Intensive home-based exercise training in cardiac rehabilitation increases exercise capacity and heart rate variability.

BACKGROUND: Reduced heart rate variability (HRV) is a risk factor for cardiac death. Animal studies have shown increased HRV and reduced mortality after physical training. We evaluated the change in exercise capacity and HRV in cardiac rehabilitation patients, randomised to routine or home-based intensive training. The design was prospective, stratified randomisation with pre-specified subgroup analysis. METHODS: Maximal bicycle exercise test and 24-h Holter were performed 1 (baseline), 4 and 12 months after myocardial infarction (MI) or coronary artery by-pass surgery (CABG). Patients were randomised to physical training either two (N) or six (I) times per week for 3 months Sixty-two patients (43 MI and 19 CABG patients) were evaluated. RESULTS: Exercise capacity increased significantly more after 3 months of training in group I (mean (S.E.)); 29.0 (3.4) vs. 7.2 (2.6) watts, P<0.001). One year later the difference in exercise capacity remained (26.5 (3.3) vs. 11.8 (3.8) watts, P<0.001). Global HRV measurements SDNN and SDANN increased significantly more in group I after training (17.1 (5.6) vs. 1.7 (3.7) and 16.2 (4.9) vs. 2.8 (3.1) ms, P<0.05) and 1 year later the differences were still significant. Subgroup analysis showed more pronounced HRV response in CABG than MI patients. CONCLUSION: Intensive exercise training in cardiac rehabilitation increases exercise capacity and global HRV, which could be of prognostic significance.

Circadian variation of heart rate variability and the rate of autonomic change in the morning hours in healthy subjects and angina patients.

BACKGROUND: Incidence of sudden cardiac death peaks during the early morning hours when there is a rapid withdrawal of vagal and an increase of sympathetic tone. The rate of autonomic change could be of prognostic importance. PATIENTS AND METHODS: A total of 65 patients with angina pectoris, free from other diseases and drug free, were Holter monitored for 24 h. A total of 30 patients were also monitored on isosorbide-5-mononitrate (IS-5-MN) and on metoprolol respectively. A total of 33 age-matched healthy subjects served as controls. Spectral components of heart rate variability (HRV) were analysed hourly, with special reference to the rapid changes of autonomic tone during the night and early morning hours. Circadian variation was assessed in two ways: (1) Mean HRV day (8 a.m.-8 p.m.) and night (0-5 a.m.) were compared. (2) For the morning/night hours (0-10 a.m.), individual hourly values for max. and min. HRV, the difference max.-min. (gradient), the rate of change per hour between max. and min. (velocity) and the largest difference between two consecutive hours (max. velocity) were recorded and the mean value for the group calculated. RESULTS: During the night/morning hours, healthy controls demonstrated faster HF max. velocity (P=0.002) and higher HF gradient (P=0.011) than angina patients. Metoprolol and IS-5-MN increased the HF gradient (P=0.008 and P=0.003, respectively), and metoprolol tended to increase the max. velocity (P=0.02). Metoprolol substantially decreased the LF/HF gradient (P=0.001), velocity (P=0.008) and max. velocity (P=0.0001). CONCLUSION: Rapid vagal withdrawal seemed to be a sign of a healthy autonomic nervous system in the control group but was significantly slower in angina patients. IS-5-MN and metoprolol tended to normalise vagal withdrawal and metoprolol slowed down the rapid increase in sympathetic predominance in the morning in patients.

Patients with uncomplicated coronary artery disease have reduced heart rate variability mainly affecting vagal tone.

AIM: To investigate whether uncomplicated chronic coronary artery disease causes changes in heart rate variability and if so, whether the heart rate variability pattern is different from that described in patients with acute myocardial infarction. METHODS: Heart rate variability was studied in 65 patients with angina who had no previous myocardial infarcts, no other diseases, and were on no drug that could influence the sinus node. Results were compared with 33 age matched healthy subjects. The diagnosis of coronary artery disease in angina patients was established by coronary angiography in 58, by thallium scintigraphy in six, and by exercise test only in one. Patients and controls were Holter monitored 24 hours outside hospital, and heart rate variability was calculated in the frequency domain as global power (GP: 0.01-1.00 Hz), low frequency peak (LF: 0. 04-0.15 Hz), high frequency peak (HF: 0.15-0.40 Hz), LF/HF in ms(2), and in the time domain as SDNN (SD of normal RR intervals), SDANN (SD of all five minute mean normal RR intervals), SD (mean of all five minute SDs of mean RR intervals), rMSSD (root mean square of differences of successive normal RR intervals) (all in ms), and pNN50 (proportion of adjacent normal RR intervals differing more than 50 ms from the preceding RR interval) as per cent. RESULTS: The mean age in patients and controls was 60.4 (range 32-81) and 59.1 (32-77) years, respectively (NS), the male/female ratio, 57/65 and 24/33 (NS), and the mean time of Holter monitoring, 23.0 (18-24) and 22.8 (18-24) hours (NS). Mortality in angina patients was 0% (0/65) at one year, 0% (0/56) at two years, and 3% (1/33) at three years. Compared with healthy subjects angina patients showed a reduction in GP (p = 0.007), HF (p = 0.02), LF (p = 0.02), SD (p = 0.02), rMSSD (p = 0.01), and pNN50 (p = 0.01). No significant difference was found in RR, LF/HF, SDNN, or SDANN. CONCLUSIONS: Uncomplicated coronary artery disease without previous acute myocardial infarction was associated with reduced high and low frequency heart rate variability, including vagal tone. SDANN and SDNN, expressing ultra low and very low frequencies which are known to reflect prognosis after acute myocardial infarction, were less affected. This is in agreement with the good prognosis in uncomplicated angina in this study.

