[Clinical relevance of genetic testing in hypertrophic cardiomyopathy]. / Rilevanza clinica del test genetico nella cardiomiopatia ipertrofica.

More than two decades have elapsed since the discovery that sarcomere gene defects cause familial hypertrophic cardiomyopathy (HCM). Since then, genetic testing in HCM has developed, and become an important tool in clinical practice for diagnosis and prognosis overall in the Western countries. However its practical benefits are still understimated and clinicians often question about cost-effectiveness of genic testing in HCM patients and their families. This resistance is in contrast with considerable evidence supporting the role of genetics in tailoring management for HCM patients. Several current clinical uses of genetic testing in HCM, ranging from diagnosis in ambiguous situations, identification of disease phenocopies and HCM complex genotypes and confirmation of inherited disease in family members are reviewed. In the near future it is hoped that next generation sequencing will provide further diffusion of genetic testing in HCM and improvement in care.

Obesity and its association to phenotype and clinical course in hypertrophic cardiomyopathy.

OBJECTIVES: This study sought to assess the impact of body mass index (BMI) on cardiac phenotypic and clinical course in a multicenter hypertrophic cardiomyopathy (HCM) cohort. BACKGROUND: It is unresolved whether clinical variables promoting left ventricular (LV) hypertrophy in the general population, such as obesity, may influence cardiac phenotypic and clinical course in patients with HCM. METHODS: In 275 adult HCM patients (age 48 ± 14 years; 70% male), we assessed the relation of BMI to LV mass, determined by cardiovascular magnetic resonance (CMR) and heart failure progression. RESULTS: At multivariate analysis, BMI proved independently associated with the magnitude of hypertrophy: pre-obese and obese HCM patients (BMI 25 to 30 kg/m(2) and >30 kg/m(2), respectively) showed a 65% and 310% increased likelihood of an LV mass in the highest quartile (>120 g/m(2)), compared with normal weight patients (BMI <25 kg/m(2); hazard ratio [HR]: 1.65; 95% confidence interval [CI]: 0.73 to 3.74, p = 0.22 and 3.1; 95% CI: 1.42 to 6.86, p = 0.004, respectively). Other features associated with LV mass >120 g/m(2) were LV outflow obstruction (HR: 4.9; 95% CI: 2.4 to 9.8; p < 0.001), systemic hypertension (HR: 2.2; 95% CI: 1.1 to 4.5; p = 0.026), and male sex (HR: 2.1; 95% CI: 0.9 to 4.7; p = 0.083). During a median follow-up of 3.7 years (interquartile range: 2.5 to 5.3), obese patients showed an HR of 3.6 (95% CI: 1.2 to 10.7, p = 0.02) for developing New York Heart Association (NYHA) functional class III to IV symptoms compared to nonobese patients, independent of outflow obstruction. Noticeably, the proportion of patients in NYHA functional class III at the end of follow-up was 13% among obese patients, compared with 6% among those of normal weight (p = 0.03). CONCLUSIONS: In HCM patients, extrinsic factors such as obesity are independently associated with increase in LV mass and may dictate progression of heart failure symptoms.

[Disease progression and systolic dysfunction in patients with hypertrophic cardiomyopathy: genetic basis, pathophysiology and clinical presentation]. / Progressione di malattia e disfunzione sistolica nei pazienti con cardiomiopatia ipertrofica: basi genetiche, fisiopatologia e presentazione clinica.

Progressive heart failure associated with left ventricular remodeling and systo-diastolic dysfunction is one of the most severe complications of hypertrophic cardiomyopathy (HCM). Such condition, for the lack of a better term, is referred to as end-stage (ES) HCM. During the last decade, we have begun to understand the mechanisms underlying progression from a hyperdynamic left ventricle to the striking patterns of ES. To date, different aspects of HCM progression remain obscure, including potential strategies for management and prevention. On the basis of recent evidence, it is appropriate to emphasize these aspects, which may be difficult to identify, particularly in the early stages when systolic function appears relatively preserved. Nevertheless, it is at these early stages that treatment may potentially interfere with the clinical evolution of HCM toward ES and heart failure. The possibility of early identification of patients at risk of ES progression may ultimately impact on the natural history of the disease in this challenging patient subgroup.