Autonomic Derangement Research Articles

Autonomic dysfunction in mild cognitive impairment: a transcranial Doppler study

The contribution of early microvascular and autonomic derangements to the pathogenesis of mild cognitive impairment (MCI) is unclear. Aim of this study is to evaluate cerebrovascular reactivity (CVR) and cardiac autonomic function in patients with MCI by means of transcranial Doppler (TCD). Fifteen patients with MCI and 28 controls underwent carotid ultrasound and TCD evaluation, including assessment of mean flow velocity (MFV) in the middle cerebral artery at baseline, after CO(2) inhalation and after hyperpnoea. End-tidal CO(2) , mean arterial blood pressure (MAP), heart rate (HR), and respiratory rate were monitored throughout the procedure, and CVR was calculated. MAP, end-tidal CO(2) , and MFV variations during hypercapnia and hyperventilation showed no between-group differences. CVR was similar in controls and MCI (2.30 vs 2,39, respectively, P = 0.767). HR significantly increased in hypercapnia (+9.4%, P < 0.0001) and hyperventilation (+18.7%, P < 0.0001) in controls, while in MCI it significantly increased in hyperventilation (+10.4%, P = 0.002), but not in hypercapnia (+1.1%, P = 0.635). This study demonstrates that patients with MCI have a normal CVR, but they exhibit signs of autonomic dysfunction after CO(2) challenge. Should this finding be confirmed in larger studies, HR response to CO(2) challenge could become a marker of MCI.

Autonomic Changes in Preoperative Uncomplicated Diabetic Patients with Postural Changes

Diabetic autonomic neuropathy is a critical complication frequently encountered in anaesthetic and surgical practice. Power spectral analysis is a noninvasive tool for monitoring frequency analysis of heart rate variability (HRV) and autonomic control of the heart. This study examined HRV changes in preoperative diabetic patients without overt signs of autonomic dysfunction and in matched controls (n=18 per group). HRV values at -15 degrees, 0 degrees, 15 degrees, 45 degrees and sitting positions were compared between groups and for each position. HRV in diabetic patients was lower than in controls at all positions (absolute units). Low-frequency power (normalized units) and the low-frequency/high-frequency ratio increased significantly at 45 degrees and in sitting positions in controls but not in diabetic patients. Pre-existing autonomic derangements in diabetic patients without overt clinical symptoms can be aggravated by high-degree tilting or sitting positions. Consequently, great care should be taken during the intra- and perioperative management of these patients.

Gender-Specific Predictors of Functional Outcome after Stroke Rehabilitation: Potential Role of the Autonomic Nervous System

The aim of this study was to assess the impact of cardiac autonomic derangement on gender-associated functional outcome of patients with subacute ischemic stroke undergoing a hospital-based rehabilitation program. The study population included 126 consecutive first-ever stroke survivors (mean age 59.7 ± 11.6 years). Time-domain measures of heart rate variability (HRV) by 24-hour Holter monitoring (HM) were considered in all cases. By the end of the rehabilitation program an unfavorable functional outcome with dependency (Barthel Index score of <75) was found in 27 men (40.3%) and in 31 women (52.5%; p = 0.168). Multivariate analysis demonstrated that high age, low Barthel Index score and low Rankin Scale score on admission were independent predictors of an unfavorable functional outcome in both men and women. The standard deviation of normal-to-normal RR intervals on HM was an independent predictor of rehabilitation outcome only in men (OR 15.29, 95% CI 2.47–46.58, p = 0.001). The presence of insular damage on neuroimaging studies was independently associated with an unfavorable functional outcome only in female (OR 18.89, 95% CI 2.34–71.4, p = 0.006). HRV does not predict functional outcome after rehabilitation in women. Instead, insular damage appears to have a role in determining the final results of rehabilitation in women but not in men.

