How Hypertrophic Cardiomyopathy Became a Contemporary Treatable Genetic Disease With Low Mortality

Abstract

Hypertrophic cardiomyopathy (HCM) is a relatively common genetic heart disease encumbered throughout much of its almost 60-year history by a large measure of misunderstanding and the perception of a grim outcome without effective treatment options. However, it is now apparent that the majority of patients affected with HCM can achieve normal or near-normal life expectancy without disability, and usually do not require major treatment interventions. Nevertheless, for those patients with HCM who are at risk for (or experience) disease-related complications, a constellation of comprehensive nonpharmacologic management strategies have evolved over the last 15 years, altering the natural history and disease course for many, including implantable defibrillators, heart transplant, external defibrillation/therapeutic hypothermia, advances in surgical myectomy, and alcohol ablation. In particular, expanded contemporary risk stratification strategies have led to a more reliable selection of patients likely to achieve primary prevention of sudden death with implantable defibrillators. Most recently, large cohort studies using current management strategies and therapeutic measures have shown that it is now possible to achieve significantly improved survival with a low HCM-related mortality of 0.5% per year across all ages, and including children and young adults characteristically with the most aggressive disease course. These clinical management initiatives, instituted by the practicing cardiology community, have succeeded in preserving life and restoring an active lifestyle for thousands of patients with HCM, while providing many with a measure of reassurance and a reasonable expectation for an extended (if not normal) life span.

Clinical Course and Quality of Life in High-Risk Patients With Hypertrophic Cardiomyopathy and Implantable Cardioverter-Defibrillators

“…31 Our findings in HCM generally support the principle of patient satisfaction with the ICD initiative, focused on preservation of life in high-risk patients with this complex genetic disease. 1,3,4,6,8,9 Attention to patient concerns, and apprehension related to ICD shocks, could ultimately mitigate the modestly elevated levels of shock anxiety identified in this study.…”

“…First, data from our international multicenter HCM population reinforces the principle that device therapy is efficacious in terminating VT/VF, restoring sinus rhythm, and preventing sudden death. [1][2][3][4][5][6][7][8][9][10][11] As a result of this >15-year ICD initiative, 3,9 substantial numbers of patients prophylactically implanted with devices have survived with good quality of life. The data reported here are also consistent with our prior experience (and that of other investigators), albeit with a slightly lower ICD event rate, probably attributable to greater numbers of primary prevention devices implanted most recently as this therapy continues to penetrate into HCM practice.…”

“…1 The implantable cardioverter-defibrillator (ICD) is now established as a fundamental therapy for prevention of sudden death in this patient population, independent of age, and based on a series of multicenter studies and meta-analyses over the past >15 years. [1][2][3][4][5][6][7][8][9][10][11] Nevertheless, a remaining question is whether ICD interventions that terminate ventricular tachycardia/ ventricular fibrillation (VT/VF) trigger deterioration in clinical course or impairment in quality of life (including psychological). Therefore, to address whether longterm clinical course and mortality risk subsequent to termination of life-threatening arrhythmias is distinctive in HCM, we have assembled a large multicenter international cohort of high-risk HCM patients with ICDs.…”

ICD Therapy for Primary Prevention in Hypertrophic Cardiomyopathy

“…34 The first patient clinically diagnosed with HCM came to medical attention due to several siblings dying suddenly at a young age. 35 Despite this, the lack of clear associated genetic markers has led some authors to argue that a family history should not be an established risk factor.…”

Further Refining Risk in Hypertrophic Cardiomyopathy With Late Gadolinium Enhancement by CMR

“…With contemporary management strategies including implantable cardioverter-defibrillators (ICDs) in patients at increased risk of SCD and other therapies, including medications, myectomy, alcohol septal ablation, and heart transplantation in appropriate patients, the prognosis for HCM has improved over the last several decades (2). However, risk stratification remains a significant challenge (1) and selecting patients appropriately for ICD therapy can be problematic.…”