title: Predictive power of T-wave alternans and of ventricular gradient hysteresis for the occurrence of ventricular arrhythmias in primary prevention cardioverter-defibrillator patients.
abstract: OBJECTIVE
  Left ventricular ejection fraction lacks specificity to predict sudden cardiac death in heart failure. T-wave alternans (TWA; beat-to-beat T-wave instability, often measured during exercise) is deemed a promising noninvasive predictor of major cardiac arrhythmic event. Recently, it was demonstrated that TWA during recovery from exercise has additional predictive value. Another mechanism that potentially contributes to arrhythmogeneity is exercise-recovery hysteresis in action potential morphology distribution, which becomes apparent in the spatial ventricular gradient (SVG). In the current study, we investigated the performance of TWA amplitude (TWAA) during a complete exercise test and of exercise-recovery SVG hysteresis (SVGH) as predictors for lethal arrhythmias in a population of heart failure patients with cardioverter-defibrillators (ICDs) implanted for primary prevention.
  
  
  METHODS
  We performed a case-control study with 34 primary prevention ICD patients, wherein 17 patients (cases) and 17 patients (controls) had no ventricular arrhythmia during follow-up. We computed, in electrocardiograms recorded during exercise tests, TWAA (maximum over the complete test) and the exercise-recovery hysteresis in the SVG. Statistical analyses were done by using the Student t test, Spearman rank correlation analysis, receiver operating characteristics analysis, and Kaplan-Meier analysis. Significant level was set at 5%.
  
  
  RESULTS
  Both SVGH and TWAA differed significantly (P < .05) between cases (mean ± SD, SVGH: -18% ± 26%, TWAA: 80 ± 46 μV) and controls (SVGH: 5% ± 26%, TWAA: 49 ± 20 μV). Values of TWAA and SVGH showed no significant correlation in cases (r = -0.16, P = .56) and in controls (r = -0.28, P = .27). Receiver operating characteristics of SVGH (area under the curve = 0.734, P = .020) revealed that SVGH less than 14.8% discriminated cases and controls with 94.1% sensitivity and 41.2% specificity; hazard ratio was 3.34 (1.17-9.55). Receiver operating characteristics of TWA (area under the curve = 0.699, P = .048) revealed that TWAA greater than 32.5 μV discriminated cases and controls with 93.8% sensitivity and 23.5% specificity; hazard ratio was 2.07 (0.54-7.91).
  
  
  CONCLUSIONS
  Spatial ventricular gradient hysteresis bears predictive potential for arrhythmias in heart failure patients with an ICD for primary prevention, whereas TWA analysis seems to have lesser predictive value in our pilot group. Spatial ventricular gradient hysteresis is relatively robust for noise, and, as it rests on different electrophysiologic properties than TWA, it may convey additional information. Hence, joint analysis of TWA and SVGH may, possibly, improve the noninvasive identification of high-risk patients. Further research, in a large group of patients, is required and currently carried out by our group.
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Sumche
authors.initials: S
authors.lastname: Man
authors.forename: Priscilla V
authors.initials: PV
authors.lastname: De Winter
authors.forename: Arie C
authors.initials: AC
authors.lastname: Maan
authors.forename: Joep
authors.initials: J
authors.lastname: Thijssen
authors.forename: C Jan Willem
authors.initials: CJ
authors.lastname: Borleffs
authors.forename: Wilbert P M
authors.initials: WP
authors.lastname: van Meerwijk
authors.forename: Marianne
authors.initials: M
authors.lastname: Bootsma
authors.forename: Lieselot
authors.initials: L
authors.lastname: van Erven
authors.forename: Ernst E
authors.initials: EE
authors.lastname: van der Wall
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Schalij
authors.forename: Laura
authors.initials: L
authors.lastname: Burattini
authors.forename: Roberto
authors.initials: R
authors.lastname: Burattini
authors.forename: Cees A
authors.initials: CA
authors.lastname: Swenne
mesh_terms: D016022:Case-Control Studies; D016757:Death, Sudden, Cardiac / Q000517:prevention & control*; D017147:Defibrillators, Implantable; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011322:Primary Prevention; D012372:ROC Curve; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D017180:Tachycardia, Ventricular / Q000503:physiopathology* / Q000517:prevention & control*