Reduced heart rate variability in ischemic heart disease is only partially caused by ischemia. An HRV study before and after PTCA.

BACKGROUND: Reduced heart rate variability (HRV) after acute myocardial infarction (AMI) indicates poor prognosis. HRV in patients with uncomplicated coronary artery disease is reduced, and an association with poor prognosis has been suggested. The mechanism of the HRV reduction is not known, but ischemia is a possibility. AIM: To evaluate, in angina patients with no prior AMI, no other disease and drug-free, if complete revascularization and thus important reduction of ischemia by means of PTCA influences HRV. PATIENTS AND METHODS: Twenty-four-hour Holter recordings were performed at baseline prior to PTCA in 48 patients with angina and in 41 age-matched healthy control subjects. The recording was repeated 1 and 6 months after complete revascularization. In addition, HRV was registered during controlled respiration in the supine and standing positions and during cold pressure test at baseline in all angina patients and controls and in 17 consecutive angina patients 6 months after PTCA. RESULTS: Compared to controls, angina patients had a significantly reduced mean RR interval (p = 0.02), SD (p = 0.003), rMSSD (p = 0.03), pNN50 (p = 0.03), total power (p = 0.003), low- (p = 0.004) and high-frequency peak (p = 0.04), but normal SDNN, SDANN and LF/HF. One and 6 months after PTCA, 42/46 and 32/40 follow-up patients, respectively, were free of angina. Six months after PTCA, there was a significant recovery of vagal modulation seen in the frequency domain during controlled respiration, but only nonsignificant trends in HRV parameters analyzed over 24 h. CONCLUSION: Patients with uncomplicated angina had reduced HRV, mainly affecting vagal activity, but normal low frequency variability associated with mortality. Complete revascularization caused a partial normalization of vagal modulation indicating that ischemia may be one of but not the only mechanism of the HRV reduction in uncomplicated chronic coronary artery disease.

Long-term effect of endoscopic transthoracic sympathicotomy on heart rate variability and QT dispersion in severe angina pectoris.

UNLABELLED: We evaluated short and long-term effects on QT dispersion and autonomic balance after endoscopic transthoracic sympathicotomy (ETS). Heart rate variability (HRV) reflects autonomic balance of the heart. QT dispersion is a marker of cardiac electrical instability in patients with ischemic heart disease. Holter recordings for 24 h and a twelve-lead ECG were made prior to, 1 month, 1 year and 2 years after ETS. HRV was analysed in time domain and spectral analysis was performed during controlled respiration in supine position and during head up tilt. Dispersion of QT time and QTc were calculated. Of 88 patients, 62 (60) were eligible for HRV (QT-dispersion) analysis after 1 month, 39 (38) patients after 1 year and 23 (24) patients after 2 years. The HRV analysis showed a significant change of indices reflecting sympatho-vagal balance indicating significantly reduced sympathetic (LF) and increased vagal (HF, rMSSD) tone. These changes still persisted after 2 years. Global HRV increased over time with significant elevation of SDANN after 2 years. QT dispersion was significantly reduced 1 month after surgery and the dispersion was further diminished 2 years later. CONCLUSION: ETS changed HRV and QT dispersion which could imply reduced risk for malignant arrhythmias and death after ETS.

Potential risk of beta-blockade withdrawal in congestive heart failure due to abrupt autonomic changes.

Beta-Blockers reduce mortality in patients with congestive heart failure and a proposed mechanism has been changes of autonomic tone. Heart rate variability is a non-invasive tool to estimate cardiac autonomic tone. The aim was to study changes of heart rate variability in patients with congestive heart failure on placebo, on the beta1-selective antagonist metoprolol or 24 h after metoprolol withdrawal. Forty-five patients with congestive heart failure were studied with Holter recordings. Heart rate variability measurements were performed before, after 6-12 months of treatment with 150 mg metoprolol/placebo, or 24 h after discontinued metoprolol. After treatment, patients on beta-blockade had a significantly longer mean RR interval and changes of heart rate variability, suggesting elevated vagal tone. Patients monitored in the rebound phase of beta-blocker withdrawal had a significant vagal reduction to the level of the placebo group. There was also a nonsignificant trend towards increased sympathetic tone (LF/HF over 24 h), compared with the beta-blockade group. Heart rate variability indicates an elevated vagal tone during treatment with metoprolol but beta-blockade withdrawal shifts the autonomic balance towards lower vagal and higher sympathetic tone within 24 h. These results could imply a potential risk when abruptly discontinuing beta-blockade medication in these patients.