Left Ventricular Assist Improves Autonomic Imbalance in Patients with Persistent Myocardial Dysfunction

Left ventricular assist devices (LVAD) are an effective therapeutic option for end-stage heart failure (HF). Reduced heart rate variability (HRV) as a result of autonomic derangement is evident in chronic heart failure and several studies have established the independent prognostic value of HRV in chronic heart failure. In the present study we investigated whether autonomic function is restored in patients after LVAD implantation with persistent, severely depressed left ventricular function. Ambulatory Holter ECG recordings were collected in heart failure patients with an LVAD (n=8) und age-matched heart failure patients without an LVAD (n=7) both on optimal medical therapy. Cardiac dimensions and function were assessed by echocardiography or angiography. Analysis for heart rate variability revealed reduced SDNN (67±4 ms), SDANN (56±4 ms) and triangular index (18±1) in heart failure patients on optimal medical therapy. However patients with LVAD demonstrated a restoration in heart rate variability with normal SDNN (108±9 ms), SDANN (103±8 ms) and triangular index (29±2). Compared to patients without LVAD this difference was statistically significant (p<0.01). In end-stage heart failure patients autonomic imbalance indicated by severely reduced heart rate variability is restored after LVAD implantation with unloading of the failing heart.

Early autonomic dysfunction in type 1 diabetes: a reversible disorder?

Cardiac autonomic neuropathy is associated with increased morbidity and mortality rates in patients with type 1 diabetes. The prevalence of early autonomic abnormalities is relatively high compared with the frequency of manifest clinical abnormalities. Thus, early autonomic dysfunction could to some extent be functional and might lead to an organic disease in a subgroup of patients only. If this is true, manoeuvres such as slow deep-breathing, which can improve baroreflex sensitivity (BRS) in normal but not in denervated hearts, could also modify autonomic modulation in patients with type 1 diabetes, despite autonomic dysfunction. We compared 116 type 1 diabetic patients with 36 matched healthy control participants and 12 heart-transplanted participants with surgically denervated hearts. Autonomic function tests and spectral analysis of heart rate and blood pressure variability were performed. BRS was estimated by four methods during controlled (15 breaths per minute) and slow deep-breathing (six breaths per minute), and in supine and standing positions. Conventional autonomic function tests were normal, but resting spectral variables and BRS were reduced during normal controlled breathing in patients with type 1 diabetes. However, slow deep-breathing improved BRS in patients with type 1 diabetes, but not in patients with surgically denervated hearts. Standing induced similar reductions in BRS in diabetic and control participants. Although we found signs of increased sympathetic activity in patients with type 1 diabetes, we also observed a near normalisation of BRS with a simple functional test, indicating that early autonomic derangements are to a large extent functional and potentially correctable by appropriate interventions.

Postoperative Delirium

Postoperative Delirium

Abdominal obesity is associated with autonomic nervous derangement in healthy Asian obese subjects

Subjects with obesity had autonomic nervous abnormalities. This study investigated autonomic nervous modulation in subjects with obesity and its association with the indices of obesity, especially the body mass index and waist circumference, by heart rate variability analysis. Forty-seven adults with a body mass index (in kg/m(2)) greater than 28 were recruited as the obese group and 30 subjects with a body mass index less than 23 were recruited as the control group. Anthropometric measures and heart rate variability measures were obtained for both groups. The correlation between heart rate variability measures and the anthropometric measures was assessed in subjects with obesity. Subjects with obesity had lower normalized low-frequency power and normalized high-frequency power than those of the control group. The body height, body weight, waist circumference and waist-to-hip ratio correlated significantly with the spectral heart rate variability measures in Asian subjects with obesity, whereas the body mass index did not. Abdominal obesity, rather than general obesity, was related to autonomic nervous derangement in Asian subjects with obesity. The close relation between abdominal obesity and autonomic derangement may partially account for the close relationship between abdominal obesity and higher risk of mortality and morbidity in subjects with obesity.

