Impairment Of Heart Rate Variability Research Articles

Cardiac autonomic dysfunction in adult congenital heart disease

PurposeDue to recent advances in diagnosis and treatment, the number of adults with congenital heart disease (ACHD) has substantially increased. This achievement is mitigated by rhythm disorders. Here, we sought to determine alterations in heart rate variability (HRV) and their prognostic value in ACHD.MethodsNinety seven ACHD patients (39.2 ± 14.1 years, 51.5% female) and 19 controls (39.7 ± 15.0 years, 47.4% female) underwent 24-h Holter monitoring.ResultsAs compared to controls, ACHD patients offered a significantly higher burden of premature ventricular contractions (p = 0.02) and decreased HRV indices (natural logarithmic transformation of very low frequency (lnVLF): 7.46 ± 0.76 ms2 vs. 7.91 ± 0.92ms2, p = 0.03; natural logarithmic transformation of low frequency (lnLF): 6.39 ± 0.95ms2 vs. 7.01 ± 1.07ms2, p = 0.01; natural logarithmic transformation of the ratio of low to high frequency spectra (lnLF/HF): 0.81 ± 0.74 vs. 1.17 ± 0.51, p = 0.04). No differences in HRV measures were observed across ACHD lesion groups. NT-proBNP levels were significantly related to both time and frequency domain indices (natural logarithmic transformation of the standard deviation of NN intervals (lnSDNN): Spearman´s rho = -0.32, p = 0.001; natural logarithmic transformation of the standard deviation of the average NN intervals for each 5-min segment of a 24-h Holter monitoring (lnSDANN): Spearman´s rho: -0.33, p = 0.001; natural logarithmic transformation of the total power (lnTP): Spearman´s rho: -0.25, p = 0.01; lnVLF: Spearman´s rho: -0.33, p = 0.001; lnLF: Spearman´s rho: -0.35, p < 0.001; lnLF/HF: Spearman´s rho: -0.34, p = 0.001).After a mean follow-up of 3.9 ± 0.7 years, 8 patients died and 3 patients survived sudden cardiac death (SCD). Several HRV parameters were significantly higher in event-free ACHD patients than in those who died or survived SCD (natural logarithmic transformation of the average of the standard deviations of NN intervals for each 5-min segment of a 24-h Holter monitoring (lnASDNN): p = 0.04; lnPNN30: p = 0.04; lnVFL: p = 0.03; lnLF: p < 0.01). On univariate Cox regression analysis, the time domain indices lnSDNN, lnASDNN and lnPNN30, as well as the frequency domain parameters lnTP, lnVLF and lnLF were associated with death and survived cardiac arrest.ConclusionACHD is accompanied by HRV impairment that carries prognostic implications on ACHD mortality and survived SCD.

Heart Rate Variability Impairment Is Associated with Right Ventricular Overload and Early Mortality Risk in Patients with Acute Pulmonary Embolism.

The association between heart rate variability (HRV) and mortality risk of acute pulmonary embolism (APE), as well as its association with right ventricular (RV) overload is not well established. We performed an observational study on consecutive patients with confirmed APE. In the first 48 h after admission, 24 h Holter monitoring with assessment of time-domain HRV, echocardiography and NT-proBNP (N-terminal pro-B-type natriuretic peptide) measurement were performed in all participants. We pre-examined 166 patients: 32 (20%) with low risk of early mortality, 65 (40%) with intermediate-low, 65 (40%) with intermediate-high, and 4 (0.02%) in the high risk category. The last group was excluded from further analysis due to sample size, and finally, 162 patients aged 56.3 ± 18.5 years were examined. We observed significant correlations between HRV parameters and echocardiographic signs of RV overload. SDNN (standard deviation of intervals of all normal beats) correlated with echocardiography-derived RVSP (right ventricular systolic pressure; r = -0.31, p = 0.001), TAPSE (tricuspid annulus plane systolic excursion; r = 0.21, p = 0.033), IVC (inferior vena cava diameter; r = -0.27, p = 0.002) and also with NT-proBNP concentration (r = -0.30, p = 0.004). HRV indices were also associated with APE risk stratification, especially in the low-risk category (r = 0.30, p = 0.004 for SDNN). Univariate and multivariate analyses confirmed that SDNN values were associated with signs of RV overload. In conclusion, we observed a significant association between time-domain HRV parameters and echocardiographic and biochemical signs of RV overload. Impaired HRV parameters were also associated with worse a clinical risk status of APE.

