Depressed Heart Rate Variability Research Articles

The association between perceived social functioning and heart rate variability is mediated by subclinical depressive symptomatology and moderated by gender.

Chronic loneliness and low perceived social support have been recognized as risk factors for both mental and cardiovascular disorders. It has been proposed that their link to psychophysiological problems may involve changes in parasympathetic activity. However, the exact underlying psychopathological mechanisms and the moderating effects of gender are still not thoroughly examined. Thus, the present study investigated associations between perceived social functioning and resting vagal tone in the context of potential cognitive and subclinical mediators and gender differences. Three hundred twenty-five young adults (aged 18-35, 180 women) underwent an electrocardiogram measurement of 6-minute resting heart rate variability (HRV). They also completed questionnaires assessing loneliness, perceived social support, social cognitive biases, depressive and social anxiety symptoms, and general mental health. In men, HRV was significantly and negatively associated with poorer perceived social functioning, depressive symptoms, and self-reported social cognitive biases, while in women, there was a quadratic link between HRV and depressive symptoms and HRV and general mental health. Moderated mediation analysis revealed that depressive symptoms fully mediated the relationship between perceived social functioning and HRV in men. The results suggest that decreased resting vagal tone in lonely individuals is linked to depressive symptomatology rather than to specific social cognitive biases and that this association is significant only in men.

Autonomic Rebound Following Maximal Exercise in Bodybuilders and Recreationally Active Participants.

The off-season for natural bodybuilders (BB) is characterized by increased training loads and fluctuations in caloric intake, which may lead to insufficient recovery. The autonomic nervous system (ANS) plays a pivotal role in recovery. The purpose of this study was to evaluate resting ANS activity and recovery following a maximal exercise bout in off-season BB and compare them to those of recreationally active individuals. Fifteen males participated; 7 recreationally active (RA) (24.6 ± 2.1 years, 81.1 ± 10.8 kg) and 8 BB (21.8 ± 2.9 years, 89.3 ± 13.0 kg). Each performed a graded exercise test. Heart rate variability (HRV) was measured at rest and during a 45 min recovery period. HRV was analyzed as: root mean square of successive differences (lnRMSSD), standard deviation of normal-to-normal sinus beats (lnSDNN), high frequency (lnHF), low frequency (lnLF), and the ratio of low frequency to high frequency (lnLF/lnHF). A one-way ANOVA showed no differences for any resting marker of HRV, HR, and HR recovery. A significant depression in all markers of HRV was observed in the BB group at the 15 min point, and no recovery was observed before 45 min when compared to RA. The results of this study demonstrated depressed HRV recovery following the graded exercise test in BB when compared to the RA group.

Tracking Cancer: Exploring Heart Rate Variability Patterns by Cancer Location and Progression.

Reduced heart rate variability (HRV) is an autonomic nervous system (ANS) response that may indicate dysfunction in the human body. Consistent evidence shows cancer patients elicit lower HRV; however, only select cancer locations were previously evaluated. Thus, the aim of the current study was to explore HRV patterns in patients diagnosed with and in varying stages of the most prevalent cancers. At a single tertiary academic medical center, 798 patients were recruited. HRV was measured via an armband monitor (Warfighter MonitorTM, Tiger Tech Solutions, Inc., Miami, FL, USA) equipped with electrocardiographic capabilities and was recorded for 5 to 7 min with patients seated in an upright position. Three time-domain metrics were calculated: SDNN (standard deviation of the NN interval), rMSSD (the root mean square of successive differences of NN intervals), and the percentage of time in which the change in successive NN intervals exceeds 50ms within a measurement (pNN50). Of the 798 patients, 399 were diagnosed with cancer. Cancer diagnoses were obtained via medical records one week following the measurement. Analysis of variance models were performed comparing the HRV patterns between different cancers, cancer stages (I-IV), and demographic strata. A total of 85% of the cancer patients had breast, gastrointestinal, genitourinary, or respiratory cancer. The cancer patients were compared to a control non-cancer patient population with similar patient size and distributions for sex, age, body mass index, and co-morbidities. For all HRV metrics, non-cancer patients exhibited significantly higher rMSSDs (11.1 to 13.9 ms, p < 0.0001), SDNNs (22.8 to 27.7 ms, p < 0.0001), and pNN50s (6.2 to 8.1%, p < 0.0001) compared to stage I or II cancer patients. This significant trend was consistently observed across each cancer location. Similarly, compared to patients with stage III or IV cancer, non-cancer patients possessed lower HRs (-11.8 to -14.0 bpm, p < 0.0001) and higher rMSSDs (+31.7 to +32.8 ms, p < 0.0001), SDNNs (+45.2 to +45.8 ms), p < 0.0001, and pNN50s (19.2 to 21.6%, p < 0.0001). The HR and HRV patterns observed did not significantly differ between cancer locations (p = 0.96 to 1.00). The depressed HRVs observed uniformly across the most prevalent cancer locations and stages appeared to occur independent of patients' co-morbidities. This finding highlights the potentially effective use of HRV as a non-invasive tool for determining common cancer locations and their respective stages. More studies are needed to delineate the HRV patterns across different ages, between sexes and race/ethnic groups.

