American College of Cardiology

MARON AND MCKENNA et al., ACC/ESC Expert Consensus Document on Hypertrophic Cardiomyopathy
JACC 2003; 42: 000-000

American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy

A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines

General Considerations for Natural History and Clinical Course
Hypertrophic cardiomyopathy is a unique cardiovascular disease with the potential for clinical presentation during any phase of life from infancy to old age (day one to over 90 years). The clinical course is typically variable, and patients may remain stable over long periods of time with up to 25% of a HCM cohort achieving normal longevity (75 years of age or older) ^{7,30,31,34,159}. However, the course of many patients may be punctuated by adverse clinical events, largely related to sudden, unexpected death, embolic stroke, and the consequences of heart failure ^5,7,29,30,38. Hypertrophic cardiomyopathy is also a rare cause of severe heart failure in infants and very young children, and presentation in this age group itself constitutes an unfavorable prognostic sign ^53,58.

In general, adverse clinical course proceeds along one or more of several of the following pathways, which ultimately dictate treatment strategies (Figs. 1 and 2) ^5,7,11,14,26: 1) high risk for premature sudden and unexpected death; 2) progressive symptoms largely of exertional dyspnea, chest pain (either typical of angina or atypical in nature), and impaired consciousness, including syncope, near-syncope or presyncope (i.e., dizziness/lightheadedness), in the presence of preserved LV systolic function; 3) progression to advanced congestive heart failure (the “end-stage phase”) with LV remodeling and systolic dysfunction ^37,160; and 4) complications attributable to AF, including embolic stroke ^38,161-163.

However, full appreciation of the clinical implications of HCM (and its treatment strategies) requires an awareness of the unique patterns of patient referral and selection biases that have had an important impact on our perceptions of this disease ^{5,7,11,59,164}. Perhaps to a far greater extent than other cardiovascular diseases, much of the published clinical data assembled over four decades have emanated largely from a few selected tertiary centers in North America and Europe, disproportionately comprised of patients referred because of their high-risk status or severe symptoms requiring highly specialized care (such as surgery) ^59,164. On the other hand, clinically stable, asymptomatic, or elderly patients were often under-represented.

Over-dependence on frequently cited, ominous mortality rates of 3% to 6% per year for HCM-related premature death from tertiary centers may have led to an exaggeration of the overall risk and impact of this disease on patients and, thereby, contributed to a misguided perception that HCM is invariably an unfavorable disorder with inevitable, adverse consequences frequently requiring major therapeutic intervention ^7,59,165. However, more recent reports from non-tertiary centers with fewer selected, regional, and community-based cohorts not subject to tertiary center referral bias are probably more representative of the overall disease state, citing annual mortality rates in a much lower range of about 1%, with the survival of patients not dissimilar to that of the general adult U.S. population ^7,30,31. Nevertheless, of note, there are subgroups of patients within the broad HCM spectrum with annual mortality rates far exceeding 1% and conform to the rates of up to 6% per year previously attributed to the overall disease ^{7,11,41,165,166}.

Hypertrophic cardiomyopathy attributable to sarcomere protein mutations also occurs in the elderly ¹³⁹ and should be distinguished from non-genetic hypertensive heart disease or age-related changes in persons of advanced age. The determinants of extended survival in some patients with HCM are largely unresolved. It is possible that benign genetic substrates may convey favorable prognosis and normal life expectancy. However, at present, genotype data are available for only a limited number of elderly patients, with mutations in the cardiac myosin-binding protein C gene being most common ¹³⁹. Older patients with HCM characteristically show relatively mild degrees of LVH and may not experience severe symptoms. Some even have large resting subaortic gradients that are often caused by the SAM-septal contact associated with normal-sized mitral leaflets greatly displaced anteriorly, seemingly by calcium accumulation posteriorly in the mitral annulus, within a particularly small LV outflow tract ¹⁶⁷. Definitive clinical diagnosis of HCM in older patients with LVH and systemic hypertension is often difficult to resolve, particularly when LV wall thickness is less than 20 mm and SAM is absent. In the absence of genotyping, marked LVH disproportionate to the level of blood pressure elevation, unusual patterns of LVH unique to HCM ³⁶, or an obstruction to LV outflow at rest represents presumptive evidence for HCM ¹²⁷.

Not uncommonly, HCM coexists with other cardiac conditions such as systemic hypertension and/or CAD. In such patients, the management of HCM should be considered independent of any co-morbidity, and each of the disease entities should be treated on its own merit. For example, specific concerns that may arise include avoidance of angiotensin-converting enzyme (ACE) inhibitors to control hypertension in the presence of HCM-related resting or provocable LV outflow tract obstruction and failure to exclude the diagnosis of CAD in those HCM patients with angina pectoris.

In summary, it is probably most appropriate to regard HCM as a complex disease capable of producing important clinical consequences and premature death in some patients, while many other patients reach normal longevity and life expectancy with mild or no disability and without major therapeutic interventions. Many individuals affected by HCM may not require treatment for most or all of their natural lives, and they therefore deserve reassurance with regard to their prognosis.

© 2003 by the American College of Cardiology and the European Society of Cardiology