Changes in Heart Rate, Heart Rate Variability, and Heart Rate Turbulence during Evolving Reperfused Myocardial Infarction JASMIN ORTAK,* GUNTHER WEITZ,* UWE K.H. WIEGAND,* FRANK BODE,* FRANK EBERHARDT,* HUGO A. KATUS,† GERT RICHARDT,‡ HERIBERT SCHUNKERT,* and HENDRIK BONNEMEIER* From the *Medizinische Kinik II, Universit¨at zu Lubeck, Lubeck, Germany, †Ruprecht-Karls-Universit¨at-Heidelberg, ¨ ¨ Innere Medizin III, Heidelberg, Germany, and ‡Herzzentrum Segeberger Kliniken, Bad Segeberg, Germany
ORTAK, J., ET AL.: Changes in Heart Rate, Heart Rate Variability, and Heart Rate Turbulence during Evolving Reperfused Myocardial Infarction. Depressed cardiac parasympathetic activity is associated with electrical instability and adverse outcomes after myocardial infarction (MI). Heart rate turbulence (HRT), reflecting reflex vagal activity, and heart rate variability (HRV), reflecting tonic autonomic variations are both reduced in the subacute phase of MI. However, the evolution of these components of cardiac autonomic control between subacute and chronic phase of MI has not been defined. We prospectively studied 100 consecutive patients with a recent first MI with ST-segment elevation, who underwent successful direct percutaneous coronary interventions. Beta-adrenergic blockers and angiotensin-converting enzyme (ACE) inhibitors were administered according to the state-of-the-art medical practice guidelines. HRT and HRV were measured from 24-hour ambulatory electrocardiographic recordings 10 days and 12 months after the index MI. There was no significant difference in mean RR interval between the subacute and chronic phase of MI (875 ± 145 versus 859 ± 122 ms). Indices of HRV increased significantly during the observation period (SDNN: from 88.8 ± 26.8 to 116.0 ± 35.7 ms, P < 0.001; SDNNi: from 37.9 ± 15.9 to 46.0 ± 16.3 ms, P < 0.001; SDANN: from 79.6 ± 34.7 to 105.6 ± 35.4 ms, P < 0.001). In contrast, there were no significant changes in indices of HRT (turbulence onset: from −0.008 ± 0.022 to −0.012 ± 0.025%; turbulence slope: from 7.78 ± 5.9 to 8.06 ± 6.8 ms/beat). In contrast to reflex autonomic activity, there was a significant recovery of tonic autonomic activity within 12 months after MI. These different patterns of recovery of reflex versus tonic cardiac autonomic control after MI need to be considered when risk stratifying post-MI patients. (PACE 2005; 28:S227–S232) heart rate variability, heart rate turbulence, myocardial infarction, vagal activity Introduction Variations in cardiac autonomic tone have been implicated in the development of malignant ventricular arrhythmias after acute myocardial infarction (MI). A depressed cardiac parasympathetic activity is associated with electrical instability and adverse outcomes after MI.1–4 Both, heart rate turbulence (HRT), reflecting reflex vagal activity, and heart rate variability (HRV), reflecting tonic autonomic activity are decreased in the subacute phase of MI.3,4 Though there is evidence that cardiac autonomic activity recovers during convalescence after MI,5 the evolution of reflex and tonic cardiac autonomic control between subacute and chronic phase of MI has not been studied in a large numbers of patients after successful after successful reperfusion therapy by percutaneous coronary intervention (PCI) performed during treatment with β-adrenergic blockers and angiotensinconverting enzyme (ACE) inhibitors. Address for reprints: Dr. med. Hendrik Bonnemeier, Medizinische Klinik II, Universit¨at zu Lubeck, Ratzeburger Allee ¨ 160, 23538 Lubeck, Germany. Fax: +49-451-500-2363; e-mail: ¨
[email protected]