Cardiac autonomic function is preserved in young adults with major depressive disorder.

The prevalence of major depressive disorder (MDD) is highest in young adults and contributes to an increased risk of developing future cardiovascular disease (CVD). However, the underlying mechanisms remain unclear. The studies examining cardiac autonomic function that have included young unmedicated adults with MDD report equivocal findings, and few have considered the potential influence of disease severity or duration. We hypothesized that heart rate variability (HRV) and cardiac baroreflex sensitivity (BRS) would be reduced in young unmedicated adults with MDD (18-30 yr old) compared with healthy nondepressed young adults (HA). We further hypothesized that greater symptom severity would be related to poorer cardiac autonomic function in young adults with MDD. Heart rate and beat-to-beat blood pressure were continuously recorded during 10 min of supine rest to assess HRV and cardiac BRS in 28 HA (17 female, 22 ± 3 yr old) and 37 adults with MDD experiencing current symptoms of mild-to-moderate severity (unmedicated; 28 female, 20 ± 3 yr old). Neither HRV [root mean square of successive differences between normal heartbeats (RMSSD): 63 ± 34 HA vs. 79 ± 36 ms MDD; P = 0.14] nor cardiac BRS (overall gain, 21 ± 10 HA vs. 23 ± 7 ms/mmHg MDD; P = 0.59) were different between groups. In young adults with MDD, there was no association between current depressive symptom severity and either HRV (RMSSD, R2 = 0.004, P = 0.73) or cardiac BRS (overall gain, R2 = 0.02, P = 0.85). Taken together, these data suggest that cardiac autonomic dysfunction may not contribute to elevated cardiovascular risk factor profiles in young unmedicated adults with MDD of mild-to-moderate severity.NEW & NOTEWORTHY This study investigated cardiac autonomic function in young unmedicated adults with major depressive disorder (MDD). The results demonstrated that both heart rate variability and cardiac baroreflex sensitivity were preserved in young unmedicated adults with MDD compared with healthy nondepressed young adults. Furthermore, in young adults with MDD, current depressive symptom severity was not associated with any indices of cardiac autonomic function.

Exercise-induced neuroplasticity in autonomic nuclei restores the cardiac vagal tone and baroreflex dysfunction in aged hypertensive rats.

