Evolution and Transformation of Hypertrophic Cardiomyopathy From a High Risk to a Treatable Low Mortality Disease With Contemporary Clinical Research Strategies

Once considered rare and essentially untreatable with a grim prognosis and reduced life expectancy, hypertrophic cardiomyopathy (HCM) has evolved substantially over 6 decades. Ultimately, HCM has become a contemporary global disease with pharmacologic and interventional options offering effective personalized treatment for all adverse disease pathways. Striking reduction in HCM-related mortality to ≤0.5%/year in optimally treated cohorts is now comparable to that expected in the US general population, lower than most other disease risks to living, and 10-fold less than the earliest estimates. The few deaths directly related to HCM are now largely attributable to advanced (end-stage) heart failure in patients with nonobstructive HCM. Determinants of this transformation to a lower risk disease are evident in hallmark clinical inflection points and breakthroughs, including dedicated HCM programs assembling large clinical databases in which focused (and unfunded) physician-investigators have derived data directly from patients in clinical practice. Evidence-based observational studies report emergence of contemporary treatment strategies enhancing survival: implantable defibrillators prevent arrhythmic sudden death globally with 95% sensitive patient selection using an American Heart Association/American College Cardiology risk stratification algorithm; low-risk, high-benefit surgical myectomy reverses outflow obstruction and heart failure in >90% with a long-term survival benefit; and aggressive anticoagulation has reduced embolic strokes. Recent novel pharmacologic alternatives (cardiac myosin inhibitors) are proving effective in relieving obstruction/symptom burden and changing disease management. These principles and time-tested patient-centered research strategies uniquely tailored to the heterogeneous HCM clinical spectrum are pivotal in providing practice insights, offering a vulnerable population more optimistic prognosis including opportunity to achieve normal longevity not available to prior generations of patients.