for gamma-carboxylation (Glu Gla residues - needed for Ca binding needed for attachment to
phospholipid surface)
o
Vitamin K-dependent factors II, VII, IX, X; Proteins C and S

Vitamin K-depended factors synthesized in the liver

Warfarin oral agent for long-term anticoagulation

o

o
o
o
o

Interferes w/ internal recycling (reduction to hydroquinone) of oxidized Vitamin K (Vitamin K epoxide) by antagonizing
Vitamin K epoxide reductase results in decrease of gamma-carboxylation anticoagulation

Remember coumadin skin necrosis? Proteins C and S also inhibited by warfarin

Anticoagulant action has a delayed onset (2-7 days) thus need to keep on heparin for a few days
Long half-life (37 hrs)
Liver disease decreases warfarin requirements; ingestion of green leafy veggies (high in Vitamin K) increases it
Reverse effects by administration of Vitamin K or faster by fresh-frozen plasma transfusion

Indications for warfarin use:

Advantages:

o
o
o

Prophylaxis and/or treatment of DVT, PE and thromboembolitic complications of a-fib and heart valve replacement
Oral, cheap, effective
Effective at preventing recurrent DVT and prevention of PE in pts w/
DVT

Disadvantages:
o

o
o

Major adverse effect of anticoagulants

hemorrhage

Depends on intensity of anticoagulation

(need to monitor INR!), concomitant
clinical disorders, concurrent use of
other meds, and quality of management

Narrow therapeutic index w/ highly variable absorption and

pharmacodynamics

Partially genetically determined

Requires at least monthly monitoring (target INR 2-3, for greatest risk 2.5 - 3.5)

2% annual risk of major bleed, 0.1% risk of CNS bleed (even if well-controlled)
Many drug and food interactions (almost all drugs check INR after staring any new meds)
Teratogenic

Rivaroxaban - oral Xa inhibitor:

Shown to be as effective and safe as LMWH in prevention of DVT after knee and hip surgery; available in Europe
Take once a day
Phase 3 testing in the US FDA needs more safety data
Predictable pharmacokinetics and pharmacodynamics - no lab monitoring; dose is same regardless of wt, at least for prophylaxis
Probably can be used in HIT

Antiplatelet drugs
Aspirin irreversibly blocks COX-1 cant form TXA-2

TXA-2 is needed for platelet activation

One of the most cost-effective and safest medications; reduces cardiac
events by 48%
Better at low doses b/c inhibits platelet agonist TXA-2; at high doses
also inhibits prostaglandin PGI-2 (anti-platelet agent)
However, it does not affect platelet aggregation induced by other
factors (such as ADP) thus fxn is limited
Side effects GI (dyspepsia, nausea), GI bleeding, hemorrhagic strokes,
allergic rxns, asthma exacerbation in aspirin-sensitive pts; may occasionally
exacerbate gout (b/c competes w/ uric acid for excretion)

Clopidogrel (Plavix) thienopyridine

Blocks ADP receptors (one of 2 types)

Combination Tx more efficacious than monotherapy for high-risk pts
o
Examples after stent placement, clinical event despite aspirin therapy
Side effects dyspepsia and diarrhea

GP IIb/IIIa inhibitors GP IIb/IIIa essential for platelet aggregation; given IV; high risk of bleeding

Abciximab monoclonal Ab inhibits GP IIb/III a binding of fibrinogen and vW factor

Eptifibatide cyclic peptide, binds to fibrinogen binding site of GP IIb/IIIa; more specific than Abciximab
Tirofiban non-peptide small molecule inhibitor of GP IIb/IIIa
Most effective use in the setting of percutaneous coronary interventions in conjxn w/ aspirin and anticoagulant
o
Short-term use decreases restenosis, infarction and death

Fibrinolytic agents:

Predominantly use for acute MI, less so for

venous thrombosis
In small doses to reopen central venous
catheters

Streptokinase rarely used anymore

tPA and TNKase widely used
Parenteral; fixed dosing for newer agents
Use in conjxn w/ anticoagulants and
antithrombotic agents
Major complication bleeding

Arrhythmias
Automaticity - cells ability to depolarize itself to threshold in rhythmic, repeated fashion, such that spontaneous APs are generated.

Under normal conditions, ventricular and atrial myocytes do not have automaticity
Conducting system (pacemakers) SA node, AV node, ventricular conducting system (bundle of His, bundle branches, Purkinje fibers)

Ionic basis of automaticity:

Resting potential is not static; have gradual depolarization in phase 4 due to pacemaker
current IF, carried mainly by Na
o
Na channels open w/ hyperpolarization (-50mV); slow slow depolarization
o
Contribution from slow inward Ca current (activated at voltages close to end
of phase 4) and progressive decline of outward K current

Phase 0 upstroke in SA node and AV node is much slower than in Purkinje system
o
More Na channels are inactivated by depolarization Ca influx important!

Repolarization depends on inactivation of Ca channels and opening of K channels

Native and latent pacemakers have different intrinsic rates of firing:

Pacemaker firing rates depend on (1) rate/slope of spontaneous phase 4 depolarization, (2) maximum negative diastolic potential and
(3) threshold potential

In normal heart, SA node is the dominant pacemaker (60-100 bpm at rest); native b/c normally sets HR
o
Its spontaneous discharges prevent spontaneous firing of other pacemakers;

All other pacemakers are latent or ectopic

o
AV node and bundle of His 50-60 bpm
o
Purkinje system 30-40 bpm

Overdrive suppression directly suppresses automaticity of latent pacemakers;

o

Due to hyperpolarization current created by Na/K ATPase - antagonizes I F

Increases when cell is forced to fire faster than intrinsic pacemaker rate ( [Na]i forces ATPase to work harder)

Electrotonic interactions also suppress automaticity

o
o
o

Neighboring myocytes repolarize to -90mV unlike -60mV for pacemaker cells;

cells are electrically coupled so electrical potentials equlibrate

Important in AV node and distal Purkinje fibers (but may get disconnected from neighboring cells by damage ischemia)
SA node cells are less tightly coupled to atrial myocytes

Altered impulse formation due to (1) altered automaticity of pacemakers, (2) abnormal automaticity in atrial or ventricular myocytes, or
(3) triggered activity

Alterations in pacemaker automaticity:

o

Alterations in SA node automaticity

SNS (beta-1 receptors) (achieve by atropine anticholinergic)

Increases probability of pacemakers channels being open IF
Lowers AP threshold by increasing probability of Ca channels opening

SNS and PSNS (achieve by beta-blockers)

Reduced probability of pacemaker channels being open IF
Raises AP threshold by decreasing probability of Ca channels being open
Increases probability of ACh-sensitive K channels being open at rest
Escape rhythms if SA node is suppressed/fires less than normal, impulse formation can shift to a latent pacemaker

Escape rhythm = series of escape beats; protective b/c keep HR from slowing down too much

Can happen with PSNS (SA node and AV node are very sensitive, ventricles are least sensitive)
Enhanced automaticity of latent pacemakers - intrinsic rate of depolarization is faster than SA node

See ectopic beats impulse premature to normal rhythm (unlike escape beat) can turn into ectopic rhythm

May see w/ catecholamines, hypoxia, ischemia, electrolyte disturbances, and drug toxicities (digitalis)

Abnormal automaticity non-pacemaker cells are able to depolarize; may cause ectopic rhythm
o

Due to cell membranes becoming leaky with injury, and thus partially depolarized

Triggered activity under certain conditions AP can trigger abnormal depolarizations result in extra beat or

rapid arrhythmias; first AP leads to oscillations in membrane voltage (afterdepolarizations) leads to another AP if
reach threshold
Early afterdepolarizations - during repolarization phase of inciting beat
o Interrupt normal repolarization happen in plateau (mostly Ca) or in rapid repolarization (mostly Na)
o More likely to develop in conditions with prolonged QT (congenital or drug-induced)
o Can be self-perpetuating and lead to torsades de pointes
Delayed afterdepolarizations
o Occur shortly after repolarization of preceding beat is completed
o Most commonly develop with intracellular [Ca] (think digitalis toxicity) or with catecholamines
stimulation
o Can be self-perpetuating and lead to tachyarrhythmias

Altered impulse conduction

Conduction block propagating impulse is blocked when it encounters region of heart that is electrically unexcitable
o
Can be transient or permanent; unidirectional or bidirectional
o
Can be caused by ischemia, fibrosis, inflammation, and certain drugs
o
Can cause emergence of escape beats or escape rhythm
o
Usually causes bradyarrhythmias, sometimes tachyarrhythmias (reentry process)
Functional block when impulse runs into refractory cells from previous depolarization (e.g.
after antiarrhythmic drugs)
Fixed block when fibrosis/scarring replace normal myocytes

Unidirectional block and reentry:

Reentry a common mechanism by which a
combination of conduction block and altered
impulse conduction leads to tachyarrhythmias
o
Electrical impulse circulates
repeatedly around reentry path,
recurrently depolarizing a region of
cardiac tissue.
o
Need a unidirectional block for this
to work occurs where refractory
periods of adjacent cells are
heterogeneous or in states of cellular
dysfxn and in regions of fibrosis
o
2 critical conditions for reentry are:

unidirectional block

slowed conduction through

the reentry path - so that
original path has had time
to repolarize)
o
Reentry around distinct anatomical
pathways usually appears as
monomorphic tachycardia on ECG,
stable and regular

Mechanism of reentry.

A. Normal conduction. When AP

reaches a branch in conduction pathway,
the impulse travels down both fibers to
excite distal conduction tissue.
B. Unidirectional block. Forward
passage of impulse is blocked in
pathway but proceeds normally down
pathway. When impulse reaches point
y, if retrograde conduction of
pathway is intact, AP can enter from
below and conduct in retrograde
fashion.
C. When point x is reached again, if
pathway has not had sufficient time
to repolarize, then impulse stops.
D. If conduction through retrograde
pathway is sufficiently slow, it reaches
point x after pathway has recovered;
thus impulse is able to excite pathway
again and reentrant loop is formed.

Accessory pathways and the Wolff-Parkinson-White syndrome - reentry

1/1000 ppl born w/ extra connection between atrium and ventricle accessory pathway/bypass tract, allowing bypass of AV node
o

Most commonly bundle of Kent (around mitral or tricuspid annuli)

Conducts impulses faster than AV node shortened PR ventricles pre-excited

Contacts to ventricular myocardium instead of Purkinje system slower impulse spread

Wider QRS w/ abnormally slurred initial upstroke (delta wave) b/c ventricular
depolarization = combo of impulses down normal pathway and accessory pathway
Accessory pathway good for reentry (b/c refractory period usually different from
AV node makes retrograde conduction possible)

Clinical Aspects of Cardiac Arrhythmias

Bradyarrhythmias
SA node:

Sinus bradycardia SA node fires < 60 bpm; can be

normal at rest or during sleep in many ppl or in athletes

o
SA node automaticity causes:

Intrinsic age, ischemic heart

disease, cardiomyopathy

Extrinsic - meds (anti-arrhythmics beta-blockers, Ca-channel blockers),

metabolic causes (hypothyroidism)
o
Usually asymptomatic and does not require Tx (unless get Sx of decreased CO then correct)

If symptomatic (when very slow) see fatigue, lightheadedness/confusion, shortness of breath, syncope
o
Tx reduce/stop drug (if drug-induced), none if asymptomatic; if symptomatic- treat underlying condition

Sick sinus syndrome causes periods of inappropriate bradycardia

o
o
o

Often see dizziness, confusion, syncope

Tx - IV anticholinergics (atropine) or beta-adrenergics (isoproterenol) that transiently accelerate HR;

permanent pacemaker if chronic problem not corrected by removal of aggravating factors

Common in elderly ppl who are also susceptible to
supraventricular tachycardias (esp a-fib)

Bradycardia-tachycardia syndrome

thought to result from atrial fibrosis that

impairs SA node fxn
Tx combo of antiarrhythmics and
permanent pacemaker to prevent
bradycardia

Escape rhythms - from distal latent pacemakers if SA node discharge is too slow

Junctional escape beats AV node or proximal bundle of His

o
o

Normal narrow QRS

Rate 40-60 bpm - bradycardia

Not preceded by normal P-waves

May see retrograde inverted P-waves following

QRS in II, III and aVF atrial activation from
inferior direction
Usually benign and asymptomatic, but if slow enough to be
symptomatic pacemaker

Ventricular escape rhythms

o
o
o
o

30-40 bpm slower bradycardia than jxnal escape

Wide QRS seen when comes from ventricles

RBBB if escape from left, LBBB if from right

Usually symptomatic; cant sustain this rhythm b/c
decreased CO will make you feel like crap
Usually pacemaker indicated

Atrioventricular conduction system:

First-degree AV block
o
o
o

Prolonged PR but sinus rhythm

1:1 relationship between P and QRS
Usually within AV node

Reversible causes - vagal tone,

transient AV ischemia, drugs that
depress AV node conduction (digitalis, beta-blockers, certain Ca channel blockers and other antiarrhythmics)

Structural causes MI and chronic degenerative diseases of conduction system (e.g. w/ aging)
Generally benign asymptomatic condition

Second-degree AV block - some P waves not followed by QRS

o
Mobitz Type I block (Wenckebach block)

