Abstract 3377: Cardiac Resynchronization Therapy Induces Cellular Reverse Remodelling in Failing Human Hearts
While phenotypic myocardial alterations including myocyte hypertrophy and interstitial fibrosis are known to occur with advanced heart failure, no information is published on the impact CRT has on the human myocardium. Furthermore, the correlation between myocardial histologic alterations and echocardiographic measures of remodeling and stiffness is unknown. We enrolled 19 CRT eligible subjects (7 female, 9 nonischemic, mean LVEF=23%, LVEDD=6.1cm) into clinical protocol in which serial (0 and 3 months) Echocardiography and RVendomyocardial biopsies (n=12) were analyzed. Echo measurements were analyzed using ASE recommendations. LV stiffness was estimated from the deceleration time of mitral inflow. Collagen content was analyzed using immunohistochemical techniques and myocyte size was estimated with edge detection software. Complete sets of serial biopsy samples and assessable Echo data were analyzed in 7 patients. The LV end-diastolic volume (191±60 ml vs183±74 ml, P=0.046), end-systolic volume(127±49 ml vs 116±53 ml, P<0.01), mass (228±70 vs 192±67, P<0.01) and stiffness(0.20±0.11 vs 0.14±0.12, P=0.02) decreased significantly 3 months after CRT. In tissue samples, myocyte size was significantly reduced (88.9±12.5 μm vs 77.8±12.4 μm, P=0.03) and a trend toward reduction of collagen was observed(12.7±5.1 vs 9.9±4.4, P=0.16). The percent change in LV stiffness significantly correlated with changes observed in myocardial collagen (r=0.82, P=0.02).
Conclusion:CRT therapy results in the regression of myocardial cellular hypertrophy and fibrosis. These observed changes correlate with left ventricular reverse remodeling and improved compliance.