The factor of massive infusions as a modifier of cyclophosphamide cardiotoxicity: a comprehensive analysis of cardiomyopathy predictors

BACKGROUND. High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (AHSCT) is an effective treatment for resistant autoimmune diseases. However, the use of high-dose cyclophosphamide (CP) is associated with the risk of developing cyclophosphamide-induced cardiomyopathy (CIC). Massive infusion therapy may potentiate CP cardiotoxicity, but its role remains insufficiently studied.

THE AIM: to assess the contribution of infusion load to the development of CP cardiomyopathy and to find an early signs of its development.

PATIENTS AND METHODS. A prospective study was conducted involving 74 patients with multiple sclerosis receiving HDIT-AHSCT and 6 healthy volunteers. Comprehensive clinical, laboratory, and echocardiographic examinations were performed before, on the 3rd, and on the 7th day of therapy. RESULTS. In healthy individuals, infusions caused a transient elevation of NT-proBNP (max. 533.9 pg/ml) accompanied by an increase in heart chamber volumes and a rise in E/e'. Patients developed specific signs of cardiotoxicity: thickening of the walls and an increase in left ventricular (LV) myocardial mass. An NT-proBNP level >533.9 pg/ml on day 3 was associated with myocardial remodeling (ΔLV mass 15.94±26.36 g vs. -0.33±12.70 g, p=0.046) and left ventricular diastolic dysfunction (Δ E/e’ 1.21±2.10 vs. -0.19±1.39, p=0.030). Factor analysis identified three key components of cardiotoxicity, explaining 66.9% of the total data variance.

CONCLUSION. Massive infusion therapy within the HDIT-AHSCT protocol is a significant factor potentiating CP cardiotoxicity. An NT-proBNP level >533.9 pg/ml and echocardiographic signs of remodeling on day 3 serve as early markers of cardiac damage. Awareness of the CF-induced cardiomyopathy early symptoms will help to accurate identification of high-risk patients for timely prevention.

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