Cardiac autonomic dysfunction and functional outcome after ischaemic stroke

ischaemic stroke has been associated with an impairment of cardiac autonomic balance. The aim of this study was to assess the impact of cardiac autonomic derangement on functional outcome after a rehabilitation program in patients with recent ischaemic stroke. The study population included 85 consecutive first-ever stroke survivors (46 men and 39 women; mean age 60.0 +/- 12.4 years), who underwent 24-h Holter monitoring before the beginning of a 60-day rehabilitation program. Time-domain measures of heart-rate variability (HRV) were considered in all cases. By the end of the rehabilitation program an unfavorable functional outcome with dependency (Barthel Index score of <75) was found in 44.7% of patients. Multivariate analysis demonstrated that age [odds ratio (OR) 1.09, 95% CI 1.04-1.19, P = 0.002], stroke severity (OR 1.12, 95% CI 1.01-1.34, P = 0.004), Barthel Index score (OR 0.92, 95% CI 0.87-0.98, P = 0.01) and Rankin Scale score (OR 3.88, 95% CI 2.13-7.56, P = 0.02) on admission, as well as lower values of the standard deviation of normal-to-normal R wave to R wave (RR) intervals (OR 9.67, 95% CI 2.58-18.67, P = 0.006) were independent predictors of an unfavorable functional outcome. Assessment of HRV before a rehabilitation program may provide additional information on the probability of a functional recovery in stroke survivors.

Effect of Exercise Training on Autonomic Derangement and Neurohumoral Activation in Chronic Heart Failure

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. 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. 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.

Pathogenesis of Chronic Chagas Heart Disease

Chagas disease remains a significant public health issue and a major cause of morbidity and mortality in Latin America. Despite nearly 1 century of research, the pathogenesis of chronic Chagas cardiomyopathy is incompletely understood, the most intriguing challenge of which is the complex host-parasite interaction. A systematic review of the literature found in MEDLINE, EMBASE, BIREME, LILACS, and SCIELO was performed to search for relevant references on pathogenesis and pathophysiology of Chagas disease. Evidence from studies in animal models and in anima nobile points to 4 main pathogenetic mechanisms to explain the development of chronic Chagas heart disease: autonomic nervous system derangements, microvascular disturbances, parasite-dependent myocardial aggression, and immune-mediated myocardial injury. Despite its prominent peculiarities, the role of autonomic derangements and microcirculatory disturbances is probably ancillary among causes of chronic myocardial damage. The pathogenesis of chronic Chagas heart disease is dependent on a low-grade but incessant systemic infection with documented immune-adverse reaction. Parasite persistence and immunological mechanisms are inextricably related in the myocardial aggression in the chronic phase of Chagas heart disease. Most clinical studies have been performed in very small number of patients. Future research should explore the clinical potential implications and therapeutic opportunities of these 2 fundamental underlying pathogenetic mechanisms.

Cardiac Autonomic Nervous System and Risk of Arrhythmias in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL)

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited systemic microangiopathy with prevalently cerebral manifestations. Among the causes of death, sudden unexpected death seems to occur in a significant number of CADASIL patients. Because potential causes of sudden unexpected death may include cardiac arrhythmias and myocardial infarction, we evaluated risk factors for life-threatening arrhythmias, such as reduced heart rate variability, sympathetic overactivity and QT interval (QTc) prolongation, in 23 CADASIL patients. The relationship of these changes with brain MRI pattern was also investigated. Frequency domain measures of heart rate variability (10 minutes recordings) and QTc interval were recorded in 23 CADASIL patients (17 males, 6 females) and 22 healthy age- and sex-matched control subjects. The following heart rate variability spectral parameters were considered at rest during spontaneous and controlled breathing (Cb): total power, very-low-frequency component, low-frequency component, high-frequency component, low-frequency/high-frequency ratio, and Cb-total power, Cb-very-low-frequency component, Cb-low-frequency component, Cb-high-frequency component, Cb-low-frequency/high-frequency ratio. R-to-R wave and QTc interval were also analyzed. All data were statistically compared between CADASIL and control subjects. Conventional brain MRI was performed in patients with CADASIL and T1-weighted and T2-weighted lesion volumes, and were compared with each spectral component of the tachogram. During spontaneous and controlled breathing, total power spectrum and all spectral components (very low frequency component, high-frequency component, low-frequency component) of heart rate variability were significantly reduced in CADASIL patients with respect to controls (P<0.05). The low-frequency/high-frequency component ratio was significantly higher in CADASIL patients than in controls. No significant correlation between heart rate variability spectral parameters and other variables including total brain T2-weighted and T1-weighted lesion volumes were observed in CADASIL subjects. We found a statistically significant reduction in all frequency domain parameters of heart rate variability associated with a higher low frequency/high frequency ratio for CADASIL patients with respect to normal subjects. These data are consistent with autonomic derangement and suggests that CADASIL patients may be at risk for life-threatening arrhythmias. This could at least in part explain their higher recurrence of sudden unexpected death and should be taken into account in planning therapy.