Aging is accompanied by considerable deterioration of homeostatic systems, such as autonomic imbalance characterized by heightened sympathetic activity, lower parasympathetic tone, and depressed heart rate (HR) variability, which are aggravated by hypertension. Here, we hypothesized that these age-related deficits in aged hypertensive rats can be ameliorated by exercise training, with benefits to the cardiovascular system. Therefore, male 22-mo-old spontaneously hypertensive rats (SHRs) and age-matched Wistar Kyoto (WKY) submitted to moderate-intensity exercise training (T) or kept sedentary (S) for 8 wk were evaluated for hemodynamic/autonomic parameters, baroreflex sensitivity, cardiac sympathetic/parasympathetic tone and analysis of dopamine β-hydroxylase (DBH+) and oxytocin (OT+) pathways of autonomic brain nuclei. Aged SHR-S versus WKY-S exhibited elevated mean arterial pressure (MAP: +51%) and HR (+20%), augmented pressure/HR variability, no cardiac vagal tone, and depressed reflex control of the heart (HR range, -28%; gain, -49%). SHR-T exhibited a lower resting HR, a partial reduction in the MAP (-14%), in the pressure/HR variabilities, and restored parasympathetic modulation, with improvement of baroreceptor reflex control when compared with SHR-S. Exercise training increased the ascending DBH+ projections conveying peripheral information to the paraventricular nucleus of hypothalamus (PVN), augmented the expression of OT+ neurons, and reduced the density of DBH+ neurons in the rostral ventrolateral medulla (RVLM) of SHR-T. Data indicate that exercise training induces beneficial neuroplasticity in brain autonomic circuitry, and it is highly effective to restore the parasympathetic tone, and attenuation of age-related autonomic imbalance and baroreflex dysfunction, thus conferring long-term benefits for cardiovascular control in aged hypertensive individuals.NEW & NOTEWORTHY Exercise training reduces high blood pressure and cardiovascular autonomic modulation in aged hypertensive rats. The dysfunction in the baroreflex sensitivity and impaired parasympathetic tone to the heart of aged hypertensive rats are restored by exercise training. Exercise induces beneficial neuroplasticity in the brain nuclei involved with autonomic control of cardiovascular function of aged hypertensive rats.

Association between depressive symptoms and heart rate variability in older patients admitted for rehabilitation: a cross-sectional study

Heart rate variability (HRV) is associated with depressive symptoms, but this relationship in older inpatients undergoing rehabilitation remains unclear. This study investigated the relationship between HRV and depressive symptoms in older inpatients undergoing rehabilitation. Fifty patients aged ≥65 years were assessed for depressive symptoms using the Geriatric Depression Scale. HRV was assessed by frequency analysis. The relationship between depressive symptoms and HRV indices, age, sex, Short Physical Performance Battery (SPPB) score, Mini-Mental State Examination score was examined using simple linear regression. Next, the predictors from the simple linear regression analysis significant at the 0.15 level were inputted in a multiple regression model. Multiple regression analysis revealed that very low frequency HRV [β = −2.13, 95% confidence interval (CI) −3.15 to −1.11, P &lt; 0.05] and SPPB score (β = −0.30, 95% CI −0.52 to −0.08, P &lt; 0.05) were negatively associated with depressive symptoms: the lower the HRV and the more severe the mobility impairment, the higher the severity of the depressive symptoms. Very low frequency (VLF) HRV and physical performance, as measured by the SPPB score, were associated with depressive symptoms in older patients undergoing rehabilitation. VLF HRV may serve as a useful biomarker for detecting depressive symptoms in this population.

When Heart Beats Differently in Depression: Review of Nonlinear Heart Rate Variability Measures

Disturbed heart dynamics in depression seriously increases mortality risk. Heart rate variability (HRV) is a rich source of information for studying this dynamics. This paper is a meta-analytic review with methodological commentary of the application of nonlinear analysis of HRV and its possibility to address cardiovascular diseases in depression. This paper aimed to appeal for the introduction of cardiological screening to patients with depression, because it is still far from established practice. The other (main) objective of the paper was to show that nonlinear methods in HRV analysis give better results than standard ones. We systematically searched on the web for papers on nonlinear analyses of HRV in depression, in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 framework recommendations. We scrutinized the chosen publications and performed random-effects meta-analysis, using the esci module in jamovi software where standardized effect sizes (ESs) are corrected to yield the proof of the practical utility of their results. In all, 26 publications on the connection of nonlinear HRV measures and depression meeting our inclusion criteria were selected, examining a total of 1537 patients diagnosed with depression and 1041 healthy controls (N=2578). The overall ES (unbiased) was 1.03 (95% CI 0.703-1.35; diamond ratio 3.60). We performed 3 more meta-analytic comparisons, demonstrating the overall effectiveness of 3 groups of nonlinear analysis: detrended fluctuation analysis (overall ES 0.364, 95% CI 0.237-0.491), entropy-based measures (overall ES 1.05, 95% CI 0.572-1.52), and all other nonlinear measures (overall ES 0.702, 95% CI 0.422-0.982). The effectiveness of the applied methods of electrocardiogram analysis was compared and discussed in the light of detection and prevention of depression-related cardiovascular risk. We compared the ESs of nonlinear and conventional time and spectral methods (found in the literature) and demonstrated that those of the former are larger, which recommends their use for the early screening of cardiovascular abnormalities in patients with depression to prevent possible deleterious events.

