Rick Schreurs

ABSTRACT Aim Investigate hemodynamic effects, and their mechanisms, of restoring AV-coupling using pacemaker therapy in normal and failing hearts in a combined computational-experimental- clinical study. Methods Computer simulations were performed in the CircAdapt model of the normal and failing human heart and circulation. Experiments were performed in a porcine model of AV dromotropathy. In a proof-of-principle clinical study, left ventricular (LV) pressure and volume were measured in 22 heart failure patients (LV ejection fraction <35%) with prolonged PR-interval (>230ms) and narrow or non-left bundle branch block QRS complex. Results Computer simulations and animal studies in normal hearts showed that restoring of AV- coupling with unchanged ventricular activation sequence significantly increased LV filling, mean arterial pressure and cardiac output by 10-15%. In computer simulations of failing hearts and in heart failure patients, reducing PR-interval by biventricular pacing (patients: from 300±61 to 137±30ms) resulted in significant increases in LV stroke volume and stroke work (patients: 34±40% and 26±31%, respectively). However, worsening of ventricular dyssynchrony by using right ventricular (RV) pacing abrogated the benefit of restoring AV-coupling. In model simulations, animals and patients, the increase of LV filling and associated improvement of LV pump function coincided with both larger mitral inflow (E- and A-wave area) and reduction of diastolic mitral regurgitation. Conclusions Restoration of AV-coupling by biventricular pacing in normal and failing hearts with prolonged AV conduction leads to a considerable hemodynamic improvement. These results indicate that biventricular or physiological pacing, but not RV pacing, may improve cardiac function in patients with heart failure and prolonged PR-interval