The effect of rapid lipid lowering with atorvastatin on autonomic parameters in patients with coronary artery disease

Many cardiovascular disease states are associated with autonomic dysfunction, specifically sympathetic activation and parasympathetic withdrawal. Both these autonomic derangements are independently associated with adverse prognostic outcomes. HMG CoA reductase inhibitors (statins) reduce cardiovascular mortality and morbidity when compared to placebo in subjects with proven coronary artery disease (CAD), including sudden presumed arrhythmic death. As autonomic dysfunction is associated with arrhythmogenesis, statins may be having a beneficial effect on autonomic function in these subjects. We conducted a randomised, double-blind, placebo-controlled, cross-over study examining the effect of rapid short-term lipid lowering with a statin on autonomic function in CAD patients. Ten subjects with proven CAD (8 male, 2 female; mean age 63.4 years) were randomised to receive either 80 mg atorvastatin or placebo over a 4 week period followed by a 4 week washout, then the alternative treatment for a further 4 weeks. Autonomic parameters assessed were plasma noradrenaline levels on recumbency and 80° head-up tilt, cold pressor testing, and heart rate variability (HRV) analysis. Plasma noradrenaline levels were significantly reduced ( p = 0.050) after 20 min rest in the recumbent position, with atorvastatin compared to placebo. A nonsignificant reduction in plasma noradrenaline with atorvastatin compared to placebo was observed in the prolonged 80° head-up position ( p = 0.207). In addition, sympathovagal balance was shifted to greater vagal predominance with atorvastatin (low-frequency/high-frequency ratio in the HRV frequency domain) when compared to placebo, p = 0.06. We found that rapid lipid lowering with atorvastatin reduces sympathetic nervous system in this pilot study of CAD patients. Larger trials are required to definitively address the effects of statins on autonomic activity in these patients.

Assessment of Cardiac Autonomic Regulation and Ventricular Repolarization after Off-Pump Coronary Artery Bypass Grafting

Altered autonomic regulation precipitates cardiac arrhythmias and increases the risk of sudden cardiac death. This risk is further increased by changes in ventricular repolarization. Autonomic regulation is deranged in patients after myocardial on-pump revascularization. We aimed to clarify how off-pump coronary artery bypass grafting (CABG) affects postoperative cardiac autonomic regulation and ventricular repolarization within 4 weeks after CABG. Forty-two patients (mean age, 61.9 +/- 9.3 years; mean EURO score 2.6 +/- 1.9) were electively admitted for off-pump CABG. The electrocardiographic and respiratory waveform recordings were performed in the afternoon in the supine position for 10 minutes. Autonomic modulation was assessed using heart rate variability analysis. Power spectra were computed from 5-minute stable RR intervals using Fourier Transform analysis. Total power of spectra was defined in the range of 0.01 to 0.40 Hz, high-frequency power within 0.15 to 0.40 Hz, and low-frequency power within 0.04 to 0.15 Hz. Normalized power was defined as a ratio of power in each band/total power. The high- and low-frequency power as well as their normalized values indicated cardiac vagal and sympathetic modulation, respectively. Ventricular repolarization was assessed using QT interval, QT interval variability, and QT-RR interdependence analysis. QT intervals were determined from the beginning of the 5-minute segments. QT interval variability was evaluated by a T-wave template-matching algorithm. Pearson correlation between length of RR and QT interval was applied to study QT-RR characteristics. The results were tested for significance using the Fisher exact test, nonpaired t test, and analysis of variance; a P <.05 was considered significant. The frequency of arrhythmic events and heart rate increased from the fourth to the seventh postoperative day and returned to preoperative levels 4 weeks after CABG. Heart rate variability measures indicating autonomic modulation remained depressed even 4 weeks after the procedure. QT variability index increased from -1.2 +/- 0.5 to -0.8 +/- 0.4 on the fourth day after the operation (P <.05) and returned to -1.0 +/- 0.5 4 weeks after CABG (P = not significant). QT-RR correlation decreased from 0.41 to 0.23 (P <.05) and remained significantly impaired as long as 4 weeks after CABG. Observed faster heart rates until 1 week after off-pump CABG imply excessive adrenergic activation, which is comparable to on-pump CABG procedure rates. The results indicate profound autonomic derangement and loss of rate-dependent regulation after off-pump CABG even 4 weeks after operation. Restituted repolarization as assessed by QT variability index 4 weeks postoperatively corresponded with decreased frequency of rhythm disturbances 4 weeks after CABG. The loss of coupling between QT and RR intervals shows increased electrical instability postoperatively, which may serve as an additional promoter for postoperative arrhythmias, especially at higher heart rates.

