Parasympathetic Activity In Patients Research Articles

P222 Heart rate variability is a predictor to disease exacerbation in paediatric Inflammatory Bowel Disease

Abstract Background Previous studies have shown a lower level of parasympathetic activity in patients with inflammatory bowel disease (IBD) compared to healthy subjects. Heart rate variability (HRV) oscillations are used to detect autonomic instability and was found to be lower in adults with IBD compared to controls. Nevertheless, the data on the relation between the autonomic function and IBD outcome are scarce. The aim of the study was to evaluate HRV as a predictor to paediatric IBD outcome. Methods Children (<18 years of age) with IBD were prospectively recruited. For each patient, a 10-minute measurement of HRV was conducted by Pulse Oximeter (BM1000A/Shanghai Berry Electronic Tech Co., Ltd). The square root of the mean squared differences of successive RR intervals (RMSSD) was calculated. Clinical data, including demographic variables, disease activity and course, medications and laboratory results were collected during a follow-up of 12 months. The relation between RMSSD and clinical measures was evaluated. Results Overall, 34 IBD children with an average age of 15.32±2.18 years were included: 21 (61.8%) children with Crohn’s disease and 13 (38.2%) with ulcerative colitis. Children in clinical remission had a significantly higher RMSSD compared to patients with active disease (67.72±27.81 and 45.76±22.04, respectively, p=0.022). In addition, patients with normal serum C-reactive protein (<5 mg/L), patients with normal serum hemoglobin and patients with long duration of IBD (more than a year from diagnosis) had a significantly higher RMSSD (Figure 1). Children that experienced disease exacerbation during the follow-up had a significantly lower RMSSD compared to children that kept clinical remission (Figure 2). In a multivariate analysis, higher RMSSD was a significant and independent predictor of lower risk of IBD exacerbation [OR (odd ratio) = 0.941, 95% CI (confidence interval) 0.887–0.998, p=0.044)]. Conclusion HRV may not only reflect IBD activity, but also serve as a predictor to disease exacerbation in paediatric IBD.

Reduced Parasympathetic Activity in Patients With Different Types of Congenital Heart Disease and Associations to Exercise Capacity

Current research indicates an imbalance in the autonomic nervous system (ANS) pathway activities in patients with congenital heart disease (CHD). The heart rate variability (HRV) is a measure to quantify activities of the parasympathetic and sympathetic branches. This study evaluated the parasympathetic activity by means of HRV in patients with CHD, regarding diagnostic subgroups and CHD severity, and the association to exercise capacity. From July 2016 to August 2018, a total of 222 patients with different types of CHD (28.4 ± 10.1 yr; 44% female) received breathing-controlled HRV measurement in the supine position. Based on 130 adjacent heartbeats, the root mean square of successive differences (RMSSD), a parasympathetic activity surrogate was estimated and log-transformed. Additionally, all patients underwent a cardiopulmonary exercise test. For comparison, a control group (CG) of 57 (29.0 ± 7.1 yr; 61% female) healthy volunteers was recruited. Patients with CHD exhibited reduced parasympathetic activity in comparison to the CG (lnRMSSD CHD: 3.55 ± 0.57 ms vs CG: 3.93 ± 0.55 ms; P < .001), with the lowest parasympathetic activity in patients with Fontan circulation (3.07 ± 0.54 ms; P < .001). Complex CHD (3.40 ± 0.54 ms) had worse values compared with patients with simple (3.87 ± 0.55 ms; P < .001) and moderate severity (3.74 ± 0.54 ms; P < .001). Better parasympathetic activity in CHD patients was associated with increased exercise capacity (r = 0.322; P < .001). Impaired parasympathetic activity suggests limited function of the ANS in patients with CHD. Further studies should focus on the association of exercise capacity and ANS to possibly improve parasympathetic activity and functional outcomes.

