交感活性相关的周期性复极动力学可预测心肌梗死后的死亡率。
Sympathetic activity-associated periodic repolarization dynamics predict mortality following myocardial infarction.
出版信息
J Clin Invest. 2014 Apr;124(4):1770-80. doi: 10.1172/JCI70085. Epub 2014 Mar 18.
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).
背景
心室心肌增强的交感神经活动可使复极不稳定，增加死亡风险。已知交感神经活动呈低频爆发簇集；因此，我们假设交感神经活动会引起复极的低频周期性变化。我们开发了一种评估交感神经对复极影响的技术，并在低频谱范围内（≤0.1 Hz）确定了周期性成分，我们称之为周期性复极动力学（PRD）。
方法
我们在多项实验研究中研究了 PRD 的生理特性，包括稳定通气的猪模型（n=7）和涉及固定心房起搏的人体研究（n=10）、被动头高位倾斜试验（n=11）、低强度运动试验（n=11）和β受体阻滞剂（n=10）。我们在 908 例急性心肌梗死（MI）幸存者中测试了 PRD 的预后能力。最后，我们在 2965 例行临床指征运动试验的患者中测试了 PRD 和 T 波交替（TWA）的预测值。
结果
PRD 与基础呼吸活动无关（P<0.001）或心率变异性（P=0.002）无关。此外，PRD 被交感神经系统激活增强，而交感神经系统活性的药物阻断抑制了 PRD（P≤0.005）。在急性 MI 后，PRD 是 5 年总死亡率的最强单一风险预测因素（风险比 4.75，95%CI 2.94-7.66；P<0.001）。在接受运动试验的患者中，PRD 的预测价值很强，与 TWA 互补。
结论
我们已经描述并确定了与交感神经活动相关的复极低频节律调制。增加的 PRD 可作为急性 MI 幸存者和接受运动试验的患者死亡率的预测指标。
试验注册
ClinicalTrials.gov NCT00196274。
资金
本研究由德国图宾根大学应用临床研究（252-1-0）资助。
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