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

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