June 21, 2018Open Access
View Full PaperIntrinsic mitral valve alterations in hypertrophic cardiomyopathy sarcomere mutation carriers
Key Result
Subclinical HCM sarcomere mutation carriers had elongated anterior mitral valve leaflets relative to LV end-diastolic volume index compared to healthy controls (0.57 vs 0.51 mm/mL/m2, P=0.013).
Study Design
Type
Observational (n=192)
Structured PICO
Are sarcomere mutations associated with intrinsic mitral valve alterations in carriers prior to the development of left ventricular hypertrophy?
P
Population
192 genotyped individuals, including 50 with overt HCM, 79 with subclinical HCM, and 63 mutation-negative healthy relatives, evaluated for mitral valve structure and function.
E
Exposure
Presence of sarcomere mutations (subclinical HCM and overt HCM)
C
Comparator
Mutation-negative, healthy relatives (normal controls)
O
Outcome
Mitral valve and papillary muscle echocardiographic parameters (including anterior MV leaflet length relative to LV end-diastolic volume index, papillary-septal separation, and relative antero-posterior position ratio of the papillary muscles)surrogate
Sarcomere mutations are associated with primary structural abnormalities of the mitral valve apparatus that predispose to systolic anterior motion, even in carriers with normal left ventricular wall thickness.
Main Result
Absolute Event Rate: 0.57% vs 0.51%
p-value: p=0.013
Abstract
Aims: Mitral valve (MV) abnormalities are recognized features of hypertrophic cardiomyopathy (HCM), and there is preliminary evidence suggesting they are intrinsic phenotypic manifestations of sarcomere mutations, present in mutation carriers without left ventricular (LV) hypertrophy (subclinical HCM). However, further study is required to characterize the nature of these changes and their functional impact. Thus, we performed comprehensive echocardiographic analysis of MV structure and function on a genotyped population. Methods and results: MV and papillary muscle echocardiographic parameters were measured in 192 genotyped individuals, including 50 overt HCM, 79 subclinical HCM, and 63 mutation-negative, healthy relatives as normal controls. Compared to controls, subclinical HCM subjects had elongated anterior MV leaflets relative to LV end-diastolic volume index (0.57 ± 0.02 vs. 0.51 ± 0.02 mm/mL/m2, P = 0.013) and anteriorly displaced papillary muscles decreased papillary-septal separation (31.1 ± 0.7 vs. 34.2 ± 0.9 mm, P = 0.004) and relative antero-posterior position ratio of the papillary muscles (0.67 ± 0.01 vs. 0.71 ± 0.01, P = 0.011. Similar findings were identified comparing overt HCM to controls. These MV changes were associated with an increased prevalence of systolic anterior motion (SAM) of the MV amongst subclinical HCM subjects. Conclusions: Sarcomere mutations are associated with primary abnormalities of the MV apparatus, specifically excess anterior leaflet length relative to LV cavity size and anterior displacement of the papillary muscles; both features predisposing to SAM. These abnormalities appear to be early phenotypic consequences of sarcomere mutations, observed in mutation carriers with normal LV wall thickness.
Cite This Study
Groarke et al. (Thu,) conducted a observational in Hypertrophic cardiomyopathy (n=192). Sarcomere mutations (subclinical HCM) vs. Mutation-negative healthy relatives was evaluated on Anterior MV leaflet length relative to LV end-diastolic volume index (p=0.013). Subclinical HCM sarcomere mutation carriers had elongated anterior mitral valve leaflets relative to LV end-diastolic volume index compared to healthy controls (0.57 vs 0.51 mm/mL/m2, P=0.013).