Bertil Wennerblom

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.

Heart rate variability in premenstrual dysphoric disorder

Measuring heart rate variability (HRV) is a way to assess the autonomic regulation of the heart. Decreased HRV, indicating reduced parasympathetic tone, has previously been found in depression and anxiety disorders. The objective of this study was to assess HRV in women with premenstrual dysphoric disorder (PMDD). To this end, time domain variables and frequency domain variables were assessed in 28 women with PMDD and in 11 symptom-free controls during both the symptomatic luteal phase and the non-symptomatic follicular phase of the menstrual cycle. Two variables reflecting vagal activity in the time domain, the root mean square of differences of successive normal RR intervals (rMSSD) and standard deviation of normal RR intervals (SDNN) were lower in PMDD patients, but this difference was statistically significant in the follicular phase only. The most important vagal measure in the frequency domain, supine high frequency (HF), also appeared lower in PMDD subjects during the follicular phase. It is suggested that PMDD may be associated with reduced vagal tone compared to controls and that this difference is most apparent in the non-symptomatic follicular phase of the menstrual cycle.

Effects of High Frequency Exercise in Patients before and after Elective Percutaneous Coronary Intervention

Background: The aim of this study was to evaluate the effects of high frequency exercise for patients before and after an elective percutaneous coronary intervention (PCI), with special reference to maximal aerobic capacity, muscle function, health related quality of life (HRQoL), waist–hip ratio (WHR) and restenosis. Methods: A randomised, controlled study was performed in Sweden between 2004 and 2006 in thirty-seven patients (five women) with stable coronary artery disease (CAD), age 63.6 ± 6.9 years, randomised to either high frequency exercise or control group. The patients in the training group performed three endurance resistance exercises and trained on a cycle ergometer 30 min, 5 times a week for 8 months at 70% of VO2max. Results: Patients in the training group significantly improved their maximal aerobic capacity (15 (9–46) vs. 8 (0–18)% p ≤ 0.05), shoulder flexion (p ≤ 0.01), shoulder abduction (p ≤ 0.01) and heel-lift (p ≤ 0.05) compared to the control group. There were no significant differences between the groups in HRQoL, WHR and restenosis. Conclusion: High frequency exercise in patients treated with PCI seems to improve maximal aerobic capacity and muscle function, which may reduce the risks of further progression of atherosclerosis. However, further larger studies are needed to fully investigate the effects of exercise in patients with PCI.

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.

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.

Relationship Between Palpography and Virtual Histology in Patients With Acute Coronary Syndromes

OBJECTIVES The purpose of this study was to correlate adverse events at long-term follow-up in patients after an acute coronary syndrome with coronary plaque characteristics derived from simultaneous evaluation of their mechanical and compositional properties using virtual histology (intravascular ultrasound virtual histology) and palpography. BACKGROUND Fibroatheroma is the plaque morphology with the highest risk of causing adverse cardiac events. Palpography can potentially assess the local mechanical plaque properties with the possibility of identifying fibroatheroma with the highest risk of rupture. METHODS A total of 114 patients with acute coronary syndrome from the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) trial underwent a single ultrasound imaging investigation of their 3 coronary vessels with the co-registration of intravascular ultrasound virtual histology and palpography. Major adverse cardiac events (MACE) (cardiac death, cardiac arrest, myocardial infarction, or unstable or progressive angina) were collected up to a median follow-up of 3.4 years and adjudicated to originally treated culprit versus untreated nonculprit lesions. RESULTS In total, 488 necrotic core-rich plaques were identified and subclassified as thin-cap fibroatheroma (n = 111), calcified thick-cap fibroatheroma (n = 213), and noncalcified thick-cap fibroatheroma (n = 164) and matched to their co-registered palpography data. A total of 16 MACE, adjudicated to untreated nonculprit lesions, were recorded at follow-up. In patients in whom MACE developed, fibroatheroma were larger (plaque area 10.0 mm(2) [range: 8.4 to 11.6 mm(2)] vs. 8.2 mm(2) [range: 7.7 to 8.8 mm(2)] (p = 0.03) compared with patients who were MACE free. By palpography, the maximum and the density strain values did not differ between the varying subtypes of fibroatheroma of patients with or without MACE during follow-up. CONCLUSIONS In acute coronary syndromes, patients treated with stents and contemporary pharmacotherapy, palpography did not provide additional diagnostic information for the identification of fibroatheroma with a high risk of rupture and MACE during long-term follow-up. (Providing Regional Observations to Study Predictors of Events in the Coronary Tree [PROSPECT]: An Imaging Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466).

