Abstract 1878: Beneficial Electrophysiological Effects of bi-Ventricular Pacing for Cardiac Resynchronization Therapy in a Canine Model of Dyssynchronous Heart Failure
Background: Cardiac resynchronization therapy (CRT) using bi-ventricular (bi-V) pacing improves cardiac function and mortality in patients with heart failure and dyssynchronous contraction (DHF). However, the mechanisms by which bi-V pacing restores DHF-induced electrophysiological remodeling remain controversial. We test the hypothesis that bi-V pacing has enhanced beneficial effects on DHF beyond resynchronization of contraction.
Methods and Results: Adult dogs underwent RV pacing (190–200 bpm) for 6 weeks (DHF: n = 6), or 3-week DHF followed by 3 weeks of resynchronization by either bi-V pacing (n = 6) or RA pacing (A-pace: n = 5) at the same pacing rate. Myocytes were isolated from LV anterior (ANT) and lateral (LTR) walls in non-failing (NF), DHF, bi-V and A-pace dogs. Whole cell patch clamp was performed to measure action potential (AP), transient outward (Ito), inward rectifier (IK1) and delayed rectifier K+ currents (IK). L-type Ca2+ current (ICa,L) and [Ca2+]i transients (CaT) were measured in the absence (baseline) and presence of isoproterenol (ISO) (35°C). The QRS duration was wider in bi-V than in A-pace, the other ECG and hemodynamic parameters were not statistically different between Bi-V and A-pace dogs. Bi-V abbreviated DHF-induced prolongation of APD in the LTR but not ANT cells and diminished the regional gradient of APD, whereas A-pace less abbreviated APD in the LTR cells and still remained the gradient. Bi-V partially restored the DHF-induced down regulation of IK1 and IK but not Ito, whereas A-pace restored only IK1 but not IK and Ito. Furthermore, bi-V fully restored the DHF-induced reduction of ICa,L at baseline and its ISO response, whereas A-pace did not restore ICa,L at baseline but restored its ISO responsiveness. The CaT amplitude at baseline and in ISO were partially restored by both bi-V and A-pace but the restoration was more complete with bi-V compared to A-pace.
Conclusion: Although both bi-V and A-pace resynchronize the LV contraction, DHF-induced downregulation of K+ currents, Ca2+ current and handling were less completely restored by A-pace compared with bi-V pace, suggesting bi-V pacing not only resynchronizes LV contraction but improves regional heterogeneity of repolarization and Ca2+ homeostasis in DHF.