e16003 Background: Tyrosine kinase inhibitors (TKI) can lead to cardiotoxicity either directly by causing left ventricular dysfunction, or indirectly by increasing blood pressure. In light of prior studies at our institution documenting a high rate of symptomatic heart failure in patients with renal cell carcinoma undergoing treatment with sunitinib, we instituted a prospective screening protocol to characterize the incidence and natural history of TKI-associated cardiotoxicity. Methods: From March-December 2008, patients receiving TKI therapy for renal cell carcinoma received cardiac biomarker screening (NT- BNP and Troponin I at baseline and after week 4 of each cycle) and transthoracic echocardiography (baseline, 1 month, 3 months, and every 3 months thereafter). If biomarkers were elevated or a decline in ejection fraction was observed, patients were referred for cardiology evaluation. Results: Twenty-six patients have been included since the protocol's initiation. No elevations in cardiac troponin I have been observed to date. Eight patients (31%) had elevations in NT-BNP (a sensitive marker for heart failure). The TKIs involved included sunitinib (5 patients), sorafenib (2 patients), and bevacizumab (1 patient). One patient who was treated with sunitinib had frank left ventricular systolic dysfunction. Seven of the eight patients with elevated NT-BNP values had baseline hypertension, and five patients had significant increases in blood pressure during TKI treatment. In all patients with follow-up biomarkers, NT-BNP levels fell after initiation of heart failure therapy. TKI treatment appeared to ‘unmask’ previously subclinical cardiac injury, including prior silent myocardial infarction (one patient), left ventricular hypertrophy (four patients), and valvular disease (three patients). Updated data from the ongoing screening protocol will be presented. Conclusions: The Stanford TKI screening protocol identified a high rate of subclinical cardiotoxicity and allowed for early initiation of heart failure therapy. Further studies are needed to determine if this approach can decrease cardiac morbidity and improve oncologic outcomes by preventing discontinuation or dose interruption of TKI therapy. [Table: see text]
RENAL CELL CARCINOMA PRESENTING WITH HIGH-OUTPUT HEART FAILURE DUE TO ARTERIOVENOUS FISTULA
