Dynamic right ventricular-pulmonary arterial uncoupling during maximum incremental exercise in exercise pulmonary hypertension and pulmonary arterial hypertension

Abstract

Despite recent advances, the prognosis of pulmonary hypertension (PH) remains poor. While the initial insult in PH implicates the pulmonary vasculature, the functional state, exercise capacity, and survival of such patients are closely linked to right ventricular (RV) function. In the current study, we sought to investigate the effects of maximum incremental exercise on the matching of RV contractility and afterload (i.e. right ventricular-pulmonary arterial [RV-PA] coupling) in patients with exercise PH (ePH) and pulmonary arterial hypertension (PAH). End-systolic elastance (Ees), pulmonary arterial elastance (Ea), and RV-PA coupling (Ees/Ea) were determined using single-beat pressure-volume loop analysis in 40 patients that underwent maximum invasive cardiopulmonary exercise testing. Eleven patients had ePH, nine had PAH, and 20 were age-matched controls. During exercise, the impaired exertional contractile reserve in PAH was associated with blunted stroke volume index (SVI) augmentation and reduced peak oxygen consumption (peak VO₂ %predicted). Compared to PAH, ePH demonstrated increased RV contractility in response to increasing RV afterload during exercise; however, this was insufficient and resulted in reduced peak RV-PA coupling. The dynamic RV-PA uncoupling in ePH was associated with similarly blunted SVI augmentation and peak VO₂ as PAH. In conclusion, dynamic rest-to-peak exercise RV-PA uncoupling during maximum exercise blunts SV increase and reduces exercise capacity in exercise PH and PAH. In ePH, the insufficient increase in RV contractility to compensate for increasing RV afterload during maximum exercise leads to deterioration of RV-PA coupling. These data provide evidence that even in the early stages of PH, RV function is compromised.

Keywords: exercise pulmonary hypertension; pulmonary arterial hypertension; right ventricular–pulmonary arterial coupling.

Fig. 1.

(a) Heart rate increased significantly in all three groups with ePH demonstrating impaired chronotropic reserve compared to controls and PAH. (b) Stroke volume index (SVI) significantly increased during exercise in controls only, with a blunted increase in SVI augmentation (rest-to-exercise response) seen in ePH and PAH. (c) Cardiac index (CI) increased significantly in all three groups, with a blunted increase in CI augmentation seen in ePH and PAH. (d) Oxygen consumption (VO₂) (mL/kg/min) increased significantly in all three groups, with a blunted increase in VO₂ (mL/kg/min) augmentation seen in PAH and ePH. Data are presented as mean ± standard deviation with the blue bars representing data at rest and red bars representing data at peak exercise.

Fig. 2.

(a) End-systolic elastance (Ees) significantly increased in controls and ePH but not in PAH suggesting an impaired exertional contractile reserve in PAH. (b) Arterial elastance (Ea) increased significantly in all three groups with the greatest increase seen in PAH. (c) There was significant decrease in RV-PA coupling (Ees/Ea) from rest-to-peak exercise in PAH. Data are presented as mean ± standard deviation with the blue bars representing data at rest and red bars representing data at peak exercise.

Fig. 3.

Peak stroke volume index (SVI) is associated with peak right ventricular–pulmonary arterial (RV–PA) uncoupling. A scatter plot of change in peak SVI vs. peak RV–PA coupling is depicted. Peak RV–PA coupling is a strong determinant of SVI at peak exercise.