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.

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.

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.

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.

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.

Modifications of long-term heart rate variability produced in an experimental model of diet-induced metabolic syndrome.

Metabolic syndrome (MetS) has been linked to a higher prevalence of cardiac arrhythmias, the most frequent being atrial fibrillation, but the mechanisms are not well understood. One possible underlying mechanism may be an abnormal modulation of autonomic nervous system activity, which can be quantified by analysing heart rate variability (HRV). Our aim was to investigate the modifications of long-term HRV in an experimental model of diet-induced MetS to identify the early changes in HRV and the link between autonomic dysregulation and MetS components. NZW rabbits were randomly assigned to control (n = 10) or MetS (n = 10) groups, fed 28 weeks with high-fat, high-sucrose diet. 24-hour recordings were used to analyse HRV at week 28 using time-domain, frequency-domain and nonlinear analyses. Time-domain analysis showed a decrease in RR interval and triangular index (Ti). In the frequency domain, we found a decrease in the low frequency band. Nonlinear analyses showed a decrease in DFA-α1 and DFA-α2 (detrended fluctuations analysis) and maximum multiscale entropy. The strongest association between HRV parameters and markers of MetS was found between Ti and mean arterial pressure, and Ti and left atrial diameter, which could point towards the initial changes induced by the autonomic imbalance in MetS.

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.

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.

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.

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.

Persistent Increase of Sympathetic Activity in Post-Acute COVID-19 of Paucisymptomatic Healthcare Workers.

Healthcare workers (HCWs) represent a population with a significant burden of paucisymptomatic COVID-19, as the general population. We evaluated autonomic nervous system activity by means of heart rate variability (HRV) in HCWs during health surveillance visits. Short-term electrocardiogram (ECG) recordings were obtained 30 days (IQR 5.25-55.75) after a negative naso-pharyngeal swab for SARS-CoV-2 in 44 cases and compared with ECGs of 44 controls with similar age and sex distribution. Time and frequency domain HRV were evaluated. HCWs who used drugs, had comorbidities that affected HRV, or were hospitalized with severe COVID-19 were excluded. Frequency domain HRV analysis showed a significantly higher low/high-frequency power ratio (LF/HF) in the case study compared with controls (t = 2.84, p = 0.006). In time domain HRV analysis, mean standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) were significantly lower for cases compared with controls (t = -2.64, p = 0.01 and t = -3.27, p = 0.002, respectively). In the post-acute phase of infection, SARS-CoV-2 produces an autonomic imbalance mirrored by a reduction in HRV. These results are consistent with epidemiological data that suggest a higher risk of acute cardiovascular complications in the first 30 days after COVID-19 infection.

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.

Analysis of CACNA1C and KCNH2 Risk Variants on Cardiac Autonomic Function in Patients with Schizophrenia.

BACKGROUND: Cardiac autonomic dysfunction (CADF) is a major contributor to increased cardiac mortality in schizophrenia patients. The aberrant function of voltage-gated ion channels, which are widely distributed in the brain and heart, may link schizophrenia and CADF. In search of channel-encoding genes that are associated with both CADF and schizophrenia, CACNA1C and KCNH2 are promising candidates. In this study, we tested for associations between genetic findings in both genes and CADF parameters in schizophrenia patients whose heart functions were not influenced by psychopharmaceuticals. METHODS: First, we searched the literature for single-nucleotide polymorphisms (SNPs) in CACNA1C and KCNH2 that showed genome-wide significant association with schizophrenia. Subsequently, we looked for such robust associations with CADF traits at these loci. A total of 5 CACNA1C SNPs and 9 KCNH2 SNPs were found and genotyped in 77 unmedicated schizophrenia patients and 144 healthy controls. Genotype-related impacts on heart rate (HR) dynamics and QT variability indices (QTvi) were analyzed separately in patients and healthy controls. RESULTS: We observed significantly increased QTvi in unmedicated patients with CADF-associated risk in CACNA1C rs2283274 C and schizophrenia-associated risk in rs2239061 G compared to the non-risk allele in these patients. Moreover, unmedicated patients with previously identified schizophrenia risk alleles in KCNH2 rs11763131 A, rs3807373 A, rs3800779 C, rs748693 G, and 1036145 T showed increased mean HR and QTvi as compared to non-risk alleles. CONCLUSIONS: We propose a potential pleiotropic role for common variation in CACNA1C and KCNH2 associated with CADF in schizophrenia patients, independent of antipsychotic medication, that predisposes them to cardiac arrhythmias and premature death.

Effect of Preanesthetic Fluid Loading on Postinduction Hypotension and Advanced Cardiac Parameters in Patients with Chronic Compressive Cervical Myelopathy: A Randomized Controlled Trial.