Abnormal Heart Rate Turbulence Predicts the Initiation of Ventricular Arrhythmias

Abnormal heart rate turbulence (HRT) reflects autonomic derangements predicting all-cause mortality, yet has not been shown to predict ventricular arrhythmias in at-risk patients. We hypothesized that HRT at programmed ventricular stimulation (PVS) would predict arrhythmia initiation in patients with left ventricular dysfunction. We studied 27 patients with coronary disease, left ventricular ejection fraction (LVEF) 26.7 +/- 9.1%, and plasma B-type natriuretic peptide (BNP) 461 +/- 561 pg/mL. Prior to arrhythmia induction at PVS, we measured sinus cycles after spontaneous or paced premature ventricular contractions (PVCs) for turbulence onset (TO; % cycle length change following PVC) and slope (TS; greatest slope of return to baseline cycle). T-wave alternans (TWA) was also measured during atrial pacing. At PVS, abnormal TO (> or =0%) predicted inducible ventricular tachycardia (VT; n = 10 patients; P < 0.05). TO was greater in inducible than in noninducible patients (2.3 +/- 3.1% vs -0.02 +/- 2.8%, P < 0.05) and correlated with LVEF (P < 0.05) but not with BNP. TS did not differ between groups. Conversely, ambulatory HRT differed significantly from HRT at PVS (TO -0.55 +/- 1.08% vs 0.85 +/- 3.02%, P < 0.05; TS 2.63 +/- 2.09 ms/RR vs 8.70 +/- 6.56 ms/RR, P < 0.01), and did not predict inducible VT but trended (P = 0.05) to predict sustained VT on 739 +/- 179 days follow-up. TWA predicted inducible (P < 0.05) and spontaneous (P = 0.0001) VT but did not co-migrate with HRT. Abnormal HRT measured at PVS predicted the induction of sustained ventricular arrhythmias in patients with ischemic cardiomyopathy. However, HRT at PVS did not correlate with ambulatory HRT, nor with TWA, both of which predicted spontaneous ventricular arrhythmias. Thus, HRT may reflect the influence of autonomic milieu on arrhythmic susceptibility and is likely complementary to traditional arrhythmic indices.

Prognostic Implications of Right-Sided Insular Damage, Cardiac Autonomic Derangement, and Arrhythmias After Acute Ischemic Stroke

Acute stroke is associated with impairment of cardiac autonomic balance and increased incidence of arrhythmias. These abnormalities appear more relevant in the case of involvement of the right insula in the infarct area. The aim of this study was to assess the impact of right-sided insular damage, cardiac autonomic derangement, and arrhythmias on clinical outcome after acute ischemic stroke. Holter monitoring for 24 hours was performed in 208 consecutive patients with first-ever acute ischemic stroke. Time- and frequency-domain measures of heart rate variability and arrhythmias were considered in all cases. All patients were followed for a 12-month period after the initial event. During the 12-month follow-up period, 48 patients died (1-year probability of death, 0.23; 95% CI, 0.17 to 0.30). Multivariate analysis demonstrated that age (hazard ratio [HR], 1.06; 95% CI, 1.01 to 1.10; P=0.0087), stroke severity on admission (HR, 1.25; 95% CI, 1.13 to 1.39; P=0.0001), presence of right-sided insular damage (HR, 2.01; 95% CI, 1.13 to 1.39; P=0.0187), as well as lower values of the SD of all normal-to-normal RR intervals (HR, 3.32; 95% CI, 1.67 to 6.24; P=0.002), and presence of nonsustained ventricular tachycardia during Holter monitoring (HR, 2.99; 95% CI, 1.58 to 5.67; P=0.0007) were independent predictors of 1-year mortality. The integration of traditional risk stratifiers with autonomic and arrhythmic markers, and the careful search for right-sided insular involvement, may represent an effective approach for identification of stroke patients at risk for early mortality.

