Fluoropyrimidine induced cardiotoxicity in colorectal cancer patients: a multimodal approach

Background Fluoropyrimidines are among the most commonly used chemotherapeutic agents in the treatment of colorectal cancer, yet fluoropyrimidine-related cardiotoxicity remains a major and often underdiagnosed clinical problem. In this context, the integration of cardiovascular, renal, and genetic markers may improve risk stratification and the early detection of cardiotoxicity. Purpose The aim of this study was to evaluate a multimodal baseline assessment in colorectal cancer patients treated with fluoropyrimidines. Methods One hundred and eight outpatients with a first diagnosis of localized or metastatic colorectal cancer were consecutively enrolled. All patients underwent a comprehensive baseline evaluation prior to initiation of a fluoropyrimidine-containing chemotherapy regimen. The multimodal assessment included: clinical cardiovascular evaluation; routine blood chemistry to estimate glomerular filtration rate (GFR) using the MDRD formula; genetic analysis of variants in fluoropyrimidine metabolism genes associated with cardiotoxicity risk; transthoracic echocardiography to assess left ventricular ejection fraction (LVEF) and estimate central venous pressure; and renal echo-Doppler examination to evaluate RRI. Peak systolic and end-diastolic velocities of the segmental renal arteries were obtained by pulsed Doppler flow, and renal resistive index (RRI) was subsequently calculated. Results The overall mean age was 68±3 years; 52 patients (48%) were male and 56 (52%) were female. At baseline, mean RRI was 0.636±0.082. A statistically significant inverse correlation was observed between RRI and baseline GFR (Pearson r=−0.272, p=0.031), supporting the interplay between renal perfusion and systemic vascular function. Thirty-one patients completed the one-year follow-up. During follow-up, 32% developed a significant increase in blood pressure, while acute coronary syndromes requiring revascularization and hospitalizations for heart failure occurred in 6% and 8% of patients, respectively. Although patients experiencing cardiovascular events showed higher RRI values over time, no statistically significant association was detected. The higher incidence of arterial hypertension occurred during the first month of therapy, regardless of the inclusion of bevacizumab in the chemotherapy regimen. Conclusions These findings highlight the potential role of RRI as part of a broader, multimodal diagnostic strategy for fluoropyrimidine-induced cardiotoxicity. Integrating renal vascular assessment with cardiac imaging, clinical evaluation, and fluoropyrimidine metabolic profiling may improve early identification of patients at increased cardiovascular risk. Further prospective studies are needed to better define and optimize risk stratification and management strategies for fluoropyrimidine-induced cardiotoxicity within an integrated and multidisciplinary cardio-oncology framework.