Abstract
Background: Sudden cardiac death (SCD) accounts for over 400,000 annual deaths in the United States with coronary artery disease (CAD) as the leading cause. Implantable cardioverter defibrillators (ICDs) are indicated based on a left ventricular ejection fraction (LVEF) cutoff of ≤35%; however, most SCDs occur in those with LVEF >35%, highlighting the need for additional risk markers. Cardiac magnetic resonance imaging (MRI) allows accurate assessment of ventricular volumes, LVEF, mass, and late gadolinium enhancement (LGE) to identify infarcted tissue.
Hypothesis: Cardiac MRI metrics add prognostic value to clinical variables and LVEF for the prediction of sudden arrhythmic events (SAE) in patients with CAD.
Methods: This prospective observational cohort [DETERMINE and PRE-DETERMINE] across 66 centers in the US included 761 patients with a history of CAD. All patients underwent cine and LGE MRI. Quantitative analysis of LVEF, LV mass, infarct mass, and grey zone mass was performed by a central blinded core laboratory. SAE was a composite of SCD, resuscitated VF arrest, or ICD therapy for VT/VF. MRI variables were analyzed using Fine-Gray models with non-SCD as competing event, in three steps: (1) unadjusted [basic model], (2) adjusted for age, sex, BMI, diabetes, smoking, atrial fibrillation [clinical model], (3) adjusted for clinical variables and MRI-derived LVEF [full model].
Results: Mean age was 63.4 years [IQR: 55.5-70.8], and 78.6% were male. Median [IQR] for MRI LVEF was 40.3% [32.7- 48.0] and 233 patients (30.6%) had LVEF≤35%. Median LV mass and infarct mass were 111g [91.4-133.9] and 14.7 g [7.4-22.9], respectively. During a median follow-up of 11.4 years, 63 (8.3%) patients experienced SAE, about half of which (31/63) were in those with LVEF >35%. Lower LVEF, and higher LV mass, infarct mass, and grey zone mass were all significantly associated with SAE in basic and clinical models (Figure). In full model further adjusted for LVEF, LV mass (aHR: 1.11; 95% CI 1.04 - 1.19, p=0.001 per 10 g increase) and infarct mass (aHR: 1.09; 95% CI 1.01-1.18, p=.029 per 5g increase) remained significant, while grey zone was no longer associated.
Conclusion: In CAD patients, greater MRI-detected LV mass and infarct mass are associated with significantly increased risks for SAEs independent of LVEF and traditional clinical risk markers. Incorporating these novel MRI metrics alongside LVEF in future risk models may enhance sudden arrhythmic risk prediction.