The delicate balance of permissive cardiotoxicity strategy in cancer-related cardiac dysfunction at a tertiary Centre: a comparative analysis

Abstract Cancer therapy-related cardiac dysfunction (CTRCD) is a common cause of early suspension of chemotherapy (QT), potentially impacting survival rates. Permissive cardiotoxicity emphasises the continuation of cancer treatments while managing cardiotoxic effects. This study assesses clinical outcomes in patients with CTRCD undergoing a permissive strategy. Methods Retrospective analysis of outpatients (P) with CTRCD referred to a cardio-oncology outpatient clinic at a tertiary centre from April 2021 to December 2023. Results 110P were diagnosed with CTRCD, of these 31P underwent permissive cardiotoxicity strategy. 61% were female and median age of 59 years (IQR 54-69). 65% had 2 or more cardiovascular risk factors and 4P presented pre-existing reduced ejection fraction HF. Breast cancer and haematological malignancies accounted for 77% cases, 48% were stage IV. The majority of cardiotoxic QT regimens included HER2-targeted agents, alkylating agents, and taxanes. 68% developed asymptomatic CTRCD. The baseline median LVEF was 60% (IQR 54–64), which declined to a minimum of 49% (IQR 45–54). All patients started cardioprotective therapy (74% were treated with 3 or 4 classes of foundational HF prognosis-modifying drugs; 29% treated with sacubitril/valsartan). Over a median follow-up of 13 months, 20P continued their planned QT (Subgroup A), while 11 discontinued treatments later (Subgroup B). In Subgroup B, only 3P stopped due to severe symptomatic CTRCD. Comparative analysis showed that older age, male sex, hypertension and pre-existing HF were associated with QT suspension (p<0.05). Although Subgroup B had a higher incidence of NT-proBNP elevation (p=0.012) and lower median minimum LVEF (p=0.008), the relative impairment from baseline did not differ significantly between subgroups. In Subgroup B, 7P (64%) died after QT suspension, with a median survival of 152 days after suspension. In contrast, no deaths or significant cardiac events were reported in Subgroup A, and 13P (42%) already completed prescribed oncological therapy. Conclusion In this cohort under permissive cardiotoxicity strategy, 9% experienced severe CTRCD, leading to suspension of QT; 42% resumed oncologic treatment with no mortality. A permissive cardiotoxicity approach enabled more patients to complete life-saving treatments. The current HF guideline-directed medical therapy and specialized cardio-oncology care may facilitate permissive cardiotoxicity strategies for potentially improved outcomes.