Right ventricular pacing improves right heart function in experimental pulmonary arterial hypertension: a study in the isolated heart

Abstract

Right heart failure in pulmonary arterial hypertension (PH) is associated with mechanical ventricular dyssynchrony, which leads to impaired right ventricular (RV) function and, by adverse diastolic interaction, to impaired left ventricular (LV) function as well. However, therapies aiming to restore synchrony by pacing are currently not available. In this proof-of-principle study, we determined the acute effects of RV pacing on ventricular dyssynchrony in PH. Chronic PH with right heart failure was induced in rats by injection of monocrotaline (80 mg/kg). To validate for PH-related ventricular dyssynchrony, rats (6 PH, 6 controls) were examined by cardiac magnetic resonance imaging (9.4 T), 23 days after monocrotaline or sham injection. In a second group (10 PH, 4 controls), the effects of RV pacing were studied in detail, using Langendorff-perfused heart preparations. In PH, septum bulging was observed, coinciding with a reversal of the transseptal pressure gradient, as observed in clinical PH. RV pacing improved RV systolic function, compared with unpaced condition (maximal first derivative of RV pressure: +8.5 + or - 1.3%, P < 0.001). In addition, RV pacing markedly decreased the pressure-time integral of the transseptal pressure gradient when RV pressure exceeds LV pressure, an index of adverse diastolic interaction (-24 + or - 9%, P < 0.01), and RV pacing was able to resynchronize time of RV and LV peak pressure (unpaced: 9.8 + or - 1.2 ms vs. paced: 1.7 + or - 2.0 ms, P < 0.001). Finally, RV pacing had no detrimental effects on LV function or coronary perfusion, and no LV preexcitation occurred. Taken together, we demonstrate that, in experimental PH, RV pacing improves RV function and diminishes adverse diastolic interaction. These findings provide a strong rationale for further in vivo explorations.

Bisoprolol Delays Progression Towards Right Heart Failure in Experimental Pulmonary Hypertension

“…Male Wistar rats were used (150 to 175 g, 30 in total), and experimental PH was induced by monocrotaline (60 mg/kg). 9,18 …”

Perspectives on novel therapeutic strategies for right heart failure in pulmonary arterial hypertension: lessons from the left heart

“…However, these patients display a ''LHF-like'' dyssynchrony due to a complete right bundle branch block as a (late) complication of cardiac surgery and are, therefore, not representative for the PAH population in general. We recently explored the clinical potential of resynchronisation therapy in an experimental model of PAH-induced right heart failure, in the absence of conduction disturbances [84]. We found that pre-excitation of the RV free wall resulted in improved RV systolic function and reduced adverse LV diastolic interaction.…”

“…However, we recently demonstrated that LV and RV dyssynchrony are essentially different: the origin of PAH-related ventricular dyssynchrony lies in regional differences in the duration of the contraction, rather than regional differences in onset of the contraction (e.g. due to a conductance delay); and is highly afterload dependent [83,84].…”

Potential Role of Biventricular Pacing Beyond Advanced Systolic Heart Failure

“…54 In an animal model of RV failure, the improvement in RV function could be produced by RV free wall pre-excitation. 52 An acute study of 67 patients with pulmonary artery hypertension showed enhancement of RV contractility by CRT. 55 To date, there have been very few studies of the longterm benefit of CRT in these patients and their associated response rate.…”