Mobitz Type II block

PR becomes longer until dropped beat

Group beating
Next PR is short again
Usually benign; may be seen in kids, trained
athletes and ppl w/ high vagal tone, esp. in
sleep; but may also be seen during MI or ischemia of AV node (usually transient)
If symptomatic (high grade block) - pacemaker
Dropped beat w/o PR prolongation
If persists for > 2 beats high-grade AV block
Usually conduction block below AV node
Bundle of His and distal Purkinje
Usually wide QRS
More serious than Type I b/c may progress to
3rd degree block w/o warning
Usually pacemaker indicated, even in
asymptomatic pts

Third-degree block (complete heart block) complete failure

of conduction between atria and ventricles

o
No relationship between P-waves and QRS AV dissociation

PR intervals are variable, but RR is constant

See wide QRS (b/c comes from ventricles)

Also see AV dissociation in v-tach

o
Most common causes acute MI, drug toxicity (digitalis), age
o
Usually symptomatic
o
Permanent pacemaker is almost always necessary

Tachyarrhythmias
Supraventricular arrhythmias:

Regular sinus tach, atrial tach, atrial flutter, AVNRT, AVRT (WPW syndrome)
Irregular atrial fibrillation, multifocal atrial tachycardia

Sinus tachycardia normal P-waves and QRS complexes; usually SNS tone or vagal tone
o
o

See in exercise; fever, hypoxemia, hyperthyroidism, hypovolemia and anemia

Tx treat underlying condition

Atrial premature beats (APBs) from automaticity or reentry in

atrial focus outside of SA node; often exacerbated by SNS stimulation

o
Usually asymptomatic/benign, but can cause palpitations
o
Abnormal early P-waves

Abnormal b/c not from SA node

o
Normal QRS (unless aberrant)
o
Tx only if symptomatic (remove caffeine/alcohol/stress,
use beta-blockers if needed)

Atrial flutter rapid regular atrial activity at 180-350 bpm

o
o
o

o
o
o
o
o

Atrial fibrillation chaotic rhythm (350-600 bpm)

o
o
o
o

o
o

Usually caused by reentry in large anatomically fixed circuit (commonly

along tricuspid annulus) macro-reentrant rhythm
P-waves - sinusoidal/sawtooth
Not all the impulses conduct to ventricles typically 1:2 conduction

If ventricular rate < 100 bpm may be asymptomatic; if faster

palpitations, dyspnea, weakness
May be paroxysmal or persistent; frequently becomes a-fib; usually in presence of other heart disease
Antiarrhythmic meds may worsen condition b/c allow AV node more time to conduct (results in 1:1 conduction) esp. if atrial
rate slows down to 220 bpm (then every impulse can be conducted)
Associated w/risk of atrial thromboembolism
Tx ventricular rate control (for symptomatic): electrical cardioversion; pacemaker; pharm beta-blockers, Ca-channel
blockers (verapamil, diltiazem), digoxin; class IA, IC or III antiarrhythmics; catheter ablation of reentrant loop
Vagal maneuvers or adenosine can slow AV nodal conduction to visualize atrial activity

Cant see discrete P-waves (unlike in atrial flutter)

instead see squiggly line between QRS
Irregularly irregular rhythm (look at RR)
In untreated a-fib, ave. ventricular rate 140-160
Impulses often originate in or around pulmonary veins

Multiple macro-reentrant circuits

Often associated with LA or RA enlargement (thus see in heart failure, HTN, CAD or pulmonary disease)

Symptoms depend on LV rate and condition

Dangerous b/c (1) can compromise CO HTN, pulmonary congestion and (2) thromboembolism in the atria - promotes blood
stasis thrombus, esp LA think embolization and stroke
Tx (1) ventricular rate control, (2) attempts to restore sinus rhythm and (3) anticoagulation (heparin, coumadin)

Rate control still in a-fib, but control HR

Block AV node with drugs beta-blockers, Ca channel blockers (non-DHP), digoxin
Anticoagulate (lower stroke risk by > 2/3) - with coumadin, NOT aspirin or anti-platelet agents
Consider when - patient feeling well; patient prefers; failed rhythm control attempts

Rhythm control conversion to normal sinus rhythm

Convert to NSR - electrical cardioversion, drugs (IA, IC and III antiarrhythmics), catheter ablation / maze
Often anticoagulate
Consider when - patient feels better in NSR, correctable precipitating cause

Paroxysmal supraventricular tachycardias (PSVT):

Sudden onset and termination,

Atrial rates 140-250 bpm,
Narrow QRS (b/c not from ventricles)
Mechanism usually reentry

AV nodal reentrant tachycardia (AVNRT) most

common PSVT in adults

In some ppl, parts of AV node conduct at different

velocities (slow has short refractory period)
APB (atrial premature beat) travels down slow
path (b/c fast still refractory) and then
can propagate backwards along the fast
pathway (which recovered by then) and
down slow path again

Regular tachycardia (> 200 bpm)

Narrow QRS

P-waves may not be apparent (retrograde P hidden in QRS)

P waves may be inverted (b/c depolarization of atria from below) and

superimposed onto distal part of QRS in II, III, aVF;

Often seen in teenagers and young adults, and is usually well-tolerated, but
may have palpitations; may cause SOB, lightheadedness

Tx increase vagal tone (Valsalva, carotid massage), IV adenosine, IV Cachannel blockers or beta-blockers; may need catheter ablation of slow AV
pathway
Usually no long-term treatment needed but may need chronic drugs

Atrioventricular reentrant tachycardias (AVRT) like AVNRT but one limb of reentrant loop is accessory pathway

Ectopic atrial tachycardia from automaticity of atrial focus or from reentry; paroxysmal or persistent

Ventricular pre-excitation syndrome Wollf-Parkinson-White Syndrome

1/1000 ppl born w/ extra connection between atrium and ventricle accessory pathway/bypass tract,
allowing bypass of AV node (most commonly bundle of Kent (around mitral or tricuspid annuli)
o
Shortened PR interval ventricles pre-excited
o
Wide QRS with delta wave abnormally slurred initial upstroke

QRS wide b/c contacts to ventricular myocardium instead of Purkinje system slower
impulse spread
o
Accessory pathway is good for reentry (b/c refractory period usually different from AV node
makes retrograde conduction possible) susceptible to PSVT

Orthodromic AVRT (down AV first) narrow QRS, retrograde P

Antidromic AVRT (down accessory first) - wide QRS, retrograde P

Usually benign
Tx Na channels blockers (class IA, IC and III) - slow conduction in both AV node and accessory pathway

Atrial rate > 100 bpm

Sinus tachycardia - but P-wave morphology different from sinus rhythm
May be caused by digitalis toxicity and aggravated by increased SNS tone (high adrenergic states)
Benign (and not uncommon) if brief, but may or may not be symptomatic if persistent
May need drug therapy (beta-blockers, Ca blockers, antiarrhythmics) or catheter ablation

Multifocal atrial tachycardia

Irregular rhythm (irregular R-R intervals) w/ > 3 P-wave morphologies;

average atrial rate > 100 bpm
Varying PP and PR intervals
P waves may be blocked
Unlike AF, isoelectric baseline between P-waves
Usually seen in setting of severe pulmonary disease and hypoxemia

If atrial rate < 100bpm called Wandering atrial pacemaker

Tx verapamil; treat underlying condition

Ventricular arrhythmias PVB, VT, VF

Ventricular premature beats (VPBs) often asymptomatic and

benign; common in healthy ppl

o
Wide QRS not related to preceding P-wave

Bigeminy when every other beat is a VPB; trigeminy

when every 3rd beat is a VPB; quadrigeminy every 4th

Consecutive VPBs couplets, triplets.

Arises when ectopic venticular focus fires an action potential

o
In abnormal heart, increases risk of VF and VT
o
Tx symptomatic control w/ beta-blockers if needed; ICD is advanced structural disease
Ventricular tachycardia - > 3 VPBs
o
Wide QRS (unlike supraventricular tachycardia)
o
AV dissociation (like 3rd degree heart block)
o
100 200 bpm;
o
Monomorphic (QRS regular and look the same) and polymorphic
(due to multiple ectopic foci or changing reentry loop)

Sustained VT: > 30 sec; severe symptoms (syncope) or needs termination by cardioversion or antiarrhythmics

Non-sustained VT when episodes are self-terminating

o
Common in ppl w/ structural heart disease (MI, myocardial ischemia, heart failure, valvular diseases, congentital stuff)
o
Of concern because of potential for VF
o
Symptoms depend on rate of tachycardia palpitations, syncope, pulmonary edema, cardiac arrest
o
Tx acute = electrical cardioversion; IV antiarrhythmics in hemodynamically stable (amiodarone, procainamide, lidocaine), ICD

W/o structural disease beta-blockers, Ca-channel blockers or catheter ablation

 Torsades de pointes polymorphic VT w/ varying amplitudes of QRS

o
Can be due to early afterdepolarizations (triggered activity)

esp. w/ long QT (electrolyte disturbances, persistent

bradycardia or class III antiarrhythmics, congenital)
o
Usually symptomatic light-headedness, syncope; frequently
self-limited
o
Significant danger of becoming VF
o
Tx electrical cardioversion, correct underlying abnormality
(electrolyte imbalance, give IV magnesium), increase HR
(pacing) to shorten QT, antiarrhythmics
Ventricular fibrillation immediately life-threatening arrhythmia b/c
no coordinated contraction of ventricles cessation of CO
o
Chaotic and irregular rhythm w/o discrete QRS
o
Usually in severe underlying heart disease; major cause of
mortality from acute MI

Often triggered by an episode of v-tach

o
Tx prompt electrical defibrillation;

once safe rhythm correct precipitants of arrhythmia;

may give IV antiarrhythmics;

ICD if no precipitant is found

Antiarrhythmics
Rate of rise of AP - most important in rapid conduction velocity; depends on # of
Na channels open (need to be present AND activated).
Duration of AP directly relates to duration of QT - we like it long so that extra
beat does not happen.

Ionic currents in human ventricular AP:

Na current is rapid but brief

Ca current is very fast but much smaller than INa
o
Ca crucial for latter phase of upstroke but also for plateau;
same Ca that activated contrxn - activates Na/Ca exchanger
o
Ca influx drives Ca out, Na in (inward current of Na b/c each
Ca brings in 3 Na)
Repolarization:
o
First K current (Ito transient outward current) is very
fast, responsible for early repolarization
o
Delayed rectifier K channels (IKR and IKS)

IKR is dominant by far over IKS in normal resting

conditions

IKS very important during SNS stimulation.

IKR - key part in rapid repolarization that ends AP

IK1 current - in resting membrane potential
o
Turns off during plateau and turns on during repolarization.
o
In intrinsic pacemaker very little IK1 - thus more positve resting
potential and more excitable.

Refractory periods:

Absolute refractory period - cant get AP at all b/c Na channels inactivated

Effective refractory - can get AP but too wimpy to propagate to another cell
Relative refractory - need impulse stronger than usual to activate AP
SNP (super-normal period) - vulnerable window - more sensitive than normal to
activation.

Reasons for diastolic depolarizations (the main ones)

If current - activated by hyperpolarization, important in early part of depolarization; HR can be

influenced by changing its slope
Ca current - (Ca sparks) - activates Na/Ca exchange current and is responsible for late part of
depolarization
Threshold - when special Ca channels are activated
Upstroke is slower and conduction velocity is slower

X. Mechanisms of Arrhythmi a
A. Sinus tachycardia or bradycardia
B. Abnormal Impulse formation (automaticity, ectopic focus, triggered activity)
C. Abnormal Conduction (slowed conduction, accessory pathways, reentry)
XI. Abnormal Impulse Formation
A. Ectopic focus (latent pacemaker or
Reactivation
triggered beats as DADs or EADs)
of I ?
B. Early afterdepolarizations (EADs)
EAD
0
1. re -depolarization duri ng plateau
mV
2. Preferentially when APD is long
(low HR or long QT syndrome )
Em
3. Involves re -activation of I Ca which
partially recovered during long AP
DAD
4. Can lead to Torsade de Point es, a
form of VT, and then to VF
-80
SR Ca overload & Spontaneous
Release ( INa/Ca = Iti &!DAD)
C. De layed afterdepolarizations (DADs)
Ca

Depolarized sick cells - slower conduction

velocity due to inactivation of Na current.

