Sildenafil Preserves Exercise Capacity in Patients With Idiopathic Pulmonary Fibrosis and Right-sided Ventricular Dysfunction

Abstract

Background: Idiopathic pulmonary fi brosis (IPF) is a progressive lung disease with pulmonary vasculopathy. Objective: The purpose of this study was to determine whether sildenafi l improves 6-min walk distance (6MWD) in subjects with IPF and right ventricular dysfunction. Methods: The IPFnet, a network of IPF research centers in the United States, conducted a randomized trial examining the effect of sildenafi l on 6MWD in patients with advanced IPF, defi ned by carbon monoxide diffusing capacity , 35% predicted. A substudy examined 119 of 180 randomized subjects where echocardiograms were available for independent review by two cardiologists. Right ventricular (RV) hypertrophy (RVH), right ventricular systolic dysfunction (RVSD), and right ventricular systolic pressure (RVSP) were assessed. Multivariable linear regression models estimated the relationship between RV abnormality, sildenafi l treatment, and changes in 6MWD, St. George's Respiratory Questionnaire (SGRQ), the EuroQol instrument, and SF-36 Health Survey (SF-36) from enrollment to 12 weeks. Results: The prevalence of RVH and RVSD were 12.8% and 18.6%, respectively. RVSP was measurable in 71 of 119 (60%) subjects; mean RVSP was 42.5 mm Hg. In the subgroup of subjects with RVSD, subjects treated with sildenafi l experienced less decrement in 6MWD (99.3 m; P 5 .01) and greater improvement in SGRQ (13.4 points; P 5 .005) and EuroQol visual analog scores (17.9 points; P 5 .04) than subjects receiving placebo. In the subgroup with RVH, sildenafi l was not associated with change in 6MWD ( P 5 .13), but was associated with greater relative improvement in SGRQ (14.8 points; P 5 .02) vs subjects receiving placebo. Sildenafi l treatment in those with RVSD and RVH was not associated with change in SF-36. Conclusions: Sildenafi l treatment in IPF with RVSD results in better preservation of exercise capacity as compared with placebo. Sildenafi l also improves quality of life in subjects with RVH and RVSD.CHEST 2013; 143(6):1699-1708Abbreviations: 6MWD 5 6-min walk distance; BNP 5 brain natriuretic peptide; D lco 5 carbon monoxide diffusing capacity; IPF 5 idiopathic pulmonary fi brosis; PAH 5 pulmonary arterial hypertension; PH 5 pulmonary hypertension; QOL 5 quality of life; RHC 5 right-sided heart catheterization; RV 5 right ventricular; RVH 5 right-sided ventricular hypertrophy; RVSD 5 right-sided ventricular systolic dysfunction; RVSP 5 right-sided ventricular systolic pressure;

Prognostic value of right ventricular ejection fraction in pulmonary arterial hypertension

“…RVEF may also prove useful to identify subsets of patients who respond to PAH therapy. As an example, in a study of PH in the setting of idiopathic pulmonary fibrosis, treatment with sildenafil was associated with improvement in exercise capacity, however, only in the subgroup of patients with RV dysfunction at echocardiography [25]. RVEF might detect RV dysfunction earlier than RHC; whether repeated measurement of RVEF may ultimately contribute to fewer invasive investigations in the follow-up of patients treated for PAH requires further study.…”

Pulmonary hypertension associated with left heart and lung diseases

“…Sildenafil was reported to improve 6-minute walking distance in a small open-label study [38], but a subsequent controlled trial did not meet this endpoint [39]. Interestingly, improved quality of life and echocardiographic data were reported in this trial [39]. However, taken together, the current evidence does not support the use of specific treatment for PH associated with interstitial lung disease, COPD, and CPFE.…”

“…Negative results were also reported for ambrisentan and macitentan in IPF patients. Sildenafil was reported to improve 6-minute walking distance in a small open-label study [38], but a subsequent controlled trial did not meet this endpoint [39]. Interestingly, improved quality of life and echocardiographic data were reported in this trial [39].…”

Pulmonary Hypertension in the Course of Diffuse Parenchymal Lung Diseases—State of Art and Future Considerations

“…In 19% of them the signs of right ventricle systolic failure was present. This group achieved a significant improvement in the course of sildenafil treatment, with less decrease of 6MWD compared to placebo, p = 0.01 [58].…”

“…The primary end point (6MWD ≥ 20% improvement) was not achieved, either [57]. In 2013, Han et al published the results of sub-study of STEP-IPF that included 119 patients in whom echocardiography was available [58]. In 19% of them the signs of right ventricle systolic failure was present.…”