Effect of exercise training on autonomic derangement and neurohumoral activation in chronic heart failure.

BACKGROUND: In chronic heart failure (CHF), persistent autonomic derangement and neurohumoral activation cause structural end-organ damage, decrease exercise capacity, and reduce quality of life. Beneficial effects of pharmacotherapy and of exercise training in CHF have been documented at various functional and structural levels. However, pharmacologic treatment can not yet reduce autonomic derangement and neurohumoral activation in CHF to a minimum. Various studies suggest that exercise training is effective in this respect. METHODS AND RESULTS: After reviewing the available evidence we conclude that exercise training increases baroreflex sensitivity and heart rate variability, and reduces sympathetic outflow, plasma levels of catecholamines, angiotensin II, vasopressin, and brain natriuretic peptides at rest. CONCLUSIONS: Exercise training has direct and reflex sympathoinhibitory beneficial effects in CHF. The mechanism by which exercise training normalizes autonomic derangement and neurohumoral activation is to elucidate for further development of CHF-related training programs aimed at maximizing efficacy while minimizing workload.

Baroreflex sensitivity, blood pressure buffering, and resonance: what are the links? Computer simulation of healthy subjects and heart failure patients.

The arterial baroreflex buffers slow (<0.05 Hz) blood pressure (BP) fluctuations, mainly by controlling peripheral resistance. Baroreflex sensitivity (BRS), an important characteristic of baroreflex control, is often noninvasively assessed by relating heart rate (HR) fluctuations to BP fluctuations; more specifically, spectral BRS assessment techniques focus on the BP-to-HR transfer function around 0.1 Hz. Skepticism about the relevance of BRS to characterize baroreflex-mediated BP buffering is based on two considerations: 1) baroreflex-modulated peripheral vasomotor function is not necessarily related to baroreflex-HR transfer; and 2) although BP fluctuations around 0.1 Hz (Mayer waves) might be related to baroreflex BP buffering, they are merely a not-intended side effect of a closed-loop control system. To further investigate the relationship between BRS and baroreflex-mediated BP buffering, we set up a computer model of baroreflex BP control to simulate normal subjects and heart failure patients. Output variables for various randomly chosen combinations of feedback gains in the baroreflex arms were BP resonance, BP-buffering capacity, and BRS. Our results show that BP buffering and BP resonance are related expressions of baroreflex BP control and depend strongly on the sympathetic gain to the peripheral resistance. BRS is almost uniquely determined by the vagal baroreflex gain to the sinus node. In conclusion, BP buffering and BRS are unrelated unless coupled gains in all baroreflex limbs are assumed. Hence, the clinical benefit of a high BRS is most likely to be attributed to vagal effects on the heart instead of to effective BP buffering.

Dispersion of repolarization in cardiac resynchronization therapy.

BACKGROUND: Proarrhythmic effects of cardiac resynchronization therapy (CRT) as a result of increased transmural dispersion of repolarization (TDR) induced by left ventricular (LV) epicardial pacing in a subset of vulnerable patients have been reported. The possibility of identifying these patients by ECG repolarization indices has been suggested. OBJECTIVES: The purpose of this study was to test whether repolarization indices on the ECG can be used to measure dispersion of repolarization during pacing. METHODS: CRT devices of 28 heart failure patients were switched among biventricular, LV, and right ventricular (RV) pacing. ECG indices proposed to measure dispersion of repolarization were calculated. The effects of CRT on repolarization were simulated in ECGSIM, a mathematical model of electrocardiogram genesis. TDR was calculated as the difference in repolarization time between the epicardial and endocardial nodes of the heart model. PATIENTS: The interval from the apex to the end of the T wave was shorter during biventricular pacing (102 +/- 18 ms) and LV pacing (106 +/- 21 ms) than during RV pacing (117 +/- 22 ms, P < or =.005). T-wave amplitude and area were low during biventricular pacing (287 +/- 125 microV and 56 +/- 22 microV.s, respectively, P = .0006 vs RV pacing). T-wave complexity was high during biventricular pacing (0.42 +/- 0.26, P = .004 vs RV pacing). Simulations: Repolarization patterns were highly similar to the preceding depolarization patterns. The repolarization patterns of different pacing modes explained the observed magnitudes of the ECG repolarization indices. Average and local TDR were not different between pacing modes. CONCLUSION: In patients treated with CRT, ECG repolarization indices are related to pacing-induced activation sequences rather than transmural dispersion. TDR during biventricular and LV pacing is not larger than TDR during conventional RV endocardial pacing.

