Compromised cardiac autonomic function in non-diabetic subjects with 1 h post-load hyperglycemia: a cross-sectional study.

BACKGROUND: A compromised cardiac autonomic function has been found in subjects with insulin resistance related disorders such as obesity, impaired glucose tolerance (IGT) and type 2 diabetes and confers an increased risk of adverse cardiovascular outcomes. Growing evidence indicate that 1 h plasma glucose levels (1hPG) during an oral glucose tolerance test (OGTT) ≥ 155 mg/dl identify amongst subjects with normal glucose tolerance (NGT) a new category of prediabetes (NGT 1 h-high), harboring an increased risk of cardiovascular organ damage. In this study we explored the relationship between 1 h post-load hyperglycemia and cardiac autonomic dysfunction. METHODS: Presence of cardiac autonomic neuropathy (CAN) defined by cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV), assessed by 24-h electrocardiography were evaluated in 88 non-diabetic subjects subdivided on the basis of OGTT data in: NGT with 1 h PG < 155 mg/dl (NGT 1 h-low), NGT 1 h-high and IGT. RESULTS: As compared to subjects with NGT 1 h-low, those with NGT 1 h-high and IGT were more likely to have CARTs defined CAN and reduced values of the 24 h time domain HVR parameters including standard deviation of all normal heart cycles (SDNN), standard deviation of the average RR interval for each 5 min segment (SDANN), square root of the differences between adjacent RR intervals (RMSSD), percentage of beats with a consecutive RR interval difference > 50 ms (PNN50) and Triangular index. Univariate analyses showed that 1hPG, but not fasting and 2hPG, was inversely associated with all the explored HVR parameters and positively with CARTs determined presence of CAN. In multivariate regression analysis models including several confounders we found that 1hPG was an independent contributor of HRV and presence of CAN. CONCLUSION: Subjects with 1hPG ≥ 155 mg/dl have an impaired cardiac autonomic function.

Polygenic risk for psychotic disorders in relation to cardiac autonomic dysfunction in unmedicated patients with schizophrenia.

Cardiac autonomic dysfunction (CADF), mainly characterized by increased heart rate, decreased heart rate variability, and loss of vagal modulation, has been extensively described in patients with schizophrenia (SCZ) and their healthy first-degree relatives. As such, it represents an apparent physiological link that contributes to the increased cardiovascular mortality in these patients. Common genetic variation is a putative underlying mechanism, along with lifestyle factors and antipsychotic medications. However, the extent to which CADF is associated with genetic factors for SCZ is unknown. A sample of 83 drug-naive SCZ patients and 96 healthy controls, all of European origin, underwent a 30-minute autonomic assessment under resting conditions. We incorporated parameters from several domains into our model, including time and frequency domains (mean heart rate, low/high frequency ratio) and compression entropy, each of which provides different insights into the dynamics of cardiac autonomic function. These parameters were used as outcome variables in linear regression models with polygenic risk scores (PRS) for SCZ as predictors and age, sex, BMI, smoking status, principal components of ancestry and diagnosis as covariates. Of the three CADF parameters, SCZ PRS was significantly associated with mean heart rate in the combined case/control sample. However, this association was was no longer significant after including diagnosis as a covariate (p = 0.29). In contrast, diagnostic status is statistically significant for all three CADF parameters, accounting for a significantly greater proportion of the variance in mean heart rate compared to SCZ PRS (approximately 16% vs. 4%). Despite evidence for a common genetic basis of CADF and SCZ, we were unable to provide further support for an association between the polygenic burden of SCZ and cardiac autonomic function beyond the diagnostic state. This suggests that there are other important characteristics associated with SCZ that lead to CADF that are not captured by SCZ PRS.

Cardiac autonomic involvement in Huntington's disease.

INTRODUCTION: Huntington's disease (HD) is known as a neurodegenerative disease with movement disorder and cognitive impairment; autonomic involvement is also becoming common in some recent studies. The aim of this study is to demonstrate the presence of cardiac autonomic involvement in HD patients. METHOD: Time and frequency domain parameters obtained from the 24-h Holter ECG(hECG) were compared between 20 HD patients and 20 healthy control subjects. RESULTS: Fourteen HD patients had tachycardia, bradycardia, and extra beats. Interval between two heartbeats, normal-to-normal (NN), standard deviation of all normal-to-normal (SDNN), square root of the mean of the sum of the squares of the differences between consecutive N-N intervals in ms (rMSSD), and the ratio of the number of consecutive pairs of N-N intervals that differ by more than 50 ms to the total number of N-N intervals (pNN50) were all significantly higher in the patient group than in the control group during 24-h hECG monitoring. However, hECG monitoring showed that the patient group had significantly higher values of the frequency-domain metrics high frequency (HF) than the control group did (P = 0.003). Very low frequency (VLF) was lower in the patient group (P = 0.009). There was no difference in low frequency (LF) in both groups. In comparison to the control group, LF/HF was much reduced in the patient group (P = 0.001). CONCLUSION: Cardiac disfunction increases, and autonomic functions change in HD, but more comprehensive studies are needed to distinguish sympathetic and parasympathetic involvement.