Depressive rumination and heart rate variability: A pilot study on the effect of biofeedback on rumination and its physiological concomitants.

ObjectiveRecent studies suggest that lower resting heart rate variability (HRV) is associated with elevated vulnerability to depressive rumination. In this study, we tested whether increases in HRV after HRV-biofeedback training are accompanied by reductions in rumination levels.Materials and methodsSixteen patients suffering from depression completed a 6-week HRV-biofeedback training and fourteen patients completed a control condition in which there was no intervention (waitlist). The training included five sessions per week at home using a smartphone application and an ECG belt. Depressive symptoms and autonomic function at rest and during induced rumination were assessed before and after each of the two conditions. We used a well-established rumination induction task to provoke a state of pervasive rumination while recording various physiological signals simultaneously. Changes in HRV, respiration rate, skin conductance, and pupil diameter were compared between conditions and time points.ResultsA significant correlation was found between resting HRV and rumination levels, both assessed at the first laboratory session (r = -0.43, p < 0.05). Induction of rumination led to an acceleration of heart rate and skin conductance increases. After biofeedback training, resting vagal HRV was increased (p < 0.01) and self-ratings of state anxiety (p < 0.05), rumination (p < 0.05), perceived stress (p < 0.05), and depressive symptoms (QIDS, BDI; both p < 0.05) were decreased. In the control condition, there were no changes in autonomic indices or depressive symptomatology. A significant interaction effect group x time on HRV was observed.ConclusionOur results indicate that a smartphone-based HRV-biofeedback intervention can be applied to improve cardiovagal function and to reduce depressive symptoms including self-rated rumination tendencies.

Early indicators of vulnerability to depression: The role of rumination and heart rate variability

BackgroundDespite the evidence of increased levels of rumination and reduced heart rate variability (HRV) in depression, whether these measures can be considered early indicators of vulnerability to depression has yet to be investigated. Therefore, the present study aimed to investigate both levels of rumination and resting HRV in individuals with familial risk for depression that is the most reliable risk factor for the disorder. MethodsRumination and vagally-mediated HRV were assessed using the Ruminative Response Scale and a smartphone-based photoelectric volumetric pulse wave assay, respectively, in 25 individuals who had family history of depression (but did not report current depressive symptoms), 15 individuals who reported depressive symptoms (but had no family history of depression), and 25 controls (without depressive symptoms and family history of depression). Results: Individuals with depressive symptoms and those with a family history of depression were characterized by higher levels of rumination and lower cardiac vagal control than controls. LimitationsGiven the small sample size, this study should be used to design larger confirmatory studies; the cross-sectional nature of the study does not allow discussing the results in terms of cause-effect relationships. ConclusionsOur findings suggested that individuals at risk of developing depression, also in absence of depressive symptoms, are defined by defective self-regulation capacity that may lead to future depression episodes. Increased ruminative thoughts and reduced HRV may represent early indicators of vulnerability to depression. Effective prevention programs designed to reduce rumination and/or increase HRV may reduce the risk of developing a full-blown depressive episode.

Heart rate dynamics in the prediction of coronary artery disease and myocardial infarction using artificial neural network and support vector machine.

Atherosclerosis leads to coronary artery disease (CAD) and myocardial infarction (MI), a major cause of morbidity and mortality worldwide. The computer-aided prognosis of atherosclerotic events with the electrocardiogram (ECG) derived heart rate variability (HRV) can be a robust method in the prognosis of atherosclerosis events. A total of 70 male subjects aged 55 ± 5 years participated in the study. The lead-II ECG was recorded and sampled at 200 Hz. The tachogram was obtained from the ECG signal and used to extract twenty-five HRV features. The one-way Analysis of variance (ANOVA) test was performed to find the significant differences between the CAD, MI, and control subjects. Features were used in the training and testing of a two-class artificial neural network (ANN) and support vector machine (SVM). The obtained results revealed depressed HRV under atherosclerosis. Accuracy of 100% was obtained in classifying CAD and MI subjects from the controls using ANN. Accuracy was 99.6% with SVM, and in the classification of CAD from MI subjects using SVM and ANN, 99.3% and 99.0% accuracy was obtained respectively. Depressed HRV has been suggested to be a marker in the identification of atherosclerotic events. The good accuracy observed in classification between control, CAD, and MI subjects, revealed it to be a non-invasive cost-effective approach in the prognosis of atherosclerotic events.

