The influence of left ventricular outflow tract obstruction on the clinical outcome of hypertrophic cardiomyopathy remains unresolved.

Background— Nonobstructive hypertrophic cardiomyopathy (HCM) has been regarded as the predominant hemodynamic form of the disease on the basis of assessment of outflow gradient under resting conditions. We sought to prospectively define the prevalence, clinical profile, and significance of left ventricular (LV) outflow tract obstruction under resting conditions and with physiological exercise in a large HCM cohort. Methods and Results— We prospectively analyzed 320 consecutive HCM patients (age, 47±17 years), measuring LV outflow gradient at rest, with Valsalva maneuver, and with exercise echocardiography. LV outflow obstruction was present at rest and/or with exercise in 225 patients (70%); 119 had rest gradients ≥50 mm Hg and were not exercised. Of the other 201 patients with gradients <50 mm Hg at rest (average, 4±9 mm Hg), 106 developed mechanical obstruction to LV outflow resulting from mitral valve–septal contact after exercise (80±43 mm Hg), including 76 with marked gradients ≥50 mm Hg and 46 with heart failure symptoms. The remaining 95 patients (30%) had no or small gradients (<30 mm Hg) both at rest and with exercise. Valsalva maneuver underestimated the presence and magnitude of exercise-induced obstruction. Conclusions— Among those patients who come to clinical evaluation, HCM is a predominantly obstructive disease in which LV outflow gradients, frequently associated with heart failure symptoms and often identified only with exercise, are evident in most patients (ie, 70%). Identification of LV outflow obstruction with exercise echocardiography may broaden management options in HCM by identifying symptomatic patients not otherwise regarded as potential candidates for septal reduction therapy. Assessment of subaortic gradients with exercise should be a routine component of the evaluation of HCM patients without outflow obstruction under resting conditions.

Background Clinical impact of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) is largely unresolved. Thus, we analyzed the prognostic implications of AF in a large, community-based HCM population assembled from Italian and US cohorts. Methods and Results Occurrence of AF and outcome were assessed in 480 consecutive HCM patients (age at diagnosis, 45±20 years; 61% male) who were followed up for 9.1±6.4 years. AF occurred in 107 patients (22%; incidence, 2%/y) and was independently predicted by advancing age, congestive symptoms, and increased LA size at diagnosis. Patients with AF had increased risk for HCM-related death (OR, 3.7; P <0.002) because of excess heart failure–related mortality but not sudden, unexpected death. This risk associated with AF was substantially greater in patients with outflow obstruction or with earlier development of AF (≤50 years of age). AF patients were also at increased risk for stroke (OR, 17.7; P =0.0001) and severe functional limitation (OR for NYHA class III or IV, 2.8; P <0.0001). Compared with those with exclusively paroxysmal AF, patients developing chronic AF showed higher combined probability of HCM-related death, functional impairment, and stroke ( P <0.0001). In a subgroup of 37 patients with AF (35%), the clinical course was largely benign in the absence of stroke and severe symptoms. Conclusions In a community-based HCM population, AF (1) was common, with 22% prevalence over 9 years; (2) was associated with substantial risk for heart failure–related mortality, stroke, and severe functional disability, particularly in patients with outflow obstruction, those ≤50 years of age, or those developing chronic AF; and (3) was nevertheless compatible with benign outcome in 35% of patients.

Microvascular dysfunction, reflected by an inadequate increase in myocardial blood flow in response to dipyridamole infusion, is a recognized feature of hypertrophic cardiomyopathy. Its long-term effect on the prognosis is unknown. We prospectively evaluated a cohort of patients with hypertrophic cardiomyopathy after they had undergone quantitative assessment of myocardial blood flow by positron-emission tomography (PET).

Background —Death resulting from hypertrophic cardiomyopathy (HCM), particularly when sudden, has been reported to be largely confined to young persons. These data emanated from tertiary HCM centers with highly selected referral patterns skewed toward high-risk patients. Methods and Results —The present analysis was undertaken in an international population of 744 consecutively enrolled and largely unselected patients more representative of the overall HCM spectrum. HCM-related death occurred in 86 patients (12%) over 8±7 years (mean±SD). Three distinctive modes of death were as follows: (1) sudden and unexpected (51%; age, 45±20 years); (2) progressive heart failure (36%; age, 56±19 years); and (3) HCM-related stroke associated with atrial fibrillation (13%; age, 73±14 years). Sudden death was most common in young patients, whereas heart failure– and stroke-related deaths occurred more frequently in midlife and beyond. However, neither sudden nor heart failure–related death showed a statistically significant, disproportionate age distribution ( P =0.06 and 0.5, respectively). Stroke-related deaths did occur disproportionately in older patients ( P =0.002). Of the 45 patients who died suddenly, most (71%) had no or mild symptoms, and 7 (16%) participated in moderate to severe physical activities at the time of death. Conclusions —HCM-related cardiovascular death occurred suddenly, or as a result of heart failure or stroke, largely during different phases of life in a prospectively assembled, regionally based, and predominantly unselected patient cohort. Although most sudden deaths occurred in adolescents and young adults, such catastrophes were not confined to patients of these ages and extended to later phases of life. This revised clinical profile suggests that generally held epidemiological tenants for HCM have been influenced considerably by skewed reporting from highly selected populations. These data are likely to importantly affect risk stratification and treatment strategies importantly for the prevention of sudden death in HCM.