Congenital causes of EADs & DADs

(1) Long QT:

LQT-1 is the most prominent. IKS

channel (unimportant at rest) has loss
of fxn - get arrhythmias at high HR
when exercise - since not activated by
SNS - increased refractoriness when
want fast HR.
LQT-2 - IKR loss of fxn, prominent at
low HR (sleep)
LQT-3 - Na channel mutations - Na
current dies not turn off properly,
increased Na current - bad news;
prominent at low HR (sleep)
LQT-8 - Ica gain of fxn

(2) Brugada Syndrome & short QT syndrome

Brugada INa loss of function (slowed conduction and reduced APD)

SQT-1 IKr gain of function
SQT-2 IKs gain of function

(3) Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

Ryanodine receptor ( RyR2) mutations, spontaneous SR Ca release

(4) Sick sinus syndrome (HCN4 If channel mutation)

Antiarrhythmic Drugs
4 classes of antiarrhythmics:

Class I block fast Na channels - phase 0 depolarization

Class II beta-blockers

Class III block repolarizing K-current, prolonging effective

refractory period w/ little effect on rise of phase 0 depolarizn

Class IV Ca-channel blockers - block slow L-type Ca channels

Other adenosine, Mg, K, digoxin

Goals of antiarrhythmic therapy:

Treat increased automaticity lower frequency of APs by:

o
Reducing slope pf spontaneous depolarization phase (4)
and prolonging effective refractory period

Inhibit reentrant rhythms by:

o
Lengthening tissues refractory period
o
Additionally impairing impulse propagation within slow retrograde limb by blocking slow Na channels

Eliminate triggered activity by:

o
Suppressing early and delayed afterdepolarizations but this is dangerous as they can suppress normal electrical rhythm

Class IA antiarrhythmics - Procainamide, Disopyramide, Quinidine

Effects (medium dissociation rate from Ina):

o
o
o

o
o
o

Block INa (fast channels) and some block of IKr, so Vmax and AP duration and ERP
Slow conduction velocity, particularly in chronically depolarized ventricular cells

Due to slow dissociation from Na channels

Decrease abnormal automaticity (Phase 4) in ectopic foci in ventricular & Purkinje cells

Also some affinity for resting Na channels in normal tissue may decrease Vmax and
automaticity in Purkinje fibers
Thus careful when use these for Tx of AV block
Quinidine, however, has antimuscarinic effect can actually AV conduction
Prolong QT interval (due to IKr block which prolongs AP)
May actually cause complete heart block!
Alpha-adrenergic receptor blocking properties can cause hypotension, and
baroreflex-mediated tachycardia (due to vasodilatation)

Therapeutic uses
o
o

Reentry arrhythmias - by ERP and conduction in unhealthy pathway

V-tach & A-tach induced by delayed afterdepolarizations (ectopic foci) - by
depressing abnormal automaticity (Na/Ca?), increasing DAD required to trigger
AP, and by depressing conduction in depolarized cells
Converting AF (but IK block more common)

On EKG, see mildly prolonged QRS and QT (can be significant at high doses afterdepolarizations and drug-induced arrhythmias)

Quinidine:

Also has anticholinergic properties AV node conduction (thus may need to combine w/ beta-blocker, verapamil, diltiazem, digoxin
negative inotropic agents)
Alpha-adrenergic blockade may cause hypoTN (esp. if given IV and in large quantities) thus given only PO
Hepatic metabolism reduce dosage in ppl w/ liver dysfxn

Side effects GI (diarrhea, nausea, vomiting); excessive QT prolongation (may cause torsades de pointes), raises blood level

of digoxin; CNS effects (HA, tinnitus, dizziness); in high doses may also suppress CO
Procainamide:

Unike quinidine, does not prolong AP/QT as much but still may provoke torsades de pointes
Less anticholinergic effects than quinidine less facilitation of AV node conduction
Side effects milder hypoTN than w/ quinidine (due to some peripheral vasidilatation), negative inotropic effect; fever and rash;

lupus-like syndrome (1/3) - reversible

50% hepatic metabolism to NAPA - excreted by kidney (accumulates in renal failure, prolongs AP and ERP but not phase 0 or 4)

Disopyramide:

Much fewer GI side effects than quinidine

Does not increase serum digoxin levels
Much greater anticholinergic effects thus see constipation, urinary retention, and exacerbation of glaucoma
More pronounced negative inotropic effect careful in ppl with LV systolic dysfxn; may have QT prolongation (torsades de pointes)
Given PO, renal excretion (toxic in ppl w/ renal insufficiency)

Class IB antiarrhythmics - Lidocaine, Phenytoin, Mexiletine

Effects: (fast dissociation rate from INa)
o
Block INa (more reversible), so less Vmax and conduction velocity
o
Reduced INa - AP duration and ERP
o
Much stronger INa block in depolarized (sick or ischemic) cells
o
Has some IF block (reducing Purkinje automaticity)
o
Does not alter nodal cell automaticity much (or HR).
Therapeutic uses:
o

Ventricular arrhythmias, especially post-MI or digitalis toxicity.

Lidocaine can prevent VF in acute phase of MI, but cannot decrease mortality associated w/post MI (unlike betablockers)
NOT for atrial arrhythmias - b/c of low Na channel affinity and shorter AP duration in atrial cells (less time to bind
and block) thus do not use in A-fib, atrial flutter and SVT
Re-entry arrhythmias - causes a 2 -way block (especially in ischemia/ depolarized cells)
IV lidocaine suppresses delayed afterdepolarizations (dont expect torsades de pointes)

o
o
o

Lidocaine:

Commonly used acutely to suppress ventricular arrhythmias in hospitalized pts; IV almost exclusively b/c high first-pass metabolism
Rapid distribution, hepatic metabolism need to give as continuous infusion after 2-3 loading boluses
o
Half-life depends on hepatic blood flow (lower infusion rate in ppl w/ liver disease)
Side effects most commonly CNS (confusion, dizziness, seizures) dose-related; can be severe in post-MI patients

Mexiletine:

Given PO, unlike lidocaine (resistant to first-pass metabolism)

90% hepatic metabolism reduce dose in hepatic dysfxn
Side effects CNS (dizziness, tremor, slurred speech) and GI (nausea, vomiting)

Phenytoin useful in treating digitalis-induced arrhythmias

Class IC antiarrhythmics Propafenone (prototype), Flecainide, Encainide, Lorcainide

Effects: (very slow dissociation rate from INa) most potent Na channel blockers
o
Block INa more, so Vmax and conduction velocity
o
Reduced INa, but unaltered APD & ERP (so, may also block K channels)
o
Very strong INa block in depolarized (sick) cells

Therapeutic uses
o

Supraventricular tachyarrhythmias - in ppl w/ structurally normal hearts

Note can precipitate heart failure in ppl w/ underlying LV dysfxn AVOID

Flecainide:

Well absorbed PO; 40% excreted unchanged in urine; rest converted to inactive metabolites by liver
Side effects aggravation of ventricular arrhythmias and precipitation of CHF in ppl w/ LV dysfxn; CNS confusion, dizziness, blurred
vision

Propafenone:

Also has a weak beta-blocking action

Hepatic metabolism
Side effects extracardiac not common; include dizziness and disturbances of taste

Class II antiarrhythmics beta-blockers - Propranolol

Beta-receptor activation cAMP and PKA ICa, INa, IKs and SR Ca uptake/release
o
o
o
o

Beta-blocker mechanism of action - mostly by suppressing SNS activity

o
o
o
o
o

Atrial and ventricular arrhythmias related to SNS discharge (exercise, emotional stimulation)
Supraventricular arrhythmias - can control rate in atrial tachycardia (but not convert AF).

Protect ventricles from increased rate during atrial fibrillation.

Propranolol and other blockers decrease the number of ventricular arrhythmias and the incidence of ventricular fibrillation
after acute MI. Their use in heart failure may also have antiarrhythmic benefit.

Beta-blocker problems:
o
o
o
o
o
o
o

spontaneous activity and conduction velocity in SA node (HR)

spontaneous conduction velocity and refractory period of AV node (inhibit reentrant rhythms)
Prolong PR interval; QRS and QT usually unchanged (thus can treat ventricular arrythmias related to prolongation of QT)
At high concentrations, propranolol acts like a Class I antiarrhythmic and blocks Na channels (membrane stabilizing effect).

In normal concentrations of propranolol, it has little effect on Na channels.

myocardial metabolic rate (balancing supply-demand)

Therapeutic uses:
o
o

SR Ca DADs and triggered arrhythmias

cAMP-dependent activation of IF and SR Ca enhance rates of phase 4 depolarization and HR
spontaneous depolarization of latent/abnormal pacemakers
AV node conduction velocity; AP duration and ERP

Drowsiness, fatigue (most common with propranolol; CNS effect), sometimes depression
Increased airway hyper-reactivity in asthmatics due to 2-effects (can us 1-AR selective)
Depressed ventricular contractility (reduced Ca cycling)
Blockade of peripheral -receptors, leaves -receptors unopposed for vasoconstriction may create issues in peripheral
vascular disease
Augments hypoglycemic effects of insulin: catecholamines are released during hypoglycemia, to counteract the fall in plasma
glucose by increasing glycogenolysis.
Increased VLDL-triglycerides, decreased HDL-cholesterol inhibits lipoprotein lipase (which catabolizes VLDL; and inhibits
lecithin cholesterol acyltransferase (LCAT) which esterifies an unesterified cholesterol for HDL uptake)
Impotence

Pharmacokinetics - propranolol is lipid soluble and can be administered PO or IV

Class 3 antiarrythmics K-channel blockers amiodarone, ibutelide, sotalol, bretylium, dofetilide

Effects:
o

K channel conductance (typically IKr) and APD and ERP - significantly prolong AP in Purkinje and ventricular muscle; little
effect on conduction velocity

Dofetilide very specific for IKr block

Amiodarone blocks IKr, but also somewhat INa, ICa and -AR features of other classes
Prolong PR interval and SA nodal rate

Therapeutic uses:
o
Ventricular arrhythmias, especially post-MI or high-risk patients with low ejection
o
Adjunct therapy for patients with implantable defibrillators (to limit frequent shocks).
o
Converting atrial fibrillation to sinus rhythm usually adenosine or ibutelide.
o
Sotalol and Amiodarone are nonspecific beta-blockers as well as K channel blockers thus may delay AV node conduction in
addition to prolonging ERP
Problems
o
o
o
o
o

with both Sotalol and Amiodarone:

Proarrhythmogenic - prolonged QT interval can lead to torsades de pointes
Depressed contractility Bradycardia Pulmonary fibrosis with chronic amiodarone may be due to hypersensitivity rxn
Altered thyroid function with amiodarone may get hypothyroidism or hyperthyroidism

Amiodarone has effects of all classes (beta-blocker, depresses slope of phase 0 depolarization like class I, weak Ca channel blockade (IV))

Thus, decreases SA node firing rate, suppresses automaticity, interrupts reentrant circuits, prolongs PR, QRS, QT
Also vasodilator (blocks alpha-receptors and Ca channels) more prominent than negative inotropic effect CO usually does not suffer
More effective than most other antiarrhythmics for ventricular and supraventricular tachyarrhythmias a-fib, AF, v-tach, v-flutter
First-line agent for emergency Tx of ventricular arrhythmias during cardiac resuscitation (VF, VT) better than lidocaine
Works for arrhythmias in ppl with LV systolic dysfxn fewer proarrhythmic complications than other agents
Effective for ling-term suppression of a-fib and a-flutter
Slow GI absorption; highly lipophilic, sequestered in tissues, slow hepatic metabolism; excretion NOT renal (unlike sotalol)
Side effects see above

Class IV agents Ca channel blockers verapamil, diltiazem (not dihydropyridines)

Effects: inhibit ICa (L-type)
o
Bind stronger to active and inactive ICa, so depolarized cells more affected o
Reduce upstroke and propagation in SA and AV node b/c uptroke here depends on Ca current
o
SA node slowing largely counteracted by baroreceptor reflex
o
Prolonged PR interval Therapeutic uses:
o
Re-entry arrhythmias through AV node b/c increase refractory period of AV node
o
Paroxysmal supraventricular tachycardias - verapamil terminates 60-80% of episodes of PSVT within several minutes.
o
Decreases ventricular responsiveness to atrial fibrillation (rate control).
Pharmacokinetics - bioavailable PO, IM or IV
Problems:
o
Because of potent effects on AV conduction, should not be used in patients with pre-existing conduction problems; can cause
complete AV block
o
Negative inotrope
o
Hypotension
o
Constipation
o
Additive effects with beta blockers on the heart negative inotropic and chronotropic effects may lead to heart failure

Adenosine

When give IV, most effective drug for rapid termination of reentrant PSVT by slowing AV node conduction
By binding to adenosine receptors (A1 on SA and AV node), it activates K channels hyperpolarization slows SA node and conduction
through AV node
Inhibits adenylate cyclase cAMP IF and inward Ca current
Prolongs PR and RR interval
Side effects transient (half-life 10 sec) HA, chest pain, flushing, bronchoconstriction
o
Caffeine/theophylline is a competive antagonist may need higher doses of adenosine
o
Dypiridamole inhibits adenosine breakdown

Digoxin:

Vagomimetic effect suppresses AV conduction and increases AV node refractory period by increasing K conductance
o
Good for control of HR in AF first line for AF Tx, also in combo w/ procainamide

Step 1 ABC, IV, O2 monitor

No pulse (use epi/vasopressin for all pulseless)

Wide QRS
o

Fast VT or VF

Tx defibrillate VF, synchronized cardioversion (VT), epi/vasopressin, antiarrythmics (I, III esp. amiodarone or
lidocaine)

Slow 3 degree block/ventricular escape

Remember 1st and 2nd degree blocks have narrow QRS b/c signals get through AV node not junctional

Tx epi/vasopressin; pacing

Narrow QRS PEA (pulseless electrical activity)

o
o

rd

Causes 6Hs and 6Ts hypovolemia, hypoxia, hydrogen ions (acidosis), hypothermia, hyper- or hypokalemia, hypoglycemia,
toxins/tablets, cardiac tamponade, tension pneumothorax, thrombosis (MI or PE), trauma (blood loss hypovolemia)
Tx epi (1mg every 3-5 min)/atropine (?), determine cause; ultrasound; defibrillators are useless

No QRS - asystole
o

Tx epi/vasopressin; atropine

Pulse:

Wide QRS
o

Fast stable VT, SVT with aberrancy

Tx antiarrhythmics (amiodarone or lidocaine), synchronized cardioversion

Slow 3 degree block/ventricular escape

Tx transthoracic pacing

rd

Normal QRS
o Fast sinus tach, a-fib, atrial flutter, MAT, PSVT, SVT/AVNRT

Tx HR control (beta-blocker metoprolol 5mg IV q5min or Ca-channel blocker (diltiazem 10mg IV q5min);
synchronized cardioversion
nd

Slow sinus brady, sick sinus syndrome, junctional escape, 2

Tx atropine, then pacing

degree block

Peripheral Arterial Disease

Stroke result of CAD
o
o

Symptoms that you can get as result of CAD:

o
o
o

Aspirin or another antiplatelet Tx shown to reduce relative risk of stroke by 27%

Discontinue tobacco
Control HTN, cholesterol and DM

Carotid endarterectomy incision anterior to SCM muscle, exposing carotid bifurcation

o
o

Duplex ultrasound usually the only test needed

Can also use CT angiography or MR angiography

Medical therapy for carotid stenosis:

o
o
o

Stroke neuronal death; clinical neurological deficit w/symptoms > 24 hrs

TIA focal cerebral hemispheric ischemic symptoms; < 24 hrs (can be just minutes);

Unilateral motor or sensory deficits; cognitive or motor speech impairment not too many Sx
Amaurosis fugax transient monocular blindness; embolization to retina from ophthalmic artery;

Like a shade coming over one eye; usually complete loss of vision in one eye

Diagnosis:
o
o

In US, 500,000 people die or are disabled by stroke annually; 3rd leading cause of death and leading cause of disability
of strokes are due to cerebral infarction and are potentially associated with CAD

Plaque usually very smooth between layers of media leaves smooth surface when removed
Most carotid symptoms are due to plaque embolization from carotid artery, and not due to occlusion of carotids.