Exercise-resembling effects of periodic somatosensory stimulation in heart failure.

BACKGROUND: The mechanism of the beneficial effects of exercise training on autonomic derangement and neurohumoral activation in chronic heart failure (CHF) is largely unexplained. In our here-presented hypothesis-generating study we propose that part of these effects is mediated by the exercise-accompanying somatosensory nerve traffic. To demonstrate this, we compared the effects of periodic electrical somatosensory stimulation in patients with CHF with the effects of exercise training and with usual care. METHODS: In a randomized controlled study we measured, in CHF patients, changes in blood pressure, baroreflex sensitivity (BRS), neurohormones, exercise capacity and quality of life (QOL) in response to periodic somatosensory stimulation in the form of 2 Hz transcutaneous electrical nerve stimulation (TENS) at both feet, in response to conventional exercise training (EXTR) and, as control (CTRL), in patients with usual care only. RESULTS: Group sizes were N=31 (TENS group), N=25 (EXTR group) and N=30 (CTRL group), respectively. Practically all improvements in BRS, neurohormone concentrations, exercise capacity and QOL in the TENS group were comparable to, or sometimes even better than in the EXTR group. These improvements were not observed in the CTRL group. CONCLUSIONS: This study demonstrates that periodic electrical somatosensory stimulation is as effective as exercise training in improving BRS, neurohormone concentrations, exercise capacity and QOL in CHF patients. These results encourage exploration of exercise modalities that concentrate on rhythm rather than on effort, with the purpose to normalize autonomic derangement and neurohumoral activation in CHF.

Rehabilitation: Periodic somatosensory stimulation increases arterial baroreflex sensitivity in chronic heart failure patients.

BACKGROUND: One of the beneficial effects of exercise training in chronic heart failure (CHF) is an improvement in baroreflex sensitivity (BRS), a prognostic index in CHF. In our hypothesis-generating study we propose that at least part of this effect is mediated by neural afferent information, and more specifically, by exercise-induced somatosensory nerve traffic. OBJECTIVE: To compare the effects of periodic electrical somatosensory stimulation on BRS in patients with CHF with the effects of exercise training and with usual care. METHODS: We compared in stable CHF patients the effect of transcutaneous electrical nerve stimulation (TENS, N = 23, LVEF 30 ± 9%) with the effects of bicycle exercise training (EXTR, N = 20, LVEF 32 ± 7%). To mimic exercise-associated somatosensory ergoreceptor stimulation, we applied periodic (2/s, marching pace) burst TENS to both feet. TENS and EXTR sessions were held during two successive days. RESULTS: BRS, measured prior to the first intervention session and one day after the second intervention session, increased by 28% from 3.07 ± 2.06 to 4.24 ± 2.61 ms/mmHg in the TENS group, but did not change in the EXTR group (baseline: 3.37 ± 2.53 ms/mmHg; effect: 3.26 ± 2.54 ms/mmHg) (P(TENS vs EXTR) = 0.02). Heart rate and systolic blood pressure did not change in either group. CONCLUSIONS: We demonstrated that periodic somatosensory input alone is sufficient and efficient in increasing BRS in CHF patients. This concept constitutes a basis for studies towards more effective exercise training regimens in the diseased/impaired, in whom training aimed at BRS improvement should possibly focus more on the somatosensory aspect.

Exercise training increases oxygen uptake efficiency slope in chronic heart failure.

