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CLINICAL STUDIES

Jpn Circ J 1999; 63: 577 – 582

Effects of Exercise Training on the Heart Rate Variability and QT Dispersion of Patients With Acute Myocardial Infarction Shinichi Fujimoto, MD; Shiro Uemura, MD; Yoshio Tomoda, MD; Hiromitsu Yamamoto, MD; Yasuo Matsukura, MD; Manabu Horii, MD; Emi Iwamoto, MA; Toshio Hashimoto, MD; Kazuhiro Dohi, MD Heart rate variability (HRV) reflects the autonomic tone of the heart, and QT dispersion reflects the regional inhomogeneity of ventricular repolarization. The purpose of the present study was to determine the effects of early exercise training on HRV and QT dispersion in patients with acute myocardial infarction (AMI). Forty patients (mean age: 59 years) with AMI were randomized to training rehabilitation (group Tr, n=20) or conventional rehabilitation (group C, n=20). Two weeks after AMI, group Tr underwent 10 min of exercise using a bicycle ergometer (80% of anaerobic threshold) twice a day. At the end of the second and fourth weeks, 12-lead and 24-h Holter ECGs were recorded. QT intervals were measured and corrected using Bazett’s formula (QTc), and QTc dispersion (QTcd) was defined as the difference between maximum and minimum QTc. HRV was accessed by the high-frequency component (HF: 0.15–0.40 Hz) of the HRV power spectrum (parasympathetic activity) and the ratio of low frequency (0.04–0.15 Hz) to HF (L/H ratio: sympathetic activity). In group Tr, HF increased (82.5 to 131.1 ms2), the L/H ratio decreased (3.9 to 2.6), and QTcd decreased (77.2 to 57.2 ms). In group C, none of the indices changed. It was concluded that early exercise training improves sympathovagal balance and decreases QTcd, and may reduce the arrhythmogenic substrate following AMI. (Jpn Circ J 1999; 63: 577 – 582) Key Words: Exercise; Heart rate variability; Myocardial infarction; QT dispersion

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dvances in the treatment of myocardial infarction (MI), including thrombolysis and coronary angioplasty, have significantly reduced mortality in patients following MI.1,2 However, based on recent multicenter trials, up to 10% of patients who survive to the time of discharge from the hospital die within 1 year. Furthermore, one-third of the survivors died because of ventricular arrhythmias during a 2-year follow-up period.3 Recent studies suggest that impaired autonomic regulation and regional heterogeneity of ventricular repolarization play important roles in the genesis of life-threatening ventricular arrhythmias after acute MI (AMI).4,5 Heart rate variability (HRV) and QT dispersion are non-invasive measurements that provide information concerning the autonomic regulation of the heart and the spatial heterogeneity of ventricular repolarization, respectively. It has also been reported that exercise training added to cardiac rehabilitation has beneficial effects, not only on exercise capacity, but also on the mortality rate in patients with AMI.6–8 However, little is known about the effects of exercise training, especially started early after MI, on HRV and QT dispersion. The purpose of the present study was to determine the effects of early exercise training on HRV and QT dispersion in patients during the subacute phase of MI. (Received December 21, 1998; revised manuscript received March 10, 1999; accepted March 25, 1999) First Department of Internal Medicine, Nara Medical University, Kashihara, Japan Mailing address: Shinichi Fujimoto, MD, First Department of Internal Medicine, Nara Medical University, 840 Shijyocho Kashihara City, Nara 634-0813, Japan

Japanese Circulation Journal Vol.63, August 1999

Methods Study Population Of the 206 male patients admitted to Nara Medical University from May 1994 to May 1996 with their first AMI, we studied 40 consecutive patients (mean age: 59±11 years) who were successfully treated with direct coronary angioplasty within 12 h of the onset of chest pain. The following exclusion criteria were used: (1) the presence of multivessel disease, (2) a left ventricular ejection fraction ≤40%, (3) ≥3,000 ventricular arrhythmias per day, (4) the presence of atrial fibrillation, (5) the presence of valvular heart disease, (6) the presence of left ventricular hypertrophy, (7) the presence of left or right bundle branch block, (8) pacemaker implantation, (9) the presence of ventricular aneurysm, (10) the presence of diabetes mellitus, or (11) treatment with digoxin, antiarrhythmic drugs, beta-blocking agents or angiotensin converting enzyme inhibitors. Patients were randomized to either the training rehabilitation group (group Tr) or the conventional rehabilitation group (group C). Informed consent was obtained from each patient. Rehabilitation Program Each group participated in a conventional 4-week cardiac rehabilitation program,9 which comprised mainly light daily activities, but not active training. The estimated maximal metabolic equivalent (MET) is 2 for the second week (walking in the room), and 5 for the 4th week (taking a bath). Two weeks after AMI, patients in group Tr underwent additional exercise training for 2 weeks, using a bicycle ergometer at a work load of 80% of their anaerobic threshold for 10 min twice a day (Fig 1).

