title: Sympathetic activity-associated periodic repolarization dynamics predict mortality following myocardial infarction.
abstract: BACKGROUND
  Enhanced sympathetic activity at the ventricular myocardium can destabilize repolarization, increasing the risk of death. Sympathetic activity is known to cluster in low-frequency bursts; therefore, we hypothesized that sympathetic activity induces periodic low-frequency changes of repolarization. We developed a technique to assess the sympathetic effect on repolarization and identified periodic components in the low-frequency spectral range (≤0.1 Hz), which we termed periodic repolarization dynamics (PRD).
  
  
  METHODS
  We investigated the physiological properties of PRD in multiple experimental studies, including a swine model of steady-state ventilation (n=7) and human studies involving fixed atrial pacing (n=10), passive head-up tilt testing (n=11), low-intensity exercise testing (n=11), and beta blockade (n=10). We tested the prognostic power of PRD in 908 survivors of acute myocardial infarction (MI). Finally, we tested the predictive values of PRD and T-wave alternans (TWA) in 2,965 patients undergoing clinically indicated exercise testing.
  
  
  RESULTS
  PRD was not related to underlying respiratory activity (P<0.001) or heart-rate variability (P=0.002). Furthermore, PRD was enhanced by activation of the sympathetic nervous system, and pharmacological blockade of sympathetic nervous system activity suppressed PRD (P≤0.005 for both). Increased PRD was the strongest single risk predictor of 5-year total mortality (hazard ratio 4.75, 95% CI 2.94-7.66; P<0.001) after acute MI. In patients undergoing exercise testing, the predictive value of PRD was strong and complementary to that of TWA.
  
  
  CONCLUSIONS
  We have described and identified low-frequency rhythmic modulations of repolarization that are associated with sympathetic activity. Increased PRD can be used as a predictor of mortality in survivors of acute MI and patients undergoing exercise testing.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00196274.
  
  
  BACKGROUND
  This study was funded by Angewandte Klinische Forschung, University of Tübingen (252-1-0).
authors.forename: Konstantinos D
authors.initials: KD
authors.lastname: Rizas
authors.forename: Tuomo
authors.initials: T
authors.lastname: Nieminen
authors.forename: Petra
authors.initials: P
authors.lastname: Barthel
authors.forename: Christine S
authors.initials: CS
authors.lastname: Zürn
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.forename: Jari
authors.initials: J
authors.lastname: Viik
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: Kjell
authors.initials: K
authors.lastname: Nikus
authors.forename: Christian
authors.initials: C
authors.lastname: Eick
authors.forename: Tim O
authors.initials: TO
authors.lastname: Greiner
authors.forename: Hans P
authors.initials: HP
authors.lastname: Wendel
authors.forename: Peter
authors.initials: P
authors.lastname: Seizer
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schreieck
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.forename: Georg
authors.initials: G
authors.lastname: Schmidt
authors.forename: Axel
authors.initials: A
authors.lastname: Bauer
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology; D055724:Electrophysiological Phenomena; D005260:Female; D006329:Heart Conduction System / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality* / Q000503:physiopathology*; D011379:Prognosis; D034421:Sus scrofa; D013564:Sympathetic Nervous System / Q000503:physiopathology