In Amateur Athletes With Type 1 Diabetes, a 9-Day Period of Cycling at Moderate-to-Vigorous Intensity Unexpectedly Increased the Time Spent in Hyperglycemia, Which Was Associated With Impairment in Heart Rate Variability.

In type 1 diabetes, autonomic dysfunction may occur early as a decrease in heart rate variability (HRV). In populations without diabetes, the positive effects of exercise training on HRV are well-documented. However, exercise in individuals with type 1 diabetes, particularly if strenuous and prolonged, can lead to sharp glycemic variations, which can negatively impact HRV. This study explores the impact of a 9-day cycling tour on HRV in this population, with a focus on exercise-induced glycemic excursions. Twenty amateur athletes with uncomplicated type 1 diabetes cycled 1,500 km. HRV and glycemic variability were measured by heart rate and continuous glucose monitoring. Linear mixed models were used to test the effects of exercise on HRV, with concomitant glycemic excursions and subject characteristics considered as covariates. Nighttime HRV tended to decrease with the daily distance traveled. The more time the subjects spent in hyperglycemia, the lower the parasympathetic tone was. This result is striking given that hyperglycemic excursions progressively increased throughout the 9 days of the tour, and to a greater degree on the days a longer distance was traveled, while time spent in hypoglycemia surprisingly decreased. This phenomenon occurred despite no changes in insulin administration and a decrease in carbohydrate intake from snacks. In sports enthusiasts with type 1 diabetes, multiday prolonged exercise at moderate-to-vigorous intensity worsened hyperglycemia, with hyperglycemia negatively associated with parasympathetic cardiac tone. Considering the putative deleterious consequences on cardiac risks, future work should focus on understanding and managing exercise-induced hyperglycemia.

Impact of Elective Percutaneous Transluminal Coronary Angioplasty (PTCA) on Heart Rate Variability in Patients with Coronary Artery Disease

Coronary artery disease (CAD) is a major public health problem in India and is one of the leading causes of mortality and morbidity. Impairment of heart rate variability (HRV) has been observed in patients with CAD. Percutaneous transluminal coronary angioplasty (PTCA) is one of the common modalities of treatment of CAD. In this study we have studied the effect of successful elective PTCA on HRV parameters in patients with CAD. Material and Method: HRV parameters in both time and frequency domain were studied in 30 male patients before PTCA, one day and three day after PTCA. Results: - The time and frequency domain parameters between pre PTCA and 1st day post PTCA were not found to be statistically significant. Changes in the time domain parameter rMSSD and SDNN was statistically significant between pre and 3rd day post PTCA but no significant difference was observed in pNN50. A significant decrease in LF n.u and increase in HF n.u was observed between pre and 3rd day post PTCA. Conclusion: Revascularization with PTCA results in improvement of the autonomic tone. Improved autonomic modulation is seen as early as 3rd day post PTCA. It indicates that restoring the blood flow reverses to some extent the autonomic modulatory effect of coronary artery disease.