Effects of empagliflozin versus placebo on cardiac sympathetic activity in acute myocardial infarction patients with type 2 diabetes mellitus: the EMBODY trial

BackgroundProtection from lethal ventricular arrhythmias leading to sudden cardiac death (SCD) is a crucial challenge after acute myocardial infarction (AMI). Cardiac sympathetic and parasympathetic activity can be noninvasively assessed using heart rate variability (HRV) and heart rate turbulence (HRT). The EMBODY trial was designed to determine whether the Sodium–glucose cotransporter 2 (SGLT2) inhibitor improves cardiac nerve activity.MethodsThis prospective, multicenter, randomized, double-blind, placebo-controlled trial included patients with AMI and type 2 diabetes mellitus (T2DM) in Japan; 105 patients were randomized (1:1) to receive once-daily 10-mg empagliflozin or placebo. The primary endpoints were changes in HRV, e.g., the standard deviation of all 5-min mean normal RR intervals (SDANN) and the low-frequency–to–high-frequency (LF/HF) ratio from baseline to 24 weeks. Secondary endpoints were changes in other sudden cardiac death (SCD) surrogate markers such as HRT.ResultsOverall, 96 patients were included (46, empagliflozin group; 50, placebo group). The changes in SDANN were + 11.6 and + 9.1 ms in the empagliflozin (P = 0.02) and placebo groups (P = 0.06), respectively. Change in LF/HF ratio was – 0.57 and – 0.17 in the empagliflozin (P = 0.01) and placebo groups (P = 0.43), respectively. Significant improvement was noted in HRT only in the empagliflozin group (P = 0.01). Whereas intergroup comparison on HRV and HRT showed no significant difference between the empagliflozin and placebo groups. Compared with the placebo group, the empagliflozin group showed significant decreases in body weight, systolic blood pressure, and uric acid. In the empagliflozin group, no adverse events were observed.ConclusionsThis is the first randomized clinical data to evaluate the effect of empagliflozin on cardiac sympathetic and parasympathetic activity in patients with T2DM and AMI. Early SGLT2 inhibitor administration in AMI patients with T2DM might be effective in improving cardiac nerve activity without any adverse events.Trial Registration: The EMBODY trial was registered by the UMIN in November 2017 (ID: 000030158). UMIN000030158; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034442.

A model-based analysis of autonomic nervous function in response to the Valsalva maneuver.

The Valsalva maneuver (VM) is a diagnostic protocol examining sympathetic and parasympathetic activity in patients with autonomic dysfunction (AD) impacting cardiovascular control. Because direct measurement of these signals is costly and invasive, AD is typically assessed indirectly by analyzing heart rate and blood pressure response patterns. This study introduces a mathematical model that can predict sympathetic and parasympathetic dynamics. Our model-based analysis includes two control mechanisms: respiratory sinus arrhythmia (RSA) and the baroreceptor reflex (baroreflex). The RSA submodel integrates an electrocardiogram-derived respiratory signal with intrathoracic pressure, and the baroreflex submodel differentiates aortic and carotid baroreceptor regions. Patient-specific afferent and efferent signals are determined for 34 control subjects and 5 AD patients, estimating parameters fitting the model output to heart rate data. Results show that inclusion of RSA and distinguishing aortic/carotid regions are necessary to model the heart rate response to the VM. Comparing control subjects to patients shows that RSA and baroreflex responses are significantly diminished. This study compares estimated parameter values from the model-based predictions to indices used in clinical practice. Three indices are computed to determine adrenergic function from the slope of the systolic blood pressure in phase II [α (a new index)], the baroreceptor sensitivity (β), and the Valsalva ratio (γ). Results show that these indices can distinguish between normal and abnormal states, but model-based analysis is needed to differentiate pathological signals. In summary, the model simulates various VM responses and, by combining indices and model predictions, we study the pathologies for 5 AD patients.NEW & NOTEWORTHY We introduce a patient-specific model analyzing heart rate and blood pressure during a Valsalva maneuver (VM). The model predicts autonomic function incorporating the baroreflex and respiratory sinus arrhythmia (RSA) control mechanisms. We introduce a novel index (α) characterizing sympathetic activity, which can distinguish control and abnormal patients. However, we assert that modeling and parameter estimation are necessary to explain pathologies. Finally, we show that aortic baroreceptors contribute significantly to the VM and RSA affects early VM.

