Author + information
- Perry M. Elliott, MBBS, MD∗ ()
- ↵∗Reprint requests and correspondence:
Dr. Perry M. Elliott, Institute of Cardiovascular Science, Paul O'Gorman Building (Room G26), University College London, 72 Huntley Street, London WC1E 6DD, United Kingdom.
Everything should be made as simple as possible but not simpler.
Albert Einstein (1)
Hypertrophic cardiomyopathy (HCM) is a common inherited disease that affects approximately 1 in 500 people. In 50% to 60% of adolescents and adults with the condition, it is inherited as an autosomal dominant trait caused by mutations in cardiac sarcomere protein genes. A further 5% of patients have metabolic or storage disorders, neuromuscular disease, chromosome abnormalities, and genetic syndromes such as cardiofacial-cutaneous disorders. Although the disease is compatible with normal life expectancy, it is associated with premature death from ventricular arrhythmia, heart failure, and stroke in a substantial minority of patients (2,3).
Approximately 25% of patients with HCM have a resting pressure gradient between the body and outflow tract of the left ventricle. This is nearly always caused by contact between the anterior mitral valve leaflet and the interventricular septum in systole. In some patients with no evidence of outflow obstruction at rest, it can develop during physiological and pharmacological interventions that reduce left ventricular end-diastolic volume or increase left ventricular contractility. Current practice guidelines recommend echocardiography during exercise stress testing in nonobstructive patients with exertional symptoms as the demonstration that latent obstruction in this context has a profound effect on their subsequent management (2,3).
In this issue of the Journal, Maron et al. (4) characterize a subset of patients who have HCM but no evidence of dynamic left ventricular outflow tract obstruction at rest or immediately after exercise. Their major conclusion is that nonobstructive HCM carries a low risk of disease-related adverse events including end-stage heart failure and cardiovascular death. Such a message is obviously good news for patients who fall into this category, but there is a danger that it may also be an oversimplification, which, if interpreted uncritically in clinical practice, might result in a failure to monitor and treat patients whose disease is progressive and potentially life-threatening.
A considerable body of evidence examining clinical outcomes in patients with HCM already exists. From these data we have learned that patients with and without obstruction are vulnerable to disease-related complications and careful examination of the data in the paper by Maron et al. suggests that their cohort is no different in this respect. While the annual mortality in their study was <1%, the rate of disease-related events, many of which were life-threatening or potentially disabling, was in fact quite high. Specifically, 34 of 249 nonobstructive patients (13.7%) died suddenly, had an appropriate implantable cardioverter-defibrillator discharge or developed progressive heart failure, meaning that ∼2% of the cohort experienced a serious event each year. Add to this, the 19% who developed atrial fibrillation or stroke, and the cumulative disease-related morbidity and mortality is considerable. This finding is made all the more remarkable when one considers that the study cohort was biased toward individuals who most probably had a better outcome by excluding patients with severe heart failure symptoms at their initial evaluation.
The low mortality in this study can be seen as a testament to the beneficial effect of targeted therapy, specifically, implantable cardioverter-defibrillators, cardiac transplantation, and stroke prophylaxis. However, the low annual death rate should not mask the fact that sudden cardiac death and progressive heart failure remain a significant problem in nonobstructed patients (5–7). Prevention of sudden cardiac death is facilitated by the use of validated prediction tools and ever more sophisticated defibrillator technology (2,3). In contrast, the treatment of progressive left ventricular dysfunction is largely empirical and is extrapolated (with no supporting evidence) from trials in patients with systolic heart failure caused by ischemic heart disease and dilated cardiomyopathy (2,3). Nevertheless, as the study by Maron et al. corroborates, it is possible to identify a subset of patients at risk of end-stage heart failure by using a relatively simple clinical approach (2,3,5–7). Patients at risk of heart failure require more frequent monitoring, usually in a specialist setting, not only to treat symptoms, but also to detect the consequences of adverse cardiac remodeling including atrial arrhythmia and pulmonary hypertension, the latter a key factor determining the timing and suitability for cardiac transplantation.
It is often implied that the attempt to understand hypertrophic cardiomyopathy is a fool’s errand because of its uniquely heterogeneous nature, but most published evidence suggests that adverse events are in fact predictable and often preventable. Modification of the underlying disease processes that result in ventricular failure is, at least for the moment, an aspiration, but research into this fascinating family of diseases is moving rapidly toward a focus on preventive and personalized interventions, built on an increasingly intricate appreciation of their complex phenotypes.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Elliott is a consultant for and has received speaker fees from Genzyme Inc. and Shire; and is a consultant for MyoKardia and Amicus.
- American College of Cardiology Foundation
- ↵BrainyQuotes. Albert Einstein quotes. Available at: http://www.brainyquote.com/quotes/quotes/a/alberteins103652.html. Accessed February 11, 2016.
- Authors/Task Force members,
- Elliott P.M.,
- Anastasakis A.,
- Borger M.A.,
- et al.
- Gersh B.J.,
- Maron B.J.,
- Bonow R.O.,
- et al.,
- for the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
- Maron M.S.,
- Rowin E.J.,
- Olivotto I.,
- et al.
- Harris K.M.,
- Spirito P.,
- Maron M.S.,
- et al.
- Biagini E.,
- Coccolo F.,
- Ferlito M.,
- et al.
- Coats C.J.,
- Rantell K.,
- Bartnik A.,
- et al.