Cardiac output to peak oxygen consumption slope to unmask cardiac limitations in patients with multiple myeloma

Abstract Background The slope of cardiac output (CO) to metabolic demand (oxygen uptake, VO2) has been proposed as a diagnostic tool in heart failure with preserved ejection fraction (HFpEF) to unmask central and peripheral exercise limitations (Foulkes et al., 2025). While values 5 indicate reduced CO reserve, a slope 6 suggests impaired peripheral oxygen extraction (Chomsky et al., 1996). Cardiac involvement in patients with multiple myeloma (MM) may mimic HFpEF and impairs prognosis. However, resting cardiological examination may not capture these limitations. Thus, HFpEF risk stratification tools, such as H2FPEF and HFA-PEFF scores, may prove useful in patients with MM. Purpose To assess CO/VO2, H2FPEF, and HFA-PEFF scores in MM patients with and without previously diagnosed cardiac involvement with combined cardiopulmonary exercise testing (CPET) and stress echocardiography. Methods Nine MM patients with exertional dyspnea under maintenance therapy and previously treated with high dose melphalan and consecutive stem cell transplantation underwent incremental CPET with simultaneous stress echocardiography on upright bicycle ergometry. CO was measured every two minutes, and VO2 was recorded breath-by-breath. The CO/VO2 slope was calculated from linear regression analysis between CO and VO2 across all exercise stages. Standard CPET and echocardiographic variables were analyzed descriptively. Results Nine patients (7 men, 2 women; mean age 68 ± 7.5 years) were included. Mean predicted peak oxygen consumption (VO2peak) was 92 ± 26 %; three patients were below 18.0 mL/min/kg, the threshold for independent living. Mean CO/VO2 slope was 5.53 ± 1.57, but with considerable interindividual variations (3.15 to 7.65). Five patients showed peripheral limitations (CO/VO2 slope 6), three patients showed markedly reduced slopes (CO/VO2 slope 5), suggesting central limitations. Of these, only one had known cardiac involvement. In addition, mean minute ventilation to carbon dioxide production slope (VE/VCO2) was markedly elevated (44.0 ± 9.0), illustrating impaired ventilatory efficiency. Mean H2FPEF score was 3 ± 2 pts, and mean HFA-PEFF score was 4 ± 1 pts, suggesting an intermediate risk for HFpEF. Conclusions Central and peripheral limitations are common in MM patients. While one patient was known to have cardiac involvement following routine resting cardiological examination, CO/VO2 revealed central limitations in two additional patients suggesting cardiac involvement of MM. Thus, the CO/VO2 slope could have an additive value to unmask central limitations, such as subclinical cardiac involvement and cancer therapy-related cardiac dysfunction in MM. In addition, the H2FPEF and HFA-PEFF score could be useful to risk-stratify MM patients for subclinical signs of HFpEF.For image description, please refer to the figure legend and surrounding text. For image description, please refer to the figure legend and surrounding text.