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Dr. Vasken Dilsizian, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland Medical Center, 22 South Greene Street, Room N2W78, Baltimore, Maryland 21201
hypertrophic cardiomyopathy (hcm) is a genetic disease with an autosomal pattern of inheritance, characterized by left ventricular hypertrophy in the absence of another cause of increased cardiac mass. Patients with HCM often report chest pain and demonstrate abnormal stress-induced thallium perfusion defects without accompanying epicardial coronary artery disease (Fig. 1). Because myocardial thallium uptake is, in part, a function of sarcolemmal cell membrane integrity, thallium defects observed in HCM may reflect disturbed cellular active cation transport system and not necessarily reduced regional myocardial perfusion. Thus, we postulated that defective Na-K ATPase transport and/or calcium pump apparatus in HCM patients may result in reduced potassium (and, therefore, thallium) extraction, increased Na-Ca exchange, and excess intracellular calcium in the heart. Because uptake of technetium-99m sestamibi is not dependent on the active Na-K ATPase transport system, dissociation of thallium uptake from sestamibi uptake, if present, might yield insights into a fundamental cellular abnormality in HCM (Figs. 2 and 3)⇓⇓.
Do thallium defects in HCM represent myocardial ischemia or fundamental disturbance of the cellular active cation uptake? In HCM, thallium abnormalities during exercise may represent either reduced rate and/or efficiency of thallium transport across the sarcolemma or diminished myocardial perfusion due to small-vessel disease. An abnormality in potassium transport might provide evidence of a fundamental pathophysiologic process in this disease that could lead, through a digitalis-like effect, to increased intracellular levels of calcium ion. In turn, increased intracellular calcium may play an important role in the induction of myocardial disarray and hypertrophy in HCM and be responsible for the hyperdynamic systolic function and impaired left ventricular relaxation and diastolic filling commonly observed in these patients. Of note, patients with reversible thallium defects have a greater degree of impaired diastolic filling than do patients with normal thallium uptake, and verapamil therapy has been shown to improve both thallium defects and impaired left ventricular diastolic function in such patients (1). Reversible thallium defects also occur in young patients with HCM and are frequently related to cardiac arrest and syncope (2). Areas of myocardial ischemia may be causally related to the subsequent development of scar, which has also been implicated as a marker of poor prognosis in HCM patients.
Sestamibi is not dependent on potassium transport across the cell membrane. Therefore, reproducible evidence of exercise-induced perfusion defects by both thallium and sestamibi in 10 patients with HCM (Figs. 1, 2, and 3) supports the contention that reversible thallium defects represent true abnormalities in regional myocardial perfusion and not a fundamental disturbance of the active Na-K ATPase transport system. That thallium defects in HCM reflect myocardial ischemia is supported by other pieces of evidence, including abnormal lactate metabolism during atrial pacing, improvement of thallium defects after surgical relief of left ventricular outflow obstruction, cardiac magnetic resonance and postmortem evidence of patchy areas of fibrotic myocardial tissue and large regions of transmural scar, and the high prevalence of abnormally thickened intramural coronary arteries in the areas of scarred myocardium.
The authors have reported that they have no relationships to disclose.
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