Pirfenidone is Associated with Decreased Indexed End Diastolic and Systolic Volumes in Patients with HFpEF and a Known History of Idiopathic Pulmonary Fibrosis

Abstract

Background To date, there remains to be a lack of effective treatment modalities for HFpEF, which accounts for approximately 50% of all cases of congestive heart failure. Pirfenidone is a novel anti-fibrotic agent that has been shown to improve pulmonary function in patients with Idiopathic Pulmonary Fibrosis. In pre-clinical studies, pirfenidone has been implicated in decreasing myocardial fibrosis and diastolic dysfunction (Kuwahara et al, Circulation 2002). The effects of this medication on markers of LV function and structure in humans with a history of IPF and HFpEF has not been studied. Hypothesis We hypothesize that patients taking pirfenidone will have favorable changes in echocardiographic parameters of LV function and structure. Methodology We performed a retrospective review of 24 patients with a history of HFpEF and IPF being treated with pirfenidone. All patients had pre and post treatment echocardiograms. Changes in parameters of LV structure (indexed LV mass, end diastolic and end systolic volumes), diastolic function (indexed left atrial volume, trans-mitral Doppler flow patterns, tissue Doppler indices), systolic function (EF) and global LV strain were compared before and after pirfenidone administration. Results mean age of patients involved was 70±6.8 years and patients were predominantly males(76%). 34% patients had a history of CAD, 62% HTN, 16% Atrial fibrillation, 61% hyperlipidemia, 23% diabetes, 25% CKD and 46% obesity. 88% of patients had stage 1 diastolic dysfunction at baseline and 12% with stage 2 diastolic dysfunction. Mean NT pro BNP was 2287±3444 pg/ml . Post pirfenidone treatment, there was a significant reduction in indexed LV end diastolic(-11.9±1.1ml/m2) and end systolic (-6.2±2.3ml/m2) volumes. No significant changes were noted in other parameters. Conclusion Treatment with pirfenidone was associated with decreases in indexed LV end diastolic and end systolic volumes in patients with HFpEF and a known history of IPF. However, contrary to the rest of the hypothesis, no improvements were noted in markers of LV diastolic, systolic function and strain. Our study was retrospective in nature and limited by its small sample size.