Infarct mass and left ventricular mass predict sudden arrhythmic events, and do not predict non-sudden arrhythmic deaths in patients with coronary artery disease

Background: Sudden cardiac death (SCD) is a leading cause of mortality, particularly in coronary artery disease (CAD). When considering implantable cardioverter defibrillator (ICD) placement, clinicians must balance SCD risk against competing risks such as heart failure, myocardial infarction, and non-cardiac deaths. This study evaluated the added prognostic value of cardiac magnetic resonance (CMR) metrics beyond clinical factors and left ventricular ejection fraction (LVEF) for predicting sudden arrhythmic events (SAE) and non-SAE outcomes in CAD patients across a broad LVEF spectrum.

Methods: The DETERMINE and PRE-DETERMINE studies enrolled CAD patients across 66 U.S. centers who underwent cine and LGE-CMR to measure LVEF, LV mass, infarct mass, and grey zone mass (1). The primary endpoint was SAE: SCD, resuscitated cardiac arrest, or appropriate ICD therapy for VT/VF. All deaths not meeting SAE criteria were classified as “non-SAE” outcomes. Secondary endpoints included cardiac and all-cause mortality. Fine-Gray models examined associations of CMR metrics with outcomes, adjusted for (1) age/sex; (2) age/sex, and clinical factors (atrial fibrillation, smoking, diabetes, BMI); and (3) age/sex, clinical factors, and LVEF. Cumulative incidence curves were generated for high vs. low values of key parameters.

Results: Among 761 patients (79% male, median age 63 years [IQR: 55.5–70.8]), 233 (30.6%) had LVEF ≤35% (median LVEF 40%). Median LV mass, infarct mass, and grey zone mass were 111g, 14.7g, and 10.9g. Over a median follow-up of 11.4 years, 63 patients experienced SAEs, including 31 (49%) with LVEF >35%. Non-SAE events occurred in 230 patients. In age/sex and clinical-adjusted models, LVEF, LV mass, infarct mass, and grey zone mass were all significantly associated with SAE. In fully adjusted models (including LVEF), infarct mass (aHR 1.089, 95% CI 1.009–1.176, P=0.029) and LV mass (aHR 1.112, 95% CI 1.044–1.185, P< 0.001) remained independent predictors of SAE. Conversely, none of the CMR metrics, except LVEF in the age/sex and clinical models, predicted non-SAE outcomes (Fig 1).

Cumulative incidence curves showed clear separation between high vs. low LVEF, LV mass, and infarct mass (all p< 0.001). Importantly, patients with preserved LVEF but high infarct mass had higher SAE risk than those with reduced LVEF but low infarct burden (Fig 2).

For secondary outcomes, LVEF, infarct mass, and LV mass were significant predictors of cardiac death (n=95) and all-cause mortality (n=318) in basic and clinical models. After full adjustment, only LV mass remained significant for both endpoints (Fig 3).

Conclusion: CMR-derived infarct and LV mass provide prognostic value beyond clinical variables and LVEF in CAD patients. The added value of infarct mass to LVEF is specific to sudden arrhythmic events, consistent with the role of infarct scar as the substrate for ventricular arrhythmias. These metrics may help refine risk stratification for SCD and improve patient selection for ICD implantation.

Figure 1. Forest plots illustrating the associations between CMR metrics and sudden arrhythmic events (SAE) versus non-SAE outcomes across: A) basic model, B) clinical model, and C) full model
Figure 2. Cumulative incidence curves for SAE outcomes adjusted for age and sex, comparing: A) high vs. low LVEF, B) high vs. low infarct mass, C) high vs low LVEF and infarct mass, and D) high vs. low LV mass
Figure 3. Forest plots showing the associations between CMR metrics and: A) cardiac mortality, and B) all-cause mortality