Purpose Hypotension during the early intraoperative phase is common and can lead to adverse perioperative outcomes. Fluid preloading is one of the methods to limit its occurrence. Patients with chronic compressive cervical myelopathy may have autonomic dysfunction, which can aggravate hemodynamic alterations during anesthesia. This study compared the occurrence of postinduction hypotension and changes in cardiac dynamic indices in patients with and without crystalloid preloading undergoing decompressive cervical spine surgery. Methods This randomized controlled trial was conducted over 15 months after obtaining patient consent, approval of the institute ethics committee, and trial registration. We compared preanesthetic fluid loading with Ringer's lactate (20 mL/kg over 30 minutes) with no preloading (2 mL/kg/h maintenance) in 60 consecutive patients undergoing cervical spine surgery. The ANSiscope was used to determine baseline cardiac autonomic function. Noninvasive cardiac output monitor was used to assess changes in heart rate, mean arterial pressure, cardiac index (CI), stroke volume variation (SVV), and total peripheral resistance index during study intervention, anesthetic induction, tracheal intubation, and change in position from supine to prone. Results The incidences of postinduction hypotension were 26.7% (8/30) and 86.7% (26/30) and the median doses of mephentermine used were 0 and 6 mg, respectively, in patients with and without fluid preloading (both p < 0.001). Preloading resulted in improvement in CI, reduction in SVV, and lesser vasopressor use. Conclusion Preloading reduced the occurrence of postinduction hypotension and vasopressor use, improved CI, and reduced SVV during the early intraoperative period. Registration number of Clinical Trial The trial was registered with Clinical Trial Registry of India (CTRI/2018/07/014970 on 19/07/2018).

Association of Cardiac Autonomic Responses with Clinical Outcomes of Myasthenia Gravis: Short-Term Analysis of the Heart-Rate and Blood Pressure Variability.

Introduction: The aim of the study was to assess cardiac and autonomic function in patients with myasthenia gravis (MG) and to explore its relationship with disease outcomes. Methods: Thirty-eight patients with an MG were enrolled (median age 40.5 years; median disease duration 5.5 years). Cardiovascular parameters, baroreflex sensitivity (BRS), spectral indices of short-term heart rate (HRV), and systolic blood pressure variability (SBPV) were compared with age- and gender-matched controls (n = 30). Cardiac autonomic function was assessed during the response to standing (tilt) and deep breathing tests (expiration/inspiration ratio-E/I). Results: HR and BP responses to the tilt test were similar in both groups. MG patients, as compared to controls, were characterized by altered SBPV at rest, significantly reduced HR response to the deep breathing test (p < 0.001), increased sympathovagal balance after tilt (delta LF/HF-RRI, p = 0.037), and lower values of BRS (p = 0.007) and hemodynamic parameters, i.e., cardiac index, index contractility, left ventricular work index, at rest and during tilt. There was no association between disease duration and autonomic parameters. Disease severity, as determined by MGFA (Myasthenia Gravis Foundation of America) corrected for age and sex, was an independent predictor of diminished vagal tone (E/I ratio) and increased sympathetic response to tilt (delta LF/HF-RRI) as measured with HRV. Lower BRS was associated with greater disease severity and older age. Hemodynamic parameters were predominantly predicted by age and sex. Conclusion: Our results confirm cardiac autonomic dysfunction among MG patients with predominant parasympathetic impairment. Clinicians should consider evaluation of autonomic balance in MG patients with, or at risk for, cardiovascular disease.

Continuous monitoring with wearables in multiple sclerosis reveals an association of cardiac autonomic dysfunction with disease severity.

Background: Dysfunction of the autonomic nervous system is common in multiple sclerosis patients, and probably present years before diagnosis, but its role in the disease is poorly understood. Objectives: To study the autonomic nervous system in patients with multiple sclerosis using cardiac autonomic regulation measured with a wearable. Methods: In a two-week study, we present a method to standardize the measurement of heart rate variability using a wearable sensor that allows the investigation of circadian trends. Using this method, we investigate the relationship of cardiac autonomic dysfunction with clinical hallmarks and subjective burden of fatigue and autonomic symptoms. Results: In 55 patients with multiple sclerosis and 24 healthy age- and gender-matched controls, we assessed the cumulative circadian heart-rate variability trend of two weeks. The trend analysis revealed an effect of inflammation (P = 0.0490, SMD = -0.5466) and progressive neurodegeneration (P = 0.0016, SMD = 1.1491) on cardiac autonomic function. No association with subjective symptoms could be found. Conclusions: Trend-based heart rate variability measured with a wearable provides the opportunity for unobtrusive long-term assessment of autonomic functions in patients with multiple sclerosis. It revealed a general dysregulation in patients with multiple sclerosis.

SGLT2-inhibitors reduce the cardiac autonomic neuropathy dysfunction and vaso-vagal syncope recurrence in patients with type 2 diabetes mellitus: the SCAN study.

