Right ventricular dysfunction in systemic sclerosis-associated pulmonary arterial hypertension

Abstract

Background: Systemic sclerosis–associated pulmonary artery hypertension (SScPAH) has a worse prognosis compared with idiopathic pulmonary arterial hypertension (IPAH), with a median survival of 3 years after diagnosis often caused by right ventricular (RV) failure. We tested whether SScPAH or systemic sclerosis–related pulmonary hypertension with interstitial lung disease imposes a greater pulmonary vascular load than IPAH and leads to worse RV contractile function.

Methods and results: We analyzed pulmonary artery pressures and mean flow in 282 patients with pulmonary hypertension (166 SScPAH, 49 systemic sclerosis–related pulmonary hypertension with interstitial lung disease, and 67 IPAH). An inverse relation between pulmonary resistance and compliance was similar for all 3 groups, with a near constant resistance×compliance product. RV pressure–volume loops were measured in a subset, IPAH (n=5) and SScPAH (n=7), as well as SSc without PH (n=7) to derive contractile indexes (end-systolic elastance [Ees] and preload recruitable stroke work [Msw]), measures of RV load (arterial elastance [Ea]), and RV pulmonary artery coupling (Ees/Ea). RV afterload was similar in SScPAH and IPAH (pulmonary vascular resistance=7.0±4.5 versus 7.9±4.3 Wood units; Ea=0.9±0.4 versus 1.2±0.5 mm Hg/mL; pulmonary arterial compliance=2.4±1.5 versus 1.7±1.1 mL/mm Hg; P>0.3 for each). Although SScPAH did not have greater vascular stiffening compared with IPAH, RV contractility was more depressed (Ees=0.8±0.3 versus 2.3±1.1, P<0.01; Msw=21±11 versus 45±16, P=0.01), with differential RV-PA uncoupling (Ees/Ea=1.0±0.5 versus 2.1±1.0; P=0.03). This ratio was higher in SSc without PH (Ees/Ea=2.3±1.2; P=0.02 versus SScPAH).

Conclusions: RV dysfunction is worse in SScPAH compared with IPAH at similar afterload, and may be because of intrinsic systolic function rather than enhanced pulmonary vascular resistive and pulsatile loading.

Figure 1

Example of left ventricular pressure volume loops obtained via preload reduction with inferior vena cava balloon occlusion (IVCBO; top left) and Valsalva maneuver (top right). Relationship of end-systolic elastance (bottom left) and preload recrutiable stroke work (bottom right) by each preload reduction method (n=20 for each).

Figure 2

Pulmonary Vascular Resistance-Compliance Relationship. A)R_PA vs. C_PA in SScPAH (n=166) or IPAH (n=67). Data are fit by non-linear regression, and best fit curves given by C_PA=0.70/ (0.082+R_PA) and C_PA=0.73/ (0.086+R_PA), respectively. B) Log(R_PA)-Log(C_PA) plot shows overlapping data between groups (p=0.71 for group effect by analysis of covariance). C) Product of R_PAxC_PA for pulmonary or D) systemic vascular system, each plot versus respective mean pressure for patients in both SScPAH and IPAH. The RC product was highly constrained in the pulmonary system, with no significant difference between groups when controlling for age and pressure. The systemic RC product was far more variable (p<0.00001; F-test).

Figure 3

Pulmonary Vascular Resistance-Compliance Relationship. A) R_PA vs. C_PA in SScPAH (n=166) or SSc-ILD-PH (n=49). Data are fit by non-linear regression, and best fit curves given by C_PA=0.70/ (0.082+R_PA) and C_PA=0.70/ (0.082+R_PA), respectively. B) Log(R_PA)-Log(C_PA) plot shows overlapping data between groups (p=0.57 for group effect by analysis of covariance). C) Product of R_PAxC_PA for pulmonary or D) systemic vascular system, each plot versus respective mean pressure for patients in both SScPAH and SSc-ILD-PH.

Figure 4

Right Ventricular (RV) Pressure-Volume Loops in six patients, three with A) IPAH and three with B) SScPAH. Steady-state loops (left) in both cohorts show RV pressure rising throughout ejection and peaking at end-systole, consistent with increased RV afterload from PAH. The black dot identifies the end-systolic pressure-volume point, and the dashed line mean loop width (stroke volume). Ea was determined by the ratio of end systolic pressure to SV. In the loops generated during Valsalva maneuver (right), the data are all shifted upward due to the rise in intra-thoracic pressure, but while this is held, phase-2 of the Valsalva maneuver results in a beat-to-beat decline in filling volume, various PV relations including the end-systolic pressure volume relationship (black line). The slope is end-systolic elastance (E_es).

Figure 5

Steady-State signal-averaged right ventricular (RV) pressure-volume loops for IPAH (top) and SScPAH (bottom). Pressure rises throughout ejection consistent with increased afterload.

Figure 6

Steady-State signal-averaged right ventricular (RV) pressure-volume loops for patients without PH, SSc (top, n=7) and without SSc (bottom, n=1). The loops are more rectangular in shape than those in Figure 5, as pressure stays constant or decreases during ejection.