Contribution of Impaired Parasympathetic Activity to Right Ventricular Dysfunction and Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.

The beneficial effects of parasympathetic stimulation have been reported in left heart failure, but whether it would be beneficial for pulmonary arterial hypertension (PAH) remains to be explored. Here, we investigated the relationship between parasympathetic activity and right ventricular (RV) function in patients with PAH, and the potential therapeutic effects of pyridostigmine (PYR), an oral drug stimulating the parasympathetic activity through acetylcholinesterase inhibition, in experimental pulmonary hypertension (PH). Heart rate recovery after a maximal cardiopulmonary exercise test was used as a surrogate for parasympathetic activity. RV ejection fraction was assessed in 112 patients with PAH. Expression of nicotinic (α-7 nicotinic acetylcholine receptor) and muscarinic (muscarinic acetylcholine type 2 receptor) receptors, and acetylcholinesterase activity were evaluated in RV (n=11) and lungs (n=7) from patients with PAH undergoing heart/lung transplantation and compared with tissue obtained from controls. In addition, we investigated the effects of PYR (40 mg/kg per day) in experimental PH. PH was induced in male rats by SU5416 (25 mg/kg subcutaneously) injection followed by 4 weeks of hypoxia. In a subgroup, sympathetic/parasympathetic modulation was assessed by power spectral analysis. At week 6, PH status was confirmed by echocardiography, and rats were randomly assigned to vehicle or treatment (both n=12). At the end of the study, echocardiography was repeated, with additional RV pressure-volume measurements, along with lung, RV histological, and protein analyses. Patients with PAH with lower RV ejection fraction (<41%) had a significantly reduced heart rate recovery in comparison with patients with higher RV ejection fraction. In PAH RV samples, α-7 nicotinic acetylcholine receptor was increased and acetylcholinesterase activity was reduced versus controls. No difference in muscarinic acetylcholine type 2 receptor expression was observed. Chronic PYR treatment in PH rats normalized the cardiovascular autonomic function, demonstrated by an increase in parasympathetic activity and baroreflex sensitivity. PYR improved survival, increased RV contractility, and reduced RV stiffness, RV hypertrophy, RV fibrosis, RV inflammation, and RV α-7 nicotinic acetylcholine receptor and muscarinic acetylcholine type 2 receptor expression, as well. Furthermore, PYR reduced pulmonary vascular resistance, RV afterload, and pulmonary vascular remodeling, which was associated with reduced local and systemic inflammation. RV dysfunction is associated with reduced systemic parasympathetic activity in patients with PAH, with an inadequate adaptive response of the cholinergic system in the RV. Enhancing parasympathetic activity by PYR improved survival, RV function, and pulmonary vascular remodeling in experimental PH.

Abstract 12661: Respiratory Muscle Weakness is an Independent Determinant for Decreased Parasympathetic Activity in Patients With Chronic Heart Failure

Background: Decreased parasympathetic activity and respiratory muscle weakness are known as indicators for poor outcome in patients with chronic heart failure (CHF). Although the effect of respiratory modulation on autonomic system has been documented, the relationship between respiratory muscle strength and parasympathetic activity is still unknown. The present study aimed to investigate the influence of respiratory muscle weakness on parasympathetic activity in CHF patients. Methods: We studied 254 patients with compensated CHF (60.3±12.0 years, 202 males) who received cardiac rehabilitation during hospitalization and after hospital discharge. Maximal inspiratory pressure (PI max ) was measured as a respiratory muscle strength using a spirometer 2 months after the discharge. Patients received symptom limited cardiopulmonary exercise test (CPX) and then heart rate recovery (HRR) during the first minute after the cessation of CPX was assessed as a parasympathetic activity. HRR of ≤18 /min was determined as a decreased parasympathetic activity. Patients were divided into three groups based on the tertile of PI max : low PI max (PI max &lt;58.7 cmH 2 O), moderate PI max (58.7≤ PI max &lt;83.6 cmH 2 O) and high PI max (PI max ≥83.6 cmH 2 O) groups. We compared the HRR among the three groups and identified the determinant for HRR of ≤18 /min using a multivariate logistic regression analysis. Results: Ninety-four patients among the studied patients, 47 in the low PI max group, 28 in the moderate PI max group and 19 in the high PI max group, showed HRR of ≤18 /min. The low PI max group showed significantly lower HRR as compared with the other two groups (P=0.001 and &lt;0.001, respectively). The multivariate logistic regression analysis identified the PI max as a significant independent determinant for HRR of ≤18 /min (odds ratio=0.832, P=0.008, Figure). Conclusion: Respiratory muscle weakness was an independent determinant for decreased parasympathetic activity in patients with CHF.

