Cardiovascular MRI Characterization of the Arrhythmogenic Heart in Nonischemic Cardiomyopathy

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PROJECT SUMMARY Cardiovascular disease is the leading cause of morbidity and mortality. Sudden cardiac death (SCD) associated with ventricular tachycardia or fibrillation (VT/VF) is responsible for 50% of deaths in patients with structural heart disease. The implantable cardioverter defibrillator (ICD) is an established therapy for reducing arrhythmic mortality. Current guidelines for use of primary prevention ICD (i.e., patients without VT/VF history, but at risk) mainly emphasize left ventricular ejection fraction (LVEF). However, only a small percentage of ICD recipients actually receive appropriate ICD shocks, resulting in unnecessary costs and morbidity. While there is strong evidence that ICDs reduce mortality in patients with coronary artery disease, the benefit of primary prevention ICDs in patients with nonischemic cardiomyopathy (NICM) is less robust. Furthermore, SCD mostly occurs in patients with moderate systolic dysfunction who are currently not eligible for an ICD, further highlighting the limitations of LVEF to choose appropriate ICD candidates. Given the limitations of LVEF, there is a pressing need for better risk stratification strategies to identify which NICM patients are most likely to benefit from ICD therapy. Our three specific aims seek to 1) identify the biological basis of cardiac MR (CMR) radiomic phenotyping of the myocardium by investigating the association between endocardial/epicardial electrograms (EGM) and CMR radiomic markers; 2) investigate CMR imaging markers that can identify patients with mild to moderate systolic dysfunction (LVEF of 36% to 50%) at risk of ventricular arrhythmia, who are likely to benefit from prophylactic ICD therapy and ultimately reduce total SCD burden; and 3) identify NICM patients with LVEF 35% undergoing primary prevention ICD implantation who are less likely to benefit from ICD by developing a novel risk prediction model integrating CMR markers. Precise identification of individuals who are at risk of SCD will (a) reduce mortality by offering ICD therapy to patients with mild to moderate systolic dysfunction who are currently not eligible, and (b) reduce morbidity and healthcare costs in ICD-eligible patients who are at low risk of SCD and unlikely to obtain a worthwhile benefit.