Self-Compassion and Its Association With Ruminative Tendencies and Vagally Mediated Heart Rate Variability in Recurrent Major Depression.

BackgroundRecurrent Major Depressive Disorder (MDD) is one of the most disabling mental disorders in modern society. Prior research has shown that self-compassion protects against ruminative tendencies, a key feature of recurrent MDD. In addition, self-compassion has been found to be positively related to higher psychophysiological flexibility (indexed by a higher vagally mediated heart rate variability; vmHRV) in young, healthy adults. To our knowledge, there is a lack of studies on how self-compassion relates to vmHRV in patients with recurrent MDD. The aim of the current study was to investigate whether higher self-compassion would associate with (1) lower ruminative tendencies and (2) higher vmHRV in a sample of adults with recurrent MDD.MethodsWe included a sample of 63 patients (46 females) between 20 and 71 years old (M = 40.24, SD = 12.8) with a history of three or more depressive episodes. They filled out the Self-Compassion Scale (SCS), Beck Depression Inventory (BDI), and Rumination Rating Scale (RRS). ECG (used to derive vmHRV) was acquired while resting and the square root of the mean squared differences of successive RR interval values (RMSSD) was calculated as measure of vmHRV.ResultsAs hypothesized, self-compassion was associated with lower ruminative tendencies. However, self-compassion was not associated with level of vmHRV. Several confounding variables were controlled for in the statistical analyses, and higher age predicted lower vmHRV across all statistical analyses.ConclusionThe results confirmed our hypothesis that higher self-compassion would be associated with lower ruminative tendencies in recurrent MDD. Contrary to our expectation, we did not find that the tendency to be more self-compassionate was associated with higher vmHRV. As such, higher self-compassion seems to relate with a lower tendency to ruminate about past mistakes and events but does not seem to relate to a flexible autonomic stress response (as indexed by higher vmHRV). Other potential explanatory factors for lower vmHRV in recurrent MDD is suggested as focus for exploration in future studies.

Association between depressive symptoms and long-term heart rate variability in older women: Findings from a population-based cohort

IntroductionCross-sectional studies highlighted changes in autonomic nervous system (ANS) activity in geriatric depression. However, few longitudinal studies assessed this link which remains still debated. We examined the longitudinal association between lifetime depression history, current depressive disorders, and the evolution of ANS activity in older community women. MethodsThe present data stemmed from the PROOF study, a population-based cohort of 1011 community-dwellers followed-up at 2-year intervals for 10 years. Only data from female participants was analyzed (n = 508, mean age 68.5 ± 0.88 years), as very few men had depression in our population. Depressive symptoms and depression history were collected at baseline. Participants were classified in four groups according to presence or absence of history of depression (HD) or current depressive symptomatology (CD): HD+/CD+, HD−/CD+, HD+/CD− and HD−/CD−. ANS activity was assessed during the follow-up through 24-h heart rate variability (HRV). Longitudinal associations between depressive status and HRV indices during the follow-up were investigated using multivariate linear mixed models. ResultsCompared to HD−/CD− group, women belonging to HD−/CD+ group had greater baseline parasympathetic tone, as measured by lower LF index and LF/HF balance. The longitudinal analysis exhibited a significant enhancement of LF/HF balance with time, measuring an increase of sympathetic tone in HD−/CD+ group. ConclusionOur findings suggest that late-onset depressive symptoms may be associated with subsequent autonomic dysregulation in older women. These results highlight the importance of detecting and managing depressive symptoms to limit their consequences on ANS functioning, and the risk of cardiovascular events.

Using 24-h Heart Rate Variability to Investigate the Sleep Quality and Depression Symptoms of Medical Students.