Abnormal heart rate responses to exercise in non-severe COPD: relationship with pulmonary vascular volume and ventilatory efficiency.

BACKGROUND: Despite being a prognostic predictor, cardiac autonomic dysfunction (AD) has not been well investigated in chronic obstructive pulmonary disease (COPD). We aimed to characterise computed tomography (CT), spirometry, and cardiopulmonary exercise test (CPET) features of COPD patients with cardiac AD and the association of AD with CT-derived vascular and CPET-derived ventilatory efficiency metrics. METHODS: This observational cohort study included stable, non-severe COPD patients. They underwent clinical evaluation, spirometry, CPET, and CT. Cardiac AD was determined based on abnormal heart rate responses to exercise, including chronotropic incompetence (CI) or delayed heart rate recovery (HRR) during CPET. RESULTS: We included 49 patients with FEV1 of 1.2-5.0 L (51.1-129.7%), 24 (49%) had CI, and 15 (31%) had delayed HRR. According to multivariate analyses, CI was independently related to reduced vascular volume (VV; VV ≤ median; OR [95% CI], 7.26 [1.56-33.91]) and low ventilatory efficiency (nadir VE/VCO2 ≥ median; OR [95% CI], 10.67 [2.23-51.05]). Similar results were observed for delayed HRR (VV ≤ median; OR [95% CI], 11.46 [2.03-64.89], nadir VE/VCO2 ≥ median; OR [95% CI], 6.36 [1.18-34.42]). CONCLUSIONS: Cardiac AD is associated with impaired pulmonary vascular volume and ventilatory efficiency. This suggests that lung blood perfusion abnormalities may occur in these patients. Further confirmation is required in a large population-based cohort.

Post-acute exercise cardiovagal modulation in older male adults with and without type 2 diabetes.

PURPOSE: We examined heart rate variability (HRV) and baroreflex sensitivity (BRS) disease- and age-related response at 10-and 60-min after an acute high-intensity interval (HIIE) and moderate continuous exercise (MICE) in older adults with and without type 2 diabetes mellitus (T2DM) and healthy young adults. METHODS: Twelve older male adults with (57-84 years) and without T2DM (57-76 years) and 12 healthy young male adults (20-40 years) completed an isocaloric acute bout of HIIE, MICE, and a non-exercise condition in a randomized order. Time and Wavelets-derived frequency domain indices of HRV and BRS were obtained in a supine position and offline over 2-min time-bins using Matlab. RESULTS: HIIE but not MICE reduced natural logarithm root mean square of successive differences (Ln-RMSSD) (d = - 0.85; 95% CI - 1.15 to - 0.55 ms, p < 0.001), Ln-high-frequency power (d = - 1.60; 95% CI - 2.24 to - 0.97 ms2; p < 0.001), and BRS (d = - 6.32; 95% CI - 9.35 to - 3.29 ms/mmHg, p < 0.001) in adults without T2DM (averaged over young and older adults without T2DM), returning to baseline 60 min into recovery. These indices remained unchanged in older adults with T2DM after HIIE and MICE. Older adults with T2DM had lower resting Ln-RMSSD and BRS than aged-matched controls (Ln-RMSSD, d = - 0.71, 95% CI - 1.16 to - 0.262 ms, p = 0.001; BRS d = - 3.83 ms/mmHg), 95% CI - 6.90 to - 0.76, p = 0.01). CONCLUSIONS: Cardiovagal modulation following acute aerobic exercise is intensity-dependent only in adults without T2DM, and appears age-independent. These findings provide evidence of cardiac autonomic impairments in older adults with T2DM at rest and following aerobic exercise.

Evaluation of cardiac autonomic dysfunctions in children with type 1 diabetes mellitus.

