Hemodynamic predictors of survival in scleroderma-related pulmonary arterial hypertension

Abstract

Rationale: Pulmonary arterial hypertension (PAH) related to systemic sclerosis (SSc) has a poorer prognosis compared with other forms of PAH for reasons that remain unexplained.

Objectives: To identify risk factors of mortality in a well-characterized cohort of patients with PAH related to systemic sclerosis (SSc-PAH).

Methods: Seventy-six consecutive patients with SSc (64 women and 12 men; mean age 61 +/- 11 yr) were diagnosed with PAH by heart catheterization in a single center, starting in January 2000, and followed over time. Kaplan-Meier estimates were calculated and mortality risk factors were analyzed.

Measurements and main results: Forty (53%) patients were in World Health Organization functional class III or IV. Mean pulmonary artery pressure was 41 +/- 11 mm Hg, pulmonary vascular resistance (PVR) was 8.6 +/- 5.6 Wood units, and cardiac index was 2.4 +/- 0.7 L/min/m(2). Median follow-up time was 36 months, with 42 deaths observed. Survival estimates were 85%, 72%, 67%, 50%, and 36% at 1, 2, 3, 4, and 5 years, respectively. Multivariate analysis identified PVR (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.03-1.18; P < 0.01), stroke volume index (HR, 0.94; 95% CI, 0.89-0.99; P = 0.02), and pulmonary arterial capacitance (HR, 0.43; 95% CI, 0.20-0.91; P = 0.03) as strong predictors of survival. An estimated glomerular filtration rate less than 60 ml/min/1.73 m(2) portended a threefold risk of mortality.

Conclusions: Our results suggest that specific components of right ventricular dysfunction and renal impairment contribute to increased mortality in SSc-PAH. Understanding the mechanisms of right ventricular dysfunction in response to increased afterload should lead to improved targeted therapy in these patients.

Figure 1.

Algorithm of selection of patients. Highlighted box indicates patients included. Patients with overlap syndrome (n = 15) included 6 with polymyositis/dermatomyositis, 3 with systemic lupus erythematosus, 1 with rheumatoid arthritis, 1 with Sjögren syndrome, 3 with mixed connective tissue disease, and 1 with combined rheumatoid arthritis and Sjögren syndrome. Patients excluded with other overlapping diagnoses (n = 3) included one patient with acute pulmonary embolism, one with sarcoidosis, and one with severe restrictive disease due to obesity. * Refers to patients already on pulmonary arterial hypertension (PAH)-specific therapy before diagnostic catheterization. COPD = chronic obstructive pulmonary disease; ILD = interstitial lung disease; mPAP = mean pulmonary artery pressure; PCWP = pulmonary capillary wedge pressure; PH = pulmonary hypertension; PVH = pulmonary venous hypertension; PVR = pulmonary vascular resistance; SSc = systemic sclerosis.

Figure 2.

Survival curves for all patients and by World Health Organization functional class (WHO FC).

Figure 3.

Survival curves by median values of pulmonary vascular resistance (PVR), stroke volume index (SVI), and pulmonary artery capacitance (SV/PP).