Autonomic function in elderly uremics studied by spectral analysis of heart rate

Aging determines an altered response of the autonomic nervous system (ANS) to physiologic stresses. A widespread autonomic damage is well recognized in chronic renal failure (CRF). We studied 30 CRF patients, aged 19 to 85 years, who were on bicarbonate hemodialysis. Surface electrocardiogram was recorded on lying and 65 degrees head-up tilt standing positions. A dedicated software, using an autoregressive modeling technique, allowed to calculate power spectral analysis (PSA) of heart rate variability, assessing a low-frequency band in the range 0.03 to 0.15 Hz, and a high-frequency band in the range 0.15 to 0.33 Hz. Low-frequency and high-frequency components are regarded, but not invariably, as specific markers of sympathetic and parasympathetic activities, respectively, and the low-frequency/high frequency ratio as an index of sympathovagal balance. In normal controls, low-frequency band value and low-frequency/high-frequency ratio on standing resulted significantly reduced in the group older than 65 years when compared with those younger than 65 years; an opposite finding was seen in high-frequency band value on standing. In uremic patients, low-frequency band on lying resulted significantly lower only in elderly uremics when compared with elderly controls, whereas low-frequency band on standing was significantly lower in elderly than in younger uremics. Regression analysis showed a significant inverse relationship between aging and most low-frequency band values, especially in uremics. The comparison of linear regression models confirmed that a sympathetic autonomic derangement is greatly present in older uremics, in particular after 50 years of age. Our data support assertion that combination of aging and CRF increases the chance of autonomic derangement being present.

Modeling and Simulation of Baroreflex Regulation of Heart Rate in Response to Respiratory Fluctuations in Arterial Pressure

Autonomic derangement can be assessed by depressed baroreflex sensitivity in a restrictive left ventricular diastolic filling pattern. However, it is unclear how reflex or other compensations affect the inspiratory fall of systolic arterial pressure (IFSAP) during acute airway obstruction. In an in-vivo situation, it is particularly difficult to isolate individual effects of heart rate, vascular tone, pleural pressure variation, and ventricular interdependence. For this reason, a computer model study was undertaken. A previously validated computer model of the cardiopulmonary system was adapted for this study, relating mechanisms such as baroreflex regulation of heart rate to IFSAP. The model provided time-course simulations of hemodynamics by numerically integrating 28 nonlinear, time-varying differential equations. Two models for baroreflex gain were tested, including a simple 1st-order relationship between systolic arterial pressure (SAP) and R-R interval (RRI) and the autoregressive moving average (ARMA) model reported in literature. The ARMA model predicted the next RRI based on SAP from several previous cardiac cycles and previous RRI predictions. Experimental data were obtained retrospectively from 22 patients with chronic airway obstruction before and during breathing through an external resistance. The computer model provided good fits to arterial pressure waveforms: correlation coefficients (r) ranging from 0.71 to 0.96 (mean±SD: 0.87±0.06) with a simple 1st-order SAP-RRI model. The ARMA model did not improve the goodness of fit.

Neurohormonal abnormalities in heart failure: impact of exercise training.

Endurance exercise training appears to beneficially alter the clinical course of chronic heart failure. The specific mechanisms responsible for exercise-induced benefits, however, are not completely understood. This review examines the impact of endurance exercise training on neurohormonal mechanisms, which play a central role in the progression of chronic heart failure. Few studies, however, have been specifically designed to elucidate exercise-induced mechanisms responsible for the suppression of neurohormonal activation in patients with chronic heart failure and the literature on this topic is derived from a limited number of small, single-center studies. The available data suggests that endurance exercise training programs of moderate duration (approximately 16 weeks) are efficacious in suppressing circulating levels of catecholamines, angiotensin II, arginine vasopressin, and aldosterone. Additionally, endurance exercise training improves baroreceptor sensitivity and heart rate variability, suggesting that exercise ameliorates the autonomic derangement in chronic heart failure by increasing the parasympathetically mediated component of heart rate variability. Pharmacologic suppression of sympathetic activity has proved, by and large, to be successful at reducing mortality in patients with chronic heart failure. Exercise-induced modulation of sympathetic activity may also be instrumental at reducing morbidity and mortality but this has not been carefully investigated and is a fertile area for further research.