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a serious complication of diabetes, impacting the autonomic nerves that regulate the heart and blood vessels. Timely recognition and treatment of CAN are crucial in averting the onset of cardiovascular complications. Both clinically apparent autonomic neuropathy and subclinical autonomic neuropathy, particularly CAN pose a significant risk of morbidity and mortality in children with type 1 diabetes mellitus (T1DM). Notably, CAN can progress silently before manifesting clinically. In our study, we assessed patients with poor metabolic control, without symptoms, following the ISPAD 2022 guideline. The objective is is to determine which parameters we can use to diagnose CAN in the subclinical period. METHODS: Our study is a cross-sectional case-control study that includes 30 children diagnosed with T1DM exhibiting poor metabolic control (average HbA1c > 8.5% for at least 1 year) according to the ISPAD 2022 Consensus Guide. These patients, who are under the care of the pediatric diabetes clinic, underwent evaluation through four noninvasive autonomic tests: echocardiography, 24-h Holter ECG for heart rate variability (HRV), cardiopulmonary exercise test, and tilt table test. RESULTS: The average age of the patients was 13.73 ± 1.96 years, the average diabetes duration was 8 ± 3.66 years, and the 1-year average HbA1c value was 11.34 ± 21%. In our asymptomatic and poorly metabolically controlled patient group, we found a decrease in HRV values, the presence of postural hypotension with the tilt table test, and a decrease in ventricular diastolic functions that are consistent with the presence of CAN. Despite CAN, the systolic functions of the ventricles were preserved, and the dimensions of the cardiac chambers and cardiopulmonary exercise test were normal. CONCLUSIONS: CAN is a common complication of T1DM, often associated with the patient's age and poor glycemic control. HRV, active orthostatic tests, and the evaluation of diastolic dysfunctions play significant roles in the comprehensive assessment of CAN. These diagnostic measures are valuable tools in identifying autonomic dysfunction at an early stage, allowing for timely intervention and management to mitigate the impact of cardiovascular complications associated with T1DM.

Effects of obstructive sleep apnea during rapid eye movement sleep on cardiac autonomic dysfunction: Results from the Shanghai sleep health study cohort.

In our large-scale study, the correlation between obstructive sleep apnea (OSA) related to rapid eye movement (REM) sleep and cardiac autonomic dysfunction was assessed by standard polysomnography (PSG). Cardiac autonomic dysfunction was evaluated by the measurement of heart rate variability (HRV). The cardiovascular disease (CVD) risk was determined using the cross-sectional prevalence of CVD and its overall 10 year risk according to the Framingham risk score (FRS). 4152 individuals were included in the study. A higher apnea-hypopnea index during REM sleep (AHIREM ) was correlated with increased CVD risk. The adjusted odds ratios (95% CIs) for CVD prevalence and its high 10 year risk in participants having severe OSA during REM sleep (AHIREM ≥30 events/h) were 1.452 (1.012-2.084) and 1.904 (1.470-2.466) in the demographic adjusted model and 1.175 (0.810-1.704) and 1.716 (1.213-2.427) in the multivariate adjusted model, respectively, compared with the group with a AHIREM of <5 events/h. Fully adjusted multivariate linear regression models showed the independent association between AHIREM and a more elevated ratio of low-frequency and high-frequency (LF/HF) and LF in normalised units [LF (n.u.)] (P = 0.042, P = 0.027 in all participants and P = 0.033, P = 0.029 in participants with AHI during non-REM sleep <5 events/h, respectively). Mediation analysis demonstrated that OSA during REM sleep and CVD risk was significantly mediated by LF/HF and LF (n.u.). OSA during REM sleep may be a marker behind CVD risk because it promotes cardiac autonomic dysfunction.

Relation of endothelial and cardiac autonomic function with left ventricle diastolic function in patients with type 2 diabetes mellitus.