The association of family history of hypertension and overweight induced early impairment in markers of oxidative stress and in heart rate variability

Considering the high prevalence of hypertension worldwide and the changes in lifestyle, the understanding of the mechanisms involved in the genesis of hypertension are important to reach more precise interventions. Our objective was to evaluate cardiovascular, autonomic and oxidative stress parameters in individuals with family history of hypertension (FH) with or without overweight. We performed a cross‐sectional study and selected 65 healthy sedentary men (24.08 ± 5.84 years) distributed into 4 groups: negative FH eutrophic (FNE, n=18) or with overweight (FNO, n=19) and positive FH eutrophic (FHE, n=17) or with overweight (FHO, n=17). The heart rate variability (HRV) was analyzed at rest by spectral analysis. The oxidative stress markers were evaluated in plasma. A positive correlation between levels LDL and WC/HC ratio was demonstrated (r: 0.54 p = 0.003) in FHE and FHO groups. We observed an increase in diastolic blood pressure in the FHO and FNO groups in relation to the FNE and FHE groups (p = 0.010). When we evaluated the cardiac sympathetic modulation (LF‐PI), we observed a significant increase in the FNO and FHO groups when compared to the FNE group (p = 0.0001). Furthermore, the FHO (2.30 ± 0.8) and FHE groups (2.52 ± 1) presented higher cardiac sympato‐vagal balance (LF/HF) compared to FNO (1.85 ± 0.67) and FNE groups (2.01 ± 0.84) (p =0.04). We observed an increase in systemic hydrogen peroxide concentration in the FHO group when compared to the other groups (p=0.003). Moreover, there was an increase in NADPH oxidase in plasma in FNO and FHO groups in relation the FNE and FHE groups (p = 0.04). In addition, there was an increase in plasma nitrite levels in FHO group compared to FNO, FNE and FHE groups (p=0.01). In conclusion our findings demonstrated that despite young and apparently healthy, the group with overweight and FH showed early impairment in HRV and in markers of oxidative stress. In addition, this group presented all dysfunctions observed in the presence of these risk factors alone, which may be associated with increased cardiovascular risk and target organ damage in this population.Support or Funding InformationUNINOVE, CNPq, CAPES, FAPESP.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract P331: Transition From Pre-Diabetes To Diabetes Is Associated With Worsening Of Cardiac Autonomic Neuropathy: Reversal By Anti-Diabetic Drugs

Cardiac autonomic neuropathy (CAN) occurs early in the course of diabetes leading to significant cardiovascular mortality and morbidity. Manifested as impaired heart rate variability (HRV) and baroreflex sensitivity (BRS), CAN represents an independent risk predictor of cardiac mortality. CAN development is linked to hyperglycemia; however, current understanding extends cardiovascular risk to pre-diabetic patients with slight glycemic changes. Here, we assessed the incidence and manifestation of CAN in a rat model of metabolic challenge prior to and after the development of diabetes. Rats were fed a hypercaloric (HC) diet (4.035 KCal/g vs. 3 KCal/g for control rats) composed of: weight (calories) 18.06 % fat (38.68%), 15.8% protein (15.66%), and 46.13% carbohydrates (45.73%). Stable fasting hyperglycemia developed by 16 weeks of feeding. The pre-diabetic stage was associated with signs of perivascular and epicardiac adipose inflammation (4- and 40- fold increase in IL-1β and TGF-β and 2-fold increase in NK-κB expression; and macrophage infiltration) and increased brainstem oxidative stress accompanied with impairment of HRV (total power decrease from 3098 ± 233 to 89 ± 88μs 2 ) and the parasympathetic arm of the baroreflex (slope decrease from -1.02 ± 0.12 to -0.34 ± 0.04). These abnormalities were reversed upon treatment with non-hypoglycemic doses of either metformin or pioglitazone or upon lowering the rat caloric intake. On the other hand, after progression to diabetes, the autonomic deficit progressed to the sympathetic arm of the baroreflex (Slope reduction from -0.35 ± 0.02 to -0.09 ± 0.03). The same hypoglycemic doses of metformin and pioglitazone failed to reverse the impaired HRV and BRS. Whereas, reduction of hyperglycemia to control levels by insulin was only capable of reversing the sympathetic impairment (BRS slope of -0.28 ± 0.04). Our present results outline a framework for sequential involvement of different detrimental mechanisms in the course of metabolic disease leading to differential impact on cardiac autonomic control. Furthermore, our findings emphasize the value of early intervention with antidiabetic drugs with potential protective pleiotropic effects.

Carotid Body Ablation: a New Target to Address Central Autonomic Dysfunction.