Indicated in patients w/asymptomatic stenosis (60-99%) and symptomatic stenosis (50-99%)

Better than best medical therapy

Carotid angioplasty and stenting - newer therapy; done percutaneously usually through femoral artery.

o
Typically w/ protection to avoid embolic debris going to brain - use protective umbrellas - filters to capture embolic debris
Some studies showed results of stenting and carotid endarterectomy to be virtually identical
o
But some studies found that stenting carries a higher risk of stroke in both symptomatic and asymptomatic pts

Aneurysm - permanent, localized dilatation of artery w/ at

least 50% increase in diameter compared with expected normal diameter

Most common location - infrarenal aorta
Prevalence of AAA - 2-5% in men > 60; incidence is increasing
o
Mainly disease of men and more likely in smokers
Rupture of AAA - 15,000 deaths per year in US; 80-90% overall mortality; 40-50% mortality if survive to hospital
o
10th leading cause of death in men > 55 years old

Diagnosis of AAA:
o
o
o

75% asymptomatic at diagnosis first symptom is usually rupture

< 1/3 with rupture have prior diagnosis of AAA
Usually found incidentally - physical exam (rarely), radiology exam

Elective repair:

Diameter is a very important criterion to determine risk of rupture; exponential risk curve according to diameter w/
very steep increase after 5-6 cm

Men > 55 mm

Women > 50 mm

Growth > 10 mm in a year

Tend to repair if symptomatic

Studies showed no significant advantages of early repair thus repair when risk of rupture outweighs risk of repair.
o
Traditional open repair - replacement of diseased segment with a synthetic graft transabdominally pr retroperitoneally
o
Endovascular repair less invasive; in the last 10 yrs graft from inside w/o clamping the aorta and opening it up.

Very small incision in abdomen or percutaneous catheters.

Mortality of elective AAA repair:
o
Open - 1-6%; greater systemic mortality
o
Endovascular - 1-2%; greater local mortality
o
Morbidity (percentage of complications) is similar just different kind (see above)
o
Benefit of endovascular is not sustained curves eventually converge

Advantage of endovascular repair in survival early on, but in 2-3 years survival is the same.

Think that people die of comorbidities - just those with open repair die earlier on.

Aortic dissection - disruption of intima and media, w/ blood-filled

cleavage plane in outer media

Has nothing to do with aneurysm! (dissecting aneurysm = stupid)
o
Dissections usually start in normal diameter aorta, and then may dilate (become
aneurysms) due to weakened wall

Type A - ascending aorta involved

o

Very lethal disease if untreated (mortality 60% w/medical Tx), needs surgical repair

Rupture, cardiac tamponade, disruption of coronaries and aortic valve,

stroke

Type B - descending thoracic aorta, typically after left subclavian artery branches off;
no involvement of ascending aorta
o
Treated medically unless there are complications decrease LV contraction force
by beta-blockers and antihypertensives

Aneurysm, rupture, ischemia (visceral, renal or extremity), pain, HTN

Renal artery stenosis HTN, renal insufficiency

Etiology > 90% due to atherosclerosis of renal arteries; < 10% due to fibromuscular dysplasia
o
o

Atherosclerosis - typically at the origins of renal arteries, usually in the first 1 cm; usually spillover of aortic plaque.
Medial subtype (middle to distal part of renal artery, may involve first-order branches) in 90% of fibromuscular dysplasia

Classically women (90-95%) in 4th-5th decade of life

Physiology:
o
o

Normal response BP rises and renin release is inhibited

RAS - renin is released despite increased systemic BP - b/c BP is low in the kidney even if it is high systemically

Renovascular HTN - most common cause of correctable HTN (0.2-5% of 60 mln Americans w/ HTN)

Diagnosis:
o
o

Anatomic - duplex sonography, CT angiography, catheter arteriography, MR angiography

Functional - renal vein renin sampling, captopril scintigraphy

Interventions
o
o
o
o

Angioplasty and stenting > 95% of patients

Surgery
Bypass
Endarterectomy - very rare now

Treatment does not always improve HTN. Usually detection is too late to repair kidneys - still have renal failure and HTN.

Chronic mesenteric ischemia:

Signs and symptoms:

o
o
o
o

Postprandial pain - 10-15 min after every meal, vague epigastric pain, lasts one to a few hrs
Weight loss
Epigastric bruit
Stigmata of arterial occlusive disease -

High mortality (90%) w/o treatment - esp. if have manifestations of prior vascular disease or have risk factors of vascular disease
o

Mesenteric infarction

Usually have high-grade stenosis or complete occlusion of all 3 mesenterics (celiac axis, SMA, IMA)

Treatment:
o
o

Surgical - endarterectomy (less common now), antegrade bypass (celiac axis to SMA), retrograde bypass (common iliac to
SMA)
Endovascular - stenting

Peripheral arterial occlusive disease (PAD):

Asymptomatic
Claudication - pain in large muscle group with walking (hip, thigh, calf) any or all groups distal to lesion
o
o
o
o
o
o

Rest pain - constant, severe pain in forefoot or toes; early on worse with elevation; improves with dependency
o

o
o

Reproducible - need to get it every time they walk, not once in a while.
Resolves with rest - rapidly (30 sec - 2-3 min)
Recurs with resumption of walking
Often burning or aching pain, sometimes severe muscle fatigue or numbness.
Risk to the limb is low (risk of amputation 7% at 5 yrs, 12% at 10 yrs)
Risk to life is greater - means bad atherosclerosis and probably CAD.

Usually because die of MI, not because of limb problems.

Usually worse when go to bed - take away gravity effect that was drawing blood into the foot. Hard to fall asleep - need to
get up and walk, sleep sitting up, etc.

Quickly (few weeks) progresses to pain at rest all the time brief history
See in severe arterial insifficiency
Involves distal foot in vast majority; calf or thigh are uncommon

Tissue loss toes, metatarsal heads, heel

o
Skin ulcer painful, dry, indolent
o
Gangrene
Really common disease - 20-25% of ppl by age 75

Claudication:

Relative indication for intervention

Low risk to limb

Identify and treat risk factors

Tobacco, cholesterol, blood pressure, diabetes

Ischemic rest pain/tissue loss = critical limb ischemia

Absolute indication for intervention

80-90% risk of limb loss - within a year

Treatment options:
o
o
o

Bypass with synthetic graft - best for aortoiliac disease

Bypass with vein - best for infrainguinal disease

4-year patency of veins >>>> artificial grafts

Angioplasty/stenting - better for aortoiliac than infrainguinal; better for stenosis than occlusion; better for short lesions than
long lesions

Endovascular options in CLI

o
o
o
o
Survival

Angioplasty plain, cryoplasty, cutting balloon

Stents - balloon-expandable, self-expanding
Stent grafts
Atherectomy mechanical, laser
same with endovascular and bypass - try endovascular first.

Congenital Heart Disease

Embryology:

Heart tube forms from mesodermal cells

o
In the middle of 3rd wk, mesodermal cells proliferate at cranial end of early embryonic disk
form 2 longitudinal cell clusters = angioblastic cords
o
Angioblastic cords canalize and become paired
endothelial cords
Fusion of 2 tubes, sinus venosus to aortic arches
o
By day 22, single endocardial tube is formed
continuous w/ aortic arch system rostrally and
venous system caudally
o
Day 22-23 heart begins to beat and blood starts
circulating
Elongation, looping
Primitive heart chambers form - truncus
arteriosus, bulbus cordis, primitive ventricle,
primitive atrium, and sinus venosus

AV canal connects primitive atrium

and ventricle

Sinus venosus eventually

incorporated into RA forms
coronary sinus and part of RV wall

Bulbus cordis and truncus arteriosus make future ventricular outflow tracts parts of proximar aorta and
pulmonary artery
o
Day 23 bending starts U-shaped loop w/ round end pointing first ventrally and then to the right (day 28)

Atrium and sinus venosus now above and behind truncus arteriosus, bulbus cordis and ventricle
Endocardial cushion and septation - between wks 4 and 6
o
Septum primum (primary atrial septum) grows from atrial
roof downward

Ostium primum opening between seprum primum

and endocardial cushions around AV canal blood
flows here
o

Eventually ostium primum closes, but ostium

secundum forms in the center of septum primum

After ostium primum closes, septum secundum

(more muscular) starts developing to the right of
septum primum and partially fuses w/ endocardial
cushions, forming foramen ovale; regressing
septum primum now serves as a valve allows
RALA flow through foramen ovale

In fetus, RA pressure > LA pressure

o
Endocardial cushions in AV canal grow and cause septation of AV canal into L and R later
give rise to tricuspid and mitral orifices
o
End of wk 4 primitive ventricle begins to grow, leaving median muscular ridge primitive IV
septum; free wall does not fuse w/ endocardial cushions, leaving IV foramen remains open until
end of wk 7, when membranous septum forms
Aortopulmonary septum and outflow formation
o
Wk 5 bulbar ridges form in bulbus cordis and
truncus arteriosus, fuse in midline and spiral 18
degrees form aortopulmonary septum divides
bulbus cordis and truncus arteriousus into 2
arterial channels pulmonary artery (bulbus
cordis) and aorta (truncus arteriosus)
o
Development of semilunar valves just before
completion of aortopulmonary septum

3 outgrowths of subendocardial mesenchymal tissue around aortic and

pulmonary orifices; shaped by apoptosis
o
AV valves development

After R and L AV canals are formed, surrounding subendocardial mesenchymal tissue proliferates similarly to above
valves shaped by apoptosis; chordae tendineae form once connections to myocardium are replaced by CT
Rhythm origin and pathways

Fetal and transitional circulations:

Fetal circulation
o
o

Oxygenated blood leaves placenta through umbilical vein

About shunted through ductus venosus bypassing hepatic
vasculature and goes directly into IVC

Remaining blood goes to liver and then IVC

Thus, IVC blood is a mixture of oxygenated and

deoxygenated blood O2 tension greater than in SVC
blood mainly goes to brain and myocardium
Most IVC blood goes to LA through foramen ovale (inferior
border of septum secundum crista dividens overrides IVC
opening into RA) to LV 9% to myocardium, 62% to upper body
and brain, 29% to the rest of body

Remainder of IVC blood mixes w/ deoxygenated blood

of SVC RV ductus arteriosus to descending aorta
(88%) or pulmonary arteries to lungs (12%)
Pulmonary vessels are constricted due to low
O2 tension of blood

Transitional circulation
o

o
o
o

Right after birth, ductus venosus, ductus arteriosus and foramen ovale close

B/c low resistance placental flow is removed and SVR increases

Also pulmonary vascular resistance drops b/c lungs expand and walls thin out, and there is vasodilatation of
pulmonary vasculature due to increased pulmonary O2 tension
Rise in pulmonary blood flow is most marked on day 1, but continues for next several wks
LA pressure rises due to more blood going to lungs and RA pressure falls due to constriction of ductus venosus

LA pressure > RA pressure foramen ovale closes

Ductus arteriosus begins to close b/c most oxygenation is in lungs now

PGE-1 formed in response to hypoxia in fetal life, keeping DA patent levels decline after birth
If DA does not close condition known as patent ductus arteriosus
LV begins to hypertrophy, RV undergoes gradual reduction in wall thickness