BACKGROUND AND AIMS: Diabetes mellitus (DM) is a risk factor for left ventricle (LV) diastolic dysfunction. Aim of this study was to investigate whether endothelial and/or autonomic dysfunction are associated with LV diastolic dysfunction in DM patients. METHODS: We studied 84 non-insulin-dependent type 2 DM (T2DM) patients with no heart disease by assessing: 1) LV diastolic function by echocardiography; 2) peripheral vasodilator function, by measuring flow-mediated dilation (FMD) and nitrate-mediate dilation (NMD); 3) heart rate variability (HRV) on 24-h Holter electrocardiographic monitoring. RESULTS: Twenty-five patients (29.8%) had normal LV diastolic function, while 47 (55.9%) and 12 (14.3%) showed a mild and moderate/severe diastolic dysfunction, respectively. FMD in these 3 groups was 5.25 ± 2.0, 4.95 ± 1.6 and 4.43 ± 1.8% (p = 0.42), whereas NMD was 10.8 ± 2.3, 8.98 ± 3.0 and 8.82 ± 3.2%, respectively (p = 0.02). HRV variables did not differ among groups. However, the triangular index tended to be lower in patients with moderate/severe diastolic dysfunction (p = 0.09) and a significant correlation was found between the E/e' ratio and both the triangular index (r = -0.26; p = 0.022) and LF amplitude (r = -0.29; p = 0.011). CONCLUSIONS: In T2DM patients an impairment of endothelium-independent, but not endothelium-dependent, dilatation seems associated with LV diastolic dysfunction. The possible role of cardiac autonomic dysfunction in diastolic dysfunction deserves investigation in larger populations of patients.

Association of cardiac autonomic dysfunction with higher levels of plasma lipid metabolites in recent-onset type 2 diabetes.

AIMS/HYPOTHESIS: Emerging evidence suggests that in addition to hyperglycaemia, dyslipidaemia could represent a contributing pathogenetic factor to diabetic neuropathy, while obesity and insulin resistance play a role in the development of diabetic cardiac autonomic neuropathy (CAN) characterised by reduced heart rate variability (HRV), particularly in type 2 diabetes. We hypothesised that distinct lipid metabolites are associated with diminished HRV in recent-onset type 2 diabetes rather than type 1 diabetes. METHODS: We analysed 127 plasma lipid metabolites (11 acylcarnitines, 39 NEFA, 12 sphingomyelins (SMs), 56 phosphatidylcholines and nine lysophosphatidylcholines) using MS in participants from the German Diabetes Study baseline cohort recently diagnosed with type 1 (n = 100) and type 2 diabetes (n = 206). Four time-domain HRV indices (number of normal-to-normal (NN) intervals >50 ms divided by the number of all NN intervals [pNN50]; root mean square of successive differences [RMSSD]; SD of NN intervals [SDNN]; and SD of differences between adjacent NN intervals) and three frequency-domain HRV indices (very-low-frequency [VLF], low-frequency [LF] and high-frequency [HF] power spectrum) were computed from NN intervals recorded during a 3 h hyperinsulinaemic-euglycaemic clamp at baseline and in subsets of participants with type 1 (n = 60) and type 2 diabetes (n = 95) after 5 years. RESULTS: In participants with type 2 diabetes, after Bonferroni correction and rigorous adjustment, SDNN was inversely associated with higher levels of diacyl-phosphatidylcholine (PCaa) C32:0, PCaa C34:1, acyl-alkyl-phosphatidylcholine (PCae) C36:0, SM C16:0 and SM C16:1. SD of differences between NN intervals was inversely associated with PCaa C32:0, PCaa C34:1, PCaa C34:2, PCae C36:0 and SM C16:1, and RMSSD with PCae C36:0. For VLF power, inverse associations were found with PCaa C30:0, PCaa C32:0, PCaa C32:1, PCaa C34:2 and SM C16:1, and for LF power inverse associations were found with PCaa C32:0 and SM C16:1 (r = -0.242 to r = -0.349; p ≤ 0.0005 for all correlations). In contrast, no associations of lipid metabolites with measures of cardiac autonomic function were noted in participants recently diagnosed with type 1 diabetes. After 5 years, HRV declined due to ageing rather than diabetes, whereby prediction analyses for lipid metabolites were hampered. CONCLUSIONS/INTERPRETATION: Higher plasma levels of specific lipid metabolites are closely linked to cardiac autonomic dysfunction in recent-onset type 2 diabetes but not type 1 diabetes, suggesting a role for perturbed lipid metabolism in the early development of CAN in type 2 diabetes. Graphical abstract.

Cardiac autonomic dysfunctions are recovered with vitamin D replacement in apparently healthy individuals with vitamin D deficiency.

