Pushing boundaries: Innovating ultrafast ultrasound imaging to explore genotype-phenotype interplay in young hypertrophic cardiomyopathy – Real-time diagnosis and personalized management

Hypertrophic cardiomyopathy (HCM) is the most common form of cardiomyopathy, affecting 1 in 500 individuals globally. When HCM presents in childhood, adolescence, or early adulthood (0-30yo), it carries a high risk of morbidity and mortality, threatening young lives. Notably, HCM is a leading cause of sudden cardiac death (SCD) in adolescents and young adults without prior warning – a devastating condition affecting over 8000 European youths per year.Despite genetic advances, this knowledge has yet to prevent HCM progression or major complications like arrhythmias, stroke, heart failure, or SCD. Early prediction of adverse outcomes is crucial to identify patients who may benefit from advanced therapies like implantable cardioverter-defibrillators (ICD) and heart transplantation.5D ULTRAFAST-HCM will develop new biomarkers using advanced ultrasound to address the limitations of 2D ultrafast ultrasound imaging (UUI) in capturing the heart's complex 3D structure over cardiac cycles (4D), emphasizing the need for volumetric imaging. It will develop innovative 5D-UUI technology (4D with real-time AI-driven post-processing) for unprecedented whole-heart imaging, enabling assessment of new biomarkers. Preliminary data show that increased myocardial stiffness, abnormal fiber organization, and reduced microperfusion are key indicators in young HCM patients. We hypothesize that these factors, quantified through 5D-UUI, are directly linked to adverse outcomes. We will (i) refine 5D-UUI for clinical use, automate acquisition and analysis, (ii) validate new biomarkers predicting high-risk cases, and (iii) develop a new risk prediction model for improved ICD indication.5D ULTRAFAST-HCM will establish this groundbreaking bedside imaging technology and revolutionize patient management. Its success will create a pioneering diagnostic tool that simplifies data collection, enhances patient experience, and offers AI-driven, operator-independent analysis for precise risk assessment.