Bridging the gap: integrating stress echocardiography, iFR, CFR, and FFR in the evaluation of coronary artery disease

Cardiac wasting, a complex and understudied phenomenon, is observed in up to 40% of patients with advanced cancer, contributing to 20-30% of mortality within this cohort. This condition represents a significant determinant of impaired quality of life and increased mortality, highlighting its clinical importance. Numerous pathophysiological mechanisms have been identified in clinical and pre-clinical research as key drivers in the development and progression of cardiac wasting, including elevated circulating inflammatory cytokines, enhanced catabolic processes, hormonal dysregulation, dysfunction of the growth hormone-insulin-like growth factor I (GH-IGF-I) axis, oxidative stress, psychosocial factors, myosin heavy chain isoform switching, and, critically, cardiotoxic effects of anticancer therapies. Clinically, cardiac wasting manifests through a spectrum of symptoms and consequences, including muscle wasting, heart failure-like symptoms, impaired global longitudinal strain (GLS), and structural and functional alterations in the heart, particularly within the left ventricle. These cardiac alterations contribute to progressive cardiovascular decline. Preclinical and clinical studies have confirmed these observations across various models and patient cohorts, demonstrating significant cardiac changes, such as a 33% reduction in cardiomyocyte cross-sectional area, up to 21% decrease in left ventricular mass and 11% reduction in heart weight, and a 50% reduction in left ventricular axon length. Additionally, fibrosis in pre-clinical studies, preservation of left ventricular ejection fraction in some studies, and mild decreases in others, along with an 8.1% reduction in GLS and a 12.1% loss in left ventricular wall thickness, are observed, in conjunction with elevated circulating levels of interleukin-6 (IL-6). Given the substantial morbidity and mortality associated with cardiac wasting in advanced cancer, it is imperative to incorporate comprehensive cardiac assessment into routine follow-up care, refine patient stratification strategies, employ advanced diagnostic technologies in clinical trials, and prioritize research into the cardiovascular impacts of cancer treatments. A concerted focus on advancing the field of cardio-oncology is essential for mitigating the adverse outcomes of cardiac wasting in this vulnerable patient population.