Joint Program in Nuclear Medicine

Hypertrophic Cardiomyopathy

David A. Israel, MD PhD
Finn Mannting, MD PhD

June 13, 2000

Presentation

A 42 year-old man presented with ECG abnormalities at rest. A stress test was requested.

Imaging Findings

Myocardial SPECT perfusion imaging was performed with Tc-99m tetrofosmin using a stress/rest protocol. Stress imaging was performed following treadmill exercise. The patient was exercised for 14:00 minutes of a standard Bruce protocol, and reached a peak heart rate of 169 BPM (95% MPHR) without symptoms. Systolic pressure rose from 115 to 150 mm Hg. The ST-T wave abnormalities which were present at rest normalized with stress. Short axis, vertical long axis, and horizontal long axis tomographic views were analyzed. Gated images (not presented) were analyzed for wall motion and ejection fraction.

The rest images show high tracer uptake in apex, the apical third of the inferior wall and septum. During stress there appears to be relative hypoperfusion to this portion of the myocardium except for the septum. The gated SPECT revealed mildly increased LV volume and normal global systolic LV function with an ejection fraction of 63%. There was mild apical hypokinesis. On the basis of these findings, a focal hypertrophic cardiomyopathy was suspected, and subsequently demonstrated by echocardiography.

Discussion

Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate myocardial hypertrophy which occurs in the absence of an obvious hemodynamic load such as aortic stenosis or systemic hypertension. There are several distinct variants of hypertrophic cardiomyopathy; for example, a subset of patients with hypertrophic cardiomyopathy have a pressure gradient in the left ventricular outflow tract, a variant which in the past has been called idiopathic hypertrophic subaortic stenosis (IHSS).

In hypertrophic cardiomyopathy there is a marked increase in myocardial mass, and the ventricular cavities are small. The walls are stiff, and relax poorly during diastole, leading to increased end-diastolic pressure and resulting in pulmonary congestion and dyspnea. The left ventricle is typically more affected than the right, and the atria are variably hypertrophied secondary to increased pressure needed to fill the ventricles, and dilated secondary to the frequently associated A-V regurgitation.

There are several distinct patterns of involvement.

Typically, there is greatest hypertrophy of the interventricular septum and anterolateral wall. Hypertrophy localized to the septum has been called asymmetrical septal hypertrophy (ASH).
Concentric hypertrophic cardiomyopathy can occur, and can be difficult to distinguish from the physiological hypertrophy that can be seen in highly trained athletes.
Another variant is apical hypertrophic cardiomyopathy, in which predominantly the apex is involved; this is much more common in Japan (roughly one-quarter of hypertrophic cardiomyopathy cases), than in other populations. Apical hypertrophic cardiomyopathy is characterised by giant negative precordial T-waves, lack of an outflow pressure gradient, and a benign course.
There are several other, less common variants in which there is hypertrophy localized to different distinct parts of the myocardium.

Microscopically, there is a characteristic whorled pattern of disorganized muscle bundles. There are abnormalities in the cell-to-cell arrangement and in the myofibrillar architecture within individual cells. There is fibrosis and scar formation. Most patients have abnormal intramural coronary arteries in affected areas, with thickened vessel walls and luminal narrowing, and these abnormalities may contribute to myocardial ischemia in these patients.

Hypertrophic cardiomyopathy occurs in about 0.02 to 0.2 percent of the population. It is genetically transmitted in about half the patients as an autosomal dominant trait (four different chromosomal loci have been identified, and over three dozen different mutations are known to date). Mutations have been identified in the cardiac myosin heavy chain gene, the cardiac troponin T gene, and the tropomyosin gene. The etiology has not been identified in the other half of patients. The actual disease mechanism remains unknown, with a diverse variety of theories implicating abnormal cellular calcium fluxes, abnormal sympathetic stimulation, abnormalities of intramural vasculature, and primary structural abnormalities.

Pathophysiology

Most patients have abnormalities of diastolic function due to high filling pressures. A minority of patients exhibit a sub-aortic pressure gradient, which is thought to be due to abnormal anterior motion of the mitral valve towards the hypertrophied septum during systole, "systolic anterior motion" (SAM). Many exhibit myocardial ischemia, probably related to abnormally narrowed intramural vessels, increased oxygen demand, and increased intraventricular pressures resulting in subendocardial ischemia.

Symptoms

Most patients with hypertrophic cardiomyopathy are asymptomatic. The most common symptom is dyspnea. angina, fatigue, and syncope are also common. Palpitations, paroxysmal nocturnal dyspnea, congestive heart failure, and dizziness are less frequent. Syncope may result from inadequate cardiac output with exertion or be a result of arrhythmias. The ECG is usually abnormal, commonly revealing ST-segment and T-wave abnormalities. There may be evidence of LVH. There are often giant negative T-waves in the precordial leads in apical hypertrophic cardiomyopathy. Ventricular arrhythmias, which may lead to sudden death, are found in 75% of hypertrophic cardiomyopathy patients undergoing ambulatory monitoring.

Imaging

The most widely used modality is echocardiography. It can evaluate the morphologic distribution and severity of the disease, the functional aspects such as contractility and degree of gradients, and other associated features such as "systolic anterior motion" of the anterior mitral valve leaflet. The extent of associated valvular abnormalities are also readily evaluated.

Scintigraphic myocardial imaging with SPECT allows assessment of relative thicknesses of myocardial walls at rest. Ischemic changes are common findings in hypertrophic cardiomyopathy in the absence of obstructive coronary artery disease. A subset of patients in whom findings of ischemia are common are young patients with a history of syncope or subsequent sudden death, suggesting that myocardial ischemia is a cause of death in younger patients. Fixed defects, probably indicative of myocardial scarring, occur primarily in patients with impaired systolic function.

Natural History

Many patients are asymptomatic or mildly symptomatic, and clinical deterioration is slow, with some patients actually showing spontaneous improvement. Annual mortality is probably close to 1%. Sudden death from arrhythmia is a known risk, and may be as high as 6% per year in children. Progression to a dilated cardiomyopathy occurs in 10 to 15%, probably as a consequence of small vessel ischemia.

References

Braunwald, E. Heart Disease: A Textbook of Cardiovascular Medicine, 5th Ed. W.B. Saunders and Company, 1997.

Topol, E. Textbook of Cardiovascular Medicine Lippincott-Raven, 1998.

Murray, I.P.C, Ell, P.J. Nuclear Medicine in Clinical Diagnosis and Treatment, 2nd Ed. Churchill-Livingstone, 1999.

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J. Anthony Parker, MD PhD, Tony_Parker@CareGroup.Harvard.edu