Improving cardiovascular autonomic function in postmenopausal women with hypertension: a pilot study of supervised versus home-based aerobic exercise.

The Relationship Between Brain–Heart Autonomic Signaling and Aging: A Gender-Specific Longitudinal Perspective from the Baltimore Longitudinal Study on Aging

Does empagliflozin modulate the autonomic nervous system among individuals with type 2 diabetes and coronary artery disease? The EMPA-HEART CardioLink-6 Holter analysis

Introduction: Patients (pts) with ischemic cardiomyopathy (ICM) may have impaired heart rate variability (HRV) which is associated with worse prognosis. We tested the hypothesis that cardiac mesenchymal stem cell (MSC) implantation is associated with improvement in HRV in patients with severe LV dysfunction and abnormal HRV at baseline Methods: The POSEIDON Trial evaluated transendocardial MSC implantation in pts with ICM. We examined 24-48 hour ambulatory monitoring data from 25 pts at baseline, immediately post MSC implant, and intermittently up to 13 months following implantation. HRV was assessed using 3 parameters: (1) standard deviation of NN intervals (SDNN), (2) the square root of the mean squared differences of successive NN intervals (RMSSD), and (3) standard deviation of the average normal NN intervals (SDANN). HRV indices were correlated to changes in ejection fraction (EF), end systolic volumes (ESV), end diastolic volumes (EDV), and sphericity index (SI) using t-test. Results: The cohort had a mean age of 62 ± 10 years, EF 26.5 ± 9.4%, ESV 204.2 ± 80.6 ml and EDV 271.5 ± 85.4 ml. Compared with pre-implantation values, RMSSD trended to improve in the cohort (30.2 ± 15 to 51.9 ± 39.3 msec, p=0.08), significantly improved in the group with EF improvement (24.6 ± 10 to 57.3 ± 43.5, p= 0.04) and tended to improve in the group with improved EDV, ESV, SI (Table). SDNN and SDANN also tended to improve in the cohort, but showed significant improvement in the group with less structural improvement noted by EDV or ESV decrease by <5% (Table). Conclusions: There was a trend towards improvement in HRV after MSC implant. RMSSD, a variable more closely related with vagal tone, correlated better with greater improvements in EF, EDV, ESV and SI and may be a better marker of anatomical improvement. In contrast, SDNN and SDANN, which track not only vagal tone but diurnal variation, tended to improve in the overall cohort but showed improvement in the group with less structural improvement.

The effects of man-made electromagnetic fields (EMFs) on the cardiovascular system have been investigated in many studies. In this regard, the cardiac autonomic nervous system (ANS) activity due to EMFs exposure, assessed by heart rate variability (HRV), was targeted in some studies. The studies investigating the relationship between EMFs and HRV have yielded conflicting results. We performed a systematic review and meta-analysis to assess the data's consistency and identify the association between EMFs and HRV measures. Published literature from four electronic databases, including Web of Science, PubMed, Scopus, Embase, and Cochrane, were retrieved and screened. Initially, 1601 articles were retrieved. After the screening, 15 original studies were eligible to be included in the meta-analysis. The studies evaluated the association between EMFs and SDNN (standard deviation of NN intervals), SDANN (Standard deviation of the average NN intervals for each 5 min segment of a 24 h HRV recording), and PNN50 (percentage of successive RR intervals that differ by more than 50 ms). There was a decrease in SDNN (ES=-0.227 [-0.389,-0.065], p=0.006), SDANN (ES=-0.526 [-1.001,-0.05], p=0.03) and PNN50 (ES=-0.287 [-0.549,-0.024]). However, there was no significant difference in LF (ES=0.061 (-0.267, 0.39), p=0.714) and HF (ES=-0.134 (0.581, 0.312), p=0.556). In addition, a significant difference was not observed in LF/HF (ES=0.079 (-0.191, 0.348), p=0.566). Our meta-analysis suggests that exposure to the environmental artificial EMFs could significantly correlate with SDNN, SDANN, and PNN50 indices. Therefore, lifestyle modification is essential in using the devices that emit EMs, such as cell phones, to decrease some signs and symptoms due to EMFs' effect on HRV.