Effects on Heart Rate Variability of Isosorbide-5-Mononitrate and Metoprolol in Patients with Recent Onset of Angina pectoris

Background: β-Blockers reduce sympathetic tone, increase vagal tone and improve prognosis in ischaemic heart disease. Nitroglycerin, being a vasodilator, may theoretically have an opposite effect and worsen the prognosis. The purpose of the present study was to analyse heart rate variability (HRV), which reflects autonomic tone, in angina patients on isosorbide-5-mononitrate (IS-5-MN) and/or metoprolol. Methods and Results: Thirty-two patients (32–81 years old), with recently developed angina (median duration: 3 months), showing no other disease and on no drugs, were Holter-monitored 24–48 h at baseline and after 4–5 days on IS-5-MN (mean daily dose: 33 mg), on metoprolol (mean daily dose: 184 mg) and on the combined treatment. Recordings were analysed on the Marquette Series 8000 Holter scanner. Both IS-5-MN and metoprolol significantly reduced myocardial ischaemia (ST integral) and ventricular tachycardias. Metoprolol induced significant changes in the following parameters (baseline versus metoprolol): high-frequency peak 9 ± 4 versus 11 ± 4 ms (p < 0.001), low-to-high frequency ratio 2.5 ± 0.6 versus 1.9 ± 0.6 (p < 0.0001), root mean square of RR interval difference 23 ± 7 versus 31 ± 9 ms (p < 0.0001), RR intervals differing more than 50 ms from the preceding one 4.8 ± 3.9 versus 10.0 ± 7.0% (p < 0.0001), mean of all 5-min standard deviations 50 ± 12 versus 56 ± 11 ms (p < 0.001) and mean RR interval 819 ± 90 versus 1,019 ± 120 ms (p < 0.00001). The combined treatment caused approximately the same HRV changes as metoprolol alone. IS-5-MN had no significant effect on any HRV parameter, neither alone nor in combination with metoprolol. Conclusion: A clinically effective dose of metoprolol had potentially positive effects on HRV with increase in vagal and decrease in sympathetic tone while IS-5-MN had no effect on HRV, neither positive nor negative, neither alone nor in combination with metoprolol.

High frequency home-based exercise decreases levels of vascular endothelial growth factor in patients with stable angina pectoris.

Background In coronary artery disease (CAD), circulating angiogenic factors have been seen to increase, possibly as a response to ischaemia. Regular physical activity (PA) is recommended for prevention and treatment of CAD, but more research is needed to optimise PA regimes. We investigated the effect of home-based high frequency exercise (HFE) on angiogenic cytokines and cardiac markers in patients with stable CAD. Design This was a randomised case-control study Methods Sixty-two patients, with stable CAD, were randomised to HFE (n = 33), (aerobic exercise 70% of max, 30 min, five times/week and resistance exercise three times/week), performed at home, or usual lifestyle (control, n = 29). After eight weeks, percutaneous coronary intervention (PCI) was performed in both groups, and the HFE group continued another six months of exercise. Serum vascular endothelial growth factor (VEGF) and stromal derived factor-1 (SDF-1), plasma N-terminal-brain natriuretic peptide (NT-proBNP), high-sensitive troponin T (TnT) and copeptin were analysed. Results Data are presented as median (25th, 75th percentile) of relative changes (%) from baseline. Values of p are given for the difference between the HFE and controls. HFE decreased circulating VEGF levels, before PCI (−5% (−15%, −2%)), while VEGF levels increased in the control group (5% (−3%, 20%) p = 0.004). A significant difference in VEGF remained at three months post-PCI (HFE (−1%(−12%, 5%), control (7% (0%, 14%), p = 0.04), but not at six months after PCI. SDF-1, NT-proBNP, TnT and copeptin levels did not differ significantly. In addition, VEGF levels were positively correlated to NT pro-BNP. Conclusions Home-based HFE decreased circulating VEGF in patients with stable CAD, suggesting a reduced ischaemic burden. HFE does not increase markers of cardiac dysfunction, suggesting that it is a safe therapeutic intervention in these patients.