Abstract 17047: Nintedanib And Cardiomyopathy: A Vascular Failure?

Abstract

Description of the Case: Patient 1 is a 61-year-old woman with a history of rheumatoid arthritis-related interstitial lung disease (ILD). Six months after initiation of nintedanib, she was diagnosed with new-onset heart failure. Cardiac magnetic resonance imaging (CMR) was consistent with nonischemic cardiomyopathy (NICM) with ejection fraction (EF) of 15-25%. EKG showed new bifascicular block (right bundle branch block and left anterior fascicular block). Nintedanib was discontinued, and four months later, echocardiogram showed recovered EF (50-54%). EKG abnormalities resolved with biventricular pacing. Patient 2 is a 57-year-old-man with a history of scleroderma-related ILD and stable diastolic heart failure (EF = 55-60%). Six months after initiation of nintedanib, he was admitted for heart failure exacerbation. CMR showed NICM with EF = 35%, and EKG showed prolonged QRS (130 ms). Given the rapid progression of cardiomyopathy, nintedanib was discontinued. Discussion: We report two patients with underlying connective tissue disease who developed significant nonischemic cardiomyopathy in temporal association with initiation of nintedanib. Nintedanib is a tyrosine kinase inhibitor, antagonizing three angiogenic signaling pathways mediated by vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and platelet derived growth factor receptor (PDGFR). The nintedanib-treated cohorts of the TOMORROW and INPULSIS trials for idiopathic pulmonary fibrosis showed a high incidence of myocardial infarction (MI). With the recent SCENSIS trial, nintedanib was approved in 2019 for ILD associated with systemic sclerosis. There are likely multifactorial effects of this triple angiokinase inhibitor, seeing that it inhibits multiple growth factors essential for vascular homeostasis, the balance between mesenchymal and endothelial cell fates. Thus, there may be multiple pathways for cardiomyopathy due to “vascular failure,” including MI and importantly, cardiac fibrosis. Based on our observations, we urge other clinicians to report their experience with nintedanib use in patients with underlying connective tissue disease and to carefully monitor these patients for adverse cardiovascular effects.