Use of pulmonary arterial hypertension-approved therapy in the treatment of non-group 1 pulmonary hypertension at US referral centers

Abstract

Pulmonary hypertension (PH) is a frequent complication of left heart disease and parenchymal lung disease, and it portends increased mortality. A growing number of medications are approved for the treatment of World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH). However, they are not well studied in PH of other etiologies (WHO groups 2-5). We sought to assess treatment approaches used by PAH referral centers in this diverse group of patients. We developed a semiquantitative online survey designed to evaluate the use of PAH-approved therapy by pulmonary vascular disease centers in the United States for management of non-group 1 PH. Thirty of 50 centers completed the survey. Almost all centers (93%) reported using PAH therapy for patients with non-group 1 PH, including 77% with group 2 PH and 80% with group 3 PH. Elevated transpulmonary gradient or pulmonary vascular resistance and the presence of right ventricular (RV) dysfunction were commonly cited as supporting use of PAH therapy in patients with PH secondary to left heart disease. For patients with PH and concomitant parenchymal lung disease, degree of pulmonary function impairment and RV dysfunction were most important in influencing use of PAH therapy. In conclusion, pulmonary vascular disease treatment centers use PAH-approved therapy for patients with WHO group 2-5 PH, mostly relying on hemodynamics and assessment of RV function to identify candidates for therapy. Clinical trials designed to test the efficacy of PAH therapy in PH due to left heart and lung disease are needed, as clinical practice has extended beyond the evidence for these etiologies of PH.

Keywords: chronic obstructive pulmonary disease; heart failure; restrictive lung disease; survey.

Figure 1

Use of pulmonary arterial hypertension (PAH)–directed therapy in non–World Health Organization (WHO) group 1 pulmonary hypertension by pulmonary vascular disease referral centers. Of 30 total survey respondents, the number using PAH-approved vasodilator therapy is given. Almost all centers (29 of 30) reported prescribing PAH-approved therapy outside WHO group 1.

Figure 2

Use of pulmonary arterial hypertension (PAH)–directed therapy in World Health Organization (WHO) group 2 pulmonary hypertension (PH). A, Number of physicians who would utilize PAH-directed therapy for WHO group 2 patients by treating physician specialty. There is no difference by treating specialty in the proportion reporting that he or she would treat WHO group 2 PH (Fisher’s exact test, P = 0.37). B, Criteria used to define out-of-proportion PH in WHO group 2. Respondents were allowed to report more than one criteria. C–E, Cutoffs for transpulmonary gradient (TPG; C) and diastolic pressure gradient (DPG; D). Eighteen respondents reported that they would not consider PAH-approved therapy above a certain pulmonary arterial wedge pressure (PAWP) threshold, the numerical value of which is shown as a cumulative fraction (E). mPAP: mean pulmonary arterial pressure; dPAP: pulmonary arterial diastolic pressure; PVR: pulmonary vascular resistance; RVD: right ventricle dysfunction.

Figure 3

Use of pulmonary arterial hypertension (PAH)–directed therapy in World Health Organization (WHO) group 3 pulmonary hypertension (PH). A, Number of physicians who would utilize PAH-directed therapy for WHO group 3 patients by treating physician specialty. There is no difference by treating specialty in the proportion reporting that he or she would treat WHO group 3 PH (Fisher’s exact test, P = 0.37). B, Criteria used to define out-of-proportion PH in WHO group 3. Mean pulmonary arterial pressure (mPAP) of >35 or >40 mmHg is reported most commonly as the hemodynamic definition of out of proportion in group 3 PH. C, D, Factors influencing the decision to treat with PAH-approved therapy in patients with chronic obstructive pulmonary disease (COPD; C) and idiopathic pulmonary fibrosis (IPF; D). Other criteria reported for COPD patients included pretransplantation status (n = 2), relatively severe PH for degree of parenchymal lung disease as assessed by imaging or pulmonary function testing (n = 7), and as a last resort when other medical therapy is maximized (n = 2). FEV₁: forced expiratory volume in 1 second; RV: right ventricle; PFT: pulmonary function testing; TLC: total lung capacity; ILD: interstitial lung disease; HRCT: high-resolution computed tomography imaging.

Figure 4

Subtypes of group 5 pulmonary hypertension (PH) encountered and treated at pulmonary vascular disease treatment centers. Treatment centers reported treating various causes of group 5 PH with pulmonary arterial hypertension–approved therapy. ESRD on HD: end-stage renal disease on hemodialysis; PLCH: pulmonary Langerhans cell histiocytosis.