Date Published: March 21, 2017
Publisher: Public Library of Science
Author(s): Xiying Guo, Chaomei Fan, Lei Tian, Yanling Liu, Hongyue Wang, Shihua Zhao, Fujian Duan, Xiuling Zhang, Xing Zhao, Fengqi Wang, Hongguang Zhu, Aiqing Lin, Xia Wu, Yishi Li, Xiaolei Xu.
Severe right ventricular hypertrophy (SRVH) is a rare phenotype in hypertrophic cardiomyopathy (HCM) for which limited information is available. This study was undertaken to investigate the clinical, prognostic and genetic characteristics of HCM patients with SRVH.
HCM with SRVH was defined as HCM with a maximum right ventricular wall thickness ≥10 mm. Whole-genome sequencing (WGS) was performed in HCM patients with SRVH. Multivariate Cox proportional hazards regression models were used to identify risk factors for cardiac death and events in HCM with SRVH. Patients with apical hypertrophic cardiomyopathy (ApHCM) were selected as a comparison group. The clinical features and outcomes of 34 HCM patients with SRVH and 273 ApHCM patients were compared.
Compared with the ApHCM group, the HCM with SRVH group included younger patients and a higher proportion of female patients and also displayed higher cardiovascular morbidity and mortality. The multivariate Cox proportional hazards regression models identified 2 independent predictors of cardiovascular death in HCM patients with SRVH, a New York Heart Association class ≥III (hazard ratio [HR] = 8.7, 95% confidence interval (CI): 1.43-52.87, p = 0.019) and an age at the time of HCM diagnosis ≤18 (HR = 5.5, 95% CI: 1.24-28.36, p = 0.026). Among the 11 HCM patients with SRVH who underwent WGS, 10 (90.9%) were identified as carriers of at least one specific sarcomere gene mutation. MYH7 and TTN mutations were the most common sarcomere mutations noted in this study. Two or more HCM-related gene mutations were observed in 9 (82%) patients, and mutations in either other cardiomyopathy-related genes or ion-channel disease-related genes were found in 8 (73%) patients.
HCM patients with SRVH were characterized by poor clinical outcomes and the presentation of multiple gene mutations.
Hypertrophic cardiomyopathy (HCM) is the primary disease affecting the cardiac muscle and is characterized by heterogeneous genetic, morphological, functional, and clinical features. Left ventricular hypertrophy is the most characteristic feature of HCM [1–2]. Severe right ventricular hypertrophy (SRVH) is a relatively rare subtype of HCM in which myocardial hypertrophy primarily affects the right ventricle, which is generally ignored in HCM in clinical practice. Consequently, the anatomic, genetic, clinical, and prognostic characteristics of patients with SRVH and the clinical relevance of these characteristics have not been described well in the literature. Apical hypertrophic cardiomyopathy (ApHCM) is also a relatively rare variant of HCM and has become a well-established phenotype as a result of its investigation in previous studies; however, ApHCM still follows a variable clinical course [3–6]. Whole-genome sequencing (WGS) can be used to study the genetic basis of HCM. The aims of this study were to investigate the clinical, genetic and prognostic characteristics of HCM patients with SRVH and to compare these data with those of patients with ApHCM.
Pathological changes of the right ventricle are often considered “secondary” to changes of the left ventricle. Moreover, the complex geometry of the right ventricle makes it difficult to measure. However, the right ventricle plays an important role in cardiac pathophysiology and is an independent predictor of death secondary to heart failure, as well as SCD . We conducted WGS in 11 HCM patients with SRVH and identified novel mutations for HCM that may contribute to its diagnosis.
SRVH is an uncommon phenotype in HCM and is characterized by progressive clinical deterioration and a relatively poor prognosis. Multiple gene mutations are associated with this phenotype and may be related to the mechanisms underlying the prognosis and heterogeneity associated with HCM.