Pier Giorgio Masci1, Constantinos Doulaptsis2, Erika Bertella2, Alberico Del Torto2, Rolf Symons2, Gianluca Pontone2, Andrea Barison2, Walter Droogné2, Daniele Andreini2, Valentina Lorenzoni2, Paola Gripari2, Saima Mushtaq2, Michele Emdin2, Jan Bogaert2, Massimo Lombardi2. 1. From the Cardiovascular Magnetic Resonance Department (P.G.M., M.L.), and the Cardiology Department (A.B., A.D.T., M.E.), Fondazione CNR/Regione Toscana "G. Monasterio," Pisa, Italy; Departments of Radiology (C.D., R.S., J.B.) and Cardiology (W.D.), Gasthuisberg University Hospital, Leuven, Belgium; Centro Cardiologico Monzino, Milano, Italy (E.B., G.P., D.A., P.G., S.M.); Cardiovascular Section, Department of Clinical Sciences and Community Health, University of Milan, Milano, Italy (D.A.); and Management Institute (V.L.) and Medical Sciences (A.D.T.), Scuola Superiore Sant'Anna, Pisa, Italy (A.D.T., V.L.). masci@ftgm.it pgmasci@tiscali.it. 2. From the Cardiovascular Magnetic Resonance Department (P.G.M., M.L.), and the Cardiology Department (A.B., A.D.T., M.E.), Fondazione CNR/Regione Toscana "G. Monasterio," Pisa, Italy; Departments of Radiology (C.D., R.S., J.B.) and Cardiology (W.D.), Gasthuisberg University Hospital, Leuven, Belgium; Centro Cardiologico Monzino, Milano, Italy (E.B., G.P., D.A., P.G., S.M.); Cardiovascular Section, Department of Clinical Sciences and Community Health, University of Milan, Milano, Italy (D.A.); and Management Institute (V.L.) and Medical Sciences (A.D.T.), Scuola Superiore Sant'Anna, Pisa, Italy (A.D.T., V.L.).
Abstract
BACKGROUND: We conducted a prospective longitudinal study to investigate the yet unknown clinical significance of myocardial fibrosis in patients with non-ischemic cardiomyopathy without history of congestive heart failure (CHF). METHODS AND RESULTS: At 3 tertiary referral centers, 228 patients with non-ischemic cardiomyopathy without history of CHF were studied with cardiovascular magnetic resonance for late gadolinium enhancement (LGE) detection and quantification and prospectively followed up for a median of 23 months. The end point was a composite of cardiac death, onset of CHF, and aborted sudden cardiac death. LGE was detected in 61 (27%) patients. Thirty-one of 61 (51%) patients with LGE reached combined end point when compared with 18 of 167 (11%) patients without LGE (hazard ratio, 5.10 [2.78-9.36]; P<0.001). Patients with LGE had greater risk of developing CHF than patients without LGE (hazard ratio, 5.23 [2.61-10.50]; P<0.001) and higher rate of aborted sudden cardiac death (hazard ratio, 8.31 [1.66-41.55]; P=0.010). Multivariate analysis showed that LGE was associated with high likelihood of composite end point independent of other prognostic determinants, including age; duration of cardiomyopathy; and left ventricular volumes, mass, and ejection fraction (hazard ratio, 4.02 [2.08-7.76]; P<0.001). Improvement χ(2) analysis disclosed that LGE addition to models, including clinical data alone or in combination with parameters of left ventricular remodeling and function, yielded an improvement in outcome prediction (P<0.001). Addition of LGE to age and left ventricular ejection fraction improved risk stratification for composite end point (net reclassification improvement, 29.6%) and onset of CHF (net reclassification improvement, 25.4%; both P<0.001). CONCLUSIONS: In patients with non-ischemic cardiomyopathy without history of CHF, myocardial fibrosis is a strong and independent predictor of outcome, providing incremental prognostic information and improvement in risk stratification beyond clinical data and degree of left ventricular dysfunction.
BACKGROUND: We conducted a prospective longitudinal study to investigate the yet unknown clinical significance of myocardial fibrosis in patients with non-ischemic cardiomyopathy without history of congestive heart failure (CHF). METHODS AND RESULTS: At 3 tertiary referral centers, 228 patients with non-ischemic cardiomyopathy without history of CHF were studied with cardiovascular magnetic resonance for late gadolinium enhancement (LGE) detection and quantification and prospectively followed up for a median of 23 months. The end point was a composite of cardiac death, onset of CHF, and aborted sudden cardiac death. LGE was detected in 61 (27%) patients. Thirty-one of 61 (51%) patients with LGE reached combined end point when compared with 18 of 167 (11%) patients without LGE (hazard ratio, 5.10 [2.78-9.36]; P<0.001). Patients with LGE had greater risk of developing CHF than patients without LGE (hazard ratio, 5.23 [2.61-10.50]; P<0.001) and higher rate of aborted sudden cardiac death (hazard ratio, 8.31 [1.66-41.55]; P=0.010). Multivariate analysis showed that LGE was associated with high likelihood of composite end point independent of other prognostic determinants, including age; duration of cardiomyopathy; and left ventricular volumes, mass, and ejection fraction (hazard ratio, 4.02 [2.08-7.76]; P<0.001). Improvement χ(2) analysis disclosed that LGE addition to models, including clinical data alone or in combination with parameters of left ventricular remodeling and function, yielded an improvement in outcome prediction (P<0.001). Addition of LGE to age and left ventricular ejection fraction improved risk stratification for composite end point (net reclassification improvement, 29.6%) and onset of CHF (net reclassification improvement, 25.4%; both P<0.001). CONCLUSIONS: In patients with non-ischemic cardiomyopathy without history of CHF, myocardial fibrosis is a strong and independent predictor of outcome, providing incremental prognostic information and improvement in risk stratification beyond clinical data and degree of left ventricular dysfunction.
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