Clinical Pearls & Morning Reports
Hypertrophic cardiomyopathy (HCM) is predominantly an obstructive disease, with 70% of patients having mechanical impedance to left ventricular outflow (gradients ≥30 mm Hg) at rest or with physiological provocation (i.e., exercise). Clinical diagnosis of HCM is based on a hypertrophied, nondilated left ventricle — which is identified by means of echocardiography or magnetic resonance imaging (MRI) — in the absence of another cardiac, systemic, metabolic, or syndromic disease. Read the latest NEJM Review Article here.
Q: To what extent have contemporary therapeutic strategies reduced mortality in patients with HCM?
A: With contemporary therapeutic strategies, it is possible to definitively alter the clinical course of this disease. With the use of such strategies, the HCM-related mortality rate can be as low as 0.5% per year (representing a 90% reduction in mortality from 35 years ago), independent of age and including children and young adults, in whom the natural history of disease has traditionally been the most aggressive.
Q: Do the specific genetic changes identified in a patient with HCM influence management or aid in prognosis?
A: HCM is inherited in an autosomal dominant pattern, associated with mutations (nucleotide sequence variants) in 11 or more genes encoding proteins of thick and thin myofilament contractile components of the cardiac sarcomere or Z disk, with beta-myosin heavy chain and myosin-binding protein C genes most commonly involved. Genetic testing panels show vast heterogeneity and diverse molecular pathways, with more than 2000 sarcomere mutations identified. However, genotype–phenotype correlations have been inconsistent, and single (or multiple) sarcomere variants are unreliable in predicting prognosis, with no specific role in risk stratification. Thus, important management decisions in cases of HCM are based solely on clinical criteria.
A: Prophylactic defibrillator placement should be considered for young and middle-aged patients whose clinical profiles include one or more conventional risk factors judged to be major. On the basis of the history taking, imaging studies, and ambulatory electrocardiographic monitoring, the most important established risk markers are unexplained syncope, extreme left ventricular wall thickness, HCM-related sudden death in a first-degree relative, and multiple or prolonged episodes of nonsustained ventricular tachycardia. Left ventricular apical aneurysm with regional scarring and extensive myocardial fibrosis, seen as late gadolinium enhancement on MRI, has been added to the risk-stratification algorithm for HCM. Paradoxically, patients with HCM who survive into the seventh decade and beyond, even those with risk markers, are largely protected from sudden death (rate, 0.2% per year, which is similar to the rate in the general population).
A: Pharmacologic therapy is the first option and the mainstay of treatment in patients with obstructive HCM. Cardioactive medications administered to mitigate symptoms of heart failure, chest pain, or both in patients with obstructive HCM traditionally include atrioventricular nodal blocking agents and disopyramide. Patients with disabling symptoms and an impaired quality of life due to long-standing left ventricular outflow obstruction at rest or with physiological provocation (gradient, ≥50 mm Hg) are candidates for primary transaortic septal myectomy or, in selected patients, alcohol septal ablation. By abolishing subaortic gradients and normalizing left ventricular and pulmonary arterial pressures, myectomy permanently reverses symptoms of heart failure (regardless of their prior duration), restoring quality of life in 90 to 95% of patients, including more than 70% who become completely asymptomatic. Percutaneous alcohol ablation with myocardial contrast echocardiography has become the primary alternative to myectomy. This procedure is usually reserved for selected patients of advanced age with severe symptoms that are refractory to drug therapy who are not candidates for myectomy.