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This Special Issue of Diagnostics, titled "Grand Challenges in the Diagnosis and Management of Cardiovascular and Cerebrovascular Diseases", offers a comprehensive collection of original research and reviews spanning major advances in both heart and brain health. The topics covered range from acute and chronic cardiovascular syndromes to cerebrovascular emergencies. Original investigations examine coronary imaging in Kawasaki disease, the neurological impact of intra-aortic balloon pump and ECMO support, and the prognostic role of inflammatory markers such as the neutrophil-to-lymphocyte ratio in large vessel occlusion stroke. The novel approaches highlighted in this collection include the use of machine learning models for stroke prediction in atrial fibrillation, the application of atherogenic indices to population-level risk stratification, and the functional characterization of SOX4 as a genetic determinant of familial atrial fibrillation. Complementing these are state-of-the-art reviews on atrial cardiomyopathy, acute heart failure and non-ischemic cardiomyopathies, and frameworks for early detection of pre-heart failure. Collectively, the Reprint underscores the role of imaging, genetics, biomarkers, and artificial intelligence in shaping the next generation of diagnostics and therapeutics. Guest edited by Prof. Dr. Sonu M. M. Bhaskar, this Special Issue provides a multidisciplinary perspective for clinicians, researchers, and policy leaders committed to reducing the global burden of cardiovascular and cerebrovascular disease.

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