The emerging role of left atrial strain in cardiovascular risk stratification for multiple myeloma patients undergoing carfilzomib therapy

Introduction Carfilzomib (CFZ) is a proteasome inhibitor used in the treatment of multiple myeloma (MM) known for its cardiotoxic adverse events. Cardio-Oncology guidelines emphasize cardiovascular risk assessment during cardiotoxic therapy, with echocardiography as the first-line imaging technique. Evaluations typically include left ventricular ejection fraction (EF) and global longitudinal strain (GLS); left atrial strain (LAS), not currently included in the definition of cardiotoxicity, is emerging as a potential marker of cardiac dysfunction. Recent studies highlight LAS in early myocardial damage detection and as a mortality predictor in cancer patients, but its role in CFZ-induced hypertensive events in MM remains unclear. Purpose This study explores LAS as a predictor of CFZ-related hypertensive adverse events in MM patients, with or without pre-existing hypertension. Methods 125 MM patients undergoing CFZ treatment were prospectively recruited. Baseline assessments included medical history, clinical examination, office blood pressure measurement, 24-hour ambulatory blood pressure monitoring (ABPM), Pulse Wave Velocity (PWV), electrocardiogram and transthoracic echocardiography (TTE). LAS values were analysed using Philips QLAB software. Patients were monitored for hypertensive events during CFZ therapy. Results Hypertensive events occurred in 52% of the population, primarily worsening of known arterial hypertension. LAS conduit was significantly worse in hypertensive vs. normotensive patients (-15.1 [8.32] % vs -21.0 ± 7.59 %, p=0.002). In the normotensive population, LAS acted as a predictor of adverse hypertensive events (OR 2.37 [1.02; 5.50]). In the general population analysis LAS conduit was significantly reduced in the subgroup affected by hypertensive events (-16.2 [-20.75; -12.65] % vs. -20.8 [-26.3; 15.4] %, p=0.006); combined with variables such as PWV and Blood Pressure Variability at ABPM, LAS was able to predict risk of occurrence of hypertensive events during treatment (OR 0.96 [0.92-1.00]). Conclusion LAS conduit alteration is associated with increased risk of adverse hypertensive events during CFZ therapy. Its integration in current cardiovascular evaluation protocols dedicated to normotensive MM patients could be useful to identify early myocardial damage and allow better risk stratification in candidates for cardiotoxic therapies.