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Association of Fibrosis With Mortality and Sudden Cardiac Death in Patients With Nonischemic Dilated Cardiomyopathy
Study Questions:
Does the presence of left ventricular (LV) midwall fibrosis represent an independent predictor of mortality and sudden cardiac death (SCD) in patients with nonischemic cardiomyopathy (NICM)?
Methods:
This prospective study examined 472 patients with NICM referred for cardiac magnetic resonance (CMR) imaging, and compared the presence and extent of midwall fibrosis and adverse events. Inclusion criteria included a diagnosis of NICM for at least 6 months, and required increased LV end-diastolic volume, reduced LV ejection fraction (LVEF), and absence of subendocardial late-gadolinium enhancement on the CMR study (suggesting prior myocardial infarction). The primary outcome was all-cause mortality; secondary outcomes included cardiovascular mortality or cardiac transplantation; SCD; and a composite of heart failure (HF) death, HF hospitalization, or cardiac transplant.
Results:
In this cohort of 472 patients, significant coronary artery disease was excluded by coronary angiography in 348 cases and stress imaging tests in 52 patients; the remaining subjects were less than 40 years of age with no history of angina and no more than one cardiovascular risk factor. Mean age was 51 ± 15 years, 69% were male, and mean LVEF was 37 ± 13%. Median follow-up was 5.3 years, and 73 deaths occurred during the follow-up. Midwall fibrosis was present in 142 patients (30%). Death occurred in 38/142 (27%) with midwall fibrosis, and 35/330 (11%) patients without midwall fibrosis (hazard ratio [HR], 3.0; 95% confidence interval [CI], 1.9-4.7; p < 0.001). After multivariable adjustment in separate models, the presence of midwall fibrosis was independently associated with increased all-cause mortality (HR, 2.4; 95% CI, 1.5-3.9; p < 0.001), cardiovascular mortality or transplantation (HR, 3.2; 95% CI, 2.0-5.3; p < 0.001); SCD (HR, 4.6; 95% CI, 2.8-7.7; p < 0.001); and HF death, HF hospitalization, or transplantation (HR, 1.6; 95% CI, 1.0-2.6; p = 0.049). On separate multivariable adjusted models, the extent of fibrosis was also associated with increased all-cause mortality (HR, 1.1 per 1% increment; 95% CI, 1.1-1.2; p < 0.001); the extent of fibrosis was positively associated with increased rates of each of the secondary endpoints above (p < 0.001 for each). Adding midwall fibrosis to LVEF improved risk reclassification for all-cause mortality (net reclassification improvement, 0.26; 95% CI, 0.11-0.41; p = 0.001).
Conclusions:
In patients with NICM, the presence of LV midwall fibrosis is associated with increased all-cause mortality and other adverse cardiovascular events.
Perspective:
Determining risk of adverse events in patients with NICM can be challenging, and there is significant interest in identifying improved means to risk stratify these individuals. This study finds that midwall fibrosis is present in 30% of these individuals, consistent with the prevalence previously reported in the literature. This large single-center study finds that the presence of midwall fibrosis is a strong independent predictor of future adverse events including all-cause mortality; cardiovascular mortality or transplantation; SCD; and HF death, HF hospitalization, or transplantation. Further, the extent of fibrosis was independently associated with increased rates of each of these endpoints, and the study findings demonstrate an ability to improve risk reclassification for all-cause mortality and SCD. While future multicenter studies are needed to confirm these findings, these results are intriguing, as they suggest a potential means to better risk stratify these patients and identify those who may benefit from implantable cardioverter-defibrillators.
Keywords: Hypertrophy, Left Ventricular, Coronary Artery Disease, Myocardial Infarction, Follow-Up Studies, Risk Factors, Magnetic Resonance Imaging, Heart Transplantation, Heart Diseases, Coronary Angiography, Thromboplastin, Fibrosis, Magnetic Resonance Spectroscopy, Death, Sudden, Cardiac, Cardiomyopathy, Dilated, Defibrillators, Implantable, Exercise Test
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