Jasmine inhalation reduces sympathetic and enhances parasympathetic activity in patients after moderate and severe traumatic brain injury

Jasmine inhalation reduces sympathetic and enhances parasympathetic activity in patients after moderate and severe traumatic brain injury

Assessment of Autonomic Function in Children with Autism and Normal Children Using Spectral Analysis and Posture Entrainment: A Pilot Study

Objective: The dysfunction of the autonomic nervous system investigated in Children with Autism compared with healthy one. Cardiovascular autonomic disturbances are possibly associated with the pathogenesis of Autism in children. The purpose of this study is to use the spectral and coherence analysis of heart rate variability signal (HRV), respiration signal and peripheral blood flow signal (PBF) to assess the autonomic activity of normal children and children with Autism for the clinical usefulness of the applied methods of signal processing and timefrequency analysis for screening and treatment of Autism in children. Methods: Twenty four children who had Autism and who were not taking any medications and Twenty three age and sex matched controls (Children) were participated in this study at Department of Neurology at Johns Hopkins Hospital, Baltimore, MD, USA and Regional Medical Center, Cookeville, TN, USA. PBF and respiration signals as well as HRV signal derived from Electrocardiogram (ECG) were measured during supine and standing positions. Autopower, cross power and coherence spectra were produced to investigate the sympathetic and parasympathetic activity in both groups. Results: The results clearly indicate that in children with Autism, the coherence values are less than in control group in both low frequency (LF) and high frequency (HF) bands at coherence spectra between HRV and PBF as well as HRV and respiration in both supine and standing position. Also, the ratio of amplitude at nearly frequency of 0.1 Hz in auto power spectra and coherence spectra is less in Autism group than in matched control (p<0.001). Conclusion: Autopower and coherence spectra analysis for Children with Autism compared to normal Children seems useful in the assessment of autonomic function for Autism patients. The decreased of autonomic function specially parasympathetic activity in patients with Autism revealed by auto power and coherence spectra analysis is significant and may be related to the effective of treatment of Autism children in this disorder compared to controls. Further studies is needed using other tests and methods of signal analysis to introduce clinical indices for early detection of autonomic function in patients with Autism.

Decreased parasympathetic activity in patients with functional dyspepsia.

Functional dyspepsia (FD) can be described as the presence of symptoms such as bothersome postprandial fullness, early satiation, epigastric pain, and burning without any evidence of structural disease. The aim of this study was to evaluate the autonomic nervous system using heart rate variability (HRV) in patients with postprandial distress syndrome and epigastric pain syndrome. The study population included 64 consecutive patients with a diagnosis of FD and 62 age-matched and sex-matched healthy control individuals with no clinical evidence of gastrointestinal, systemic, or cardiovascular diseases. All patients underwent upper gastrointestinal endoscopy and 24 h Holter monitoring. There were 30 patients with postprandial distress syndrome and 34 with epigastric pain syndrome. Twenty-four hour square root of the mean squared differences of the successive normal to normal intervals (RMSSD) (30.5 ± 12.4, 35.8 ± 13.9; P=0.047), 24 h proportion derived by dividing the number of interval differences of successive normal to normal intervals greater than 50 ms (PNN50) (9.8 ± 3.9, 14.1 ± 7.3; P=0.017), daytime PNN50 (6.8 ± 1.6, 18.4 ± 13.8; P<0.001), night SD of the normal to normal intervals (SDNN) (111.4 ± 39.9, 133.4 ± 29.8; P=0.001), and night RMSSD (31.7 ± 12.4, 38.2 ± 17.5; P=0.019) were significantly lower in patients with FD than controls. Other HRV parameters were not significantly different between the two groups. Changes in these parameters showed a decreased parasympathetic tone and discordance in sympathovagal activity in FD. Our study showed decreased parasympathetic activity in the patients with FD. Further studies are required to evaluate the significance of HRV parameters and to clarify the mechanism of decreased parasympathetic activity in patients with FD.