A single session of aerobic exercise reduces blood pressure vs. pre-exercise, which is referred as postexercise hypotension (PEH). Changes in cardiac autonomic control and local vasodilatation contribute to PEH. HIV-infected patients present higher risk of hypertension, autonomic and endothelial dysfunction, which may influence the PEH. However, this phenomenon has never been studied in this population. PURPOSE: To investigate the effects of acute aerobic exercise upon systemic blood pressure, aortic pressure, and cardiac autonomic modulation in men living with HIV. METHODS: After cardiopulmonary exercise testing, 10 HIV-infected (HIV: 47.5 ± 9.7 yrs; 25.2 ± 3.0 kg.m-2) and 14 healthy men (CTL: 40.1 ± 10.5 yrs; 25.8 ± 3.4 kg.m-2) underwent cycling bouts expending 150 kcal at 50% oxygen uptake reserve (time to achieve 150 kcal - HIV: 24.1 ± 5.5 and CTL: 23.1 ± 3.0 min) and control sessions (20 min), in a randomized counterbalanced order. Systolic blood pressure (SBP), aortic pressure, and heart rate variability were assessed 30 min before and 60 min after each session, by means of oscillometric digital monitor, pulse wave reflection (tonometry), and beat-to-beat heart rate intervals, respectively. Comparisons within-between sessions were made using 2-way ANOVA with repeated measures (P ≤ 0.05). RESULTS: No difference was detected between groups for maximal oxygen uptake (HIV: 27.3 ± 4.2 vs. CTL: 31.4 ± 6.8 mL·kg-1·min-1; P= 0.1) and SBP at rest (HIV: 117.2 ± 11.6 vs. CTL: 112.2 ± 8.9 vs mmHg; P= 0.2). Resting aortic pressure was higher in HIV (107.0 ± 9.3 mmHg) vs. CTL (100.0 ± 4.3 mmHg; P= 0.03), while standard deviation of NN intervals (SDNN) was lower in HIV (28.3 ± 11.2 ms) vs. CTL (43.9 ± 20.8 ms; P= 0.04). In CTL, SBP (-9.3 ± 5.9 mmHg; P= 0.01), aortic pressure (-6.3 ± 4.6 mmHg; P= 0.03), and SDNN (-23.4 ± 44.5 ms; P= 0.05) decreased after submaximal exercise vs. control sessions. No significant change occurred in HIV for SBP (-4.2 ± 18.9 mmHg; P= 0.5), aortic pressure (-5.1 ± 13.0 mmHg; P= 0.2), or SDNN (+5.5 ± 25.6 ms; P= 0.4). CONCLUSION: Healthy, but not HIV-infected men, exhibited acute blood pressure reduction after submaximal aerobic exercise. The higher central arterial stiffness and lower vagal modulation among HIV patients may help to explain the absence of PEH in this group. Supported by FAPERJ Grant.

Objective: To explore the predictive value of very low frequency (VLF) for the efficacy of vitamin D treatment in children with postural orthostatic tachycardia syndrome (POTS). Methods: A retrospective case-control study was conducted. A total of 65 POTS children from the Department of Pediatrics of the Second Hospital of Lanzhou University from November 2023 to May 2024 were selected as the research subjects, while 102 healthy children from the same period were selected as the control group. The 25 (OH) D levels between POTS children and healthy children were compared. The frequency of eight main symptoms, including palpitations, headache, cold sweat, blurred vision, chest tightness, dizziness, fainting, and digestive discomfort in the POTS group were analyzed, the symptom scores of the orthostatic intolerance were calculated, and the parameters related to short-range heart rate variability (HRV) during the upright test, head-up tilt test (HUTT) were collected. The correlation between 25 (OH) D levels and symptom scores of orthostatic intolerance symptoms and HRV parameters in children with POTS were analyzed by Pearson correlation analysis. The total symptom scores of children with POTS were compared for 3 months before treatment and 2 months after treatment with vitamin D 800 U/d. The difference in score before and after treatment was ≥2 as responsive group, and the score difference before and after treatment was <2 as non-responsive group. The demographic characteristics including age, gender, height, weight, body mass index, as well as HRV parameters such as the standard deviation of nn intervals (SDNN), the standard deviation of the average NN intervals (SDANN), the root mean square of successive differences (rMSSD), low-frequency (LF), high-frequency (HF), very-low-frequency (VLF) were compared between the responsive group and non-responsive group. Multivariate Logistic regression was analyzed to screen independent influencing factors of vitamin D treatment efficacy for POTS. The marker molecules related to the efficacy of vitamin D treatment in children with POTS were analyzed through receiver operating characteristic (ROC) curve. Results: A total of 167 children were included in this study. There were 65 children in the POTS group, 38 males and 27 females, with the age of (10.6±2.2) years. There were 102 healthy children in the control group, 53 males and 49 females, with the age of (11.2±1.8) years.There was no statistically significant difference in gender and age between the two groups (both P>0.05). The serum 25 (OH) D level in children in the POTS group was (37±18)nmol/L, lower than that in the control group (61±17)nmol/L (P<0.05).Pearson correlation analysis showed that serum 25(OH)D was positively correlated with VLF, SDNN and HF (r=0.43, 0.65, 0.36, respectively, all P<0.05). Among the POTS children, there were 48 cases in responsive group and 17 cases in non-responsive group. Univariate analysis revealed that responsive group exhibited significantly lower values in age, SDNN, SDANN, and VLF compared to the non-responsive group (all P<0.05). Multivariate Logistic regression analysis showed that age (OR=1.47, 95%CI 1.08-2.01), SDNN (OR=1.01, 95%CI 1.00-1.22) and VLF (OR=1.01, 95%CI 1.00-1.15) were independent influencing factors in the effect of vitamin D in POTS children (all P<0.05). ROC curve analysis showed that the area under the curve of VLF predicting response to vitamin D treatment for POTS was 0.72 (95%CI 0.58-0.85, P=0.008). When the cutoff value was 1 272 ms2, the sensitivity and specificity were both 70%. Conclusion: VLF may help predict the efficacy of vitamin D treatment in children with POTS.