Heart rate variability after acute myocardial infarction in patients treated with atenolol and metoprolol.

UNLABELLED: Heart rate variability (HRV) reflects autonomous activity that influences the heart. It has been shown that HRV is depressed during acute myocardial infarction (AMI) and that it recovers with time. Beta-blockers reduce mortality after AMI and changes in sympathico-vagal activity have been suggested to be of importance. Under certain animal experimental conditions, metoprolol has been reported to increase vagal tone more than atenolol, which could have clinical implications. The purpose of the present study was to compare the effects of atenolol and metoprolol treatments on HRV during 6 weeks after AMI and to follow the post MI changes in HRV in patients on betablockers. METHODS: In an open, randomised cross-over study, 28 patients were randomised to 3+3 weeks' treatment with atenolol or metoprolol starting 2-5 days after AMI. Twenty-four hour Holter recordings were made before randomisation and after 3 and 6 weeks. HRV was analysed as HR, SDRR, SDANN, SD, rMSSD and pNN50 in the time domain and as coefficient of component variance (CCV) of HF and LF, and as LF/HF ratio in the frequency domain. RESULTS: The average daily dose in our study population was 106 mg of metoprolol and 54 mg of atenolol. There were trends toward lower heart rates daytime, lower LF/HF ratio daytime and higher rMSSD on atenolol compared to metoprolol. In the total group of 28 patients we found during the first 3 weeks, a significant increase of SDNN, SDANN (p<0.0001) and LF/HF ratio daytime and CCV-HF night-time (p<0.01). All differences and trends were unchanged between 3 and 6 weeks. CONCLUSIONS: There was no evidence of more increased vagal tone with metoprolol compared to atenolol as has been suggested from animal models. In patients also on chronic treatment with beta blockers, an increase of HRV was seen during the first weeks post MI.

Effect of endoscopic transthoracic sympathicotomy on heart rate variability in severe angina pectoris.

Endoscopic transthoracic sympathicotomy (ETS) is a recently developed technique to divide sympathetic nerves. ETS has been shown to improve symptoms and reduce ischemia in patients with severe angina pectoris. Low heart rate variability (HRV) in patients with ischemic heart disease carries an adverse prognosis. HRV reflects autonomic response of the heart and a shift in the sympathovagal balance towards parasympathetic dominance could be a marker of improved prognosis. HRV might also be used as an indicator of surgical success in sympathetic heart denervation. Heart rate was recorded in 57 patients before and after ETS. Registration was recorded during controlled respiration in the supine position and at tilt test over 10 minutes and spectral analysis was performed. Twenty-four hour Holter recordings were analyzed in the time domain. During the controlled setting, the high-frequency (HF) component (0.15 to 0.40 Hz) increased significantly whereas the low-frequency (LF) component (0.04 to 0.15 Hz) did not change significantly. The LF/HF ratio at tilt test was reduced from 1.3 to 0.8 (p <0.01). The time-domain analysis showed a significant increase of the mean RR interval (923 to 1,006 ms, p <0.001) and indexes reflecting parasympathetic tone also increased significantly (the root-mean square of difference measured from 24.3 to 29.5 ms, p <0.001 and the proportion of adjacent RR intervals >50% measured from 5.5% to 8.2%, p <0.01), whereas measurements reflecting global HRV did not change. In addition to relief of symptoms and reduced ischemia in severe angina pectoris, ETS caused a shift of sympathovagal balance toward parasympathetic tone. This might explain the anti-ischemic effect and have prognostic implications.

Angina pectoris treated by thoracoscopic sympathecotomy.

Open surgical sympathectomy has previously been shown effective in relieving severe angina pectoris. The method was hampered by high morbidity and mortality. The authors have developed a minimally invasive technique of dividing only the sympathetic chain endoscopically and obtained good results with no serious complications in patients operated on for severe palmar hyperhidrosis. This method was used in 43 patients with severe angina pectoris who were not eligible for coronary artery bypass grafting or percutaneous transluminal coronary angioplasty. There was no mortality or any severe complications. Some 19 patients became symptom-free while 22 were improved and two unchanged after surgery. The frequency of anginal attacks was significantly reduced, as was the consumption of nitroglycerine tablets. The maximum exercise capacity was significantly increased and ST-segment depression reduced.

Endoscopic transthoracic sympathicotomy for severe angina.

We evaluated the antianginal effects of endoscopic transthoracic sympathicotomy (ETS) in 24 patients not eligible for coronary bypass surgery or angioplasty. In this procedure, the sympathetic chain is electrocoagulated under general anaesthesia. No major surgical complications occurred. The frequency of anginal attacks was significantly reduced (p = 0.001). The mean increase in maximum exercise capacity was 13 (SD 21) W (p = 0.009). ST depression at maximum comparable workload was reduced by 0.052 (0.10) mV (p = 0.005). Global ejection fraction during exercise and metaiodobenzylguanidine uptake were unchanged. Heart rate variability analysis showed a reduction of the ratio between low and high frequencies at tilt test (-1.00 [0.96]; p < 0.001). We conclude that ETS can be done without major complications, alleviates angina, and increases maximum working capacity in patients with advanced coronary disease.