An abnormal heightened carotid body (CB) chemoreflex, which produces autonomic dysfunction and sympathetic overactivation, is the common hallmark of obstructive sleep apnea (OSA), resistant hypertension, systolic heart failure (HF), and cardiometabolic diseases. Accordingly, it has been proposed that the elimination of the CB chemosensory input to the brainstem may reduce the autonomic and cardiorespiratory alterations in sympathetic-associated diseases in humans. A growing body of evidence obtained in preclinical animal models support that an enhanced CB discharge produces sympathetic hyperactivity, baroreflex sensitivity and heart rate variability impairment, breathing instability, hypertension, and insulin resistance. The elimination CB chemosensory input reduces the sympathetic hyperactivity, the elevated arterial blood pressure in OSA and hypertensive models, abolishes breathing instability and improves animal survival in HF models, and restores insulin tolerance in metabolic models. These results highlight the role played by the enhanced CB drive in the progression of sympathetic-related diseases and support the proposal that the surgical ablation of the CB is useful to restore the autonomic balance and normal cardiorespiratory function in humans. Accordingly, the CB ablation has been used in pilot human studies as a therapeutic treatment for resistant hypertension and HF-induced sympathetic hyperactivity. In this review, I will discuss the supporting evidence for a crucial contribution of the CB in the central autonomic dysfunction and the pros and cons of the CB ablation as a therapy to revert autonomic overactivation. The CB ablation could be a useful method to reverse the enhanced chemoreflex in HF and severe hypertension, but caution is required before extensive use of bilateral CB ablation, which abolished ventilatory responses to hypoxia and may impair baroreceptor function.

Impaired heart rate variability in cervical dystonia is associated to depression.

Causes of cardiovascular autonomic dysfunction in cervical dystonia (CD) are poorly understood. Studies examining effects of botulinum neurotoxin (BoNT) therapy on heart rate variability (HRV) yielded contradictory results. There is compelling evidence that depression shifts autonomic balance towards sympathetic predominance. As depression is the most frequent non-motor symptom in CD, we sought to determine if it is associated to dysfunction of cardiovascular autonomic regulation. Standardized interviews, clinical examinations, self-rating forms, autonomic symptom questionnaire, and automated autonomic testing in outpatients with idiopathic CD were used. Cardiovascular autonomic screening encompassed five different analyses of HRV, and testing of orthostasis. 85 CD patients participated in the study. 21% of them had HRV impairment, 14% orthostatic hypotension. 30% of CD patients had symptoms of depression. In those, decreased HRV was more frequent than in CD patients without mood disturbance (40 vs. 13%; p=0.008). CD patients with and without depression had no other significant differences, including demographics, dystonia severity, comorbidity, medication, or BoNT therapy. Cardiovascular autonomic imbalance with sympathetic predominance is a non-motor manifestation of CD, associated to depression. Impaired HRV is a cardiovascular risk factor, moreover, emphasizing the need to identify and treat depression in dystonia.

Evidence for Autonomic Function and Its Influencing Factors in Subjects With COPD: A Systematic Review.

Cardiovascular autonomic neuropathy is one of the factors implicated in the high morbidity and mortality rate in patients with COPD. Thus, several studies and nonsystematic reviews have increasingly reported autonomic function impairment in these subjects. For a better understanding, this systematic review was performed to evaluate not only the evidence for autonomic function impairment, but also factors influencing it. The results of the studies reviewed showed a strong level of evidence to support the impairment of heart rate variability in the time domain. A similar evidence level was also found to support impairment in baroreceptor sensitivity and muscle sympathetic nerve activity. Furthermore, this review identified physical activity level, muscle function, and circadian rhythm as the major influencing factors (strong evidence) of autonomic function in subjects with COPD. However, no definite conclusion could be reached for factors such as dyspnea, anxiety, body composition, pulmonary function, age, breathing frequency, ventilatory effort, quality of life, and disease severity due to limited, conflicting, or lack of existing evidence. The results of this review highlight relevant clinical messages for clinicians and other health-care providers regarding the role autonomic function can play as an important physiological marker for prognostication and stratification. Hence, autonomic function outcomes should be identified and considered during management of patients with COPD. Moreover, this review can serve as basis for future research aimed at assessing the interventions for autonomic function abnormalities in these patients.

