Chapter 49: Alcohol Septal Ablation in Drug-Refractory Obstructive Hypertrophic Cardiomyopathy

SCOPE OF THE PROBLEM

Hypertrophic cardiomyopathy (HCM), defined clinically by the presence of hypertrophy of a nondilated left ventricle without loading conditions or other recognized causes of hypertrophy, occurs in 1 per 500 individuals in the general population, with approximately 700,000 cases in the US population.¹ HCM, inherited with an autosomal dominant Mendelian pattern, is the most common familial heart disease and the most common cause of sudden death in athletes and adolescents. HCM is caused by 1 of more than 1500 different mutations of genes encoding sarcomeric proteins. This genetic heterogeneity and the diverse and unpredictable phenotypic expressions, clinical manifestations, and prognosis limit the value of genetic testing or projections based on affected family members. The vast majority of individuals who are genotype positive/phenotype positive are asymptomatic or minimally symptomatic and are undiagnosed. Heart failure is the most common clinical presentation of HCM in adults. Diagnosis may be difficult due to compensating adjustments in lifestyle that minimize symptoms and nonspecific physical and electrocardiogram (ECG) findings. Elevation of left atrial pressure results from diastolic dysfunction and mitral regurgitation. Limitations of cardiac output in HCM resulting in fatigue, dyspnea, presyncope, and syncope are commonly related to left ventricular outflow tract (LVOT) obstruction and low end-diastolic volume because of diastolic dysfunction. LVOT obstruction (LVOT pressure gradient ≥30 mm Hg) is present in one-third of HCM patients at rest and in an additional one-third with provocation with Valsalva maneuver, nitroglycerin, post-extrasystolic potentiation, or exercise echocardiography, a preferred method of evaluating patients with no resting LVOT gradient but marked exercise tolerance. The presence of LVOT obstruction is a predictor of HCM-related progressive heart failure and heart failure death,² and relief of obstruction surgically results in better survival than achieved by patients without this treatment.³ Relief of LVOT obstruction is a principle goal of both medical and septal reduction therapies.

PATHOPHYSIOLOGY: A 60-YEAR ADVENTURE

The cardiac surgeons Drs. Brock and Morrow coined the term functional aortic stenosis in the 1950s to describe the absence of expected LVOT obstruction in the cardioplegia-arrested heart during open heart surgery, and in the 1960s, Braunwald et al⁴ used the newly developed techniques of left heart catheterization to investigate the pathophysiology of obstructive HCM. These hemodynamic studies demonstrated highly variable LVOT obstruction depending on physiologic and pharmacologic maneuvers, which altered loading conditions and contractility (Fig. 49-1). The advent of echocardiography in the early 1970s introduced a powerful new tool for understanding the pathophysiology, diagnosis, and prognosis of HCM and for monitoring treatment of HCM (Figs. 49-2 and 49-3). LVOT obstruction results from several mechanisms, including narrowing of the LVOT by septal hypertrophy, anterior location of the mitral valve encroaching on the LVOT, and systolic anterior motion (SAM) of the anterior mitral valve leaflet leading to SAM-septal contact (see Figs. 49-2 and 49-3). The anterior leaflet of the mitral valve is longer in patients with HCM, ...