Belzutifan-Associated Reversible Heart Failure With Preserved Ejection Fraction in Metastatic Renal Cell Carcinoma

Belzutifan, a hypoxia-inducible factor 2α (HIF-2α) inhibitor, is effective for metastatic renal cell carcinoma (mRCC), although its cardiovascular safety profile remains unclear.

A 52-year-old woman with mRCC developed progressive dyspnea and a 6.7-kg weight gain 27 days after initiating belzutifan as third-line therapy. Chest radiography revealed marked cardiomegaly (cardiothoracic ratio 63.4%), and echocardiography showed preserved left ventricular ejection fraction (67.1%) with mild diastolic dysfunction and findings consistent with congestive heart failure. Intensive diuretic therapy led to rapid improvement, with the cardiothoracic ratio decreasing to 42.7% and NT-proBNP declining from 912 to 203 pg/mL. After belzutifan rechallenge at a reduced dose, NT-proBNP increased again and subsequently normalized after discontinuation due to disease progression.

Belzutifan may be associated with reversible congestive heart failure with preserved ejection fraction. Cardiac evaluation should be considered in patients who develop dyspnea during belzutifan therapy.