Which is responsible for cardiac autonomic dysfunction in non-diabetic patients with metabolic syndrome: Prediabetes or the syndrome itself?

AimsCardiac autonomic dysfunction (CAD) is associated with both prediabetes and metabolic syndrome (MS). Heart rate variability (HRV) and heart rate turbulence (HRT) are reliable 24-h Holter-ECG findings of cardiac autonomic function. This study aimed to investigate the relation between MS and its components and CAD using HRV and HRT. Materials and methodsThe study included 80 non-diabetic patients with MS and 70 control subjects. All study population and the patients with MS were further analyzed for each diagnostic component of MS to investigate which criteria impaired HRV and HRT. ResultsHRV and HRT parameters were disturbed in patients in the MS group. While impairment in HRV and HRT was significantly related to the presence of the fasting plasma glucose (FPG) criterion, there were no differences between groups in terms of the other 4 MS criteria. Moreover, FPG level was significantly correlated with SDNN (r=−0.352, p<0.001), SDNN index (r=−0.423, p<0.001), SDANN (r=−0.301, p<0.001), RMSSD (r=−0.237, p<0.001), pNN50 (r=−0.237, p<0.001), turbulence onset (TO) (r=0.365, p<0.001) and turbulence slope (TS) (r=−0.365, p<0.001). Among the MS diagnostic criteria, only FPG level was an independent determinant of all HRV and HRT parameters. ConclusionsThis study confirms the relation between MS and CAD. Increased FPG alone appears to be responsible for the mentioned findings among the 5 diagnostic criteria. Accordingly, CAD may be the result of prediabetes, not MS in patients with MS.

Abstract P175: Impairment of Autonomic Function Precedes Blood Pressure Elevation in Rat Model of Pre-eclampsia

Hypertensive disorders of pregnancy including pre-eclampsia affect about 5-7% of all pregnant women and can cause severe acute morbidity, long-term disability and death among mothers and babies. Impairment of heart rate variability predicts risk of cardiovascular disease and all cause mortality. In this study we investigated the hypothesis that impairment of the autonomic function at early time point during pregnancy precedes and may lead to the elevation of blood pressure. To test this hypothesis, blood pressure and heart rate were recorded under 2% isoflurane in 7 day pregnant rats generated via mating of the transgenic female rat containing the human angiotensinogen gene with the male transgenic containing human renin (hREN), the hAGTхhREN rat (TgA, n=8) which develop increased blood pressure, proteinuria and increased sensitivity to angiotensin II in the last half of gestation. The reverse mating of male containing the human angiotensinogen gene with the female transgenic containing human renin (TgR, n=8) which do not develop preeclampsia, and pregnant SD (n=8) rats at day 7 of gestation were used as controls. By the 7th day of pregnancy, TgA rats had significantly impaired heart rate variability measured as root of mean successive differences (rMSSD) compared to SD and TgR (2.39 ±0.3 ms vs. 3.4 ± 0.2 in SD or 3.4 ±0.1 in TgR) and impaired baroreflex sensitivity measured as HF alpha (1.2±0.3 ms/mmHg vs. 2.5±0.4, SD or 1.7±0.26, TgR) There was no difference in systolic arterial pressure or heart rate among the three groups at this time point but diastolic pressure was higher in TgA and TgR (91± 3.5 vs. 85±2.4 or vs. 75 ±2 mmHg in SD rats) Although the predictive value of impaired baroreflex and heart rate variability in preeclampsia development needs further investigation, our findings suggest that these changes at early pregnancy precede and may contribute to the significant rise in pressure in the last half of gestation in this rat model of pre-eclampsia which may have significant clinical implications.