BACKGROUND: Vitamin D (VitD) has important prohormone functions in a wide range of clinical processes. Although it is known that individuals with VitD deficiency have cardiac autonomic dysfunction, there are no convincing data regarding the effect of VitD replacement. We aimed to evaluate the impact of VitD replacement on cardiac autonomic dysfunction. METHODS: Fifty-two apparently healthy subjects with VitD deficiency and 50 healthy control subjects were enrolled. Prior to VitD replacement, 24-hr Holter recordings were obtained, and HRV parameters were recorded. VitD levels were measured 2 months later after replacement, and control 24-hr Holter recordings were analyzed. RESULTS: The mean age of the patients was 36.04 ± 7.6 years, and 53.9% were female. SDNN (68.58 ± 13.53 vs. 121.02 ± 27.45 ms, p = .001), SDANN (95.96 ± 22.26 vs. 166.48 ± 32.97 ms, p = .001), RMSSD (23 vs. 59 ms, p < .001), and PNN50 (6.5% vs. 36%, p < .001) were significantly lower in patients with VitD deficiency compared with the control group. HRV parameters were improved after VitD replacement [SDNN (68.58 ± 13.53 to 119.87 ± 28.28 ms, p < .001), SDANN (95.96 ± 22.26 to 164.44 ± 33.90 ms, p < .001), RMSSD (23 to 58 ms, p < .001), and PNN50 (6.5 to 33%, p < .001)]. CONCLUSION: The present study suggested that VitD deficiency was significantly correlated with impaired cardiac autonomic functions assessed by parameters of HRV, and cardiac autonomic dysfunction improved after VitD replacement in otherwise apparently healthy individuals.

Comparison of non-invasive assessment of arrhythmias, conduction disturbances and cardiac autonomic tone in systemic sclerosis and systemic lupus erythematosus.

Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are connective tissue diseases presenting cardiac complications including different arrhythmias, then direct electrocardiographic comparison may be useful in everyday clinical decision making. We examined 86 adult SSc patients, 76 with SLE and 45 healthy controls. Among other examinations all subjects underwent 24-h Holter monitoring with time-domain heart rate variability and heart rate turbulence evaluation. Patients with various co-existing conditions which might markedly influence arrhythmias and autonomic modulation were excluded from further analysis (SSc n = 12, SLE n = 6). Finally, 76 SSc and 70 SLE subjects were eligible for this study, mean age 51.9 ± 13.1 and 46.5 ± 12.7 years (p = 0.11), with median disease duration 6.0 and 8.5 years (p = 0.15), respectively. As compared to SLE, patients with SSc were characterised by more frequent incidence of various supraventricular and ventricular arrhythmias. As compared to SSc, patients with SLE presented prolonged corrected QT intervals and also significant correlations between corrected QT length and heart rate variability indices. Both SSc and SLE subjects presented impaired sympathetic cardiac autonomic modulation, while indices associated with parasympathetic activity in SLE were not diminished. Disease duration was not associated with arrhythmias' occurrence (except for ventricular tachycardia in SSc, p = 0.02) and also with autonomic function in both groups of patients. Patients with SSc and SLE differ in terms of arrhythmias, conduction disturbances and cardiac autonomic tone. Regular Holter monitoring should be considered as a part of routine evaluation in connective tissue diseases patients, especially in systemic sclerosis.

Linear and nonlinear parameters of heart rate variability in ischemic stroke patients.

INTRODUCTION: Cardiovascular system presents cortical modulation. Post-stroke outcome can be highly influenced by autonomic nervous system disruption. Heart rate variability (HRV) analysis is a simple non-invasive method to assess sympatho-vagal balance. OBJECTIVES: The purpose of this study was to investigate cardiac autonomic activity in ischemic stroke patients and to asses HRV nonlinear parameters beside linear ones. METHODS: We analyzed HRV parameters in 15 right and 15 left middle cerebral artery ischemic stroke patients, in rest condition and during challenge (standing and deep breathing). Data were compared with 15 age- and sex-matched healthy controls. RESULTS: There was an asymmetric response after autonomic stimulation tests depending on the cortical lateralization in ischemic stroke patients. In resting state, left hemisphere stroke patients presented enhanced parasympathetic control of the heart rate (higher values for RMSSD, pNN50 and HF in normalized units). Right hemisphere ischemic stroke patients displayed a reduced cardiac parasympathetic modulation during deep breathing test. Beside time and frequency domain, using short-term ECG monitoring, cardiac parasympathetic modulation can also be assessed by nonlinear parameter SD1, that presented strong positive correlation with time and frequency domain parameters RMSSD, pNN50, HFnu, while DFA α1 index presented negative correlation with the same indices and positive correlation with the LFnu and LF/HF ratio, indicating a positive association with the sympatho-vagal balance. CONCLUSIONS: Cardiac monitoring in clinical routine using HRV analysis in order to identify autonomic imbalance may highlight cardiac dysfunctions, thus helping preventing potential cardiovascular complications, especially in right hemisphere ischemic stroke patients with sympathetic hyperactivation.

