Objectives: The aim of our study was to assess the functional and prognostic impact of right-ventricular (RV) – pulmonary artery (PA) (un)-coupling in patients with advanced systolic left heart failure (sLHF).

Background: The physiological concept of right-ventricular (RV) coupling means that in normal RV function the intrinsic RV contractility is well balanced with the pulmonary arterial (PA) vascular load. Furthermore, it is supposed that functional, hemodynamic and prognostic sequelae of pulmonary hypertension and/or right ventricular injury are directly linked to the RV-PA coupling capacity. However, the exact quantification of coupling is complex because it needs a measure that accounts for both intrinsic RV contractility and RV afterload simultaneously. This is only achieved using the pressure-volume catheter technique (PV-loop-Cath).

Methods: In 111 patients with advanced sLHF and indication for CRT (LV-EF ≤  35%, QRS ≥ 130ms) (post-hoc analysis of the prospective Magdeburger CRT Responder Trial, DRKS00011133) the RV intrinsic contractility response to pulmonary vascular afterload (RV-PA coupling) and its hemodynamic and functional clinical consequences were quantified at baseline before CRT implantation by using a combined echocardiographic, Swan-Ganz-, and PV-loop-Cath approach. RV intrinsic contractility (Ees, end-systolic elastance) and RV afterload (Ea, PA elastance) and its coupling ratio (Ees/Ea) were analyzed using a modified PV loop single-beat method.

Results: The baseline RV-PA coupling ratio was normal (Ees/Ea>1) in 28 (25%), moderately un-coupled (Ees/Ea <1 and >0.5) in 54 (49%), and severely un-coupled (Ees/Ea<0.5) in 29 (26%) patients. From normal to severe RV-PA un-coupling, we observed an increase of mean PA pressure (p<0.001), pulmonary vascular resistance (PVR) (p<0.001), trans-pulmonary gradient (TPG) (p=0.041), and a decrease of PA compliance (p<0.001). No significant differences in the diastolic pressure gradients (DPD) and resistance-compliance product (RC time) were determined. In addition, progressive RV-PA un-coupling was associated with a decrease of non-invasive parameters of RV function, such as TAPSE (p<0.001), FAC (p<0.001), and RVOT-fractional shortening (p<0.001), and an increase of tricuspid regurgitation (p<0.001), which was accompanied by a consecutive reduction of RV forward stroke volume (p<0.001). Thirty eight (35%) of the 110 study patients died during a median (interquartile range) follow-up of 48 (30.1 – 59) months. After adjusting for different clinical and (non)-invasive parameters of RV function, PA load and LV performance, low Ees/Ea ratio (HR 0.13, 95% CI: 0.032 – 0.52) and an increased PVR (HR 1.004, 95% CI: 1001 – 1006) remained independent predictors of long-term all-cause mortality in multivariate cox regression analysis. In the subgroup of patients with secondary PH (N= 74, 67%) both remained independently predictive for worse prognosis. In contrast, pre-capillary burden, such as increased DPD or TPG demonstrated no additional independent predictive value for long-term survival.

Conclusion: In patients with advanced systolic heart failure +/- secondary PH RV-PA uncoupling was associated with a higher pulmonary vascular load and worse RV function, and was independently associated with all-cause mortality. In our analysis, pre-capillary burden, such as increased TPG and/or DPD, was not associated with worse prognosis.