Association of Fibrosis With Mortality and Sudden Cardiac Death in Patients With Nonischemic Dilated Cardiomyopathy

Importance Risk stratification of patients with nonischemic dilated cardiomyopathy is primarily based on left ventricular ejection fraction (LVEF). Superior prognostic factors may improve patient selection for implantable cardioverter-defibrillators (ICDs) and other management decisions. Objective To determine whether myocardial fibrosis (detected by late gadolinium enhancement cardiovascular magnetic resonance [LGE-CMR] imaging) is an independent and incremental predictor of mortality and sudden cardiac death (SCD) in dilated cardiomyopathy. Design, Setting, and Patients Prospective, longitudinal study of 472 patients with dilated cardiomyopathy referred to a UK center for CMR imaging between November 2000 and December 2008 after presence and extent of midwall replacement fibrosis were determined. Patients were followed up through December 2011. Main Outcome Measures Primary end point was all-cause mortality. Secondary end points included cardiovascular mortality or cardiac transplantation; an arrhythmic composite of SCD or aborted SCD (appropriate ICD shock, nonfatal ventricular fibrillation, or sustained ventricular tachycardia); and a composite of HF death, HF hospitalization, or cardiac transplantation. Results Among the 142 patients with midwall fibrosis, there were 38 deaths (26.8%) vs 35 deaths (10.6%) among the 330 patients without fibrosis (hazard ratio [HR], 2.96 [95% CI, 1.87-4.69]; absolute risk difference, 16.2% [95% CI, 8.2%-24.2%]; P<.001) during a median follow-up of 5.3 years (2557 patient-years of follow-up). The arrhythmic composite was reached by 42 patients with fibrosis (29.6%) and 23 patients without fibrosis (7.0%) (HR, 5.24 [95% CI, 3.15-8.72]; absolute risk difference, 22.6% [95% CI, 14.6%-30.6%]; P<.001). After adjustment for LVEF and other conventional prognostic factors, both the presence of fibrosis (HR, 2.43 [95% CI, 1.503.92]; P<.001) and the extent (HR, 1.11 [95% CI, 1.06-1.16]; P<.001) were independently and incrementally associated with all-cause mortality. Fibrosis was also independently associated with cardiovascular mortality or cardiac transplantation (by fibrosis presence: HR, 3.22 [95% CI, 1.95-5.31], P<.001; and by fibrosis extent: HR, 1.15 [95% CI, 1.10-1.20], P<.001), SCD or aborted SCD (by fibrosis presence: HR, 4.61 [95% CI, 2.75-7.74], P<.001; and by fibrosis extent: HR, 1.10 [95% CI, 1.051.16], P<.001), and the HF composite (by fibrosis presence: HR, 1.62 [95% CI, 1.002.61], P=.049; and by fibrosis extent: HR, 1.08 [95% CI, 1.04-1.13], P<.001). Addition of fibrosis to LVEF significantly improved risk reclassification for all-cause mortality and the SCD composite (net reclassification improvement: 0.26 [95% CI, 0.11-0.41]; P=. 001 and 0.29 [95% CI, 0.11-0.48]; P=. 002, respectively). Conclusions and Relevance Assessment of midwall fibrosis with LGE-CMR imaging provided independent prognostic information beyond LVEF in patients with nonischemic dilated cardiomyopathy. The role of LGE-CMR in the risk stratification of dilated cardiomyopathy requires further investigation. JAMA.2013;309(9):896-908 www.jama.com