Pulse wave velocity and cardiac autonomic function in type 2 diabetes mellitus.

BACKGROUND: Increased carotid-femoral pulse wave velocity (PWV) has been associated with incident cardiovascular disease, independently of traditional risk factors. Cardiac autonomic dysfunction is a common complication of diabetes and has been associated with reduced aortic distensibility. However, the association of cardiac autonomic dysfunction with PWV is not known. In this study we examined the association between cardiac autonomic function and PWV in subjects with type 2 diabetes mellitus. METHODS: A total of 290 patients with type 2 diabetes were examined. PWV was measured at the carotid-femoral segment with applanation tonometry. Central mean arterial blood pressure (MBP) was determined by the same apparatus. Participants were classified as having normal (n = 193) or abnormal (n = 97) PWV values using age-corrected values. Cardiac autonomic nervous system activity was determined by measurement of parameters of heart rate variability (HRV). RESULTS: Subjects with abnormal PWV were older, had higher arterial blood pressure and higher heart rate than those with normal PWV. Most of the values of HRV were significantly lower in subjects with abnormal than in those with normal PWV. Multivariate analysis, after controlling for various confounding factors, demonstrated that abnormal PWV was associated independently only with peripheral MBP [odds ratio (OR) 1.049, 95% confidence intervals (CI) 1.015-1.085, P = 0.005], central MBP (OR 1.052, 95% CI 1.016-1.088, P = 0.004), log total power (OR 0.490, 95% CI 0.258-0.932, P = 0.030) and log high frequency power (OR 0.546, 95% CI 0.301-0.991, P = 0.047). CONCLUSIONS: In subjects with type 2 diabetes, arterial blood pressure and impaired cardiac autonomic function is associated independently with abnormal PWV.

Effects of Cognitive Behavioral Stress Management on Negative Mood and Cardiac Autonomic Activity in ICD Recipients.

BACKGROUND: Behavioral intervention studies in patients with an implantable cardioverter-defibrillator (ICD) show promise in improving psychosocial outcomes but inconclusive effects on cardiovascular outcome. We assessed the effects of cognitive behavioral stress management (CBSM) on mood state and potentially arrhythmogenic cardiovascular responses to mental stress in ICD patients, in support of further larger scale arrhythmia trials. METHODS: A total of 103 ICD recipients were randomly assigned to 10-week programs of CBSM or "Patient Education" (ED). Of these, 83 patients continued to either CBSM (n = 44) or ED (n = 39) intervention. Study end points were mood change, heart rate variability (HRV), double product elevation (DP = heart rate × systolic blood pressure) by math and anger-recall stress, and arrhythmia up to 6 months follow-up. RESULTS: Adjusting for multiple testing, CBSM was associated with moderate effect size reductions in tension/anxiety (P = 0.010), anger/hostility (P = 0.020), perceived stress (P = 0.037), and total mood disturbance (P = 0.025), greatest immediately following intervention (P < 0.05), and partially attributable to increased negative mood following ED (P < 0.01). No significant intervention effects on high frequency or low frequency spectral power of HRV, DP responses, or cardiac arrhythmias were demonstrated. CONCLUSIONS: CBSM intervention in ICD recipients resulted in reduced anxiety, anger, and perceived stress, not sustained at 6 months follow-up, and without conclusive effect on cardiac autonomic or hemodynamic responses to mental stress, or arrhythmia. Findings support conduct of larger behavioral intervention arrhythmia trial, with consideration of reinforcement training and targeting of subgroup responders to therapy.

Predictors of Cardiac Autonomic Dysfunction in Obesity-Related Hypertension.