Heart Rate Variability in Patients Hospitalized for Decompensated Diastolic Heart Failure at Admission and After Clinical Stabilization

We investigated heart rate variability (HRV) in patients hospitalized for decompensated diastolic heart failure and the effect of compensation course on HRV parameters. We also examined the association between the degree of diastolic dysfunction and HRV indices. A total of 42 patients hospitalized for decompensated heart failure, who had a measured ejection fraction ≥ 50%, and ten age- and sex-matched healthy volunteers were enrolled. All HRV indices were lower compared with the control group both at admission (p < 0.001) and after compensation, although a significant increase was observed in each index measured after clinical stabilization (p < 0.001). Improvement in HRV indices was lowest in patients with a restrictive pattern among groups of different degrees of diastolic dysfunction. Impairment in HRV in decompensated diastolic heart failure is more pronounced with increasing grade of diastolic dysfunction. It remains to be investigated whether decompensation may be predicted by marked depression in these indexes or if severely impaired HRV is a consequence of decompensation.

Effects of different levels of positive airway pressure on breathing pattern and heart rate variability after coronary artery bypass grafting surgery

The application of continuous positive airway pressure (CPAP) produces important hemodynamic alterations, which can influence breathing pattern (BP) and heart rate variability (HRV). The aim of this study was to evaluate the effects of different levels of CPAP on postoperative BP and HRV after coronary artery bypass grafting (CABG) surgery and the impact of CABG surgery on these variables. Eighteen patients undergoing CABG were evaluated postoperatively during spontaneous breathing (SB) and application of four levels of CPAP applied in random order: sham (3 cmH₂O), 5 cmH₂O, 8 cmH₂O, and 12 cmH₂O. HRV was analyzed in time and frequency domains and by nonlinear methods and BP was analyzed in different variables (breathing frequency, inspiratory tidal volume, inspiratory and expiratory time, total breath time, fractional inspiratory time, percent rib cage inspiratory contribution to tidal volume, phase relation during inspiration, phase relation during expiration). There was significant postoperative impairment in HRV and BP after CABG surgery compared to the preoperative period and improvement of DFAα1, DFAα2 and SD2 indexes, and ventilatory variables during postoperative CPAP application, with a greater effect when 8 and 12 cmH₂O were applied. A positive correlation (P < 0.05 and r = 0.64; Spearman) was found between DFAα1 and inspiratory time to the delta of 12 cmH₂O and SB of HRV and respiratory values. Acute application of CPAP was able to alter cardiac autonomic nervous system control and BP of patients undergoing CABG surgery and 8 and 12 cmH₂O of CPAP provided the best performance of pulmonary and cardiac autonomic functions.

Sepsis und Herz

In patients suffering from severe sepsis an impairment of cardiac function is seen constantly. Patients with septic shock often show a transient reduction of cardiac ejection fraction. Besides, a tremendous impairment of heart rate variability corresponding to a poor prognosis is often found. Endotoxin might play a pivotal role in the conjunction of inflammation and the disturbance of heart rate regulation. Experimental studies show that the complex interactions of endotoxin, the cardiac pacemaker current I (f), and the autonomous nervous system lead to an increase of resting heart rate and in parallel to a decrease of heart rate variability - as typically seen in patients with severe sepsis. The method of choice to quantify the degree of septic cardiomyopathy at the intensive care unit certainly is to determine cardiac output in relation to systemic vascular resistance. Unfortunately, clinical trials aiming to influence the causal pathogenesis of septic cardiomyopathy (inhibition of excess formation of nitric oxide, suppression of cytokine release etc.) were rather disappointing so far. Positive effects might be assumed for the administration of activated protein C thereby underlining the role of microcirculatory alterations in the development of septic cardiomyopathy.