Association between respiratory mechanics and autonomic function in morbid obesity

This study aimed to investigate the association between respiratory mechanics and autonomic modulation in morbidly obese patients. We evaluated 10 morbidly obese subjects (BMI = 52.9 ± 11.2 kg/m 2 ), aged 23---58 years. Assessment of respiratory mechanics was done by the forced oscillation technique (FOT), and cardiovascular autonomic function was recorded by heart rate variability analysis (HRV). The Pearson correlation coefficient was used to test the associations between respiratory mechanics and HRV variables. There were associations between the standard deviation of all RR intervals (SDNN) and airway resistance (Rm) (r = −0.82; p = 0.004), SDNN and respiratory system resistance (R0) (r = −0.79; p = 0.006), root mean square of successive differences between adjacent normal RR intervals (rMSSD) and respiratory system resistance (R5) (r = −0.643; p = 0.0451), rMSSD and R0 (r = −0.64; p = 0.047), and rMSSD and Rm (r = −0.658; p = 0.039). We concluded that the airway and respiratory system resistances are negatively associated with parasympathetic activity in patients with morbid obesity. © 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier Espana, S.L. All rights reserved.

Associação entre a mecânica respiratória e função autonómica na obesidade mórbida

This study aimed to investigate the association between respiratory mechanics and autonomic modulation in morbidly obese patients. We evaluated 10 morbidly obese subjects (BMI=52.9±11.2kg/m2), aged 23-58 years. Assessment of respiratory mechanics was done by the forced oscillation technique (FOT), and cardiovascular autonomic function was recorded by heart rate variability analysis (HRV). The Pearson correlation coefficient was used to test the associations between respiratory mechanics and HRV variables. There were associations between the standard deviation of all RR intervals (SDNN) and airway resistance (Rm) (r=−0.82; p=0.004), SDNN and respiratory system resistance (R0) (r=−0.79; p=0.006), root mean square of successive differences between adjacent normal RR intervals (rMSSD) and respiratory system resistance (R5) (r=−0.643; p=0.0451), rMSSD and R0 (r=−0.64; p=0.047), and rMSSD and Rm (r=−0.658; p=0.039). We concluded that the airway and respiratory system resistances are negatively associated with parasympathetic activity in patients with morbid obesity.

Functional stress response in patients with rheumatoid arthritis: Impact of genetic factors

It is still incompletely understood how the stress response contributes to the pathogenesis of rheumatoid arthritis (RA). To characterize neuroimmune interactions, common variants in the genes of the β2-adrenergic receptor (beta2AR) and corticotropin releasing hormone (CRH) were studied together with functional stress responses in RA patients. An allele-specific PCR was used to determine the polymorphisms of the beta2AR (position 16, 27, 164), as well as the polymorphic sequences in the 5′ flanking region of the human CRH gene in RA patients (n = 310) and controls (n = 305). The autonomic response upon stressful stimuli was investigated studying heart rate variability, and the dynamics of blood glucose levels, CRH, and cortisol production under insulin hypoglycemia (IHT). There was a highly significant distortion in the distribution of the beta2AR polymorphism at codon 16 between RA patients and controls (p = 0.00001). It was also revealed a significant decrease of parasympathetic activity in patients with homozygosity for Gly 16 compared to Arg16Gly RA patients. In addition, the CRH promoter polymorphisms exerted a significant influence on the stress response of RA patients undergoing IHT. The integrated cortisol response to hypoglycemia was significantly lower in RA patients bearing the A1B1 allele compared to the A2B2 (p = 0.016). Polymorphisms of the beta2AR and CRH are associated with disturbed functional stress reactivity on various levels in RA patients. Further studies are warranted to determine the role of genetic factors on stress response in the disease process of RA.

