Hypertrophic cardiomyopathy (HCM) is often familial (55%) and is transmitted in an autosomal dominant fashion. The rest of cases (45%) occur sporadically and possibly represent new mutation affecting contractile protime genes. It affects people of any age group ranging from infants to people over 50 years old. The true prevalence of HCM in the U.S. is approximately 0.3%.
GROSS ANATOMY (Table 1)
Hypertrophy is more prominent in the upper septal region than the rest of the myocardium and is commonly referred to ASH or asymmetric septal hypertrophy. Variations in the degree and location of hypertrophy have also been described (apical, midseptal and general hypertrophy).
Intramyocardial coronary arteries are abnormal in almost 80% of the patients. The intimal and medial layers are hypertrophied resulting in a decrease in luminal area. The combination of hypertrophy (increased MVO2 demand) and decrease in blood supply leads to myocardial ischemia. Repeated episodes of ischemia result in fibrotic changes of the myocardium.
HISTOLOGIC FEATURES (Table 2)
Microscopically, the muscle fibers display a disorganized arrangement, i.e. disarray. Instead of the normal parallel arrangement, the bundles of muscle fibers run in diverse directions. Myocardial cells are also hypertrophic and arranged in an irregular pattern forming oblique or parallel arrangement to adjacent cells. The myocardium shows a variable degree of fibrosis of the interstitial region and of the cardiac conduction system. Fibrosis is the anatomic substrate of impaired conduction necessary for initiation of reentrant tachycardias, e.g. ventricular tachycardia.
ASH and cellular disarray are major but not pathognomonic features of hypertrophic cardiomyopathy.
PATHOPHYSIOLOGIC AND HEMODYNAMIC CHARACTERISTICS (Table 3)
In HCM systolic function is normal or hyperdynamic and the predominant hemodynamic abnormality relates to diastolic function especially of the left ventricle. Diastolic failure is caused by delayed relaxation and reduction in ventricular compliance. The following contribute to these changes:
Prolongation of isovolumic relaxation period leads to a decrease in the rate of early or rapid filling phase and a significant amount of filling takes place later in diastole as a result of a forceful atrial contraction (atrial "kick"). Loss of atrial contraction, as may happen with the onset of atrial fibrillation, leads to a significant drop in stroke volume and cardiac output.
The mechanism of LVOT obstruction is as follows. The thick upper septum protrudes in the LVOT reducing the orifice size. Blood flowing through this narrowed LVOT causes a Venturi ("suction") effect which draws the anterior leaflet of the mitral valve towards the septum, further reducing the LVOT orifice size. Simultaneously, as a result of systolic anterior movement of the mitral valve (SAM), there is functional mitral regurgitation. Thus systolic murmur in HOCM is due to LVOT narrowing and mitral regurgitation. It is important to point out that the stenosis in HCM is dynamic as opposed to fixed stenosis of aortic valve disease.
Interventions or conditions that influence
LVOT gradient produce directional changes in the intensity of the two systolic
murmurs. Examples of interventions that increase the gradient and intensity
of both murmurs include a) increase in contractility, b) decrease in preload
or c) decrease in afterload. The opposite, i.e. decrease in contractility,
increase in preload or increase in afterload would diminish the gradient
and the intensity of the murmurs. (What would be the effect of increasing
afterload on the murmur of a) mitral regurgitation associated with HOCM,
b) rheumatic mitral regurgitation?)
The systolic murmur of LVOT narrowing
is characteristically crescendo-decrescendo and starts a little after the
onset of S1. It is best heard at the left lower sternal border and radiates
to the base, but unlike systolic murmur of valvular aortic stenosis, it
does not radiate to the carotids. The intensity of the murmur can be varied
by various physiologic and pharmacologic interventions. Thus, the murmur
(and gradient) can be intensified by decreasing preload (decrease venous
return) by abrupt assumption of upright posture or by Valsalva's maneuver.
The murmur intensity can be diminished by increasing afterload (squatting),
or by increasing preload (leg raising in supine position). The murmur of
mitral regurgitation is prominent in the apical region and shows the same
directional changes in response to the interventions noted above.
Chest X-ray. Cardiac size is normal or may be mildly enlarged.
Echocardiographic Studies (M-mode, 2-Dimensional, Doppler). Echocardiographic studies are essential for the diagnosis of hypertrophic cardiomyopathy. Echocardiographic findings include hypertrophic walls, ASH, and septal wall to posterior wall ratio of 1.3:1. In patients with HOCM, there is presence of SAM. Left ventricular chamber is normal or small; left atrium may be enlarged. In addition, echocardiogram is used in screening first degree relatives of patients with hypertrophic cardiomyopathy. Color Doppler studies provide additional hemodynamic information.
Cardiac Catheterization Studies.
Current echocardiographic techniques have obviated the need for cardiac
catheterization in most patients with hypertrophic cardiomyopathy. In patients
with HOCM catheterization studies reveal a characteristic tracing which
shows a gradient between the main left ventricular chamber and the subaortic
chamber proximal to the obstruction. This pull back tracing differentiates
obstructive hypertrophic cardiomyopathy from aortic stenosis. In the latter,
gradient exists between the left ventricle and the aorta. During catheterization,
one may also notice a characteristic hemodynamic response to premature
ventricular complex. Normally, stroke volume following a premature ventricular
complex is augmented because of an increase in left ventricular filling
during the compensatory pause (Frank-Starling effect) as well as from an
increase in contractility. This results in a large pulse pressure on arterial
pulse recording. In patients with obstructive hypertrophic cardiomyopathy,
post-PVC contraction results in an increase in LVOT gradient (worsening
of obstruction) and therefore no increase in stroke volume and no change
in arterial pulse pressure. Instead, left ventricular systolic pressure
is markedly increased.
