HYPERTROPHIC CARDIOMYOPATHY

INTRODUCTION

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).

CORONARY ARTERIES

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:

The decrease in left ventricular compliance causes an elevation of left ventricular diastolic pressure which in turn is transmitted to the pulmonary capillaries leading to pulmonary congestion characterized clinically by dyspnea and pulmonary rales.

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.

LEFT VENTRICULAR OUTFLOW TRACT (LVOT) OBSTRUCTION (Table 4) CLINICAL FEATURES & PATHOPHYSIOLOGIC CORRELATION (Table 5A, 5B, 5C, 5D) LABORATORY STUDIES (Table 6) TREATMENT (Table 7) COURSE AND PROGNOSIS (Table 8)

NOTE: SYMPTOMS NOT NECESSARILY RELATED TO PRESENCE OR ABSENCE OF OBSTRUCTION
 
 
 
 
 


TABLE 5A

CLINICAL PRESENTATION
 

MAY BE ASYMPTOMATIC

DIZZINESS; SYNCOPE

DYSPNEA

CHEST PAIN
 
 
 
 
 
 
 


TABLE 5B

PHYSICAL EXAM
 

PROMINENT JUGULAR "A WAVE"

CAROTID PULSE BIFID

+  EVIDENCE OF LVH  (LV LIFT)

PARADOXICAL SPLITTING OF  S2

LOUD S4+  S3

+  SYSTOLIC MURMUR
 
 
 
 


TABLE 5C

ASSOCIATED MURMURS
 

LV OUTFLOW MURMUR

MITRAL REGURGITATION MURMUR

MURMURS VARY CHARACTERISTICALLY WITH DYNAMIC AUSCULTATION MANEUVERS
 
 
 
 
 
 
 
 
 
 
 


TABLE 5D

LVOT OBSTRUCTION IN HCM

INTENSITY OF MURMUR (GRADIENT)
 
 
INCREASED (WORSENED) DECREASED (IMPROVED)
­ CONTRACTILITY
Exercise, emotional stress (i.e. increased catecholamines), administration of inotropic drugs, e.g. Epinephrine
¯ CONTRACTILITY
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)

 
 

     
TABLE 6

LABORATORY FINDINGS
 

CHEST X-RAY

EKG

AMBULATORY EKG

ECHO

CARDIAC CATHETERIZATION
 
 
 
 
 
 
 


TABLE 7

TREATMENT
 

RESTRICTION OF PHYSICAL ACTIVITY

BETA BLOCKERS

CALCIUM CHANNEL BLOCKERS

DISOPYRAMIDE

AMIODARONE

AICD

SURGERY
 
 


TABLE 8

PROGNOSIS
 

PROGRESSIVE CHF

SUDDEN DEATH

ATRIAL FIBRILLATION