Abstract 16616: Echocardiography Reveals Biventricular Abnormalities in Presymptomatic Phospholamban p.Arg14del Mutation Carriers
Introduction: Echocardiographic myocardial deformation imaging is an emerging tool for assessing cardiac function and identifying preclinical cardiomyopathies. A large subset of our patients diagnosed with dilated cardiomyopathy (DCM) or arrhythmogenic right ventricular cardiomyopathy (ARVC) carry the pathogenic phospholamban (PLN) c.40_42delAGA (p.Arg14del) founder mutation. The natural course of these mutation carriers is characterized by a presymptomatic phase of variable length, after which many carriers progress to overt disease, manifesting as DCM and/or ARVC.
Objective: To identify subclinical structural and functional cardiac abnormalities in presymptomatic carriers of an identical PLN p.Arg14del mutation using echocardiography including state-of-the-art tissue deformation imaging techniques.
Methods: Twenty-eight presymptomatic PLN p.Arg14del mutation carriers (46% males; mean [±SD] age 33±11 years), identified by genetic cascade screening, and 28 healthy matched control subjects were included in this cross-sectional study. Both groups underwent comprehensive transthoracic echocardiography including LV and RV myocardial two-dimensional strain measurements. Global LV early diastolic tissue velocity (Global e’) and global longitudinal systolic strain (GLSS) were assessed from 12 LV segments and from 3 RV segments.
Results: In the mutation carrier group, LV ejection fraction was preserved (59.0±5.2 vs. 58.8±5.3 (%), P=0.788). However, LV mass index was reduced (58.4±13.9 vs. 71.5±15.6 (g/m^2), P=0.002) and we also observed loss of diastolic function (LV early diastolic inflow 0.79±0.15 vs. 0.95±0.18 (m/sec), P=0.001; LV late diastolic inflow 0.52±0.13 vs. 0.60±0.13 (m/sec), P=0.031; Global e’ 6.7±1.3 vs. 7.4±1.2 (cm/s), P=0.081). In addition, RV GLSS was lower in mutation carriers compared with controls (25.4±4.6 vs. 31.4±4.9 (cm/s), P<0.001).
Conclusions: Presymptomatic PLN p.Arg14del mutation carriers already showed slight but significant structural remodeling (reduced LV mass) as well as loss of LV diastolic function and RV systolic function. These findings support the concept of biventricular cardiomyopathy.
Author Disclosures: W.P. te Rijdt: None. Y.M. Hummel: None. J. van Tintelen: None. R.A. de Boer: None. M.P. van den Berg: None.
- © 2014 by American Heart Association, Inc.