Left atrioventricular coupling index: a novel predictor of cardiovascular adverse events during cardiotoxic therapy in multiple myeloma patients

Introduction Carfilzomib (CFZ) is a proteasome inhibitor used in the treatment of multiple myeloma (MM) and associated with cardiotoxic adverse events. Cardio-Oncology guidelines emphasize cardiovascular risk assessment during potentially cardiotoxic therapies, with echocardiography as the preferred imaging modality (1). While standard echocardiographic evaluation relies on separate left ventricular and atrial parameters, the Left Atrioventricular Coupling index (LACi) is emerging as a novel marker that integrates atrial and ventricular function, providing insight into the interaction between the left chambers. Its clinical relevance in oncology populations, especially patients with multiple myeloma (MM), remains unknown. Purpose This study explores LACi as a predictor of cardiovascular adverse events (CVAEs) during cardiotoxic therapy. Methods A total of 158 MM patients undergoing CFZ treatment were prospectively recruited. Baseline assessments included office blood pressure measurement, 24-hour ambulatory blood pressure monitoring (ABPM), Pulse Wave Velocity (PWV), electrocardiogram (ECG), and transthoracic echocardiography (TTE). LACi was defined as the ratio between left atrial and left ventricular end-diastolic volumes, calculated using the ComPACS software suite; higher LACi values indicated greater impairment of coupling (2). Patients were monitored for CVAEs during CFZ therapy; major CV events included myocardial infarction, heart failure, arrythmias and sudden death. Results Overall, 52.5% of patients experienced CVAEs during CFZ therapy, including major CV events in 22%. Higher LACi was independently associated with an increased risk of CV events in multivariate analysis (OR 1.046 [95% CI 1.001–1.092], p = 0.043). In Cox regression analysis, LACi >28% identified patients with a higher risk of CV events during follow up (HR 2.65 [95% CI 1.21–5.78], p = 0.015). After adjustment for traditional clinical and echocardiographic parameters, including age, left ventricular ejection fraction (LVEF), left ventricular mass index (LVMi), global longitudinal strain (GLS), and left atrial volume index (LAVi), LACi remained an independent predictor of CVAEs, showing improved prognostic performance (HR 3.38 [95% CI 1.26–9.04], p = 0.015). Conclusions LACi emerges as a significant predictor of cardiovascular adverse events during cardiotoxic therapy. Patients with LACi >28% are at increased risk of cardiovascular toxicity, potentially affecting both survival and quality of life. Early identification of high-risk patients may therefore be crucial for optimized cardiovascular risk stratification and the implementation of personalized surveillance strategies.