New Perspectives on the Prevalence of Hypertrophic Cardiomyopathy Semsarian, Christopher, MBBS, PhD, MPH; Ingles, Jodie, GradDipGenCouns, PhD, MPH; Maron, Martin S., MD ...
Journal of the American College of Cardiology,
03/2015, Letnik:
65, Številka:
12
Journal Article
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Abstract Hypertrophic cardiomyopathy (HCM) is an important genetic heart muscle disease for which prevalence in the general population has not been completely resolved. For the past 20 years, most ...data have supported the occurrence of HCM at about 1 in 500. However, the authors have interrogated a number of relevant advances in cardiovascular medicine, including widespread fee-for-service genetic testing, population genetic studies, and contemporary diagnostic imaging, as well as a greater index of suspicion and recognition for both the clinically expressed disease and the gene-positive–phenotype-negative subset (at risk for developing the disease). Accounting for the potential impact of these initiatives on disease occurrence, the authors have revisited the prevalence of HCM in the general population. They suggest that HCM is more common than previously estimated, which may enhance its recognition in the practicing cardiovascular community, allowing more timely diagnosis and the implementation of appropriate treatment options for many patients.
Hypertrophic cardiomyopathy Maron, Barry J, MD; Maron, Martin S, Dr
The Lancet (British edition),
01/2013, Letnik:
381, Številka:
9862
Journal Article
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Summary Hypertrophic cardiomyopathy is a common inherited cardiovascular disease present in one in 500 of the general population. It is caused by more than 1400 mutations in 11 or more genes encoding ...proteins of the cardiac sarcomere. Although hypertrophic cardiomyopathy is the most frequent cause of sudden death in young people (including trained athletes), and can lead to functional disability from heart failure and stroke, the majority of affected individuals probably remain undiagnosed and many do not experience greatly reduced life expectancy or substantial symptoms. Clinical diagnosis is based on otherwise unexplained left-ventricular hypertrophy identified by echocardiography or cardiovascular MRI. While presenting with a heterogeneous clinical profile and complex pathophysiology, effective treatment strategies are available, including implantable defibrillators to prevent sudden death, drugs and surgical myectomy (or, alternatively, alcohol septal ablation) for relief of outflow obstruction and symptoms of heart failure, and pharmacological strategies (and possibly radiofrequency ablation) to control atrial fibrillation and prevent embolic stroke. A subgroup of patients with genetic mutations but without left-ventricular hypertrophy has emerged, with unresolved natural history. Now, after more than 50 years, hypertrophic cardiomyopathy has been transformed from a rare and largely untreatable disorder to a common genetic disease with management strategies that permit realistic aspirations for restored quality of life and advanced longevity.
Hypertrophic cardiomyopathy (HCM) has been considered a heterogeneous cardiac disease ascribed solely to single sarcomere gene mutations. However, limitations of this hypothesis suggest that ...sarcomere mutations alone do not adequately explain all HCM clinical and pathobiological features. Disease-causing sarcomere mutations are absent in ∼70% of patients with established disease, and sarcomere gene carriers can live to advanced ages without developing HCM. Some features of HCM are also inconsistent with the single sarcomere gene hypothesis, such as regional left ventricular hypertrophy and myocardial fibrosis, as well as structurally abnormal elongated mitral valve leaflets and remodeled intramural coronary arterioles, which involve tissue types that do not express cardiomyocyte sarcomere proteins. It is timely to expand the HCM research focus beyond a single molecular event toward more inclusive models to explain this disease in its entirety. The authors chart paths forward addressing this knowledge gap using novel analytical approaches, particularly network medicine, to unravel the pathobiological complexity of HCM.
