Pacing therapy for atrioventricular dromotropathy: a combined computational–experimental–clinical study

Investigate haemodynamic effects, and their mechanisms, of restoring atrioventricular (AV)-coupling using pacemaker therapy in normal and failing hearts in a combined computational-experimental-clinical study.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 (HF) patients (LV ejection fraction <35%) with prolonged PR interval (>230 ms) and narrow or non-left bundle branch block QRS complex. 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 HF patients, reducing PR interval by biventricular (BiV) pacing (patients: from 300 ± 61 to 137 ± 30 ms) 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.Restoration of AV-coupling by BiV pacing in normal and failing hearts with prolonged AV conduction leads to considerable haemodynamic improvement. These results indicate that BiV or physiological pacing, but not RV pacing, may improve cardiac function in patients with HF and prolonged PR interval.