INTRODUCTION: Cardiac Autonomic Dysfunction (CAD) is an overlooked cardiovascular risk factor in individuals with obesity-related hypertension. Despite its clinical significance, there is a notable lack of clarity regarding the pathophysiological correlates involved in its onset and progression. AIM: The present study aimed to identify potential predictors of CAD in obesity-related hypertension. METHODS: A total of 72 participants (34 men and 38 women) were enrolled. Comprehensive evaluations were conducted, including cardiac autonomic function assessments, body composition estimation and biochemical analysis. Participants were categorized as CAD-positive or CAD-negative based on Ewing's criteria for autonomic dysfunction. Univariate logistic regression analysis was performed to identify potential predictors for CAD. Multivariate logistic regression models were further constructed by adjusting clinically relevant covariates to identify independent predictors of CAD. RESULTS: Multivariate logistic regression analysis revealed that resting heart rate (HRrest), (odds ratio, confidence interval: 0.85, 0.78-0.93; p = 0.001) and percentage body fat (BF%), (odds ratio, confidence interval: 0.78, 0.64-0.96; p = 0.018) were significant independent predictors of CAD. Receiver Operating Characteristic curve analysis depicted optimal cut-off values for HRrest and BF% as > 74.1 bpm and > 33.6%, respectively. Multicolinearity analysis showed variance inflation factors (VIF) below the cautionary threshold of 3. CONCLUSIONS: The HRrest and BF% emerged as significant independent predictors of CAD in obesity-related hypertension. Therapeutic strategies should target HRrest < 74.1 bpm and BF% < 33.6% to mitigate CAD risk in this population. Future trials are required to establish causal relationships and may consider additional confounding variables in obesity-related hypertension.

Cellular and Molecular Mechanisms Underlying Altered Excitability of Cardiac Efferent Neurons in Cirrhotic Rats.

Patients with cirrhosis often exhibit cardiac autonomic dysfunction (CAD), characterized by enhanced cardiac sympathetic activity and diminished cardiac vagal tone, leading to increased morbidity and mortality. This study delineates the cellular and molecular mechanisms associated with altered neuronal activities causing cirrhosis-induced CAD. Biliary and nonbiliary cirrhotic rats were produced by common bile duct ligation (CBDL) and intraperitoneal injections of thioacetamide (TAA), respectively. Three weeks after CBDL or TAA injection, the assessment of heart rate variability revealed autonomic imbalance in cirrhotic rats. We observed increased excitability in stellate ganglion (SG) neurons and decreased excitability in intracardiac ganglion (ICG) neurons in cirrhotic rats compared to sham-operated controls. Additionally, threshold, rheobase, and action potential duration exhibited opposite alterations in SG and ICG neurons, along with changes in afterhyperpolarization duration. A- and M-type K⁺ channels were significantly downregulated in SG neurons, while M-type K⁺ channels were upregulated, with downregulation of the N- and L-type Ca2⁺ channels in the ICG neurons of cirrhotic rats, both in transcript expression and functional activity. Collectively, these findings suggest that cirrhosis induces an imbalance between cardiac sympathetic and parasympathetic neuronal activities via the differential regulation of K+ and Ca2+ channels. Thus, cirrhosis-induced CAD may be associated with impaired autonomic efferent functions within the homeostatic reflex arc that regulates cardiac functions.

Heart Rate Variability in Individuals with Down Syndrome: A Scoping Review with Methodological Considerations.

Individuals with Down syndrome (DS) present similar heart rate variability (HRV) parameters at rest but different responses to selected movement maneuvers in comparison to individuals without DS, which indicates reduced vagal regulation. The present study undertakes a scoping review of research on HRV in individuals with DS, with special attention paid to the compliance of the studies with standards and methodological paper guidelines for HRV assessment and interpretation. A review was performed using PubMed, Web of Science and CINAHL databases to search for English language publications from 1996 to 2020 with the MESH terms "heart rate variability" and "down syndrome", with the additional inclusion criteria of including only human participants and empirical investigations. From 74 studies, 15 were included in the review. None of the reviewed studies met the recommendations laid out by the standards and guidelines for providing the acquisition of RR intervals and necessary details on HRV analysis. Since authors publishing papers on this research topic do not adhere to the prescribed standards and guidelines when constructing the methodology, results of the research papers on the topic are not directly comparable. Authors need to design the study methodology more robustly by following the aforementioned standards, guidelines and recommendations.

Deceleration capacity of heart rate predicts 1-year mortality in patients undergoing transcatheter edge-to-edge mitral valve repair.