Common congential heart lesions

Incidence of CHD is 4-8 per 1,000 live births (heart - 14.1% and circulation 5.4% of congenital malformations)
Multifactorial etiology
o
Gene defect/mutation - chromosome 22q11, monosomy XO, trisomy 21
o
Maternal infections - congenital rubella
o
Maternal medications lithium, phenytoin
o
Maternal medical conditions diabetes, overall placental condition
Most common congenital heart defect = bicuspid aortic valve, then VSD (most texts will say VSD b/c didnt know abt bicuspid aortic valve)

Congenital heart lesions can be cyanotic (arterial O2 80-85%) or acyanotic

Cyanotic from right-to-left shunt, bypassing the lungs

Acyanotic intracadiac or vascular stenoses, valvular regurgitation, defects that result in left-to-right shunts (which eventually can
reverse to right-to-left); may see development of pulmonary vascular disease (Eisenmenger syndrome)

Atrial septal defect - acyanotic:

Common (1 in 1500 live births)

Most commonly at site of foramen ovale (ostium secundum ASD)
o
Is not the same thing as patent foramen ovale in most ppl PFO is clinically silent unless RA pressure become elevated
Pathophysiology shunt is left-to-right
Symptoms most infants are asymptomatic; symptoms are dyspnea on exertion, fatigue, and recurrent lower respiratory tract
infections; RA enlargement in adult may lead to tachyarrhythmias decreased stamina and palpitations
Clinical findings - prominent RV impulse along LLSB (RV heave); normal S1, fixed split S2 (b/c blood is shunted through ASD); ESM
pulmonic area; DM tricuspid area; paradoxical embolism/strokes, migraines
o
May hear systolic murmur at upper-left sternal border (b/c more blood flowing across pulmonary valve) or midsystolic murmur
(tricuspid valve); no murmurs due to ASD itself
o
Loud P2, reversed shunting, cyanosis, clubbing indicate Eisenmengers syndrome
Diagnostic studies usually see enlarged heart and increased pulmonary vascular markings on pulmonary artery; RVH and RBBB common
on ECG, left axis deviation; echo is a sensitive test
Treatment if too much blood is shunted, elective surgical repair recommended

Ventricular septal defect (VSD) acyanotic:

Common (1.5-3.5 per 1000 live births)

Most often in membranous septum (70%) and muscular septum (20%)
Pathophysiology left-to-right shunt; may cause LV volume overload may lead to heart failure; may see pulmonary vascular disease
by age 2 due to increased flow through pulmonary vasculature
Symptoms with small VSD typically asymptomatic; 10% have large defects early symptoms of CHF (tachypnea, poor feeding, failure to
thrive, frequent lower respiratory tract infxns); may have dyspnea and cyanosis if have pulmonary vascular disease; may develop
bacterial endocarditis
Clinical findings - prominent LV impulse; normal S1, S2; pan/holosystolic murmur (best heard at left sternal border, louder w/ smaller
defects); DM at apex; cardiomegaly on CXR; FTT
Treatment unnecessary in 50% of small-moderate VSDs undergo partial or complete spontaneous closure
o
If heart failure or pulmonary disease surgical closure in first few months of life
o
Moderate-sized defects w/ pulmonary vascular disease but w/ significant volume overload can be corrected later in childhood
o
Medical management bacterial endocarditis prophylaxis in all children w/ VSD

Patent ductus arteriosus:

Incidence 1/2500-5000 live births

Risk factors maternal rubella, prematurity, birth at high altitude
Pathophysiology - in fetal life, connects left PA to ascending aorta
o
Usually constricts after birth due to rise in blood O2 tension and reduction in circulating prostaglandins levels
o
Over several weeks, get intimal proliferation and fibrosis permanent closure
o
If it remains patent, blood goes from aorta to pulmonary circulation (b/c less resistance) left-to-right shunt

LA and LV become volume-overloaded can lead to left-sided heart failure w/ normal right heart
Symptoms if small PDA usually asymptomatic; if large shunt early CHF w/ tachycardia, poor feeding, slow growth and recurrent
lower resp. tract infxns; moderate lesions fatigue, dyspnea, palpitations in adolescence and adulthood; may get a-fib, may get
endarteritis (due to turbulent blood flow)
Clinical signs commonly continuous machine-like murmur best heard at L subclavicular region; diminishes in pulmonary vascular disease
o
Diagnostic studies with large PDA, see cardiomegaly (LA and LV enlargement), may see calcification of DA; LVH on ECG
Treatment therapeutic occlusion (even small ones); may need surgical division of ligation of DA

Congenital aortic stenosis:

Usually due to abnormal valve development; 5/10,000 live births; 4x more in males
o
20% also have coarctation of the aorta
Usually have bicuspid aortic valve (or dysplastic); accompanying Shones complex
o
Bicuspid aortic valves are the most common cause of AS in adults
o
Shone's syndrome (also called Shone's Complex, Shone's Anomaly) consists of a set of 4 cardiac defects: a supravalve mitral
membrane (SVMM), parachute mitral valve, subaortic stenosis (membranous or muscular) and coarctation of the aorta.
Essentially, it is both a left ventricular inflow and outflow obstruction. The prognosis is inversely related to the degree of
obstruction caused by the SVMM. The SVMM is also first to develop and likely causes the development of the other three
defects. Essentially it is also a stenosis or restriction of the aortic valve.
Pathophysiology:
o
Increased LV systolic pressure to push blood through narrowed opening leads to LV hypertrophy; may cause aortic
dilatation
o
Progressive disease
Symptoms - < 10% of infants have heart failure Sx before age 1 but if they do then see tachycardia, tachypnea, failure to thrive,
and poor feeding
o
Most older children w/ congenital AS are asymptomatic; when have Sx they are of adult AS easy fatigue, exertinal dyspnea,
angina pectoris, syncope
Clinical findings - LV impulse, systolic ejection click (esp. w./ bicuspid valve), cresendo-decrescendo ESM aortic area (w/ radiation to
neck, present from birth unlike ASD, VSD, PDA), ? Bruit; in severe disease reverse splitting of S2 (A2 after P2)
o
Diagnostic studies enlarged LV, dilated ascending aorta; often LVH on ECG
Treatment not needed if mild; but need endocarditis prophylaxis
o
Severe obstruction may need transcatheter balloon valvuloplasty (usually palliative, usually will need additional dilation or
surgical revision)

Pulmonic stenosis:

May be at level of pulmonic valve (> 90% - most common), within RV (outflow tract obstruction) or in pulmonary artery itself
Pathophysiology obstruction of RV systolic ejection increased RV pressures/ RV hypertrophy
o
Mild if peak transvalvular systolic pressure gradient > 50 mmHg
o
Moderate 50-80 mmHg
o
Severe - > 80 mmHg
Symptoms children w/ mild or moderate usually asymptomatic; usually Dx by murmur on routine exam
o
Severe stenosis exertional dyspnea, exercise intolerance, if decompensation right heart failure Sx (abdominal and pedal
edema)
Clinical findings may see prominent JV a wave; RV heave over sternum; loud late-peaking crescendo-decrescendo systolic ejection
murmur at ULSB (often w/ palpable thrill); widened S2 split w/ soft P2 (due to delayed closure of stenotic valve)
o
Pulmonic click in more moderate stenosis after S1, followed by murmur

Murmurs diminish in intensity during inspiration (unlike other right-sided murmurs)

o
Diagnostic studies enlarged RA and RV on CXR, post-stenotic PA dilatation; RVH and right axis deviation on ECG
Treatment usually no Tx required; may need to dilate valve (balloon valvuloplasty); Abx prophylaxis for endocarditis
Progressive

Coarctation of the aorta:

Incidence 1/6000 live births; often seen in Turner syndrome

2 types of coarctation preductal (2%) and postductal (98%) in relationship to DA
Pathophysiology:
o
Increased pressure load in LV LV hypertrophy, dilatation of collateral blood vessels from intercostals may erode
undersurfaces of ribs
o
Blood flow to head/upper extremities preserved b/c vessels that supply them branch off proximal to obstruction; but
diminished flow to descending aorta
Symptoms in preductal and severe postductal Sx of heart failure very shortly after birth; may see upper extremity HTN in
childhood
Clinical findings weak and delayed femoral pulses, elevated BP in upper body (15-20mmhg greater than in legs); may hear midsystolic
ejection murmur
o
Diagnostic studies CXR shows notching on inferior rib surface; LVH on ECG
Treatment prostaglandin infusion in neonates w/ severe obstruction (to keep DA patent) before surgery; elective repair in children to
prevent systemic HTN; balloon dilatation in older children, adults and ppl w/ recurrent coarctation; abx prophylaxis against endocarditis

Tetralogy of Fallot cyanotic lesion:

Results from abnormal anterior and cephaloid displacement of infundibular (outflow

tract) portion of IV septum
Tetralogy:
o
VSD due to IV septum malalignment
o
Subvalvular pulmonic stenosis due to obstruction from infundibular septum
o
Overriding aorta receives blood from both ventricles
o
RV hypertrophy due to high pressure from RV stenosis
Most common cyanotic congenital heart disease of infancy (5/10,000 live births)
Often associated w/ other cardiac defects (right-sided aortic arch, ASD, anomalous
origin of left coronary artery)
o
22q11 (DiGeorge syndrome) has ToF as one of CV manifestations
Pathophysiology:
o
Due to pulmonic stenosis, blood diverted from RV to LV through VSD
systemic hypoxemia and cyanosis
Symptoms often exertional dyspnea (systemic vasodilatation increases shunt); may
alleviate Sx by squatting increases SVR and directs more blood to lungs
Clinical findings often mild cyanosis (esp. lips, mucous membranes, digits); clubbing of
fingers and toes; RV hypertrophy may cause RV heave; S2 single (P2 is very soft); systolic ejection murmur at ULSB; no distinct murmur
due to VSD
o
Diagnostic studies prominent RV; decreased size of main pulmonary artery segment boot-shaped heart; RVH on ECG
Treatment surgical correction; before used to create left-to-right shunt (aorta to pulmonary artery) may still be used to postpone
repair to older age

Transposition of the great arteries:

Aorta comes from RV, PA from LV

7% of congenital heart defects
Most common cause of cyanosis in neonates (ToF after infancy)
Pathophysiology basically disconnects pulmonary and systemic circulations
Lethal if untreated, but compatible with life in utero (due to DA and foramen ovale) unless
foramen ovale and DA remain patent
Symptoms cyanosis usually apparent on day 1 and rapidly progresses as DA closes; RV impulse
as RV faces high systemic pressures
Treatment TGA is a medical emergency; initially maintain patent DA w. prostaglandins, also
create interatrial communication w/ balloon catheter (Rashkind procedure); then corrective
surgery (Jatene procedure transection of great vessels above semilunar valves and origin of
coronaries and switching them)

Eisenmeger syndrome:

Severe pulmonary vascular obstruction that results from chronic left-to-right shunting through a congenital cardiac defect.
Elevated pulmonary vascular resistance causes reversal of the original shunt (to the right- to-left direction) and systemic cyanosis.
o
Mechanism is unknown
Histologically, the pulmonary arteriolar media hypertrophies and intima proliferates, reducing cross-sectional area of pulmonary vascular
bed. Over time, the vessels become thrombosed, and the resistance of the pulmonary vasculature rises, causing the original left-to-right
shunt to decrease.
Eventually, if the resistance of the pulmonary circulation exceeds that of the systemic vasculature, the direction of shunt flow reverses
With reversal of the shunt to the right- to-left direction, symptoms arise from hypoxemia, including exertional dyspnea and fatigue.
Reduced hemoglobin saturation stimulates the bone marrow to produce more red blood cells (erythrocytosis), which can lead to
hyperviscosity, symptoms of which include fatigue, headaches, and stroke (caused by cerebrovascular occlusion). Infarction or rupture of
the pulmonary vessels can result in hemoptysis.
On examination, a patient with Eisenmenger syndrome appears cyanotic with digital clubbing. A prominent a wave in the jugular venous
pulsation represents elevated right-sided pressure during atrial contraction. A loud P2 is common.
CXR - proximal pulmonary artery dilatation with peripheral tapering; RVH and RA enlargement on ECG
Treatment includes the avoidance of activities that can exacerbate the right-to-left shunt - include strenuous physical activity, high
altitude, and the use of peripheral vasodilator drugs. Pregnancy is especially dangerous; the rate of spontaneous abortion is 20% to 40%
and the incidence of maternal mortality is 45%.
o
No medical therapy offers a reliably effective way to reduce the elevated pulmonary vascular resistance. Supportive measures
include endocarditis prophylaxis, management of rhythm disturbances, and phlebotomy for pts w/ symptomatic erythrocytosis.
o
The only effective long-term strategy for severely affected patients is lung or heart-lung transplantation.

Noonans syndrome

Short stature; dysmorphic face; chest deformities

CHD - valvular and supravalvar pulmonary stenosis, hypertrophic cardiomyopathy

Down syndrome:

Incidence of CHD is 40%

Commonest is VSD
Trisomy 21 is the commonest chromosomal anomaly to cause AV canal defects
o
Common atrioventricular canal = large atrial and ventricular septal defect and common/undivided AV valve above 2 ventricles
Unpredictable and quick progression to pulmonary HTN

Turners syndrome:

45 X O; short stature, cubitus valgus (elbows turned in), webbed neck, shield-like chest
Ovarian dysgenesis, ovarian failure

CHD - bicuspid aortic valve, coarctation of the aorta

Holt-Oram syndrome heart-hand syndrome

TBX5 mutation, autosomal dominant

ASD > VSD

DiGeorge syndrome:

22q11
Velocraniofacial syndrome - characteristic facial appearance, pharyngeal defects, absent parathyroid glands with hypocalcemia, and
hypoplasia of the thymus with defective immune T-cell function)
Congenital abnormalities of cardiac outflow tracts - tetralogy of Fallot, truncus arteriosus (a large VSD over which single large
outflow vessel arises), and interrupted aortic arch.

