Poor survival in patients with scleroderma and pulmonary hypertension due to heart failure with preserved ejection fraction

Abstract

Pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF) has been poorly studied in patients with systemic sclerosis (SSc). We sought to compare clinical characteristics and survival of SSc patients with PH-HFpEF (SSc-PH-HFpEF) versus pulmonary arterial hypertension (SSc-PAH). We hypothesized that patients with SSc-PH-HFpEF have a similar poor overall prognosis compared with patients with SSc-PAH when matched for total right ventricular load. The analysis included 117 patients with SSc-PH (93 with SSc-PAH versus 24 with SSc-PH-HFpEF) enrolled prospectively in the Johns Hopkins PH Registry. We examined baseline demographics and hemodynamics at diagnostic right heart catheterization (RHC), two-dimensional echocardiographic characteristics, six-minute walking distance (6MWD), treatment modalities, and laboratory values (serum NT-proBNP, creatinine, uric acid, and sodium), and assessed survival. Demographics and clinical features were similar between the two groups. Baseline RHC showed significantly higher pulmonary and right heart pressures in the SSc-PH-HFpEF compared with the SSc-PAH group. Trans-pulmonary gradient (TPG), however, was equally elevated without significant difference between the groups. SSc-PH-HFpEF patients had left atrial enlargement on echocardiography compared with SSc-PAH patients. No significant differences were found between groups for 6MWD, NT-proBNP, and other laboratory values. Although overall median survival time was 4.6 years with no difference in mortality rate between the two groups (SSc-PH-HFpEF versus SSc-PAH: 75% versus 59%; P = 0.26), patients with SSc-PH-HFpEF had a twofold increased risk of death compared with SSc-PAH patients after adjusting for hemodynamics. Concomitant intrinsic pulmonary vascular disease and HFpEF likely contribute to very poor survival in patients with SSc-PH-HFpEF.

Keywords: HFpEF; Scleroderma; left heart disease; pulmonary hypertension.

Fig. 1.

Algorithm of selection of patients. Highlighted boxes indicate patients included. There were 71 patients excluded (ILD/COPD = 58, Overlap = 2, Follow-up < 6 months = 11). SSc, systemic sclerosis; PH, pulmonary hypertension; RHC, right heart catheterization; mPAP, mean pulmonary artery pressure; PAWP, pulmonary arterial wedge pressure; ILD, interstitial lung disease; COPD, chronic obstructive pulmonary disease; FU, follow-up; SSc-PAH, scleroderma-associated pulmonary arterial hypertension; SSc-PH-HFpEF, scleroderma-associated pulmonary hypertension due heart failure and preserved ejection fraction.

Fig. 2.

Kaplan–Meier survival graphs. Patients with SSc-PH-HFpEF (scleroderma-associated pulmonary hypertension due to heart failure with preserved ejection fraction) (dotted line) compared with those with SSc-PAH (scleroderma-associated pulmonary arterial hypertension) (solid line).

Fig. 3.

Kaplan–Meier survival graphs. Patients with Ipc-PH (isolated post-capillary PH; DPG < 7 mmHg and PVR < 3 Wood units) (solid line) compared with those with Cpc-PH (combined pre- post-capillary PH; DPG ≥ 7 mmHg and PVR ≥ 3 Wood units) (dotted line).