Author + information
- Barry J. Maron, MD∗ (, )
- Ethan J. Rowin, MD and
- Martin S. Maron, MD
- Hypertrophic Cardiomyopathy Institute, Division of Cardiology, Tufts Medical Center, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Barry J. Maron, HCM Institute, Tufts Medical Center, #70, 800 Washington Street, Boston, Massachusetts 02111.
Hypertrophic cardiomyopathy (HCM) is a monogenic heart disorder with autosomal dominant inheritance for which clinical recognition and management strategies have matured significantly over the past decade (1). Indeed, HCM has been transformed from an interesting disease oddity with dismal outcome to a contemporary treatable disease with low mortality consistent with extended or normal longevity.
The earliest reports of HCM were largely limited geographically to developed countries of North America and Western Europe in patients of European ancestry, but also shortly thereafter in Japan for which a substantial literature on this disease has resulted (2). However, with enhanced awareness and diagnostic acumen, and the development of dedicated multidisciplinary HCM centers (first in Sydney, Australia) (1), the epidemiology of HCM has evolved to include patients from a wide variety of races, cultures, ethnicities, and both sexes equally. In this commentary, we wish to merge 2 major principles, that is, that HCM is a common treatable genetic disease that is now recognized to occur worldwide.
By searching the Internet and PubMed, direct contact with cardiologists in many countries, and interrogation of clinical records from the patient registries of the Tufts HCM Institute and the patient advocacy organization (Hypertrophic Cardiomyopathy Association), we now recognize clinically identified HCM patients living in 122 countries of the world (64% of the 191 countries with populations exceeding 500,000) (Figure 1). Notably, the populations of countries known to include HCM patients together account for 6.3 billion people, or 88% of the world population (i.e., 7.13 billion), including India and China, which together comprise 2.7 billion people.
Countries with HCM are located within virtually all regions of the 6 populated continents, geographically and culturally diverse as Iceland (at the Arctic Circle), Vietnam, Sri Lanka, Afghanistan, Botswana, Iran, Greenland, and Mongolia. The presence (or absence) of HCM cannot be ascertained in many of the remaining countries due to particularly underdeveloped health care systems with small numbers of physicians and cardiovascular specialists, inadequate diagnostic equipment and treatment facilities, and in some cases compounded by social instability, rampant poverty, or civil war. In many of these circumstances, genetic diseases are simply overwhelmed by more common acquired conditions, for example, infections (including HIV), stroke, systemic hypertension, ischemic heart disease, and rheumatic heart disease. Although data are incomplete, HCM clinical presentation, cardiac morphology, and genetic substrate appear remarkably similar in different regions of the world (1–5).
Genetics and Prevalence
The geographic distribution of HCM can be attributed to spontaneous (de novo) mutations among 11 genes encoding thick and thin filament proteins of the cardiac sarcomere (most commonly beta-myosin heavy chain and myosin-binding protein C) (1). This HCM genetic substrate observed today has been traced back in time to mutations occurring 5 to 10 centuries previously (3). Therefore, HCM can be considered a “new” disease only in terms of its clinical recognition. The robust clinical expression of HCM today is probably due to its often benign natural history and reproductive fitness (1).
Estimates for the prevalence of HCM have come disproportionately from developed countries with mature medical systems, reporting an occurrence of 1:500 in the general population based on clinical expression of the disease phenotype, that is, left ventricular hypertrophy by imaging. A more recent higher estimate of 1:200 takes into account a broader clinical profile based on familial transmission and contemporary imaging, as well as the high frequency of pathogenic sarcomere gene mutations known to occur in the general population (3).
By extrapolation, it is possible to estimate conservatively that as many as 20 million people in the world (including 750,000 Americans) are affected by HCM, making it far more common (up to 35-fold) than the other genetic cardiovascular diseases, for example, ion channelopathies, arrhythmogenic right ventricular cardiomyopathy, Marfan syndrome, and dilated cardiomyopathy.
However, many individuals affected by HCM are unaware of their diagnosis and/or are under-recognized for a variety of reasons: absence of symptoms and minor or subtle clinical or morphological expression, compounded by clinical inexperience with HCM and inadequate diagnostic technology, so that those patients who are inevitably identified constitute only the “tip of the iceberg.”
The present challenge for the overall HCM population is the dissemination of modern clinical diagnostic and management strategies to greater portions of the world, much of it underserved and underdeveloped with respect to technological resources. Barriers to this aspiration are not inconsequential, and unmet needs persist, requiring: 1) greater awareness for disease recognition by committed clinicians, given other more common diseases creating more pressing needs on health care systems and overwhelming HCM in cardiovascular practice, for example, ischemic heart disease, congestive heart failure, and systemic hypertension; 2) expanded patient access to modern therapies and expertise that have greatly reduced HCM-related mortality and changed the natural history of the disease for many patients (e.g., implantable defibrillators, surgical myectomy, or advanced heart failure interventions including transplantation); and 3) personal health insurance programs more widely available to all deserving citizens so that specialized care is not confined to those with economic means. Also, traditional cultural practices in some societies may present psychological barriers to patients for accepting implanted devices or other contemporary technology-based treatments; in some instances, patient hesitancy may also arise from competing homeopathic treatment strategies.
Clinically expressed HCM is the most common inherited cardiovascular disorder, with virtual worldwide occurrence encompassing a diversity of races and cultures, with 20 million people likely affected including many who are undiagnosed or undertreated. This recognition is relevant to the recent maturity achieved in the clinical management of HCM which has led to significantly reduced mortality rates (<1%/year) associated with greatly improved quality of life (1). However, to date, these advances have largely benefited patients in countries and regions that are highly developed medically and scientifically.
Significant obstacles remain in translating contemporary HCM management to countries with less developed technical resources, physician expertise, or patient access to specialized care. Arguably, the principle of transmitting contemporary care to HCM patients in greater portions of the world represents the next frontier and challenge for this complex genetic disease.
Although a widespread genetic disease, HCM suffers in priority as a public health issue, unable to realistically compete in magnitude to the potential global threats of infectious diseases or the impact of chronic cardiovascular conditions. Therefore, the answer to reducing HCM-related morbidity and mortality in currently less developed health care systems does not lie with (or justify) U.S. governmental support, nor will the dilemma be resolved by disseminating relatively inexpensive drugs such as beta-blockers and calcium channel antagonists. Rather, advances in the care of patients with genetic heart diseases such as HCM will come from emerging interest and diagnostic acumen, and the availability of technological medical resources within those countries, supported by the counsel and vision of committed disease experts.
In this regard, there is recent evidence of greater priority and focus on HCM in India (4), China (5), and elsewhere, with development of multidiscipline HCM centers dedicated to diagnosis and management of this disease. For example, in southern India, the first HCM center in that country has been created at Amrita Institute of Medical Sciences and Research in Kochi, Kerala, under the direction of Dr. Hisham Ahamed, now with a cohort of 700 patients assembled over only 3 years, many requiring specialized care. In Beijing, the Fuwai Hospital has become a national referral center for HCM, with a high-volume and well-executed surgical myectomy program (Dr. Shuiyun Wang).
In 2018, the dilemma for HCM is that of a contemporary treatable disease that we now recognize as occurring worldwide, but often in resource-challenged settings, and with all the obstacles that those circumstances present. Nevertheless, there is a rapidly emerging interest in HCM in many parts of the world, with translation into programs that improve quality of life and extend longevity, and mitigate the present disparities in the opportunity for care. It is our expectation that this important impetus, creating opportunities for HCM patients, will continue and grow.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received March 5, 2018.
- Accepted March 8, 2018.
- 2018 American College of Cardiology Foundation
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