Beta Adrenergic Blocking Agents. These drugs reduce heart rate, decrease myocardial contractility, prolong diastolic filling time and possess anti-arrhythmic properties especially against exercise- induced arrhythmias.
Calcium channel blocking agents Verapamil and diltiazem decrease myocardial contractility, slow heart rate, increase compliance and thus improve diastolic function. They also slow conduction through the AV node which helps to control ventricular rate in patients with atrial fibrillation.
Amiodarone is used for potentially serious ventricular arrhythmias. It is also effective against supraventricular arrhythmias e.g. atrial fibrillation. Potential adverse effects include thyroid, liver and lung function abnormalities - some of which can be life-threatening.
Diuretics in general are not used because they may aggravate LVOT gradient. Their use is limited in some patients to relieve pulmonary congestion.
Disopyramide, a type IA anti-arrhythmic agent is effect against ventricular and supraventricular arrhythmias and possesses negative inotropic properties. It is used in selected cases of HCM.
Digitalis is used to control ventricular rate in patients with atrial fibrillation who are intolerant to beta blockers or calcium channel blockers.
Prophylaxis against bacterial endocarditis prior to any surgical or dental procedures is also advised in patients with HOCM.
Anticoagulation. Chronic anticoagulation is recommended for those with atrial fibrillation to reduce the risk of thromboembolic complications.
Surgical reduction of the septal size (myomectomy/ myotomy) is indicated for patients with severe LVOT obstruction i.e. systolic gradients above 50mmHg and who are symptomatic despite medical therapy. Correcting hemodynamics by enlarging LVOT size also improves the associated mitral regurgitation. Recently some centers are performing septal reduction by injecting alcohol in the first septal branch of the left coronary artery producing "controlled" septal infarction.
It is believed that pacemaker therapy alters the
sequence of contraction which reduces LVOT gradient and improves symptoms.
Long term benefits, however, are questionable.
Patients with HCM may develop atrial fibrillation with severe drop in blood pressure due to loss of atrial contraction ("kick"). Restoration of sinus rhythm using electrical or pharmacologic cardioversion should be attempted. Antiarrhythmic agents used for prevention of recurrent atrial fibrillation include disopyramide or amiodarone. Chronic anticoagulation with oral warfarin is used for patients with
paroxysmal or chronic atrial fibrillation for prophylaxis against thromboembolic complications. Ventricular rate control is achieved with beta blocker, verapamil or diltiazem.
In the late stage of the disease, patients with hypertrophied
cardiomyopathy develop cardiac dilation and systolic dysfunction from further
myocardial fibrosis. The picture in this stage resembles dilated cardiomyopathy,
and the treatment is the same as in dilated cardiomyopathy i.e. diuretics,
angiotensin, converting enzyme inhibitors, etc.
HYPERTROPHIC CARDIOMYOPATHY (HCM)
NORMAL CARDIAC CHAMBER SIZE
ABNORMAL CORONARY ARTERIES
HYPERTROPHIC CARDIOMYOPATHY (HCM)
MYOCARDIAL FIBER DISARRAY
IMPAIRED DIASTOLIC COMPLIANCE
HYPERDYNAMIC SYSTOLIC FUNCTION
+ LV OUTFLOW TRACT OBSTRUCTION
+ MITRAL REGURGITATION
LEFT VENTRICULAR OUTFLOW TRACT
NOTE: SYMPTOMS NOT NECESSARILY RELATED TO PRESENCE OR ABSENCE OF OBSTRUCTION
MAY BE ASYMPTOMATIC
PROMINENT JUGULAR "A WAVE"
CAROTID PULSE BIFID
+ EVIDENCE OF LVH (LV LIFT)
PARADOXICAL SPLITTING OF S2
LOUD S4; + S3
+ SYSTOLIC MURMUR
LV OUTFLOW MURMUR
MITRAL REGURGITATION MURMUR
MURMURS VARY CHARACTERISTICALLY WITH DYNAMIC AUSCULTATION
LVOT OBSTRUCTION IN HCM
INTENSITY OF MURMUR (GRADIENT)
|INCREASED (WORSENED)||DECREASED (IMPROVED)|
Exercise, emotional stress (i.e. increased catecholamines), administration of inotropic drugs, e.g. Epinephrine
Rest, administration of negative inotropic drugs (beta blockers, calcium channel blockers)
|¯ PRELOAD , i.e. ¯ VENOUS RETURN (e.g. upright posture, nitrates, diuretics, Valsalva maneuver)|| PRELOAD i.e. VENOUS RETURN (e.g..supine posture with legs raised, squatting)|
|¯ AFTERLOAD (i.e..¯SVR) - Arterial vasodilators (e.g. hydralazine)|| AFTERLOAD (i.e.SVR) - Vasoconstrictors (e.g. Neosynephrine)|
RESTRICTION OF PHYSICAL ACTIVITY
CALCIUM CHANNEL BLOCKERS