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Fig 1. Cardiac rehabilitation program. Group Tr: training group; Group C: conventional rehabilitation group.

Measurement of Exercise Capacity Cardiopulmonary exercise testing was performed at the end of the second and fourth weeks after AMI. After warming up for 4 min at a workload of 20 W, all patients underwent a maximal, symptom-limited, graded bicycle ergometer exercise test with a workload increment of 10 W/min. During exercise testing, respiratory gas exchange was monitored continuously using a respiromonitor (AE280S; Minato Medical Science, Osaka, Japan). Peak oxygen uptake, anaerobic threshold, and exercise time were measured. Criteria for terminating the exercise test included the development of chest pain, ventricular tachycardia, ST segment depression or elevation >1 mm, or an increase in blood pressure to >250 mmHg. No patients met these criteria. Measurement of Heart Rate Variability Twenty-four hour ambulatory electrocardiograms (ECG) were recorded with Marquette 8500T Holter recorders (Marquette, Milwaukee, WI, USA) at the end of the second week, the day before exercise testing and the fourth week. Frequency domain indices of HRV were analyzed using a 256-point fast Fourier transform algorithm (HRV Program version 2A, Marquette) for 2 min. All the 2-min segments were averaged over 24 h. Power spectra were quantified by measuring the area in the low frequency (LF: 0.04–0.15 Hz) and high frequency (HF: 0.15–0.40 Hz; index of parasympathetic activity) band widths. Autonomic nervous activity was assessed by determining the HF and low to high frequency ratio (L/H ratio; index of sympathetic activity). Time domain indices of HRV were calculated as the mean NN (mean value for all normal RR intervals during 24 h), SDNN (standard deviation of all normal RR intervals during 24 h), SDANN (standard deviation of the averages of normal RR intervals for 5-min intervals during 24 h), and SDNN index (mean of the standard deviations of all normal RR intervals for all 5-min intervals during 24 h). Electrocardiographic Recording and Measurement of QT Interval Standard 12-lead ECG were recorded at the end of the

second and fourth weeks. From the recorded ECG, the QT interval was defined as the interval from the onset of the Q (or R) wave to the end of the T wave. The end of the T wave was determined as the intersection of the isoelectric line and the tangent of the maximal slope of the terminal limb of the T wave. For each lead, 5 consecutive QT intervals were measured and each measured QT interval was corrected with the proceeding RR interval by using Bazett’s formula (QTc). Five consecutive QTc were averaged in each lead. The mean QTc and sd QTc were defined as the mean and standard deviation of the averaged QTc, respectively, for all leads that could be measured. QTc dispersion was defined as the difference between the maximum and minimum averaged QTc interval in the 12-lead ECG.10 Leads in which the end of the T wave could not be clearly discerned were excluded from the analysis. Electrocardiograms with fewer than 8 leads available for analysis were excluded from the examination. Seven patients (5 in group Tr and 2 in group C) were excluded based on this criterion. Relationship Between QT Dispersion and Heart Rate Variability ∆QTc dispersion, ∆HF and ∆L/H were defined as the differences in the QTc dispersion, HF and L/H, respectively, between the second and fourth weeks. The relationships between ∆QTc dispersion and ∆HF, and ∆QTc dispersion and ∆L/H were analyzed. Statistical Analysis Continuous variables are expressed as the mean ± standard deviation. Because not all of the parameters were normally distributed, nonparametric analysis was used for comparing such values. Intragroup differences were assessed by the Mann-Whitney U test. Regression analysis was performed by the least-squares method. A p value