Heart Valve Disease

Valve disease:

Stenosis - failure of valve to open properly, blood cannot pass through valve

Regurgitation (insufficiency) - failure of valve to close properly, blood regurgitates backwards into preceding chamber

o
o

Affects all preceding chambers (usually affected in sequential manner)

Affects all preceding chambers and often the following chamber

Left vs. Right heart failure symptoms

Left heart failure symptoms

Pulmonary congestion/edema
Eventually peripheral edema, elevated JVP due to general volume overload
Right heart failure symptoms - usually follows long-standing Left heary failure (exception = pulmonic stenosis R heart only)
o
Ascites, hepatomegaly
o
Peripheral edema, elevated JVP
o
o

Common Sx of valve disease:

Fatigue (decreased CO)

Dyspnea (pulmonary vascular congestion)
Chest pain (increased oxygen demand)
Arrhythmias (i.e., atrial fibrillation)
Presyncope/syncope (decreased CO)
Ascites/hepatomegaly (right heart failure)
Edema

Normal order of valve closure

- MTAP

General clinical approach to valves:

Evaluate symptoms
Heart inspection, auscultation, palpation
If clinical concern, obtain transthoracic echocardiogram
If moderate-severe valve dysfxn w/ or w/o Sx, or mild-moderate valve dysfxn w/ Sx, consider referral to cardiologist

Rheumatic fever (not in lecture, but as a person from the third-ish world country I do care about it):

Now rare cause of valvular disease in industrialized countries due to Abx and improvement of general health care

ARF inflammatory condition, primarily involves heart, skin and connective tissue

Complication of URTI by Group A Strep; mainly in children and young adults

o
Acute streptococcal pharyngitis 3% develop ARF 2-3 wks after initial throat infxn
Pathogenesis unknown, assume autoimmune cross-reactivity
May present as rheumatic pancarditis affects all 3 layers of the heart
o
Histopathologically see Arschoff bodies focal fibrinoid necrosis surrounded by inflammatory cells (lymphos, plasma cells,
macrophages)
Valvular dysfxn usually manifests 10-30 yrs later
Clinically, with ARF see chills, fever, fatigue, migratory arthralgias (Jones criteria)
o
May be associated w/ tachycardia, LV contractility, pericardial friction rub, transient murmur of mitral or aortic
regurgitation, or middiastolic murmur at cardiac apex (Carey-Coombs murmur)
Tx of ARF high-dose aspirin (inflammation), penicillin (Strep infxn) and Tx of complications CHF and pericarditis

Chronic rheumatic fever - stenosis or valve regurgitation are common, often involving mitral valve

o
40% pts develop mitral stenosis
o
Additional 25% develop aortic stenosis or regurgitation in addition to mitral problem
ARF recurrences can cause further cardiac damage

Aortic stenosis - restriction of flow from LV to aorta in systole

Causes:
o
o
o

Age-related degenerative calcific changes (senile AS)

Bicuspid aortic valve (1-2% of ppl); younger pts (50s early 60s)
Can also result from chronic rheumatic heart disease

Key features:
o
o

Harsh, late peaking systolic murmur

Late peaking - b/c takes time for ventricle to push blood out
Tardus et parvus carotid pulse - late and diminished due to obstructed LV outflow

See LVH b/c LV works very hard to push blood across stenotic valve into aorta

Over time, heart fails

Clinical manifestations:

Angina, syncope, dyspnea (CHF) b/c push all the blood through tiny little hole
o
Angina due to increased myocardial O2 demand (due to increased muscle mass and wall stress) and reduced myocardial O2
supply (due to reduced coronary perfusion pressure in diastole)
o
Syncope with exertion b/c of stenosis unable to sufficiently increase CO
o
CHF due to increased LA and pulmonary venous pressures leading to pulmonary alveolar congestion
Harsh late-peaking systolic murmur radiating to carotids
Tardus et parvus carotid pulse sometimes even hear carotid thrill
S4 gallop - forceful LA contraction into stiff LV
Decreased S2 - single due to loss of A2 - barely closes b/c stenotic
o
May be paradoxically split due to delay of A2 (P2 before A2)
Aortic ejection click - more common in bicuspid valve

Natural history of severe AS:

Very poor for severe symptomatic uncorrected AS

Latent period for years to decades, followed by onset of severe Sx
o
Angina (survival 5 yrs), syncope (3 yrs), heart failure (2 yrs survival)

This is quickly followed by death

1 yr survival rate 57%;

Need Tx w/ surgical replacement

Diagnosis of AS:

EKG - LVH
CXR - AV calcification, cardiomegaly (L>R), and pulmonary congestion
Echocardiography - thickened immobile leaflets
Cardiac catheterization - increased transaortic pressure gradient (may be as high as
100 mmHg in advanced AS)

Pathophysiology

Normal valve area 2.5 4 cm2

o
Mild AS >1.5 cm 2, moderate 1-1.5cm2; severe < 1cm 2; critical < 0.7cm 2
Mean gradient > 50 mmHg severe
Progression averages ~0.12 cm 2/yr follow w/ yearly US
Aortic sclerosis is leaflet thickening without stenosis precursor to AS

Non-surgical Tx for severe AS:

Avoid strenuous physical activity

Maintain euvolemia
Digitalis with decreased EF
Maintain sinus rhythm atrial component to CO becomes especially important
Caution with anything that decreases LV contractility, afterload or BP - beta blockers, ACE inhibitors, nitroglycerin or any agents
that decrease CO or decrease systemic vascular resistance (SVR)
Endocarditis prophylaxis not needed

Surgery for AS (gold standard) - indicated for critical AS, or for severe AS w/ symptoms attributable to AS

Medical Tx des not work well for severe aortic stenosis b/c its purely a mechanical problem
Replacement valve pig or cow pericardium, or mechanical valve

Balloon aortic valvuloplasty - palliative or bridge to surgery:

Not an effective therapy - leaflets are very calcified and stiff, and cant affect them very well with a balloon
o
thus use as a palliative procedure in ppl who cant tolerate Sg or as a bridge to Sg

Aortic regurgitation (aortic insufficiency) - backwards flow from aorta to LV in diastole

Causes - systemic HTN, infectious endocarditis, rheumatic, congenital, aortic pathologies (aortic dissection, aortic trauma, Marfan
syndrome, syphilis)

AR results either from diseases of aortic leaflets or from dilatation of aortic root

Pathophysiology

LV volume overload (LV blood + regurgitant blood), dilation of LV, decreased contractility
o
cor bovinum heart of a cow after severe long-standing AI
LV end-diastolic pressure due to volume load of regurgitation
pulse pressure (increased systolic, decreased diastolic pressures due to regurgitation)
o
Brisk and bounding carotid pulse
May result in secondary mitral regurgitation - b/c of proximity to mitral valve regurgitant jet
prevents mitral leaflets from closing

Clinical manifestations:

Dyspnea on exertion, fatigue, decreased exercise tolerance, and sensation of forceful heartbeat (due to pulse pressure)
Decrescendo diastolic murmur best heard along LSB, w/ pt leaning forward after exhaling
Systolic flow murmur due to increased flow
S3 gallop
Brisk and bounding carotid pulses due to widened pulse pressure

Duroziez sign - systolic and diastolic thrill heard over femoral arteries with stethoscope compression
Austin Flint murmur low-pitched rumbling mid-diastolic or presystolic murmur due to mitral leaflet displacement from AR jet
o

Unlike MS murmur, does not have opening snap or presystolic accentuation

Diagnosis of AR:

EKG - can show LVH

CXR - cardiomegaly (L>R), and pulmonary congestion; generally no calcifications (unlike AS)
Echocardiography - enlarged LV and regurgitant jet
Cardiac catheterization - LV end diastolic pressure

Therapy for AR:

Maintain euvolemia extra volume not well-tolerated in valve disease

Digitalis for decreased LV function
Judicious afterload reduction to improve forward flow vasodilators (Ca channel blockers and ACEI)
Nifedipine in asymptomatic patients with AI may delay symptoms or LV dysfunction
Surgery for symptomatic AI, significant LV enlargement, or decreased LV ejection fraction

Mitral regurgitation some of LV stroke volume ejected backward into LA during systole

Etiology
o
o
o
o

Leaflets - rheumatic, endocarditis, vegetations, myxomatous

(mitral valve prolapse)
Annulus - dilatation, calcification, prosthetic perivalvular leak
Chordae tendineae - lengthening, rupture
Papillary muscles - rupture, dysfunction

Clinical manifestations:

Holosystolic murmur radiating to axilla

(basically constant blowing sound)
Dyspnea, orthopnea, PND (CHF)
Eventual right sided failure, pulmonary HTN
Carotid upstroke diminished but not late
Soft S1, S3 may be present (b/c more volume returns to LV in
early diastole)

Diagnosis:

EKG - can show LVH, LAE

CXR - cardiomegaly (L>R), and pulmonary congestion
Echocardiography - enlarged LA, LV and regurgitant jet
Cardiac catheterization - increased LA pressure w/ large V wave

Therapy for MR:

Medical diuretics (maintain euvolemia), digitalis for decreased

LV function, afterload reduction (ACE)

Surgery - for symptomatic severe MR, significant LV enlargement, or LV ejection fraction

o
o

Surgery generally deferred for asymptomatic patients

If not possible to surgically repair mitral valve replacement

Mitral valve prolapse - myxomatous redundant leaflet tissue prolapses into LA, does not always result in MR (mostly does not)

Most common congenital valvular abnormality

Early systolic click (or midsystolic) due to prolapse of the valve leaflet and late systolic murmur best heard at apex

o
o
o

Associated with connective tissue disease (Marfan, Ehlers-Danlos)

Click and murmur delayed by maneuvers that increase LV volume (sudden squatting)
Click and murmur happen faster with maneuvers that reduce LV volume (sudden standing)

Most patients asymptomatic; complications are rare (MR one of them)

No specific treatment in most cases
o

Beta blockers for chest pain syndrome or arrhythmias

Mitral stenosis restriction of flow from LA to LV in diastole

Etiology rheumatic >> congenital

o
o
o

Thickened leaflets with fused commissures, thickened chordae tendinae

2/3 of patients are female
ARF on average 20 yrs before presentation

Pathophysiology:

o
o

Stenosis with high pressure gradient, LA enlargement, high LA pressures

may lead to pulmonary vasoconstriction and pulmonary HTN and RV failure
Also decreased CO
Pressure gradient between LA and LV in diastole

LA enlargement, small LV (unlike MR)

Normal valve area 4.0-5.0 cm 2

Mild - 1.5 - 2.0 cm2 with mean

gradient < 5 mmHg; moderate 11.5 cm2; severe < 1 cm2

Clinical manifestations:

Dyspnea, orthopnea, PND, fatigue (CHF) due to increased pulmonary pressure from increased LA pressure

Wasting (markedly decreased CO) - unique feature of MS

Hemoptysis - pulmonary hemorrhage due to BV rupture b/c of high pulmonary BP

Systemic embolism (stagnation of blood in dilated LA, esp when combined w/ a-fib) may
need chronic anticoagulation w/ a-fib
Atrial fibrillation (LA enlargement disrupts integrity of cardiac conduction system)
Hoarseness (impingement of recurrent laryngeal nerve)
Right-sided heart failure due to chronic elevation of RV pressure due to pulmonary HTN

Physical exam:

Diastolic rumble (murmur - low-pitched)

o
Opening snap follows S2, loud S1
Pulmonary rales, decreased pulse pressure ( CO), irregularly irregular rhythm (a-fib),
sternal lift (RV enlargement)

Presystolic accentuation due to increased pressure gradient when LV contracts

Diagnosis:

EKG - LAE, atrial fibrillation, RVH - no LVH

CXR - enlarged LA and right heart border, pulmonary congestion, enlarged PA
Echocardiography - thickened immobile MV leaflets, LA enlargement
Cardiac catheterization - increased LA pressures, low LV pressures

Medical Tx for MS:

Rate control (digitalis, beta blocker) - with HR, mean gradient decreases for any given CO more diastolic filling time

Euvolemia
Maintain sinus rhythm
Anticoagulants for atrial fibrillation

Open surgical commissurotomy indicated for pts w/ symptomatic or pulmonary HTN

Balloon valvuloplasty is actually preferred Tx instead of Sg b/c equivalent to Sg (unless excessive calcification)

Tricuspid regurgitation:

Primary (organic) - 25% - rheumatic, myxomatous, Ebsteins anomaly, endomyocardial fibrosis, endocarditis, carcinoid disease,
traumatic (blunt chest injury, laceration), iatrogenic (pacemaker/defibrillator lead, RV biopsy)
o
More replacements, but repair favored over replacement