Hypertrophic cardiomyopathy (HCM) is the most common familial heart disease with vast genetic heterogeneity, demonstrated over the past 20 years. Mutations in 11 or more genes encoding proteins of ...the cardiac sarcomere (>1,400 variants) are responsible for (or associated with) HCM. Explosive progress achieved in understanding the rapidly evolving science underlying HCM genomics has resulted in fee-for-service testing, making genetic information widely available. The power of HCM mutational analysis, albeit a more limited role than initially envisioned, lies most prominently in screening family members at risk for developing disease and excluding unaffected relatives, which is information not achievable otherwise. Genetic testing also allows expansion of the broad HCM disease spectrum and diagnosis of HCM phenocopies with different natural history and treatment options, but is not a reliable strategy for predicting prognosis. Interfacing a heterogeneous disease such as HCM with the vast genetic variability of the human genome, and high frequency of novel mutations, has created unforeseen difficulties in translating complex science (and language) into the clinical arena. Indeed, proband diagnostic testing is often expressed on a probabilistic scale, which is frequently incompatible with clinical decision making. Major challenges rest with making reliable distinctions between pathogenic mutations and benign variants, and those judged to be of uncertain significance. Genotyping in HCM can be a powerful tool for family screening and diagnosis. However, wider adoption and future success of genetic testing in the practicing cardiovascular community depends on a standardized approach to mutation interpretation, and bridging the communication gap between basic scientists and clinicians.
In the past 25 years, major advances were achieved in the nosography of cardiomyopathies, influencing the definition and taxonomy of this important chapter of cardiovascular disease. Nearly, 50% of ...patients dying suddenly in childhood or adolescence or undergoing cardiac transplantation are affected by cardiomyopathies. Novel cardiomyopathies have been discovered (arrhythmogenic, restrictive, and noncompacted) and added to update the World Health Organization classification. Myocarditis has also been named inflammatory cardiomyopathy. Extraordinary progress accomplished in molecular genetics of inherited cardiomyopathies allowed establishment of dilated cardiomyopathy as mostly cytoskeleton, force transmission disease; hypertrophic-restrictive cardiomyopathies as sarcomeric, force generation disease; and arrhythmogenic cardiomyopathy as desmosome, cell junction disease. Channelopathies (short and long QT, Brugada, and catecholaminergic polymorphic ventricular tachycardia syndromes) should also be considered cardiomyopathies because of electric myocyte dysfunction. Cardiomyopathies are easily diagnosed but treated only with palliative pharmacological or invasive therapy. Curative therapy, thanks to insights into the molecular pathogenesis, has to target the fundamental mechanisms involved in the onset and progression of these conditions.
Abstract Background Sudden deaths in young competitive athletes are tragic events, with high public visibility. The importance of race and gender with respect to sport and the diagnosis and causes of ...sudden death in athletes has generated substantial interest. Methods The US National Registry of Sudden Death in Athletes, 1980-2011, was accessed to define the epidemiology and causes of sudden deaths in competitive athletes. A total of 2406 deaths were identified in young athletes aged 19 ± 6 years engaged in 29 diverse sports. Results Among the 842 athletes with autopsy-confirmed cardiovascular diagnoses, the incidence in males exceeded that in females by 6.5-fold (1:121; 691 vs 1:787,392 athlete-years; P ≤.001). Hypertrophic cardiomyopathy was the single most common cause of sudden death, occurring in 302 of 842 athletes (36%) and accounting for 39% of male sudden deaths, almost 4-fold more common than among females (11%; P ≤.001). More frequent among females were congenital coronary artery anomalies (33% vs 17% of males; P ≤.001), arrhythmogenic right ventricular cardiomyopathy (13% vs 4%; P = .002), and clinically diagnosed long QT syndrome (7% vs 1.5%; P ≤.002). The cardiovascular death rate among African Americans/other minorities exceeded whites by almost 5-fold (1:12,778 vs 1:60; 746 athlete-years; P <.001), and hypertrophic cardiomyopathy was more common among African Americans/other minorities (42%) than in whites (31%; P ≤.001). Male and female basketball players were 3-fold more likely to be African American/other minorities than white. Conclusions Within this large forensic registry of competitive athletes, cardiovascular sudden deaths due to genetic and/or congenital heart diseases were uncommon in females and more common in African Americans/other minorities than in whites. Hypertrophic cardiomyopathy is an under-appreciated cause of sudden death in male minority athletes.
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