Sympathetic activity–associated periodic repolarization dynamics predict mortality following myocardial infarction
Konstantinos D. Rizas, … , Georg Schmidt, Axel Bauer
Konstantinos D. Rizas, … , Georg Schmidt, Axel Bauer
Published March 18, 2014
Citation Information: J Clin Invest. 2014;124(4):1770-1780. https://doi.org/10.1172/JCI70085.
View: Text | PDF | Corrigendum
Clinical Medicine Clinical trials

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.

Conclusion. 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.

Trial registration. ClinicalTrials.gov NCT00196274.

Funding. This study was funded by Angewandte Klinische Forschung, University of Tübingen (252-1-0).

Authors

Konstantinos D. Rizas, Tuomo Nieminen, Petra Barthel, Christine S. Zürn, Mika Kähönen, Jari Viik, Terho Lehtimäki, Kjell Nikus, Christian Eick, Tim O. Greiner, Hans P. Wendel, Peter Seizer, Jürgen Schreieck, Meinrad Gawaz, Georg Schmidt, Axel Bauer

×

Figure 2

Assessment of PRD.

Options: View larger image (or click on image) Download as PowerPoint
Assessment of PRD. (A) Illustration of the weight-averaged vector of rep...
(A) Illustration of the weight-averaged vector of repolarization (T°) for each T-wave from surface ECG recorded in the Frank leads configuration. (B) Three-dimensional visualization of successive T° vectors projected into virtual spheres. The angle dT° between successive repolarization vectors was used as an estimate of instantaneous repolarization instability. (C and D) The dT° signal exhibits characteristic low-frequency oscillations. C shows dT° values for beats #219-223, corresponding to the spheres in B. (E) Quantification of PRD using wavelet analysis. PRD was defined as the average wavelet coefficient corresponding to frequencies of 0.1 Hz or less.