Right Ventricular Functional Reserve in Pulmonary Arterial Hypertension

Abstract

Background Right ventricular (RV) functional reserve affects functional capacity and prognosis in patients with pulmonary arterial hypertension (PAH). PAH associated with systemic sclerosis (SSc-PAH) has a substantially worse prognosis as compared to idiopathic PAH (IPAH), even though many measures of resting RV function and pulmonary vascular load are similar. We therefore tested the hypothesis that RV functional reserve is depressed in SSc-PAH patients. Methods and Results RV pressure-volume relations were prospectively measured in IPAH (n=9) and SSc-PAH (n=15) patients at rest and during incremental atrial pacing or supine bicycle ergometry. Systolic and lusitropic function increased at faster heart rates in IPAH patients, but were markedly blunted in SSc-PAH. The recirculation fraction, which indexes intracellular calcium recycling, was also depressed in SSc-PAH (0.32±0.05 versus 0.50±0.05; p=0.039). At matched exercise (25 Watts), SSc-PAH patients failed to augment contractility (end-systolic elastance) whereas IPAH did (p<0.001). RV afterload assessed by effective arterial elastance rose similarly in both groups; thus, ventricular-vascular coupling declined in SSc-PAH. Both end-systolic and end-diastolic RV volumes increased in SSc-PAH patients to offset contractile deficits, whereas chamber dilation was absent in IPAH (+37±10% versus +1±8%, p=0.004, and +19±4% versus −1±6%, p<0.001, respectively). Exercise-associated RV dilation also strongly correlated with resting ventricular-vascular coupling in a larger cohort. Conclusions RV contractile reserve is depressed in SSc-PAH versus IPAH subjects, associated with reduced calcium recycling. During exercise, this results in ventricular-pulmonary vascular uncoupling and acute RV dilation. RV dilation during exercise can predict adverse ventricular-vascular coupling in PAH patients.

Hemodynamic Phenotyping of Pulmonary Hypertension in Left Heart Failure

“…38 RV contractility increases in the presence of increased afterload to preserve RV-arterial coupling. 53 This is observed in PAH at rest, [60][61][62] if not during exercise. 61,62 Altered RV-arterial coupling in severe PH results in increased RV dimensions, systemic congestion, and decreased survival.…”

“…53 This is observed in PAH at rest, [60][61][62] if not during exercise. 61,62 Altered RV-arterial coupling in severe PH results in increased RV dimensions, systemic congestion, and decreased survival. 53 The observation that Cpc-PH is more likely associated with worse RV function is further underscored by the DPG-dependent clustering of PAH, Cpc-PH, and Ipc-PH in relation to RV and LV volumes and a filling pressures-dependent prediction score for precapillary PH developed from invasive and noninvasive measurements in 240 patients referred with PH 63,64 ( Figure 4).…”

Diagnosis, Treatment, and Clinical Management of Pulmonary Arterial Hypertension in the Contemporary Era

“…34 Interestingly, the pathophysiology of CTD-PAH appears somewhat unique, as these patients fail to augment RV contractility during exercise at RV afterload levels that are associated with maintained RV function in iPAH patients. 35 Thus, RV performance differs across PAH subgroups, possibly as a function of disease-specific factors rather than solely by elevated RV afterload.…”

Independence Day

“…2,7 Furthermore, in many clinical trials SSc-PAH appears less responsive to PAH therapy relative to other subgroups. 8,9 The unavailability of PAH treatments that abrogate pulmonary vascular fibrosis effectively or target bona fide SSc-PAH disease-causing pathways is likely to account for this observations to some extent. However, seeking alternative explanations by which to account for the precipitous downward clinical trajectory in SSc-PAH has long been a target of clinical investigation.…”

“…In the current edition of Circulation , Hsu and colleagues 9 provide compelling and much needed insight toward establishing the hallmark features of a right heart pathophysiology that is specific to SSc-PAH. To accomplish this, the authors analyzed differences between rest and exercise (or atrial pacing) in the right ventricular pressure-volume (RV-PV) relationship for 15 patients with SSc-PAH and 9 iPAH patients.…”