Cardiac autonomic dysfunction in drug naïve hot water epilepsy

PurposeThis study aimed to characterize the role of autonomic nervous system dysfunction in hot water epilepsy (HWE). Heart rate variability (HRV) has been established as a good index of cardio-autonomic regulation. MethodologyForty-five patients with HWE (age: 24.6±10.1 years; M:F=37:8) and 45 age and gender matched controls (age: 24.17±10.37 years; M:F=37:8) were studied. Five minutes resting lead II electrocardiogram (ECG) was obtained (AD instruments) under standard conditions and analyzed for time and frequency domain HRV parameters using LabChart software. ResultPatients with hot water epilepsy showed significant increase in LF nu (Low frequency normalized unit) and LF/HF denoting an interictal increase in sympathetic activity. In addition, reductions were noted in parasympathetic function [RMSSD (root mean square successive difference of RR intervals), HF (High frequency) nu and LF/HF]. ConclusionThis study has demonstrated an impaired sympatho-vagal balance characterized by increased sympathetic activity and reduced parasympathetic activity in patients with HWE. The present study supports the notion that the hypothalamus is involved in both, the pathogenesis of HWE and autonomic regulation.

Device Based Therapy for Treatment of Hypertension

DOI: http://dx.doi.org/10.3329/cardio.v4i2.10270Cardiovasc. j. 2012; 4(2): 111-113

Short-term oxygen administration restores blunted baroreflex sensitivity in patients with type 1 diabetes

We hypothesised that the blunted baroreflex sensitivity (BRS) typical of type 1 diabetes is caused by a higher degree of tissue hypoxia in diabetes, and tested whether oxygen increased BRS and ventilation less, equally or more than in healthy control participants (the latter suggesting higher tissue hypoxia). In addition, we also considered the possible interference between oxygen and breathing pattern. In 96 participants with type 1 diabetes and 40 age-matched healthy controls, we measured BRS (average of six different standard methods), oxygen saturation, end-tidal carbon dioxide and ventilation changes during spontaneous and controlled breathing at 15 and six breaths/min, in normoxia and during 5 l/min oxygen administration. BRS was blunted and blood pressure higher in diabetic participants during spontaneous breathing (p < 0.05). BRS increased with oxygen during spontaneous breathing in diabetic (p < 0.001) but not in control participants, and with oxygen the difference in BRS was no longer significant. Slow breathing in normoxia restored BRS to a similar extent to giving oxygen. Oxygen increased systolic and diastolic blood pressure, RR interval, heart rate variability, minute ventilation and tidal volume to a greater extent in diabetic patients than in controls, and decreased carbon dioxide similarly to controls. The increased response to hyperoxia suggests a pre-existing condition of tissue hypoxia that functionally restrains parasympathetic activity in patients with type 1 diabetes. Autonomic abnormalities can be partially and temporarily reversed by functional manoeuvres such as slow breathing or oxygen administration through enhancement of parasympathetic activity and/or correction of tissue hypoxia.

Effects of Chronic Baroreceptor Stimulation on the Autonomic Cardiovascular Regulation in Patients With Drug-Resistant Arterial Hypertension

