The Relationship of LVEF and Myocardial Scar to Long-Term Mortality Risk and Mode of Death in Patients with Non-Ischemic Cardiomyopathy.

Background: Non-ischemic cardiomyopathy (NICM) is a leading cause of reduced left ventricular ejection fraction (LVEF) and is associated with high mortality risk from progressive heart failure and arrhythmias. Myocardial scar on cardiovascular magnetic resonance imaging (CMR) is increasingly recognized as risk marker for adverse outcomes, however LV dysfunction remains the basis for determining a patient's eligibility for primary prophylaxis implantable cardioverter-defibrillator (ICD). We wanted to investigate the relationship of LVEF and scar to long term mortality and mode of death in a large cohort of patients with NICM. Methods: This study is a prospective, longitudinal outcomes registry of 1020 consecutive patients with NICM who underwent clinical CMR for the assessment of LVEF and scar at three centers. Results: During a median follow-up of 5.2 (IQR 3.8, 6.6) years 277 (27%) patients died. On survival analysis LVEF≤35% and scar were strongly associated with all-cause (log-rank test p=0.002 and p<0.001, respectively) and cardiac death (p=0.001 and p<0.001, respectively). While scar was strongly related to sudden cardiac death (SCD) (p=0.001), there was no significant association between LVEF≤35% and SCD-risk (p=0.57). On multivariable analysis including established clinical factors, LVEF and scar are independent risk-markers of all-cause and cardiac death. The addition of LVEF provided incremental prognostic value albeit insignificant discrimination improvement by C-statistic for all-cause and cardiac death, however no incremental prognostic value for SCD. Conversely, scar extent demonstrated significant incremental prognostic value and discrimination improvement for all three endpoints. On net reclassification analysis, the addition of LVEF resulted in no significant improvement for all-cause death 11.0% (95% CI -6.2-25.9%), cardiac death 9.8% (95% CI -5.7-29.3%), and SCD 7.5% (95% CI -41.2-42.9%). Conversely, the addition of scar extent resulted in significant reclassification improvement of 25.5% (95% CI 11.7-41.0%) for all-cause death, 27.0% (95% CI 11.6-45.2%) for cardiac death, and 40.6% (95% CI 10.5-71.8%) for SCD. Conclusions: Myocardial scar and LVEF are both risk markers for all-cause and cardiac death in patients with NICM. However, while myocardial scar has strong and incremental prognostic value for SCD risk stratification, LVEF has no incremental prognostic value over clinical parameters. Scar assessment should be incorporated into patient selection criteria for primary prevention ICD placement.