title: Combined cardiac magnetic resonance imaging and C-reactive protein levels identify a cohort at low risk for defibrillator firings and death.
abstract: BACKGROUND
  Annually, ≈80,000 Americans receive guideline-based primary prevention implantable cardioverter-defibrillators (ICDs), but appropriate firing rates are low. Current selection criteria for ICDs rely on left ventricular ejection fraction, which lacks sensitivity and specificity. Because scar-related myocardial tissue heterogeneity is a substrate for life-threatening arrhythmias, we hypothesized that cardiac magnetic resonance identification of myocardial heterogeneity improves risk stratification through (1) its association with adverse cardiac events independent of clinical factors and biomarker levels and (2) its ability to identify particularly high- and low-risk subgroups.
  
  
  RESULTS
  In 235 patients with chronic ischemic and nonischemic cardiomyopathy with a left ventricular ejection fraction of ≤35% undergoing clinically indicated primary prevention ICD implantation, gadolinium-enhanced cardiac magnetic resonance was prospectively performed to quantify the amount of heterogeneous myocardial tissue (gray zone [GZ]) and dense core scar. Serum high-sensitivity C-reactive protein (hsCRP) and other biomarkers were assayed. The primary end point was appropriate ICD shock for ventricular tachycardia/fibrillation or cardiac death, which occurred in 45 (19%) patients at a 3.6-year median follow-up. On univariable analysis, only diuretics, hsCRP, GZ, and core scar were associated with outcome. After multivariable adjustment, GZ and hsCRP remained independently associated with outcome (P<0.001). Patients in the lowest tertile for both GZ and hsCRP (n=42) were at particularly low risk (0.7% per year event rate), whereas those in the highest tertile for both GZ and hsCRP (n=32) had an event rate of 16.1% per year, P<0.001.
  
  
  CONCLUSIONS
  In a cohort of primary prevention ICD candidates, combining a myocardial heterogeneity index with an inflammatory biomarker identified a subgroup with a very low risk for adverse cardiac events, including ventricular arrhythmias. This novel approach warrants further investigation to confirm its value as a clinical risk stratification tool. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00181233.
authors.affiliation: Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. kwu@jhmi.edu
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Wu
authors.forename: Gary
authors.initials: G
authors.lastname: Gerstenblith
authors.forename: Eliseo
authors.initials: E
authors.lastname: Guallar
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Marine
authors.forename: Darshan
authors.initials: D
authors.lastname: Dalal
authors.forename: Alan
authors.initials: A
authors.lastname: Cheng
authors.forename: Eduardo
authors.initials: E
authors.lastname: Marbán
authors.forename: João A C
authors.initials: JA
authors.lastname: Lima
authors.forename: Gordon F
authors.initials: GF
authors.lastname: Tomaselli
authors.forename: Robert G
authors.initials: RG
authors.lastname: Weiss
mesh_terms: D000328:Adult; D000368:Aged; D015142:Baltimore; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D009202:Cardiomyopathies / Q000150:complications / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D003287:Contrast Media; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control*; D017147:Defibrillators, Implantable; D004554:Electric Countershock / Q000295:instrumentation*; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D053208:Kaplan-Meier Estimate; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009206:Myocardium / Q000473:pathology*; D018579:Patient Selection; D011237:Predictive Value of Tests; D011322:Primary Prevention / Q000295:instrumentation*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013318:Stroke Volume; D017180:Tachycardia, Ventricular / Q000175:diagnosis / Q000209:etiology / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D016896:Treatment Outcome; D014693:Ventricular Fibrillation / Q000175:diagnosis / Q000209:etiology / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; D003287:Contrast Media; D018836:Inflammation Mediators; C064925:gadodiamide; D002097:C-Reactive Protein; D019786:Gadolinium DTPA