Heart rate variability and autonomic modulation in children with obstructive sleep apnea syndrome

To evaluate the impact of pulsed-field ablation (PFA) and radiofrequency catheter ablation (RFCA) on cardiac autonomic nerve system (ANS) function after pulmonary vein isolation (PVI) by monitoring heart rate (HR) and heart rate variability (HRV) changes. In this prospective cohort clinical study, patients with paroxysmal atrial fibrillation (AF) were enrolled consecutively into PFA or RFCA groups. HRV was assessed using the standard deviation of NN intervals (SDNN) and the standard deviation of the average NN intervals over 5-min periods (SDANN). HR, SDNN, and SDANN were measured before PVI and 3 months after PVI using 24-hour Holtermonitoring. Acute electrical isolation was achieved in 100% of pulmonary veins (PVs) in the 72 patients. Over the 3-month follow-up, 36 of 36 patients in the PFA group and 36 of 36 patients in the RFCA group remained free from atrial arrhythmia episodes >30s. In the PFA group, there were no significant changes in HR, SDNN, and SDANN before and after PVI (all p>0.05). The increase in HR in the PFA group was significantly lower than in the RFCA group (3.19±10.50vs. 10.86±9.30bpm; p=0.0008). The decrease in HRV indices SDNN and SDANN in the PFA group was also significantly less than in the RFCA group (-10.72±33.89vs. -28.33±30.55ms; p=0.012, -4.67±32.55vs. -22.03±27.46ms; p=0.009). PFA results in less damage to cardiac ANS function and preserves more cardiac ANS function compared with RFCA during PVI for paroxysmal AF.

BackgroundCongenital ventricular septal defects (VSDs) are considered to have benign long‐term outcome when treated correctly in childhood. However, abnormal parameters are described in younger adults, including impaired heart rate variability (HRV). It is not known whether such abnormalities will deteriorate with age. Therefore, HRV and cardiac events, such as premature ventricular contraction, were evaluated in patients aged >40 years with congenital VSDs and compared with healthy peers.Methods and ResultsA total of 30 surgically closed VSDs (51±8 years, repair at median age 6.3 years with total range 1.4–54 years) with 30 healthy controls (52±9 years) and 30 small, unrepaired VSDs (55±12 years) with 30 controls (55±10 years) were all equipped with a Holter monitor for 24 hours. Compared with healthy peers, surgically closed patients had lower SD of the normal‐to‐normal (NN) interbeat interval (129±37 versus 168±38 ms; P<0.01), SD of the average NN intervals for each 5‐minute segment of a 24‐hour HRV recording (116±35 versus 149±35 ms; P<0.01) and 24‐hour triangular index (31±9 versus 44±11; P<0.01). SD of the NN intervals, SD of the average NN intervals for each 5‐minute segment of a 24‐hour HRV recording, and triangular index were comparable between unrepaired VSDs and healthy peers. SD of the NN intervals was <100 ms in 22% of surgically closed and 10% of unrepaired VSDs, whereas controls were within normal ranges. A high number of premature ventricular contractions (>200 events) was registered in 57% of surgical patients compared with 3% of controls (P<0.01), and 53% of unrepaired VSDs compared with 10% in controls (P<0.01).ConclusionsAdults aged >40 with congenital VSDs demonstrate impaired HRV, mainly among surgically closed VSDs. More than half demonstrated a high number of premature ventricular contractions. These novel findings could indicate long‐term cardiovascular disturbances. This necessitates continuous follow‐up of VSDs throughout adulthood.

