Cardiorespiratory fitness-based markers of vulnerability to chemotherapy-induced cardiac dysfunction in non-Hodgkin lymphoma

Background

Non-Hodgkin lymphoma (NHL) is associated with significant cardiovascular risks due to treatment-related toxicities. Cardiac monitoring relies heavily on imaging techniques, particularly echocardiography [1], but the prognostic significance of cardiopulmonary exercise testing (CPET) in anticipating cancer treatment–related cardiac dysfunction (CTRCD) remains largely underexplored [2, 3].

Purpose

to determine if baseline CPET performance correlates with later CTRCD in NHL.

Methods

A prospective cohort of 127 patients with NHL was evaluated, after excluding other malignancies, previous chemo- or radiotherapy, established coronary artery disease, or significant valvular pathology. The patients were assessed before initiating antitumor treatment and at six months follow-up using echo and CPET. CTRCD was defined according to the 2022 ESC recommendations. Patients were divided into two groups by 6-month CTRCD status.

Results

At 6 months, 18 patients (14,2%) developed CTRCD (Group I), and the others formed Group II. The cohort comprised 72 males (56.7%) and 55 females (43.3%), with a median age of 62 years (IQR = 14).

During initial CPET, achieving a respiratory exchange ratio (RER) ≥1.10 was significantly more frequent in patients without CTRCD (74.5%, 95% CI: 66–83) compared with those who developed the condition (47.1%, 95% CI: 23–71; Monte Carlo test = 5.3, p = 0.026). Oxygen consumption per heartbeat showed no meaningful difference between groups (median 10.2 vs. 12.1 mL O₂/beat; Mann–Whitney 708, p=0.40). Among muscular workload parameters, patients without CTRCD generated higher power output (124 W, IQR 38.8) compared with those who developed CTRCD (115 W, IQR 23.0; Mann–Whitney 633, p=0.049). Regarding metabolic variables, both peak VO₂ and oxygen uptake kinetics were broadly similar between groups. Peak VO₂ medians were 13.6 mL/kg/min (IQR 3.7) and 15.5 mL/kg/min (IQR 4.4), respectively (p=0.14). No significant differences were observed in VE/VCO₂ slope, anaerobic threshold, VO₂/work rate, or VE/VCO₂. However, VO₂ at anaerobic threshold was higher in the non-CTRCD group (1132 mL/min vs. 880 mL/min; Mann–Whitney 591, p=0.023). The oxygen uptake efficiency slope was also significantly lower in the CTRCD group (median 1811 vs. 2145.5; Mann–Whitney 612, p=0.034).

Conclusion

Patients who developed CTRCD demonstrated poorer cardiopulmonary performance. Those without CTRCD were more able to achieve a maximal exercise test (RER ≥ 1.10), whereas reduced ability to reach maximal effort characterized patients who later manifested CTRCD. A larger proportion of CTRCD patients showed peak VO₂ values <14 mL/kg/min. Both VO₂ at anaerobic threshold and the oxygen uptake efficiency slope were significantly lower in individuals who developed CTRCD. These findings provide an insight for early identification of patients at higher risk of CTRCD, potentially allowing for monitoring and intervention prior to the initiation of oncologic therapy.Distribution of RER ≥1.10For image description, please refer to the figure legend and surrounding text.Workload achieved by study groupsFor image description, please refer to the figure legend and surrounding text.