Advanced cancer as a heart failure like syndrome due to cardiac wasting cardiomyopathy: facts and numbers

Abstract

Cancer remains a leading cause of global morbidity and mortality, with nearly 20 million new cases and 9.7 million deaths reported in 2022. Cardiovascular disease is one of the most common causes of death in cancer patients, accounting for over 40% of fatalities. While the field of cardio-oncology has greatly focused on mitigating cardiotoxicity from cancer therapies, mounting evidence suggests that cancer itself induces significant cardiovascular dysfunction. Treatment-naïve cancer patients often have impaired left ventricular ejection fraction, reduced exercise capacity, lean mass loss, and altered heart rate variability. Patients with advanced cancer, who often face symptoms resembling heart failure, including dyspnea, exercise intolerance, and muscle wasting, also exhibit structural and functional cardiac alterations. Cachexia, prevalent in 50–80% of advanced cancer cases, contributes to cardiac wasting characterized by ventricular thinning, fibrosis, and loss of myocardial mass. Studies reveal significant reductions in left ventricular mass, left and right atrial volumes, and myocardial wall thickness in cancer patients, with these structural abnormalities linked to declines in physical performance and quality of life. Echocardiographic analysis revealed a significant reduction in left ventricular (LV) mass by 25% and 28% in cancer patients with and without cachexia, respectively. During on average 4 months of follow-up, 90 patients with cancer lost on average 9.3% of LV mass, and 44% of these patients lost >10% of LV mass. Loss of LV mass >10% may be a new way to define cardio-toxicity and presence of cardiac wasting cardiomyopathy. Wasting of the heart was independently associated with poor prognosis, but only when raw data or adjustments for height were used, but not when body surface area adjustment was applied. Body surface area contains body weight and is hence not useful in a setting of whole body cachexia. Proposed mechanisms for cardiac wasting in cancer include cancer-induced pro-thrombotic states, oxidative stress, local hypoxia, disordered neovascularization, and direct myocardial injury from oncometabolites. Preclinical studies highlight the potential of heart failure therapies, such as beta-blockers (e.g., bisoprolol) and mineralocorticoid receptor antagonists (e.g., spironolactone), in mitigating cardiac wasting and improving survival in cancer. These drugs reduce ventricular mass loss, attenuate cardiac dysfunction, and enhance survival outcomes. Given the strong parallels between advanced cancer and heart failure syndromes, clinical trials are urgently needed to explore the benefits of heart failure therapies in cancer patients. Such interventions may offer both clinically meaningful symptomatic relief and quality of life benefits, reshaping the approach to cardio-oncology care.

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