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

A Comparison of Aerobic Exercise and Resistance Training in Patients With and Without Chronic Kidney Disease

This study assessed the effectiveness of an 8-week aerobic exercise program on heart rate variability (HRV) in people living with HIV taking antiretroviral therapy. Twenty-six participants were randomly assigned to a control group or an aerobic exercise group. Resting HRV was measured for 5 min in supine position using an electrocardiogram. Estimated maximal oxygen uptake (VO2max) was assessed through a treadmill 6-min walk test. The training program consisted of aerobic exercise thrice per week at 65%-75% of heart rate max for 45 min per session. Repeated measures ANOVA was used to test for differences between groups, and Spearman's rho was used to assess for the correlation between HRV measures and estimated VO2max. There was no significant group by time interactions for any of the HRV indices. However, the standard deviation of normal-to-normal (NN) R-R intervals increased significantly in the aerobic exercise group (pre: 46.97 ± 32.70 ms vs. post: 59.49 ± 37.20 ms, p = .045). There was a strong correlation between the VO2max and the standard deviation of NN intervals (SDNN) (r = 0.617; p = .002). There was a moderate correlation between VO2max and the square root of the mean squared differences of successive normal-to-normal intervals (rMSSD) (r = 0.424; p = .049), the low frequency power (r = 0.506; p = .016), and the standard deviation of differences between successive differences of normal-to-normal intervals (SDSD) (r = 0.424; p = .049). While differences in HRV were not observed between groups, our data suggest that overall autonomic function can improve across time with aerobic exercise, and these changes are associated with greater levels of VO2max. These results advocate the importance of improvements in HRV given their association with lower risk of cardiovascular disease and mortality.

Studies have shown that physiological aging is accompanied by insulin resistance and reduction in heart rate variability (HRV) because of decreased vagal activity at the sinus node, decreased baroreflex activity, and increased sympathetic activity, resulting in reduced complexity of regulatory systems.1 The inspiratory muscle training reduces sympathetic activity, improves inspiratory muscle function, and increases the glucose transport within the musculature of the diaphragm.2,3 For this research, 21 insulin-resistant elderly patients were recruited on the basis of their results on testing with the homeostasis model assessment of insulin resistance. Variability in heart rate was evaluated while the patient was lying down resting for 10 min on a stretcher. The data were acquired using a Polar S810i® frequency meter (Polar Inc., Kempele, Finland). The subjects were divided into two groups: a control group, which was trained using no Threshold® load, and an experimental group, which underwent respiratory muscle training using a Threshold load, with 40% of inspiratory pressure reached during the first session of each week. The program lasted 12 weeks, and both groups trained daily for 30 min. Due to the small sample size, differences between the groups were tested using the Wilcoxon rank sum test. A comparison of both the clinical and laboratory characteristics of the groups before and after treatment showed values of glucose, insulin, and homeostasis model assessment of insulin resistance changed. Respiratory exercise resulted in an increase in the standard deviation of NN intervals and in coefficient of variation in the experimental group. The absolute low-frequency (LF) component decreased in the experimental group. Further, the normalized LF component of HRV was lower in the experimental group. The normalized high-frequency component increased in the experimental group. Consequently, respiratory exercise promoted a decrease in sympathovagal balance in the experimental group. A positive correlation was found between insulin and sympathetic modulation (LF% r = 0.34, p = .03) , and abdominal circumference showed a positive correlation with LF% (r = 0.53, p = .006; Figure 1). Figure 1. Sympathetic modulation and sympathovagal balance. SD, standard deviation; SDNN, standard deviation of NN intervals; CV, coefficient of variation; HF, high frequency; AC, autonomic control. The major finding of this study was that inspiratory muscle training increased HRV and decreased sympathetic modulation in elderly patients with insulin resistance, without changing the respiratory frequency, through strengthening of the inspiratory muscles. The current study identified a correlation between cardiac sympathetic modulation represented by the LF component, insulin levels, and waist circumference. Studies have demonstrated that decrease in HRV is associated with fasting glucose and insulin levels, and individuals with insulin resistance have a reduced parasympathetic component.4 In this study, we observed an increase in HRV subsequent to the trial intervention because of a small increase in the coefficient of variation of RR intervals and standard deviation of NN intervals index. However, the sympathetic and parasympathetic modulation represented by the absolute LF component was reduced. This suggests that breathing exercises enhanced autonomic function by decreasing the sympathetic activity without an increase in parasympathetic tone. This study shows that inspiratory muscular training significantly improves HRV and insulin sensitivity, and it may be a promising noninvasive treatment for elderly who cannot engage in aerobic exercise.