BACKGROUND: Risk stratification for transcatheter procedures in patients with severe mitral regurgitation is challenging. Deceleration capacity (DC) has already proven to be a reliable risk predictor in patients undergoing transcatheter aortic valve implantation. We hypothesized, that DC provides prognostic value in patients undergoing transcatheter edge-to-edge mitral valve repair (TEER). METHODS: We retrospectively analyzed electrocardiogram signals from 106 patients undergoing TEER at the University Hospital of Tübingen. All patients received continuous heart-rate monitoring to assess DC following the procedure. One-year all-cause mortality was defined as the primary end point. RESULTS: Sixteen patients (15.1%) died within 1 year. The DC in nonsurvivors was significantly reduced compared to survivors (5.1 ± 3.0 vs. 3.0 ± 1.6 ms, p = 0.002). A higher EuroSCORE II and impaired left ventricular function were furthermore associated with poor outcome. In Cox regression analyses, a DC < 4.5 ms was found a strong predictor of 1-year mortality (hazard ratio: 0.10, 95% confidence interval: 0.13-0.79, p = 0.029). Finally, a significant negative correlation was found between DC and residual mitral regurgitation after TEER (r = -0.41, p < 0.001). CONCLUSION: In patients with severe mitral regurgitation undergoing TEER, DC may serve as a new predictor of follow-up mortality.

Short-Term Heart Rate Variability in Metabolic Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: Our aim was to determine the differences in short-term heart rate variability (HRV) between patients with metabolic syndrome (MS) and healthy controls. METHODS: We searched electronic databases for primary works with short-term HRV recordings (≤30 min) that made comparisons between individuals with MS versus healthy controls. This systematic review and meta-analysis (MA) was performed according to PRISMA guidelines and registered at PROSPERO (CRD42022358975). RESULTS: Twenty-eight articles were included in the qualitative synthesis and nineteen met the criteria for the MA. Patients with MS showed decreased SDNN (-0.36 [-0.44, -0.28], p < 0.001), rMSSD (-7.59 [-9.98, -5.19], p < 0.001), HF (-0.36 [-0.51, -0.20], p < 0.00001) and LF (-0.24 [-0.38, -0.1], p = 0.001). In subsequent subanalyses, we found a decrease in SDNN (-0.99 (-1.45, -0.52], p < 0.001), rMSSD (-10.18 [-16.85, -3.52], p < 0.01) and HF (-1.04 [-1.97, -0.1] p < 0.05) in women. In men, only LF showed a significant lower value (-0.26 [-0.5, -0.02], p < 0.05). We could not perform MA for non-linear variables. CONCLUSIONS: Patients with MS showed changes in time-domain analyses, with lower values in SDNN and rMSSD. Regarding frequency-domain analyses, MS patients showed a decrease in HF and LF When sex was used as a grouping variable, the MA was only possible in one of both sexes (men or women) in rMSSD and LF/HF. Lastly, when data for both men and women were available, subanalyses showed a different behavior compared to mixed analyses for SDNN, HF and LF, which might point towards a different impact of MS in men and women.

Parental History of Hypertension: A Risk for Autonomic Dysfunction and Metabolic and Vascular Derangement in Normotensive Male Offspring.

BACKGROUND: Children of hypertensive parents have an increased propensity of developing hypertension, at an age very much prior to their parents. Understanding the pathophysiology of hypertension in such young individuals, especially baroreflex sensitivity (BRS), is necessary. Reduced heart rate variability (HRV), insulin resistance (IR), dyslipidemia, and decreased vasodilatory adipokines, namely, apelin and relaxin, in normotensives may predispose to the onset of hypertension. Thus, this study compared autonomic functions, vascular markers, and metabolic profiles between normotensive male offspring with and without parental hypertension. METHODS: This analytical cross-sectional study comprised 40 male normotensive offspring of hypertensive parents, aged 18-35 years, recruited as the study group and 40 age- and body mass index (BMI)-matched normotensive male offspring with non-hypertensive parents enrolled as controls. Cardiovascular autonomic functions, including BRS, HRV, diastolic blood pressure response to isometric handgrip test (ΔDBPIHG), Valsalva ratio, and metabolic and vascular markers, were assessed. RESULTS: The study group exhibited reduced BRS, HRV, and Valsalva ratio and higher ΔDBPIHG compared to controls, indicating impaired autonomic functions. The study group had higher IR and triglyceride levels and reduced apelin and relaxin levels. BRS showed significant correlations with HRV, Valsalva ratio, ΔDBPIHG, and metabolic and vascular markers. CONCLUSIONS: Normotensive male offspring of hypertensive parents exhibit impaired autonomic functions, as evidenced by reduced BRS, HRV, and Valsalva ratio. Additionally, they have higher IR, dyslipidemia, and decreased levels of vasodilatory adipokines, indicating an increased risk for future hypertension development. These findings signify that early identification of hypertensive potential in this high-risk population is warranted, which would enable taking necessary preventive measures.