Secondary (functional) - 75% - left heart disease (LV dysfunction or valve disease), any cause of pulmonary HTN (chronic lung

disease, pulmonary thromboembolism, left to right shunt), any cause of RV dysfunction (myocardial disease, RV ischemia/infarction)
o
> 90% of surgical interventions
o
Majority of interventions = repairs
Regurgitation due to annular dilation, often secondary to left heart failure, fxnal mitral regurgitation, RV volume and pressure overload
and cardiac dilation

Less common causes - rheumatic, congenital, or other (endocarditis, leaflet tear/prolapse, chordal rupture, papillary muscle rupture,
or myxomatous degeneration of the tricuspid valve)

Clinical presentation of severe TR

Decreased CO fatigue, decreased exercise tolerance

Right heart failure - ascites, congestive hepatopathy, peripheral edema, appetite (due to edematous splanchnic bed), abdominal
fullness

Most effective Tx annuloplasty ring

Tricuspid stenosis:

Etiology - rheumatic 90%, carcinoid, metabolic, eosinophilic, thrombosis, endocarditis, trauma, tumors
Pathophysiology - stenosis, increased pressure gradient and right atrial pressure
History - fatigue, edema, ascites, liver enlargement and discomfort
Tx - balloon valvuloplasty or prosthetic valve

Pulmonic stenosis:

Etiology - congenital, rheumatic, carcinoid

o

Rarely see in adults; mostly congenital

Pathophysiology - stenosis, RV hypertrophy

History - fatigue, syncope
Treatment - balloon or surgical valvuloplasty, prosthetic valve

Pulmonic regurgitation:

Etiology - pulmonary HTN, endocarditis

Pathophysiology - regurgitant jet into RV, RV and PA enlargement
History - fatigue
Treatment - reduce pulmonary hypertension, diuretic, prosthetic valve

Pericardial Disease
Pericardium - two-layered sac that encircles the heart

o
o
Function
o
o
o

Serous pericardium - visceral (inner layer) and parietal (outer layer) and outer fibrous layer
Minimal fluid (15-50 cc) in between visceral and parietal layers; plasma ultrafiltrate
Fixes heart within the mediastinum and limits motion
Prevents extreme dilatation of the heart during sudden rises of intracardiac volume
Barrier to limit spread of infection from lungs

Acute pericarditis - most common, but still clinically rare 0.1% (2-6% on autopsy)

Clinical course mostly spontaneously resolves w/ medical Tx; can have episodic recurrences; can lead to constrictive pericarditis
Causes:
o
Infectious- viral (especially echovirus, Coxsackie B), tuberculous, bacterial (purulent, mainly pneumococcus and staph)

Noninfectious

Uremia complication of CKD

Post-MI pericarditis

Early form - first few days, inflammatory localized pericarditis

Dressler syndrome late (2 wks to several months), autoimmune

Neoplastic disease usually metastatic, not primary; neoplastic effusions can lead to cardiac tamponade

Radiation-induced can be due to chemo

Connective tissue diseases SLE, RA, progressive systemic sclerosis

Drug-induced - procainamide, hydralazine

Pathogenesis 3 stages:

Vasodilation transudation of protein-poor cell-free fluid into pericardial space more than can be reabsorbed

Increased vascular permeability leak of protein into pericardial space

Leukocyte exudation - mononuclear cells; help contain or eliminate offending infectious or autoimmune agents
o

Clinical features:

Pleuritic chest pain sharp; worse w/ inspiration, cough anything that causes rubbing of parietal and visceral pericardium
o
Positional - feel better by sitting forward
Fever due to inflammation
Pericardial friction rub - 3 components (ventricular cntrxn, ventr. relaxation, atrial cntrxn);
o
Scratchy leathery sound; best heard when pt is leaning forward while exhaling
ECG abnormalities - diffuse ST elevation in all leads except aVR (unlike localized in ischemia), T inversion, PR depression
o
No reciprocal changes, unlike in MI

Pericarditis evaluation:

Symptoms - chest pain (pleuritic)

Signs rub, soft heart sounds (due to pericardial effusion)
CXR - heart enlargement, (waterbottle sign) in setting of
pericardial effusion

ECG diffuse ST elevation in all leads except aVR (unlike

localized in ischemia), T inversion, PR depression

o
no reciprocal changes, unlike in MI
Echo - pericardial fluid
Labs - increased WBC, ESR, fluid eval; look for all kinds of
cultures, protein and LDH to see exudate vs. transudate; and
cytology for malignant cells

Pericarditis treatment:

Rest when due to viral syndrome, need some time to recover

Close follow-up to make sure there are no complications
Hospitalization occasionally, esp. when suspect heart attack

NSAIDS/aspirin best medical Tx

Steroids for more severe cases; when does not recover w/ above treatments
No anticoagulants do not want to get hemopericardium

Pathology:

Serous pericarditis early inflammatory process; scant PMN, lymphocytes, and histiocytes
Serofibrinous pericarditis - most common
o
Fibrinogen - grossly rough and shaggy appearance (bread and butter pericarditis)
o
Portions of the pericardium become thickened and fused
Purulent pericarditis - associated w/ bacterial infection (mostly staph and strep); high morbidity & mortality; need hospital admission
Hemorrhagic pericarditis - grossly bloody, associated with trauma, TB and malignancy

Cardiac tamponade - pericardial fluid compresses heart and limits its filling

Determinants - amount of fluid, rate of accumulation (slow allows time for stretching
of pericardium, while acute - does not take much fluid to compress heart), compliance
of pericardium
Common types malignant, idiopathic (viral), uremic, trauma, procedural complication

Volume-pressure relationship in pericardial fluid:

Relatively flat line at first until the critical point (arrow) extra fluid does not
create much pressure
o
Fluid added after that leads to marked increase in pericardial pressure
Left curve chronic recurrent pericardial effusion; can accumulate more fluid due to
pericardial expansion over time

Clinical features of cardiac tamponade:

Dyspnea, fatigue, orthopnea

Jugular venous distention due to blood backup in veins
Hypotension with pulsus paradoxus
o
Pulsus paradoxus - decrease in systolic BP >10 mmHg on inspiration

Normally, on inspiration RV size increases due to increased venous return

pushes IV septum to L decrease in LV stroke volume & pressure

In tamponade, this effect is more pronounced due to decreased ventricular

filling
Quiet precordium on palpation effusion dampens heart sounds
Sinus tachycardia to maintain cardiac output

Electrical alternans - amplitude of QRS changes from beat to beat

B/c in pericardial effusion heart bounces back and forth with every
beat closer to surface, further from surface, and then repeats
Check again after draining pericardial effusion (bottom panels)

Treatment (remember this is a

diastolic problem, no issue in systole):

Intravenous fluids

Pressors if hypotensive

Pericardiocentesis

Subxiphoid surgical drainage

with recurrent effusions, may want to create surgical window and drain it into pleural space

Constrictive pericarditis - diffuse thickening of the pericardium

Reaction to prior inflammation - idiopathic, unknown, post infection (viral), post cardiac surgery, post radiation, tuberculous, cancer
o
Pericardial effusion fluid undergoes organization w/ subsequent fusion of pericardial layers, followed by fibrous scar
formation
o
Sometimes, calcification of adherent layers occurs
Results in reduced distensibility of cardiac chambers
o
CO
o
filling pressures o
Abnormal diastolic filling; systolic fxn is normal

See right heart failure b/c venous return to R heart is arrested early

Clinical manifestations:

Dyspnea, orthopnea, fatigue, weight loss, anorexia

Kussmaul sign jugular veins more distended during inspiration (opposite of normal physio)

o
B/c cannot accommodate increased venous return on inspiration
Distant heart sounds b/c thickened pericardium insulates the heart
Diastolic knock b/c problem is w/ relaxation as limit of expansion is reached;
seen in severe calcific constriction
Signs of venous congestion edema, ascites, jaundice, hepatomegaly

Signs and symptoms develop over

months to years:

CO fatigue, HYPOTN, reflex

tachycardia
systemic venous pressures
JVD, hepatomegaly, ascites,
peripheral edema

Diagnosis:

ECG - low voltage, nonspecific T changes

CXR - usually normal heart size
CT/MRI - thickened pericardium, pericardial calcifications
(esp. TB)
Echo - thickened pericardium (usually difficult to tell)

Cath:

o
o
o

Prominent X and Y descent

Y descent fall in RA pressure as blood

goes into RV (more prominent due to
increased RA pressure)

W-sign (or M-sign)

In cardiac tamponade, y descent is blunted

Elevation and equalization of end-diastolic pressures

Usually left much higher than the right

Square root or Dip and plateau rapid diastolic filling followed by abrupt stop

Thats when may hear diastolic knock

Ventricular interdependence on inspiration, right heart expands, pushing IV septum to the left, and left pressure
decreases; on expiration, less RV filling allows for higher LV pressure

Treatment of constrictive pericarditis:

Conservatively Na restriction and diuretic

Definitive therapy - surgical pericardiectomy

Constriction vs. tamponade both lead to impaired

diastolic filling

Symptoms:
o
Systemic venous congestion JVD,
hepatomegaly +/- ascites, periheral edema
o
Pulmonary venous congestion pulmonary rales
o
Decreased CO hypotension and reflex
tachycardia
Constrictive pericarditis - +++ Kussmaul sign
Cardiac tamponade - +++ pulsus paradoxus

Summary:

Acute pericarditis is most often idiopathic or viral cause

and is usually self limited
o
Common findings in acute pericarditis include
pleuritic chest pain, fever, pericardial friction
rub, diffuse ST segment elevation and PR depression on ECG
Cardiac tamponade occurs with pericardial fluid accumulation under high pressure leading to compression of cardiac chambers and
decreased cardiac output
o
Fluid removal is essential in this life threatening condition
Pericarditis may lead to constrictive physiology with restricted filling of the heart because of rigid pericardium

Infective Endocarditis

Untreated 100% mortality; treated 20-25% mortality

Clinical classification:
o
o

Acute bacterial endocarditis acute fulminant infxn w/ highly virulent and invasive organism (e.g. S. aureus)

May involve previously healthy heart valves

Subacute bacterial endocarditis insidious clinical course, less virulent organisms (Strep viridans)

Most often happens with pre-existing valve damage

Pathogenesis:

Endocardial surface injury most commonly due to turbulent blood flow due to preexisting valve disease, also can be caused by
foreign objects (indwelling venous catheters, prosthetic heart valves)
Thrombus formation at injury site platelets adhere, form sterile thrombus (vegetation) NBTE (non-bacterial thrombotic
endocarditis)
Bacterial entry into circulation transient bacteremia is not uncommon, but only special snowflakes are able to cause endocarditis
o
90% Gram-positive (staph and strep e.g. S. aureus, strep viridans)
Bacterial adherence to injured endocardium adhere to fibrin and are protected by fibrin cover from phagocytosis and Abx

Complications of infectious endocarditis:

Mechanical cardiac injury

o
Abcess formation, erosion into cardiac conduction system
Thrombotic or septic emboli
o
Often to CNS (40%), kidneys, spleen incite infection or infarction there
o
Lung infarction (due to septic PE) common in IE involving right-sided valves
Immune injury mediated by Ag-Ab deposition
o
Glomerulonephritis, arthritis, vasculitis

Clinical manifestations:

Acute IE explosive rapidly progressive illness w/ high fever and shaking chills
Subacute IE less dramatic, low-grade fever and non-specific constitutional Sx (fatigue, anorexia, weakness, myalgia, night sweats)
o
Can look like flu or URTI

Embolic infarction and seeding of vasa vasorum of arteries can cause localized aneurysm formation (mycotic aneurysm) that weakens the
vessel wall and may rupture

Aorta, viscera, or peripheral organs

o
particularly dangerous in cerebral vessels rupture there can result in fatal intracranial hemorrhage.
May see skin/peripheral findings petechiae, splinter hemorrhages (under nails), Janeway lesions (painless flat irregulr discolorations on
palms and soles), Osler nodes (tender pea-sized erythematous nodules in pulp space of fingers and toes), Roth spots retinal microinfarcts
(white dots surrounded by hemorrhages)

Systemic inflammatory response fever, splenomegaly, increased WBC count with left shoft, elevated ESR and C-reactive protein,
elevated serum rheumatoid factor in 50% of pts

Treatment 4-6 wks of high dose IV Abx

Initially may use empiric Tx; but once ID organism use specific Tx

VALVE CASE DISCUSSION

Case 1
A 47 year-old woman had acute rheumatic fever at eight years of age and a murmur ever since. She did well thereafter until five years ago,
when she noticed exertional dyspnea and paroxysmal nocturnal dyspnea. Four years ago, these symptoms worsened. Orthopnea and ankle
edema appeared. Her symptoms then improved for nearly two years, only to return about two months ago. Since then, she has had to lead a
bed-chair-bathroom existence.
On examination, she was cachectic and dyspneic. Blood pressure was 96/72; pulse rate, 90 and irregularly irregular; respirations, 32. Neck
veins were distended to 11 cm above the sternal angle, and there were bibasilar rales. The PMI was in the anterior mid-axillary line - laterally
displaced. The apex impulse was normal, but a parasternal heave was present. S1 was loud. An opening snap was present, and there was a
barely audible mitral diastolic rumble with appreciable presystolic accentuation (all these describe mitral stenosis murmur). The pulmonary
component of S2 was loud and palpable (PA tap) suggests pulmonary HTN accentuated P2. The liver was two fingerbreadths below the
costal margin and was tender hepatomegaly R heart symptom, means long-standing MS. There was considerable pitting edema to the
knees. These suggest right heart problems.
ECG - atrial fibrillation, right axis deviation and right ventricular hypertrophy R heart problems are late sequelae of mitral valve disease.
Chest X ray showed a large heart with prominent left atrium, right ventricle, pulmonary arteries, and pulmonary vasculature.
Pulmonary HTN means it was a long-standing disease
Echocardiogram showed normal LV size and wall motion (MS does not affect LV pumping, just reduces amt of blood that reaches LV),
marked LA enlargement, thickened MV leaflets with 0.4 cm2 valve area (severe = < 1 cm2) and a peak MV Doppler gradient of 20mmHg.
PMI displacement seen on physical exam here does not mean LV enlargement; enlarged RV pushes it to the Left
Cardiac

catheterization revealed the following (see normal values in text):