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As the number of new post-MI risk stratification factors continues to grow, abnormal cardiac autonomic activity manifest by a depressed 24-hour time-domain HRV has become an inclusion criterion in some large primary prevention trials of implantable cardioverters defibrillators.6 However, since significant changes in cardiac autonomic activity may occur within short periods of time after MI, the temporal changes of HRV and HRT needed to be characterized. Our study was performed to examine the evolution of HRV and HRT between the subacute and chronic phases of MI in stable post-MI patients, after state-of-the-art reperfusion therapy, and during treatment with an optimal medical regimen. Methods Patient Population We prospectively screened 100 consecutive patients presenting with a first acute MI and STsegment-elevation, who underwent direct PCI at our institution. Exclusion criteria were patients with left bundle branch block, pacemaker rhythm or rhythm other than sinus, history of coronary
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artery bypass surgery, or technically unsuitable 24-hour ambulatory electrocardiographic (ECG) recordings were not included in this study. Betaadrenergic blockers and ACE inhibitors were administered according to state-of-the-art practice guidelines. All patients granted their informed consent to participate in the research protocol, which was approved by the local ethical committee. Measurement of HRT and Variability All patients underwent three-channel, timetracking 24-hour ambulatory ECG-recordings (Tracker III, Del Mar Reynolds Medical, Inc., Irvine, CA) 10 days and 12 months after the index MI. To ensure similar recording environment and level of physical activity, all patients were fully ambulatory, and woke up at approximately 7 a.m. after 6–8 hours of sleep. All 24-hour ambulatory ECG-recordings were manually edited by trained observers (J.O., H.B.) for exclusion of artifacts. At least 23 hours of recording, a minimum of 90% analyzable NN intervals and ≥5 ventricular premature complexes (VPCs) were required for a recording to be accepted. HRT was analyzed as described previously.4 VPCs preceded by artifacts or premature events within 20 RR intervals were excluded from HRT analysis. HRT was characterized by turbulence onset (TO), turbulence slope (TS), and turbulence timing (TT). TO expresses the proportional decrease in RR interval immediately after the compensatory pause of the VPC. TS, the steepest slope of the linear regression between RR-interval count and duration, expresses the subsequent increase in RR intervals. TT, is the first of the five RR-interval sequence, yielding the maximal regression slope value.7 Time-domain HRV parameters were measured according to the Task Force of the European Society of Cardiology and North American Society of Pacing and Electrophysiology,8 using a Pathfinder 700 system (Del Mar Reynolds). The following 24-hour measurements were made: (i) mean RR interval, (ii) standard deviation of NN-intervals (SDNN), (iii) mean standard deviation of NNintervals for all 5-minute segments (SDNNi), (iv) standard deviation of the averages of NN-intervals for all 5-minute segments (SDANN), (v) root mean square of difference of consecutive normal-tonormal intervals (rMSSD), and (vi) geometric triangular index (TI). Statistical Analyses Statistical analyses were made with the SPSS, version 11.0 software package (SPSS Inc., Chicago, IL). Comparison between groups was made with the Mann-Whitney U-test. Multiple comparisons between groups were made by Bonferroni’s corS228
rected analysis of variance for repeated measures. An α-corrected paired Student’s t-test was performed for interval-to-interval comparisons. Pearson’s correlation coefficient was used to examine the relation between HRT and HRV, and clinical variables. The results are presented as means ± SD. A two-tailed significance level of 0.05 was used. Results Among the 100 screened patients, 92 fulfilled the clinical and technical inclusion criteria, and had 2 acceptable 24-hour ECG recordings. The median duration of the recordings at baseline and at 12 month was 24 h, with 93.9 ± 16% and 91.2 ± 11% analyzable NN intervals, respectively. The baseline clinical characteristics of the study population are shown in Table I. There was a relatively low-risk group, with 100% open infarctrelated coronary artery, a mean left ventricular ejection fraction of 50.5%, a relatively young age,
Table I. Baseline Characteristics of 92 Patients Enrolled Age, years (mean ± SD)
