Decoding Stroke-Heart Syndrome: A Translational Framework Linking Cerebral Injury to Cardiovascular Dysfunction

Acute ischemic stroke can trigger cardiac injury independent of primary coronary disease, producing manifestations ranging from troponin elevation and electrocardiographic abnormalities to arrhythmias, left ventricular dysfunction, Takotsubo syndrome, and sudden cardiac death, collectively termed stroke-heart syndrome. Cardiac complications affect roughly a quarter of patients within the first month, cluster in the first days, and are the second most frequent cause of death after stroke; older patients, those with severe or insular strokes, those with cardiometabolic comorbidity, and women are disproportionately affected. We propose the Neurocardiac Injury Cascade, an eight-stage framework comprising brain lesion, central autonomic network disruption, catecholamine storm, immune activation, coronary microvascular dysfunction, myocardial injury, electrical instability, and cardiac remodeling. Stages three to five are explicitly modeled as a concurrent, mutually reinforcing module rather than as sequential steps, and each stage is given a definition, an expected time window, and a measurable signature. By organizing these events sequentially, the model links mechanisms with biomarker evolution, imaging findings, and stage-specific therapeutic opportunities. We further propose that chronic comorbidity, principally hypertension and diabetes, does not add stages but sets the gain at existing ones, which has direct consequences for the design of preclinical models and clinical trials. We highlight the role of the insular cortex and lateralized autonomic output, position Takotsubo syndrome as the severe phenotype of the cascade, and address the heterogeneity of post-stroke troponin elevation. This framework integrates diagnosis, risk stratification, and mechanism-based therapies to advance precision neurocardiology and guide future translational and clinical research.