Handoko – RV-pacing in experimental pulmonary hypertension

21 Right heart failure in pulmonary arterial hypertension (PH) is associated with mechanical 22 ventricular dyssynchrony, which leads to impaired right ventricular (RV) function, and by 23 adverse diastolic interaction to impaired left ventricular (LV) function as well. However, 24 therapies aiming to restore synchrony by pacing are currently not available. In this proof-of25 principle study, we determined the acute effects of RV-pacing on ventricular dyssynchrony in 26 PH. 27 Chronic PH with right heart failure was induced in rats by injection of monocrotaline (80 28 mg/kg). To validate for PH-related ventricular dyssynchrony, rats (6 PH, 6 controls) were 29 examined by cardiac magnetic resonance imaging (9.4 Tesla), twenty-three days after 30 monocrotalineor sham-injection. In a second group (10 PH, 4 controls), the effects of RV31 pacing were studied in detail, using Langendorff-perfused heart preparations. 32 In PH, septum bulging was observed, coinciding with a reversal of the trans-septal pressure 33 gradient, as observed in clinical PH. RV-pacing improved RV systolic function, compared to 34 unpaced condition (RV dP/dtmax: +8.5±1.3 %, p<0.001). In addition, RV-pacing markedly 35 decreased PTIRVP>LVP, an index of adverse diastolic interaction (-24±9 %, p<0.01), and RV36 pacing was able to resynchronize time of RV and LV peak-pressure (Δtpeak, unpaced: 9.8±1.2 37 ms vs. paced: 1.7±2.0 ms, p<0.001). Finally, RV-pacing had no detrimental effects on LV 38 function or coronary perfusion, and no LV pre-excitation occurred. 39 Taken together, we demonstrate that in experimental PH, RV-pacing improves RV function 40 and diminishes adverse diastolic interaction. These findings provide a strong rationale for 41 further in vivo explorations. 42 43 44 Handoko – RV-pacing in experimental pulmonary hypertension