Prevalence, Clinical Significance, and Genetic Basis of Hypertrophic Cardiomyopathy With Restrictive Phenotype Original Research Article

Objectives The purpose of this study was to determine the prevalence, clinical significance, and genetic basis of hypertrophic cardiomyopathy (HCM) with “restrictive phenotype” characterized by restrictive filling and minimal or no left ventricular hypertrophy. Background Hypertrophic cardiomyopathy is a heterogeneous myocardial disorder with a broad spectrum of clinical presentation and morphologic features. Recent reports indicated that some patients with restrictive cardiomyopathy, which is an uncommon condition defined by restrictive filling and reduced diastolic volumes with normal or near normal left ventricular wall thickness and contractile function, have features suggestive of HCM with mutations in cardiac troponin I, myocyte disarray at explant/autopsy, and relatives with HCM. Systematic evaluation of the restrictive phenotype in HCM patients has not been performed. Methods We evaluated 1,226 patients from 688 consecutive HCM families to identify individuals who fulfilled diagnostic criteria for “restrictive phenotype.” Results Nineteen of 1,226 affected individuals (1.5%) from 16 families (2.3%) had the “restrictive phenotype.” During follow up (53.7 ± 49.2 months), 17 patients (89%) experienced dyspnea (New York Heart Association functional class ≥2). The 5-year survival rate from all-cause mortality, cardiac transplantation, or implantable cardioverter-defibrillator discharge was 56.4%. Mutation analysis for 5 sarcomere genes was feasible in 15 of 16 probands. Mutations were found in 8: 4 in beta-myosin heavy chain, and 4 in cardiac troponin I. Conclusions The “restrictive phenotype” in isolation is an uncommon presentation of the clinical spectrum of HCM and is associated with severe limitation and poor prognosis. This phenotype may be associated with beta-myosin heavy chain and cardiac troponin I mutations.