The effect of autonomous neuropathy on bowel preparation in type 2 diabetes mellitus

The need for colonoscopy is common among diabetics. In this study, we aimed to evaluate the effect of autonomous neuropathy on bowel preparation in type 2 diabetes mellitus (DM) patients. The study population consisted of 45 patients with DM and 48 non-diabetic, age- and sex-matched subjects. All colonoscopies were performed 5 h after the last dose of sodium phosphate. Colonoscopists rated the bowel preparation quality during the procedure using the Aronchick scale. All patients underwent a detailed cardiologic examination and 24-h Holter rhythm monitoring. Orthostatic hypotension and impairment in heart rate variability were accepted as indicators of autonomous neuropathy. Gender, age, blood pressure, and heart rates did not differ significantly between groups (p > 0.05). Autonomous neuropathy was detected in 14 (31.1%) patients in the DM group and in two (4.2%) in the control group (p < 0.05). Optimal bowel cleansing was achieved in 93.8% of controls and 73.3% of diabetics; bowel cleansing was suboptimal in 26.7% of diabetics and 6.2% of controls (p < 0.05). Optimal bowel cleansing was achieved in six of 14 (42.8%) diabetic patients with autonomous neuropathy; however, optimal bowel cleansing was achieved in 27 of 31 (87.1%) diabetic patients without autonomous neuropathy (p < 0.05). Although optimal bowel cleansing was more prevalent among control patients than in diabetic patients without autonomous neuropathy, the difference was not significant (87.1% vs 93.8%; p > 0.05). These data suggest that optimal bowel cleansing is poorer in diabetics with autonomous neuropathy than in those without autonomous neuropathy and controls.

Impaired heart rate variability and altered cardiac sympathovagal balance after antidepressant overdose

Antidepressant overdose may be associated with significant cardiotoxicity, and recent data have shown that acute toxic effects are associated with impaired heart rate variability. This study was designed to examine the feasibility of non-invasive heart rate variability recording in patients that present to hospital after deliberate antidepressant ingestion. This was a prospective study of 72 consecutive patients attending the Emergency Department after deliberate antidepressant overdose and 72 age-matched patients that ingested paracetamol, as a control group. Single time-point continuous electrocardiographic recordings were used to allow spectral analyses of heart rate variability determined in low-frequency (LF) and high-frequency (HF) domains. The LF:HF ratio was used to represent overall sympathovagal cardiac activity. Antidepressant overdose was associated with reduced overall heart rate variability: 1329 vs. 2018 ms(2) (P = 0.0239 by Mann-Whitney test). Variability in the LF domain was higher (64.8 vs. 49.8, P = 0.0006), whereas that in the HF domain was lower (24.3 vs. 36.4, P = 0.0001), and the LF:HF ratio was higher in the antidepressant group (2.4 vs. 1.2, P = 0.0003). Antidepressant overdose is associated with impaired heart rate variability in a pattern consistent with excess cardiac sympathetic activity. Further work is required to establish the significance of these findings and to explore whether the impairment of heart rate variability may be used to predict the development of arrhythmia in this patient group.

Vagus nerve stimulation improves severely impaired heart rate variability in a patient with Lennox-Gastaut-Syndrome

Vagus nerve stimulation (VNS) is a new therapeutic option for refractory epilepsy. We report a patient with Lennox-Gastaut-Syndrome (LGS) and a severe impairment of heart rate variability (HRV), we could demonstrate in our patient that HRV was improved by VNS.