Derangement of heart rate variability during a catastrophic earthquake: a possible mechanism for increased heart attacks.

At 1:47 AM on September 21, 1999, the middle part of Taiwan was struck by a major earthquake measuring 7.3 on the Richter scale. It has been shown that the mental stress caused by an earthquake could lead to a short- or long-term increase in frequency of cardiac death probably through activation of the sympathetic nervous system. The aim of this study was to investigate the effects of emotional stress on the autonomic system during an actual earthquake. Fifteen patients receiving a 24-hour Holter ECG study starting from 10+/-4 hours before the onset of the earthquake were included for the analysis of time- and frequency-domains of heart rate variability (HRV) at several time periods. A 24-hour Holter study recorded 2-6 months before the earthquake in 30 age- and sex-matched subjects served as the control group. Heart rate and the low frequency (LF) to high frequency (HF) ratio increased significantly after the earthquake and were attributed mainly to the withdrawal of the high frequency component (parasympathetic activity) of HRV. Sympathetic activation was blunted in elderly subjects > 60 years old. The concomitant ST-T depression observed in the Holter study correlated with a higher increment of LF as compared to HF components. The changes observed in HRV recovered completely 40 minutes following the earthquake. The derangement of HRV results from the withdrawal of the parasympathetic component and the arousal of sympathetic activity by the stressful earthquake. However, this autonomic derangement returned towards normal 40 minutes following the earthquake.

Early autonomic and repolarization abnormalities contribute to lethal arrhythmias in chronic ischemic heart failure: Characteristics of a novel heart failure model in dogs with postmyocardial infarction left ventricular dysfunction

OBJECTIVESUsing a model of arrhythmias associated with ischemic left ventricular (LV) dysfunction, this study investigated autonomic and electrophysiologic mechanisms associated with sudden cardiac death (SCD) in chronic heart failure (HF).BACKGROUNDLeft ventricular dysfunction from ischemic heart disease is associated with many instances of SCD. Electrophysiologic and autonomic derangements occur in HF, but their contribution to SCD risk is poorly understood.METHODSSudden death risk was assessed in 15 dogs with a healed anterior myocardial infarction (MI) during submaximal exercise and brief acute circumflex ischemia. Left ventricular dysfunction was then induced by repetitive circumflex microembolization until LV ejection fraction reached 35%. Before embolization, six dogs were susceptible to SCD, and nine were resistant.RESULTSBaroreflex sensitivity was lower in susceptible dogs (10 ms/mm Hg ± 4 ms/mm Hg vs. 20 ms/mm Hg ± 11 ms/mm Hg, p = 0.04). QT intervals from susceptible dogs were longer after MI (246 ms ± 26 ms susceptible vs. 231 ms ± 20 ms resistant, p < 0.001) and prolonged within eight weeks after LV dysfunction was established (from 246 ms ± 26 ms to 274 ms ± 56 ms, +11%, p < 0.01). Heart rate in susceptible dogs increased during transient ischemia (+20%) and with progressive LV dysfunction (102 beats/min ± 28 beats/min baseline to 154 beats/min ± 7 beats/min LV dysfunction, p = 0.003). All susceptible dogs had spontaneous sustained ventricular tachycardia culminating in SCD. In contrast, QT intervals in resistant dogs prolonged after 24 ± 6 weeks (from 231 ms ± 20 ms to 238 ms ± 15 ms, p < 0.05), and heart rates were unchanged. Only one resistant dog died suddenly with LV dysfunction.CONCLUSIONSDepressed vagal and elevated sympathetic control of heart rate coupled with abnormal repolarization are associated with high SCD risk when post-MI LV dysfunction develops.