Abstract 16078: Left Ventricular Scarring is a Common Substrate of Electrical Instability in Young Subjects Dying Suddenly With Mitral Valve Prolapse
BACKGROUND- Mitral valve prolapse (MVP) occurs in up to 5% of the general population. Since it may be associated with sudden death (SD), the we evaluated the prevalence of MVP in young SD victims and the pathological substrate accounting for electrical instability.
METHODS- The study has been carried by selecting young SD victims with MVP as the sole cardiac abnormality found at autopsy and 15 age-matched controls who died due to extracardiac causes (mean age 28 years, range 15-43). Gross and histology were carried out according to the SD protocol with sampling from the mitral valve leaflets and ventricular myocardium. In selected cases, primary antibodies against the phosphorilated form of Smad 2 were used.
RESULTS- MVP was the cause of SD in 27 (17 F, mean age 29,7 years, range 14-40) out of 481 cases of cardiovascular SD (6%). Two had Marfan stigmata. Twelve (44%) had an in vivo diagnosis of MVP with mild incompetence and 5 (18.5%) were on beta-blockers due to non sustained ventricular arrhythmias. SD occurred mostly at rest (70%); two women died during pregnancy. MVP leaflets had a four-fold increase in thickness compared to the normal valves (p<0,0001) and showed fragmented elastin and collagen with accumulation of proteoglycans in the fibrosa layer. Histology of the left ventricular myocardium showed a significant endoperimysial and replacement type fibrosis in MVP hearts, particularly at the level of papillary muscle implantation to the left ventricular free wall (100%). By histomorphometry, fibrosis was 26,9±10,9% vs 7,2±4,7% in controls (p<0,0001) and cardiomyocyte diameter was 17,6±4,9 vs 13,2±0,8 in controls (p=0,0006). Immunohistochemistry showed increased nuclear staining for of p-Smad-2 in both mitral valve and cardiac interstitium of MVP cases (p=0.02).
CONCLUSION- MVP represent a no-so rare cause (6%) of arrhythmic SD in the young. Scarring of the left ventricular myocardium, due to increased activation of the intracellular TGF-beta pathway similar to that observed in the valve leaflets, might explain the electrical instability. These myocardial abnormalities, likely induced by stretching of papillary muscles, suggest a role of contrast-enhancement cardiac magnetic resonance in risk stratification of MVP patients.
- © 2011 by American Heart Association, Inc.