Cardiac output, L/Min 1.8 - low
Pulse rate 92 - high
Pressures: mmHg
o
Left ventricle 108/12 - normal, diastolic is a bit low
o
Pulmonary capillary wedge, mean 33 - equivalent to LA pressure; normally about 16 or less
o
Pulmonary artery 125/65; 75 very high (higher than LV pressure - suprasystemic), normally should be 1/3 of systemic pressure
o
Right ventricle 125/20 - high
o
Right atrium, mean 19 - high
Calculated mitral valve area, 0.3 cm2 - severe < 1 cm2

The valvular abnormality is mitral stenosis, caused by rheumatic fever.Fortunately, this is now uncommon in this country, but sadly remains
prevalent in "third world" countries. The history described in the first paragraph is typical in that decades go by before the insidious scarring
of the mitral valve cause enough stenosis to be a clinical problem, and thereafter gradual progression of symptoms develops. Her short
improvement of symptoms was likely due to development of reactive pulmonary arteriolar hyperplasia, limiting blood flow to the left heart and
hence limiting increased left sided pressure. The physical exam is also typical, the dyspnea resulting from the stenotic valve causing increased
left atrial pressure needed to force blood across the valve, this pressure being transmitted through the pulmonary veins to the pulmonary
capillaries and causing transudation into the parenchyma resulting in stiffer lungs and dyspnea. The cachexia is due both to low cardiac output
across the severely stenotic valve and the work of breathing. The irregularly irregular pulse suggests atrial fibrillation which commonly occurs
in the presence of a pressure or volume overloaded atrium. The diastolic rumbling murmer, opening snap, and loud S1 are typical of mitral
stenosis. [There is an error here: in the absence of atrial contraction, with atrial fibrillation, presystolic accentuation of the murmer can't
happen.] The loud P2, elevated neck veins, distended liver, and lower extremity edema all represent high right heart pressures secondary to the
elevated pulmonary vein pressures. The low blood pressure is due to low cardiac output (low flow across the stenotic valve). The right axis
deviation and right ventricular hypertrophy on ECG also result from high right sided pressure. The enlarged RA, RV, and LA on chest X-ray and
echo, in the presence of a normal LV is consistent with pressure excess behind the mitral valve, but an underfilled "protected" LV. The laterally
displaced apex impulse does not represent the usual LV dilation, rather here it represents displacement of the LV by the large RV and/or a very
enlarged RV. The parasternal heave is the enlarged and hypertensive RV. The cardiac catheterization data are consistent with the above
discussion: low cardiac output, elevated pressures except in the LV, and a very stenotic mitral valve (normal: ~ 4-5 cm2). Though medical
management can be temporizing, this woman badly needs a larger valve orifice. This can be accomplished either by surgery (mitral valve repair
or replacement depending on the anatomic circumstances) or percutaneous balloon valvuloplasty (applicable in certain patients). With relief of
her mitral stenosis she should markedly improve symptomatically.
QUESTIONS
1. What is the valvular abnormality? What is its cause? How does the calculated mitral valve area compare to normal?
Mitral stenosis. Cause ARF in childhood. Severely narrowed (< 1 cm2)
2. Is this slow course of clinical worsening typical? Why was there a temporary improvement in symptoms?
Yes. Rheumatic heart disease in an insidious slowly progressing disease. Pulmonary vasoconstriction to protect lung from increased pressure due to MS. But
over time, arteries themselves begin to hypertrophy until become very thick and muscular, and we see pulmonary HTN.
3. What is the cause of the elevated right heart pressures and left atrial pressure? Is left ventricular pressure normal or abnormal and why?
Blood flow backup in preceding chambers. LV pressure is normal. Usually low or normal b/c not getting enough blood.

4. What treatment can be offered this patient for symptom relief at this time?
Medical diuretic (decrease volume); digitalis may help her a-fib (parasympathetic effect on AV node) it will do rate control, thus decreasing mean
gradient for any given CO by allowing more time to fill in diastole (also can use beta-blockers), anticoagulants
5.
What definitive treatment options may apply to this patient?
Surgical balloon valvuloplasty or valve replacement/surgical repair

CASE 2
A 59-year old woman denied having had symptoms of rheumatic fever in childhood. She was always healthy and active until six months prior to
admission, when she noticed both dyspnea and lower chest discomfort on mild exertion but no other symptoms of heart failure. There was no
past history of bacterial endocarditis.
On physical examination, she had normal body habitus. Blood pressure was 130/70; pulse 80 and regular. The jugular veins were not distended,
the carotid pulsations were normal and the lungs were clear. The apical impulse was diffuse; S1 was diminished. There was early systolic
click and a grade 3/6 apical holosystolic murmur transmitted to the axilla. (unlike diastolic murmur of MS). No opening snap, S3, or
diastolic murmurs were heard. There were no aortic murmurs.
The ECG showed normal sinus rhythm and left axis deviation and left atrial enlargement.
Chest X ray showed enlargement of the left ventricle and left atrium. No valvular calcification was seen.
Echocardiogram showed an enlarged LV and normal wall motion, with an anteriorly directed retrograde jet through the mitral valve on
Doppler that passed the length of the enlarged left atrium. The posterior mitral leaflet appeared thickened with partial prolapse into LA
Cardiac catheterization was performed with the following findings:
Cardiac output, L/min
o
Total left ventricular output (angiographic) 10.4
o
Forward flow (Fick) to the aorta 3.9
o
Regurgitant flow to the left atrium 6.5
Pulmonary capillary wedge pressure, mean (mmHg) 12.0
o
V Wave (mmHg) 24.0

Left ventricular cineangiography showed an excellent and uniform contraction of the left ventricle and a large (3+) regurgitation jet into the
left atrium. There was some prominent scalloping of the posterior mitral leaflet seen.

The valvular abnormality here is mitral regurgitation (MR). By cineangiographic criteria it is moderate to moderately severe in degree (3+on a 4+
scale). The etiology is not clear and many possibilities exist. She may have developed a left ventricular cardiomyopathy with dilation of the LV
and secondary MR due to distortion of the papillary muscle, chordae, valve leaflet relationships; she may have had rupture of one or more
chordae sufficient to cause partial loss of support of the leaflets but not severe enough to cause prolapse. She likely did not have rheumatic
fever since the valve was not described as scarred on echo. Similarly, it was not described as redundant with prolapse as with myxomatous
degeneration. Ischemic papillary muscle dysfunction is possible but unlikely since the ECG was not described as suggesting this. The clear lungs
and lack of jugular distention suggest that the left ventricle so far has compensated fairly well. Similarly, the normal LV wall motion and wedge
pressure (representing LA pressure) despite enlargement also suggests good compensation. The pansystolic murmer described is typical of MR.
The cardiac output data indicate a large degree of MR with a regurgitant fraction (regurgitant volume / total output) of about 60%. The large V
wave component of the wedge (representing LA) pressure is caused by a large volume of blood regurgitating into a not-fully-compliant LA during
ventricular systole, causing a transient abnormal rise in LA pressure; this suggests, in turn, a relatively recent onset of the MR without
sufficient time (many months) for the LA to become more compliant. Initially, medical management can be quite helpful for symptom relief,
primarily through vasodilators and diuretics; in this case no excess of volume appears present, so the primary agent would be an arteriolar
dilator such as an angiotensin converting enzyme (ACE) inhibitor to decrease LV afterload and favor forward flow over regurgitant flow from
the LV. If symptoms worsen despite medical management, or if the LV shows progressive dilation or decrease in wall motion, surgical repair or
replacement of the valve would be indicated.
QUESTIONS
1. What is the valvular abnormality? How severe is it?
Mitral regurgitation. Moderately severe
2. What may have caused this abnormality?
Mitral valve prolapse
3. What is the reason for the elevated V wave?
Increase in LA pressure due to regurgitation
4. Does the normal left ventricular contraction (wall motion) determine that intrinsic left ventricular function is normal? Why?
No. Not on exam
5. How can this patient be treated now for symptom relief? What definitive treatment may she be a candidate for?
Medical no diuresis (b/c no volume overload), no digitalis (normal wall motion), afterload reduction (ACEI)
Surgery valve repair.

CASE 3
A 77-year old man was well until three years ago. At that time, he developed exertional dyspnea, orthopnea, fatigue, and peripheral edema.
Despite therapy, these symptoms increased progressively to the point of invalidism. He had no angina, but has had two syncopal episodes.
On physical examination, BP was 110/80; the pulse, 78 and regular; respirations, 24. The carotids were of small volume with slow upstroke and
down stroke. (tardus et parvus) Neck veins were moderately distended. There were bibasilar rales to the angles of the scapulae.
The PMI was in the sixth interspace and laterally displaced, diffuse and forceful. A harsh, late peaking, grade 3/6 systolic ejection
murmur was heard at the right upper sternal border and radiated to both carotid arteries. The second heart sound was markedly
diminished. There was slight pitting edema of both lower legs.
The ECG showed left ventricular hypertrophy and strain pattern. Chest X ray showed enlargement of the left ventricle, calcification in the
region of the aortic valve, moderate redistribution of vascular markings to the upper lobes of the lung.
Echocardiography showed a calcified and thickened aortic valve with reduced leaflet excursion, a Doppler mean gradient across the aortic
valve of 50mmHg and an estimated valve area of 0.5 cm2.
Cardiac catheterization yielded the following results:
Cardiac output, L/min 2.7
Pressures, mmHg
Aorta 135/78
Left ventricle 184/35
Pulmonary capillary wedge, mean 29
Pulmonary artery 75/40, 52
Right ventricle 75/12
Calculated aortic valve area, cm2 0.4
Ejection fraction 0.3

__

Cineangiography showed a large dilated left ventricle with uniformly poor contractions in systole. There was no mitral or aortic regurgitation.
The aortic valve appeared heavily calcified with minimal leaflet motion. There was considerable dilation of the ascending aorta.

The valve disease here is aortic stenosis (AS). At age 77 it most likely represents calcific degeneration of the valve; this in turn is suspected to
be usually due to some underlying abnormality of the valve and in this case the cineangiogram suggests a bicuspid aortic valve. Actually bicuspid
aortic valves will often become scarred and stenotic a decade or so earlier than in this man. Though the AS became symptomatic only three
years ago, it certainly was present and worsening for many years before that. The left ventricle is able to compensate for AS for a long time
very well by undergoing hypertrophy, but finally decompensates and eventually dilates. By the time decompensation develops, the prognosis is
relatively poor: in this case he has developed two of the three classic symptoms of AS (CHF and syncope, but not angina), with the CHF
indicating an average survival of 2 years. The physical findings are typical of severe AS, including low amplitude and slow rate of rise of his
carotids, and the murmer. The neck vein distension and rales are indicative of congestive failure from a decompensated LV and resulting
elevated diastolic pressure, reflecting back to the pulmonary capillaries (rales) and right heart (elevated neck veins and leg edema). This is
documented by the elevated LV diastolic, wedge, pulmonary artery, and right ventricular pressures at catheterization. Note the peak to peak
gradient across the AV of 49 mmHg (there should be none measurable) and the very small valve area of 0.4 - 0.5 cm2 (normal ~ 2.5 - 3 cm2).
The LV ejection fraction of 0.3 is lower than the normal of >0.55, and is another indication that the LV is failing. The only satisfactory
treatment of symptomatic AS is surgical replacement using a prosthetic valve. An LV that is hypertrophied but not dilated will likely gradually
return toward normal; this moderately dilated LV may well improve, but that is not assured. Percutaneous balloon valvuloplasty of aortic stenosis
is only palliative and temporarily (months) beneficial, in contrast to balloon valvuloplasty of mitral stenosis that typically lasts many years.
QUESTIONS
1. What is the valvular abnormality now and what is its underlying cause?
Aortic stenosis w/ calcifications due to age
2. What is the prognostic risk of this abnormality? Are the symptoms related to the prognosis?
Syncope survival 3 yrs. Symptomatic- poor prognosis
3. What is the reason for the rales? What is the reason for the pulmonary hypertension?
Blood backup due to aortic stenosis
4. With this valve abnormality, is the dilation of the left ventricle an early or late result? What is the expected response of the LV wall
thickness?
Early response is actually hypertrophy; dilation is the late response
5. How should this patient be treated?
Medical Tx not effective in AS (diuresis, digitalis, avoidance of drugs that decrease SVR or CO)
Surgery.