Beyond resting ejection fraction: prognostic value of inotropic reserve in cardio-oncology

Background Cardiotoxicity remains a major challenge in contemporary oncology, adversely affecting cancer treatment continuity and long-term cardiovascular outcomes. Conventional resting echocardiographic indices may not detect early myocardial dysfunction. Functional evaluation of left ventricular inotropic reserve (LVCR) using low-dose dobutamine stress echocardiography may allow earlier identification of patients at risk for cancer therapy–related cardiotoxicity. Purpose To assess the prognostic value of early impairment in LVCR for predicting cardiotoxicity in breast cancer patients receiving potentially cardiotoxic antineoplastic therapy. Methods This prospective observational study included 120 women with breast cancer treated with anthracycline- and/or anti-HER2 based regimens. Serial low-dose dobutamine stress echocardiography was performed at baseline, at three-month intervals during cancer therapy, and at 12 months following treatment completion. LVCR was assessed as the myocardial contractile response at peak stress. Impaired LVCR was defined as a blunted inotropic response, characterized by a <5% increase in left ventricular ejection fraction, a <2% improvement in GLS, and/or absence of improvement in wall motion score index (WMSI) >0.20. CTRCD was defined, according to the 2022 ESC Cardio-Oncology Guidelines, as a ≥10% decline in left ventricular ejection fraction to <50% and/or a >15% relative reduction in global longitudinal strain. Patients were stratified according to the development of CTRCD during follow-up; patients who did not develop CTRCD served as the comparison group. The association between LVCR impairment and CTRCD was evaluated using univariate analysis. Results During a mean follow-up of 18 ± 2 months, CTRCD occurred in 16 patients (13.3%). Patients who developed CTRCD demonstrated a significantly impaired LVCR as early as three months after initiation of cancer therapy compared with those who did not develop CTRCD (p < 0.01). Impaired LVCR was significantly associated with the subsequent development of CTRCD (OR 4.1, 95% CI 1.6–10.4, p = 0.003). Eight hospitalizations for heart failure were recorded, all occurring in patients with CTRCD. No cardiovascular deaths were observed. Preservation of LVCR was associated with recovery of left ventricular systolic function in 58% of patients. Conclusions Early impairment of left ventricular inotropic reserve precedes the development of CTRCD in patients undergoing potentially cardiotoxic cancer therapy. LVCR assessment may enhance early risk stratification and help identify patients at increased risk as well as those with potential for recovery of left ventricular function.