In patients with drug-resistant hypertension, chronic electric stimulation of the carotid baroreflex is an investigational therapy for blood pressure reduction. We hypothesized that changes in cardiac autonomic regulation can be demonstrated in response to chronic baroreceptor stimulation, and we analyzed the correlation with blood pressure changes. Twenty-one patients with drug-resistant hypertension were prospectively included in a substudy of the Device Based Therapy in Hypertension Trial. Heart rate variability and heart rate turbulence were analyzed using 24-hour ECG. Recordings were obtained 1 month after device implantation with the stimulator off and after 3 months of chronic electric stimulation (stimulator on). Chronic baroreceptor stimulation decreased office blood pressure from 185+/-31/109+/-24 mm Hg to 154+/-23/95+/-16 mm Hg (P<0.0001/P=0.002). Mean heart rate decreased from 81+/-11 to 76+/-10 beats per minute(-1) (P=0.001). Heart rate variability frequency-domain parameters assessed using fast Fourier transformation (FFT; ratio of low frequency:high frequency: 2.78 versus 2.24 for off versus on; P<0.001) were significantly changed during stimulation of the carotid baroreceptor, and heart rate turbulence onset was significantly decreased (turbulence onset: -0.002 versus -0.015 for off versus on; P=0.004). In conclusion, chronic baroreceptor stimulation causes sustained changes in heart rate variability and heart rate turbulence that are consistent with inhibition of sympathetic activity and increase of parasympathetic activity in patients with drug-resistant systemic hypertension; these changes correlate with blood pressure reduction. Whether the autonomic modulation has favorable cardiovascular effects beyond blood pressure control should be investigated in further studies.

Diminished Circadian Variation in Heart Rate Variability before Surgery in Patients Developing Postoperative Atrial Fibrillation

Objective - To evaluate the role of the autonomic nervous system for the development of atrial fibrillation (AF) after coronary artery bypass surgery. Design - Eighty patients without a previous history of AF were included. The sympathetic and parasympathetic activity were evaluated by the analysis of heart rate variability (HRV) in the frequency domain from 24-h Holter recordings and by measuring neuropeptides (neuropeptide Y, chromogranin A, chromogranin B, and pancreatic polypeptide (PP)) and catecholamines, obtained pre- and postoperatively. Results - Preoperatively, patients (36.3%) developing AF postoperatively showed a statistically significant less circadian variation in the HRV variables, the high-frequency (HF) component ( p = 0.013) and the low-frequency (LF)/HF ratio ( p = 0.007), than patients remaining in sinus rhythm. The HF component and PP, both reflecting parasympathetic activity, and all other variables in the frequency domain, decreased significantly after surgery in both patient groups ( p < 0.0001). Although catecholamines increased significantly postoperatively in both patient groups, neither catecholamines nor neuropeptides expressing sympathetic activity, differed between the two groups. PP was, however, significantly higher in patients with postoperative AF than in those with sinus rhythm post-operatively on day 1. Conclusion - The diminished circadian variation in HRV before surgery and the indirect signs of a higher parasympathetic activity in patients developing postoperative AF compared with patients remaining in sinus rhythm, may indicate a propensity for AF.

Prospective evaluation of effect of carvedilol therapy on heart rate variability in patients with dilated cardiomyopathy

The aim of the present study was to assess the effects of carvedilol therapy in addition to conventional heart failure therapy on heart rate variability (HRV) and on left ventricular function in 14 patients with mild to moderate heart failure due to idiopathic dilated cardiomyopathy (IDC). After a 3- to 4-week titration period, carvedilol was titrated up to 50mg daily, or the highest dose tolerated (at least 25mg daily). Maintenance treatment was then continued for 8 weeks. Digital 24-hour Holter recordings were obtained at baseline and after 8 weeks of carvedilol therapy. HRV for the entire 24-hour period was computed in the time domain using the Oxford Medilog Excel 2 analysis system. Measures of HRV included the mean of all coupling intervals between normal beats (RRm), the standard deviation of all normal RR intervals (SDNN), the square root of the mean of the squared differences between adjacent normal RR intervals (rMSSD), and the proportion of adjacent normal RR intervals differing >50 ms (pNN50). Additional treatment with carvedilol induced a significant increase in HRV: SDNN increased from 77+/-21 ms to 110+/-22 ms (p=0.001), rMSSD from 19+/-7 ms to 26+/-7 ms (p=0.02), and mean pNN50-value increased from 1.7+/-1.3% to 5.5+/-4.5% (p<0.01) under therapy with carvedilol. Mean heart rate on carvedilol calculated over 24 hours was 13 beats less than at baseline (75 bpm versus 88 bpm, p<0.01). After 2 months of additional treatment with carvedilol, both hemodynamic and clinical parameters improved: left ventricular ejection fraction increased from 24+/-7% to 30+/-10% (p<0.05), and New York Heart Association class decreased from 2.5+/-0.8 to 1.8+/-0.7 (p<0.05). In summary, eight weeks of additional carvedilol therapy induced a significant increase in HRV parameters related to parasympathetic activity in patients with IDC. Whether increased vagal tone may contribute to the protective effect of carvedilol has to be evaluated by further studies.