Background: Low heart rate variability (HRV) is associated with major vascular risk factors for cognitive decline, including hypertension and cardiovascular disease (CVD). Therefore, we hypothesized that higher HRV during mid- to late-life is associated with better cognitive performance. Methods: In a subset of participants from the Multi-Ethnic Study of Atherosclerosis (N = 2,961; aged 45-84 years; 55% female; 40% white, 22% African-American, 25% Hispanic, and 13% Chinese-American), we used multivariate linear regression to study the relationship of short-term HRV to global cognitive performance as measured by the Cognitive Abilities Screening Instrument (CASI; score range 0-100). Two measures of HRV, the standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (RMSSD), were computed at Exam 1 (2000-2002) and Exam 5 (2010-2012). CASI was administered at Exam 5. Results: In age-, race-, sex- and education-adjusted models, Exam 1 SDNN was significantly associated with performance on the CASI ( β = 0.74 ± 0.22; P &lt; 0.001). This association remained significant after adjustment for cardiovascular risk factors, including prevalent CVD, medication use, and APOE ε4 allele carriage ( β = 0.53 ± 0.23; P = 0.019). Furthermore, participants with highest quartile Exam 1 SDNN scored better than the adjusted mean CASI score (0.61 ± 0.22 points higher; P = 0.022), and 0.81 ± 0.29 points higher than other quartiles ( P = 0.006); participants in other Exam 1 SDNN quartiles scored similarly to each other and to the adjusted mean. In contrast, there were no associations between CASI score and Exam 5 SDNN, Exam 1 RMSSD, or Exam 5 RMSSD after adjustment for cardiovascular risk factors, and no interactions between HRV and race or APOE were present. Conclusions: Highest quartile 10-year antecedent SDNN is associated with better global cognitive performance in a multi-ethnic population of middle-aged and elderly adults, independent of sociodemographic factors, traditional cardiovascular risk factors, APOE status, and prevalent CVD. These results suggest that mid- to late-life HRV may be an early predictor of future cognitive ability.

Objective To explore characteristics of heart rate variability (HRV) in children with Kawasaki disease. Methods From October 2012 to August 2014, a total of 120 children with Kawasaki disease were selected into this study (Kawasaki disease group). According to whether complicated with coronary artery expansion or not, Kawasaki disease group were further divided into coronary artery expansion sub-group (CAL sub-group, n=46) and no coronary artery expansion sub-group (NCAL sub-group, n=74). Meanwhile, another 57 children received health examination were selected into control group in this study randomly. The HRV time domain and frequency domain over 24 hours were performed in Kawasaki disease group and control group. HRV time domain measures included standard deviation of N-N intervals(SDNN), standard deviation of all mean 5-minute N-N intervals(SDANN), standard deviation of all N-N intervals for all 5-minute segments of 24 hours(SDNN index), root mean squared successive diference(rMSSD), percent of N-N 50 in the total number N-N intervals(PNN50). HRV frequency domain measures included very low frequency(VLF), low frequency(LF), high frequency(HF), and LF/HF. There were no significant differences between two groups in general clinical data, such as gender constituent ratio, age. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Chengdu Women's & Children's Central Hospital. Informed consent was obtained from the parents of each participating child. Results The levels of SDNN, SDNN index, rMSSD and PNN50 of HRV in Kawasaki disease group were significantly lower than those in control group (t=5.82, 2.20, 4.81, 3.64; P<0.05), but there were no significant difference between two groups in the level of SDANN(t=1.92, P=0.085). The levels of VLF, LF, and HF of HRV in Kawasaki disease group were significantly lower than those in control group (t=2.50, 4.50, 2.85; P<0.05), and the level of LF/HF in Kawasaki disease was significantly higher than that in control group (t=2.14, P=0.041). Compare with NCAL sub-group, the levels of SDNN, SDANN, PNN50, and LF decreased progressively in CAL sub-group, and there were significant differences (t=3.38, 2.46, 2.15, 7.92; P<0.05). Conclusions Cardiovascular autonomic nervous functional lesion could be found in children with Kawasaki disease. HRV has a certain value to predict the development and prognosis of children with Kawasaki disease. Key words: Mucocutaneous lymph node syndrome; Heart rate variability; Child