The Biological Cost of Every Heartbeat: Imaging-Derived Cardiovascular Vulnerability in Infective Endocarditis

Biological cardiovascular vulnerability is defined as an imaging-derived construct integrating myocardial functional impairment, coronary microvascular dysfunction, and modeled hemodynamic burden, including global longitudinal strain, coronary flow reserve, and derived vascular indices. To evaluate whether advanced echocardiographic and coronary Doppler imaging parameters identify biological cardiovascular vulnerability associated with the severity and complications of infective endocarditis beyond conventional structural findings. In this retrospective single-center cohort study, we analyzed consecutive patients with definite infective endocarditis who underwent advanced echocardiographic and coronary Doppler imaging. Comprehensive transthoracic and transesophageal echocardiography assessed vegetation characteristics, left ventricular function, global longitudinal strain (GLS), diastolic indices, right ventricular function, and pulmonary artery systolic pressure. Coronary microvascular function was evaluated noninvasively using transthoracic Doppler-derived coronary flow reserve (CFR) of the left anterior descending artery. Associations with disease severity and perivalvular complications were evaluated using multivariable regression analysis. Reduced coronary flow reserve was independently associated with the composite severe infective endocarditis phenotype, as defined by perivalvular complications, severe valvular dysfunction, or endocarditis team-guided urgent surgical indication. Coronary flow reserve correlated inversely with vegetation size (r = -0.39; <i>p</i> = 0.002) and regurgitation severity (r = -0.36; <i>p</i> = 0.004). Notably, the inverse association between coronary flow reserve and vegetation size showed substantial interindividual variability, particularly among patients with similar vegetation dimensions, suggesting heterogeneity in microvascular vulnerability beyond structural lesion burden. Despite relatively preserved mean arterial pressure across age groups, advanced imaging revealed progressive increases in systemic vascular resistance, declining wall shear stress, impaired microvascular flow, and reduced myocardial reserve. Imaging-derived cardiovascular vulnerability profiles frequently diverged from chronological age, highlighting heterogeneity in cardiovascular reserve despite apparently stable conventional hemodynamic parameters. Advanced echocardiographic and coronary Doppler imaging characterize a spectrum of biological cardiovascular vulnerability that is associated with clinically adjudicated severity in infective endocarditis, rather than serving as independent prognostic predictors.