916-88 Simultaneous Measurement of Left Ventricular Volume and Parasympathetic Activity During Head-up Tilt in Vasovagal Syncope

Present study tested the hypothesis that the great decline of left ventricular volume (LVV) during Head-up tilt (HUT) triggers ventricular mechanoreceptor activation and subsequently increases parasympathetic activation associated with hypotension-bradycardia. We measured temporal changes of frequency domain heart rate variability indices (HRV) and LVV using M mode echocardiogarphy during HUT (80° up to 40 min) in 15 patients (pts, 50 ± 23 years) with syncope of undetermined etiology. HRV consisted of low (L, 0.04 Hzl, high (H, 0.15–0.40 Hz) and total (T, 0.01–1.00 Hz) components. For LVV analysis, EDV. ESV and EF were calculated using Teichholtz formula. HRV and LW indices were measured in consecutive 2 min segments throughout the study. Eight pts had positive tests (syncope was induced by HUT; Group 1, G1) and 7 pts in negative tests (Group 2, G2). Data were shown below [SSP, systolic blood pressure; mean in HR and SBP; Suo supine; Δ and Δ%, differenct es between values at 2 min of HUT and maximally changed values (Mx) during HUT; L/H, ratio of Land H components]. HR (bpm) SBP(mmHg) ΔH ΔLJH Δ%EDV Δ%ESV Δ%EF Gl (Su/Mx) 77/64 # 117/79 # 2.8 0.058 -53 + -49 * +23 G2(Su/Mx) 6S/75 # 132/124 -11.6 0.063 -19 -20 +22 * p &lt; 0.05 vs G2 # P &lt; 0.05 vs Su Before syncope, LVVs in G1 gradually and more profoundly declined than those in G2. The values of H significantly increased from supine to 2 min prior to syncope in G1. Also, the values of H at 2 min prior to syncope in G1 was significantly higher than those at Mx in G2 (14 ± 7 vs. 7 ± 4 ms, p &lt; 0.05). Simultaneous measurements of LW and HRV during HUT are useful for evaluating pathophysiology of neurally mediated syncope. Preceding decrease of LVV can trigger exaggerated parasympathetic activity in patients with vasovagal syncope.

Cardiac parasympathetic activity in severe uncomplicated coronary artery disease.

Previous studies have suggested that coronary artery disease is independently associated with reduced cardiac parasympathetic activity, and that this is important in its pathophysiology. These studies included many patients with complications that might be responsible for the reported autonomic abnormalities. To measure cardiac parasympathetic activity in patients with uncomplicated coronary artery disease. 44 patients of mean (SD) age 56 (8) with severe uncomplicated coronary artery disease (symptoms uncontrolled on maximal medical treatment; > 70% coronary stenosis at angiography; normal ejection fraction; no evidence of previous infarction, diabetes, or hypertension). Heart rate variability was measured from 24 hour ambulatory electrocardiograms by counting the number of times successive RR intervals exceeded the preceding RR interval by > 50 ms, a previously validated sensitive and specific index of cardiac parasympathetic activity. Mean (range) of counts were: waking 112 (range 6-501)/h, sleeping 198 (0-812)/h, and total 3912 (151-14 454)/24 h. These mean results were unremarkable, and < 10% of patients fell below the lower 95% confidence interval for waking, sleeping, or total 24 hour counts in normal people. There was no relation between the severity of coronary artery disease or the use of concurrent antianginal drug treatment and cardiac parasympathetic activity. In contrast with previous reports no evidence of a specific independent association between coronary artery disease and reduced cardiac parasympathetic activity was found. The results of previous studies may reflect the inclusion of patients with complications and not the direct effect of coronary artery disease itself.