Calcium-Antagonist Receptors in the Atrial Tissue of Patients with Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy is characterized by a nondilated, hypertrophied left ventricle in the absence of any overt cause. A possible role of adrenergic innervation or of cellular calcium regulation is suggested by the presence of hyperdynamic left ventricular function and by the clinical and symptomatic improvement seen in patients treated with β-receptor antagonists or calcium antagonists. Therefore, we measured the density of calcium-antagonist receptors and β-adrenoceptors in the atrial myocardium of 16 patients with hypertrophic cardiomyopathy and 19 patients with various other cardiac disorders. For comparison, we also measured the number of voltage-sensitive sodium channels. Calcium-antagonist binding sites, measured as the amount of dihydropyridine bound to atrial tissue, were increased by 33 percent in patients with hypertrophic cardiomyopathy (mean [±SD], 397±104 fmol per milligram of protein in patients with hypertrophic cardiomyopathy, as compared with 299±108 in patients with other cardiac disorders; P<0.01). The densities of saxitoxin-binding sites on voltage-sensitive sodium channels and β-adrenoceptors were the same in the two groups, although the density of β-adrenoceptors was higher in atrial samples from patients receiving β-receptor antagonists (165±86 fmol per milligram of protein [patients receiving β-blockers] vs. 85±60 [patients not receiving β-blockers]; P<0.04). The increase in the number of calcium-antagonist receptors in hypertrophic cardiomyopathy suggests that abnormal calcium fluxes through voltage-sensitive calcium channels may play a pathophysiologic part in the disease. (N Engl J Med 1989; 320:755-61.) HYPERTROPHIC cardiomyopathy is a disorder characterized by a nondilated, hypertrophied left ventricle in the absence of any overt cause.¹ Histologically, there is marked myocardial hypertrophy and fiber disarray.^{2 , 3} Functionally, the ventricle is hyperdynamic in systole and displays delayed relaxation and decreased compliance in diastole.^{4 5 6 7} Hypertrophic cardiomyopathy is transmitted as an autosomal dominant trait in approximately 50 percent of patients.⁸ A molecular origin of hypertrophic cardiomyopathy has not been determined. Although abnormal adrenergic function has been proposed as a cause,^{9 10 11} abnormalities have not been detected in the myocardial norepinephrine concentration,^{12 , 13} in the numbers of β-adrenoceptors, or in the level of catecholamine-sensitive.