Cardiac rhythm profile and heart rate variability in cancer therapy-related cardiac dysfunction among non-Hodgkin lymphoma patients
Authors:   Department of Heart Failure, Public Healthcare Institution – Institute of Cardiology, Chisinau, Republic of Moldova, Bursacovschi Daniela , Revenco Valeriu ,   Department of Cardiology, “Nicolae Testemitanu” State University of Medicine and Pharmacy, Chisinau, Republic of Moldova, Robu Maria ,   Department of Hematology, “Nicolae Testemitanu” State University of Medicine and Pharmacy, Chisinau, Republic of Moldova, Arnaut Oleg ,   Department of Human Physiology and Biophysics, “Nicolae Testemitanu” State University of Medicine and Pharmacy, Chisinau, Republic of Moldova,   Bioinformatics and Computational Medicine Laboratory, “Nicolae Testemitanu” State University of Medicine and Pharmacy, Chisinau, Republic of Moldova,   National Cancer Registry, Public Healthcare Institution – Oncological Institute, Chisinau, Republic of Moldova
Published: February 2025

Background. Predicting the baseline risk of cancer therapy-related cardiac dysfunction in clinical settings remains challenging, even with numerous established risk factors related to both cancer and cardiovascular health. The role of incorporating Holter ECG monitoring into the routine assessment of patients undergoing cancer therapy is not well established. It is not fully understood that this method can enhance the early detection of cancer therapy-related cardiac dysfunction, allowing for timely therapeutic adjustments and improving of the patient’s outcomes. Aim. Emphasize the utility of Holter ECG monitoring in routine clinical practice for the early detection and risk stratification of cancer therapy-related cardiac dysfunction (CTRCD), while also investigating the relationship between cumulative doxorubicin dose and changes in cardiac electrical activity. Materials and patients. The study involved 127 non-Hodgkin lymphoma patients set to begin antitumor treatment. The patients were evaluated at 2 visits: first one before initiation of anti-tumoral treatment and the second at the 6 months period. All patients performed comprehensive echocardiography, blood test analysis and Holter ECG 24h recording. Descriptive statistics for numerical variables included central tendency and dispersion measures. Group differences were assessed using the Mann-Whitney-Wilcoxon test and visualized with box plots, while correlations (Spearman test, 95% CI) were displayed in a heatmap. Categorical data frequencies were reported with 95% CIs, and Pearson's Chi-squared test (Monte Carlo) was used for hypothesis testing, maintaining a significance level of 0.05. Outcomes. At the 6-month follow-up, chemotherapy-induced cardiotoxicity (CTRCD) was identified in 18 patients (14.2%), including both symptomatic and asymptomatic cases. Patients with CTRCD exhibited significantly lower initial heart rate variability (HRV) indices, including SDNN (54.0 vs. 67.0, p=0.007) and SDNNi (42.5 vs. 64.0, p<0.001). Sinus tachycardia was more frequent in the CTRCD group (66.7% vs. 34.0%, p=0.010), highlighting the importance of HRV monitoring for early CTRCD detection. At 6 months, CTRCD patients had a significantly higher median 24-hour heart rate (81.0 bpm vs. 73.5 bpm, p=0.019) and a greater number of supraventricular (847.5 vs. 205.5, p=0.016) and ventricular extrasystoles (204.0 vs. 80.0, p=0.047). Additionally, they received a significantly higher cumulative doxorubicin dose (510.0 mg/m² vs. 200.0 mg/m², p=0.008), which correlated positively with Holter ECG parameters, including supraventricular (Spearman 0.35) and ventricular extrasystoles (Spearman 0.33), as well as QT interval (Spearman 0.23). These findings underscore the need for rigorous cardiac monitoring in chemotherapy patients. Conclusions. These findings highlight the utility of Holter ECG in monitoring rhythm variability and identifying early signs of cardiotoxicity among cancer patients undergoing therapy, especially those receiving cardiotoxic agents like doxorubicin.