Sarin produces delayed cardiac and central autonomic changes

The aim was to evaluate the acute and delayed effects of low dose sarin exposure on cardiac autonomic and brainstem catecholaminergic function in mice. The rationale was to expand our knowledge of the cardiovascular effects of this neurotoxic, acetylcholinesterase (AChE) inhibitor. C57BL/6 male mice with telemetric arterial catheters were injected with saline or sarin (8 μg/kg, 0.05× LD 50; sc, two injections) with blood pressure (BP) measurements made at 1 and 10 weeks after sarin exposure. BP and pulse interval variability (PI) and low and high frequency spectral oscillations were measured using autoregressive spectral analysis. In situ hybridization (ISH) was used to quantify tyrosine hydroxylase (TH) mRNA expression in brainstem cardiovascular centers. Sarin had no effect on blood AChE activity, heart rate (HR) or BP. There was a biphasic response in PI variance, an early increase (+ 140%) and a delayed decrease (− 62%) at more than 2 months after sarin exposure. There were no changes in BP variance. Assuming that increased PI variance is a positive outcome, the short-term response to sarin should be protective. This is opposite for the delayed decrease in PI variance which is associated with adverse cardiovascular effects. There was an increase in TH mRNA in both locus coeruleus (0.18 ± 0.05 vs. 1.4 ± 0.2 μCi/g; control vs. sarin) and dorsal vagal complex (0.09 ± 0.06 vs. 1.17 ± 0.03 μCi/g; control vs. sarin). Results show that a dose of sarin which had no peripheral cholinergic effects caused changes in autonomic modulation, a short-term enhancement followed by a delayed impairment in heart rate variability. Sarin-induced cardiac effects suggest a controversial aspect to the use of pharmacological agents which target AChE for management of cardiovascular risk.

Heart rate variability during extracorporeal membrane oxygenation and recovery in severe neonatal disease

Background Heart rate variability (HRV) reveals information on the functional state of the autonomic nervous system (ANS) in neonates. During severe illness, heart rate variability is impaired. Aim This study was initiated to measure the changes in HRV in neonates during extracorporeal membrane oxygenation (ECMO) and recovery from severe respiratory and circulatory failure. Moreover, we compared our data with HRV data of healthy newborns and we investigated the differences in HRV parameters between ECMO-survivors and non-survivors. Study design This study is of an observational character. We performed short-term recordings of heart rate variability in 14 neonates during ECMO and recovery. We computed time- and frequency-domain HRV parameters. Results ECMO significantly affects time-domain HRV parameters. Severe neonatal illness causes a significant reduction of all calculated HRV parameters; clinical recovery is accompanied by an increase of HRV. In comparison with normative data of healthy newborns, however, HRV remains impaired. The ECMO–development ratio separated the non-survivors from the survivors during ECMO therapy. Conclusions During severe neonatal illness, HRV is impaired. It remains to be clarified whether the impairment of HRV during severe illness can predict the neurological outcome. The ability of the E/D ratio as an HRV parameter to serve as a predictive tool has to be corroborated in larger group of patients.

Temporal changes in cardiovascular autonomic regulation in type II diabetic patients: association with coronary risk variables and progression of coronary artery disease

AIM: This research was designed to study the temporal changes in cardiovascular autonomic regulation, assessed by 24-hour heart rate (HR) variability, and the possible relation of changes in HR variability to cardiovascular risk factors and progression of coronary artery disease (CAD) among type II diabetic subjects.METHOD: In a single-center substudy of The Diabetes Atherosclerosis Intervention Study (DAIS), 53 patients assigned to fenofibrate (n = 26) or placebo (n = 27), underwent time and frequency domain and fractal analysis of HR variability, coronary risk variable analyses and quantitative coronary angiograms at baseline and after three years' follow-up. RESULTS: Twenty-four hour standard deviation of sinus intervals (SDNN) decreased from 113 ± 35 to 94 ± 30 msec (P < 0.001) during the three year period. Low frequency power spectral component and short-term fractal scaling exponent also decreased (P < 0.001 and P < 0.05, respectively). The reduction of SDNN was weakly related to a change in the triglyceride level (r = −0.33, P < 0.05), glucose level (r = −0.28, P < 0.05) and total cholesterol concentration (r = −0.35, P < 0.01). Furthermore, the reduction of SDNN was related to a decrease in the minimum lumen and mean segment diameter of the coronary arteries (r = 0.36, P < 0.01, and r = 0.39, P < 0.01, respectively). This association was more marked in the placebo group (r = 0.50, P < 0.01 and r = 0.44, P < 0.05, respectively) than among the patients randomized to fenofibrate (not significant for both). CONCLUSIONS: Cardiovascular autonomic regulation assessed by HR variability deteriorates rapidly in type II diabetic subjects with CAD during the time course. Impairment in HR variability is associated with changes in common coronary risk variables and with a progression of CAD.