BACKGROUND: In patients with type 2 diabetes mellitus (T2DM) the vaso-vagal syncope (VVS) recurrence could be due to the alteration of autonomic system function, evaluated by heart rate variability (HRV), and by 123I-metaiodobenzylguanidine (123I-mIBG) myocardial scintigraphy indexes: Heart to Mediastinum ratio (H/Mlate), and Washout rate (WR). The SGLT2-I could modulate/reduce autonomic dysfunction in T2DM patients with VVS. This effect could reduce the VVS recurrence in T2DM patients. METHODS: In a prospective multicenter study, after propensity score matching, we studied a population of 324 T2DM patients with VVS, divided into 161 SGLT2-I-users vs. 163 Non-SGLT2-I users. In these patients as SGLT2-I-users vs. Non-SGLT2-I users, we investigated the HRV and 123I-MIBG modifications and VVS recurrence at 12 months of follow-up. RESULTS: At follow-up end, the SGLT2-I-users vs. Non-SGLT2-I users had best glucose homeostasis and lower values of inflammatory markers, and resting heart rate (p < 0.05). The SGLT2-I-users vs. Non-SGLT2-I users evidenced the lowest low frequency/high frequency ratio (LF/HFr), a significant difference for all the indexes of autonomic dysfunction via ECG Holter analysis, and higher values of H/Mlate (p < 0.05). Finally, comparing SGLT2-I-users vs. Non-SGLT2-I users, we found a higher rate of VVS recurrence events, specifically of the vasodepressor VVS recurrence at 1-year follow-up (p < 0.05). We did not find a significant difference of mixed and cardio-inhibitory VVS recurrence events at 1 year of follow-up in the study cohorts (p > 0.05). At the Cox regression analysis H/Mlate (0.710, [0.481-0.985]), and SGLT2-I therapy (0.550, [0.324-0.934]) predicted all causes of syncope recurrence at 1 year of follow-up. CONCLUSIONS: Non-SGLT2-I users vs. SGLT2-I-users had alterations of the autonomic nervous system, with a higher rate of VVS recurrence at 1 year of follow-up. The indexes of cardiac denervation predicted the VVS recurrence, while the SGLT2-I reduced the risk of VVS recurrence. CLINICAL TRIAL REGISTRATION NUMBER: NCT03717207.

A comparative study of heart rate variability and physical fitness in women with moderate and severe fibromyalgia.

The aim of this study was to compare the physical fitness and cardiac autonomic activity among women with moderate and severe fibromyalgia (FM) and healthy women. This study included 35 women with FM (age: 46.2±8.9 years) and 17 healthy women (age: 44.3±9.9 years). Participants with FM were divided into moderate FM (n=15) and severe FM (n=20) according to the total score obtained in FM impact questionnaire. The heart rate variability was monitored using a portable cardiac monitor with participants resting in supine position during 10 min. Thereafter, the participants performed the chair sit and reach test, the chair stand test, and the 6-min walk test to measure the lower-body flexibility, lower-body muscle strength, and cardiorespiratory fitness, respectively. The lower-body muscle strength and cardiorespiratory fitness were both reduced in moderate and severe FM compared to healthy women (P<0.01), with greater reduction in severe FM when compared to moderate FM (P<0.05). In addition, the parasympathetic indexes of heart rate variability were all similarly decreased in both moderate and severe FM, when compared to healthy women (P<0.05). The cardiac parasympathetic activity is similarly decreased in women with both moderate and severe FM in comparison to healthy women, despite a greater physical deconditioning in severe FM.

Cardiovascular/Stroke Risk Stratification in Parkinson's Disease Patients Using Atherosclerosis Pathway and Artificial Intelligence Paradigm: A Systematic Review.

Parkinson's disease (PD) is a severe, incurable, and costly condition leading to heart failure. The link between PD and cardiovascular disease (CVD) is not available, leading to controversies and poor prognosis. Artificial Intelligence (AI) has already shown promise for CVD/stroke risk stratification. However, due to a lack of sample size, comorbidity, insufficient validation, clinical examination, and a lack of big data configuration, there have been no well-explained bias-free AI investigations to establish the CVD/Stroke risk stratification in the PD framework. The study has two objectives: (i) to establish a solid link between PD and CVD/stroke; and (ii) to use the AI paradigm to examine a well-defined CVD/stroke risk stratification in the PD framework. The PRISMA search strategy selected 223 studies for CVD/stroke risk, of which 54 and 44 studies were related to the link between PD-CVD, and PD-stroke, respectively, 59 studies for joint PD-CVD-Stroke framework, and 66 studies were only for the early PD diagnosis without CVD/stroke link. Sequential biological links were used for establishing the hypothesis. For AI design, PD risk factors as covariates along with CVD/stroke as the gold standard were used for predicting the CVD/stroke risk. The most fundamental cause of CVD/stroke damage due to PD is cardiac autonomic dysfunction due to neurodegeneration that leads to heart failure and its edema, and this validated our hypothesis. Finally, we present the novel AI solutions for CVD/stroke risk prediction in the PD framework. The study also recommends strategies for removing the bias in AI for CVD/stroke risk prediction using the PD framework.

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.