Abstract 2891: Cardiac Resynchronization Therapy Normalizes in vivo Repolarization and Left Ventricular Action Potential Duration
Cardiac resynchronization therapy (CRT) is a non-pharmacologic treatment that reduces morbidity and mortality in clinical trials of class III and IV heart failure (HF) patients. The cellular mechanisms for the efficacy of CRT are poorly defined. We used a canine model of chronic HF (15 months of RV tachypacing to induce heart failure followed by 9 months of CRT, n=3) to study reverse remodeling of in vivo and myocyte function. A separate group of dogs with 24 months (n=4) of RV tachypacing served as HF controls. Left ventricular midmyocardial myocytes were studied using perforated patch whole cell action potential recordings at 36°C. LV mass was reduced in the CRT group compared to the HF group (201 ± 26 vs. 261 ± 18 g, respectively, p<0.05), vs. 85 ± 5 g in controls. Functional capacity (6 minute walk test) improved in the CRT group compared to the HF group (657 ± 59 vs. 334 ± 33 m, respectively, p<0.05). In vivo repolarization (QTc interval) was improved in the CRT group compared to the HF group (267 ±3 ms vs. 274 ± 9, respectively, p<0.05). Action potential duration at 50 (APD50) and 90% (APD90) repolarization was significantly longer in the HF group compared to normal controls (p<0.05). In the CRT group, the APD50 and APD90 were shorter than in HF myocytes (p<0.05) and did not differ from controls (See figure⇓). In our chronic HF model, there are adverse effects on left ventricular structure and function, and functional capacity, accompanied by significant prolongation of in vivo ventricular repolarization. We found that CRT improved LV mass, functional capacity and ventricular repolarization. CRT results in reverse remodeling of heart failure-induced abnormalities in ventricular repolarization.