BACKGROUND AND AIM: The oxygen uptake efficiency slope (OUES) is a novel measure of cardiopulmonary reserve. OUES is measured during an exercise test, but it is independent of the maximally achieved exercise intensity. It has a higher prognostic value in chronic heart failure (CHF) than other exercise test-derived variables such as(Equation is included in full-text article.)or(Equation is included in full-text article.)slope. Exercise training improves(Equation is included in full-text article.)and(Equation is included in full-text article.)in CHF patients. We hypothesized that exercise training also improves OUES. METHODS AND RESULTS: We studied 34 New York Heart Association (NYHA) class II-III CHF patients who constituted an exercise training group T (N=20; 19 men/1 woman; age 60+/-9 years; left ventricular ejection fraction 34+/-5%) and a control group C (N=14; 13 men/one woman; age 63+/-10 years; left ventricular ejection fraction 34+/-7%). A symptom-limited exercise test was performed at baseline and repeated after 4 weeks (C) or after completion of the training program (T). Exercise training increased NYHA class from 2.6 to 2.0 (P<0.05),(Equation is included in full-text article.)by 14% [P(TvsC)<0.01], and OUES by 19% [P(TvsC)<0.01]. Exercise training decreased(Equation is included in full-text article.)by 14% [P(TvsC)<0.05]. CONCLUSION: Exercise training improved NYHA class,(Equation is included in full-text article.)and also OUES. This finding is of great potential interest as OUES is insensitive for peak load. Follow-up studies are needed to demonstrate whether OUES improvements induced by exercise training are associated with improved prognosis.

Validation of ECG indices of ventricular repolarization heterogeneity: a computer simulation study.

INTRODUCTION: Repolarization heterogeneity (RH) is functionally linked to dispersion in refractoriness and to arrhythmogenicity. In the current study, we validate several proposed electrocardiogram (ECG) indices for RH: T-wave amplitude, -area, -complexity, and -symmetry ratio, QT dispersion, and the Tapex-end interval (the latter being an index of transmural dispersion of the repolarization (TDR)). METHODS AND RESULTS: We used ECGSIM, a mathematical simulation model of ECG genesis in a human thorax, and varied global RH by increasing the standard deviation (SD) of the repolarization instants from 20 (default) to 70 msec in steps of 10 msec. T-wave amplitude, -area, -symmetry, and Tapex-end depended linearly on SD. T-wave amplitude increased from 275 +/- 173 to 881 +/- 456 muV, T-wave area from 34 x 10(3)+/- 21 x 10(3) to 141 x 10(3)+/- 58 x 10(3)muV msec, T-wave symmetry decreased from 1.55 +/- 0.11 to 1.06 +/- 0.23, and Tapex-end increased from 84 +/- 17 to 171 +/- 52 msec. T-wave complexity increased initially but saturated at SD = 50 msec. QT dispersion increased modestly until SD = 40 msec and more rapidly for higher values of SD. TDR increased linearly with SD. Tapex-end increased linearly with TDR, but overestimated it. CONCLUSION: T-wave complexity did not discriminate between differences in larger RH values. QT dispersion had low sensitivity in the transitional zone between normal and abnormal RH. In conclusion, T-wave amplitude, -area, -symmetry, and, with some limitations, Tapex-end and T-wave complexity reliably reflect changes in RH.

Hypertensive stress increases dispersion of repolarization.

Several electrocardiographic indices for repolarization heterogeneity have been proposed previously. The behavior of these indices under two different stressors at the same heart rate (i.e., normotensive gravitational stress, and hypertensive isometric stress) was studied. ECG and blood pressure were recorded in 56 healthy men during rest (sitting with horizontal legs), hypertensive stress (performing handgrip), and normotensive stress (sitting with lowered legs). During both stressors, heart rates differed <10% in 41 subjects, who constituted the final study group. Heart rate increased from 63 +/- 9 beats/min at rest to 71 +/- 11 beats/min during normotensive, and to 71 +/- 10 beats/min during hypertensive stress (P < 0.001). Systolic blood pressure was 122 +/- 15 mmHg at rest and 121 +/- 15 mmHg during normotensive stress, and increased to 151 +/- 17 mmHg during hypertensive stress (P < 0.001). The QT interval was larger during hypertensive (405 +/- 27) than during normotensive stress (389 +/- 26, P < 0.001). QT dispersion did not differ significantly between the two stressors. The mean interval between the apex and the end of the T wave (Tapex-Tend) of the mid-precordial leads was larger during hypertensive (121 +/- 17 ms) than during normotensive stress (116 +/- 15 ms, P < 0.001). The singular value decomposition T wave index was larger during hypertensive (0.144 +/- 0.071) than during normotensive stress (0.089 +/- 0.053, P < 0.001). Most indices of repolarization heterogeneity were larger during hypertensive stress than during normotensive stress. Hypertensive stressors are associated with arrhythmogeneity in vulnerable hearts. This may in part be explained by the induction of repolarization heterogeneity by hypertensive stress.