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Title:

Sympathetic activity-associated periodic repolarization dynamics predict mortality following myocardial infarction.

Document type:
Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't; Article
Author(s):
Rizas, Konstantin; Nieminen, Tuomo; Barthel, Petra; Zuern, ChristineS; Kahonen, Mika; Viik, Jani; Lehtimaki, Terho; Nikus, Kjell; Eick, Christian; Greiner, TimO; Wendel, HansR; Seizer, Peter; Schreieck, Juergen; Gawaz, Meinrad; Schmidt, Georg; Bauer, Axel
Abstract:
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).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.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.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.ClinicalTrials.gov NCT00196274.This study was funded by Angewandte Klinische Forschung, University of Tübingen (252-1-0).
Journal title abbreviation:
J Clin Invest
Year:
2014
Journal volume:
124
Journal issue:
4
Pages contribution:
1770-80
Language:
eng
Fulltext / DOI:
doi:10.1172/JCI70085
Pubmed ID:
http://view.ncbi.nlm.nih.gov/pubmed/24642467
Print-ISSN:
0021-9738
TUM Institution:
I. Medizinische Klinik und Poliklinik (Kardiologie)
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