There have been numerous studies on the relationship between sleep and depression, as well as the relationship between sleep and depression, and heart rate variability (HRV), respectively. Even so, few studies have combined 24-h HRV analysis to study sleep quality and depressive symptoms. The purpose of this cross-sectional study was to investigate the relationship between depressed symptoms, sleep quality, and 24-h HRV in medical students. The particiants were all students at a medical university in Guangdong province, China. A total of 74 college students participated. They were asked to complete a questionnaire that included the Pittsburgh Sleep Quality Index (PSQI), the Beck Depression Inventory-II (BDI-II), the Positive and Negative Affect Scale (PANAS), and 24-h ECG monitoring. The results showed that 41.7% of the medical students had poor sleep quality, with higher levels of depressive symptoms and more negative emotions, and there was no difference in 24-h HRV indices between the low PSQI group and the high one. Correlation analysis showed that there was a significant relationship between sleep quality and depressive symptoms (r = 0.617), but the relationship between 24-h HRV indices and PSQI global scores, BDI scores were not significant. However, the correlation analysis of PSQI components and 24-h HRV showed that sleep disturbance was significantly negatively correlated with SDNN and LF in waking period (r = −0.285, −0.235), and with SDNN in sleeping period (r = −0.317). In general, the sleep disturbance in PSQI components can sensitively reflect the relationship between sleep quality and 24-h HRV of medical students. Individuals with higher sleep disturance may have lower SDNN during awake period and bedtime period, and lower LF in awake period. Twenty-four hour HRV has certain application value in clinical sleep quality monitoring, and its sensitivity and specificity in clinical application and daily life are still worth further investigation.

Social affiliation moderates the link between depressive symptoms and heart rate variability in healthy middle‐aged and older individuals: An intensive ecologic momentary assessment study

Depressive symptoms have been associated with lower cardiac autonomic control, thus contributing to cardiovascular diseases, especially among older adults. Interpersonal factors have been found to attenuate physiologic stress responses, but little is known about whether these factors (e.g., perceived affiliation) would moderate the relation of depressive symptoms and cardiovascular activation. The present research aimed to investigate the interplay of depressive symptoms and momentary-assessed interpersonal perceptions on cardiac vagal tone as indexed by heart rate variability (HRV). The sample consisted of 78 late middle-aged and older community-dwelling participants (48.7% male, mean age = 59.15years). Participants reported on depressive symptoms and other personal characteristics by questionnaire. Perceptions of interpersonal affiliation, ambulatory HRV, and contextual variables were recorded using ecologic momentary assessment and portable electrocardiogram (ECG) monitoring device throughout 1week (with a maximum of seven times daily). Multilevel analyses found that depressive symptoms were correlated with lower HRV, whereas momentary interpersonal perceptions of higher affiliation were associated with elevated HRV. A significant association was revealed between depressive symptoms and momentary affiliation perceptions on HRV. When individuals were involved in social interactions with higher affiliation, the effect of depressive symptoms on reducing HRV was attenuated. These findings suggested that the effects of subthreshold depressive symptoms on vagal control of the heart could be altered by the quality of interpersonal experiences.

Inhibition of myeloid differentiation factor 2 by MAC28 suppresses reactive oxygen species, inflammation and improves mitochondrial function, leading to improved cardiac function in prediabetic rats

Abstract Background Chronic inflammation involves in the left ventricular (LV) dysfunction in high-fat diet (HFD)-induced prediabetes, along with cardiac mitochondrial dysfunction. This involved an activation of myeloid differentiation factor 2 (MD2)/toll-like receptor 4 (TLR4) by lipopolysaccharide, leading to inflammatory cytokines production in the heart. MAC28 is a novel MD2 inhibitor, which had been shown to provide effects against LPS-induced cytokine secretion from macrophages. However, the potential benefits of MAC28 on the LV function and its underlying mechanisms in HFD-induced prediabetic rats are unknown. Purpose We tested the hypothesis that MAC28 improves LV function in prediabetic rats by reducing cardiac oxidative stress, inflammation, and cardiac mitochondrial dysfunction. Methods Male Wistar rats were fed either a normal diet (ND, n=8) or HFD (n=24) for 16 weeks. At week 12, HFD-fed rats developed prediabetes and LV dysfunction. At this time, these HFD-fed rats were divided into 3 treatment groups (n=8/group): 1) vehicle (HFDV; 1% Na-carboxymethyl cellulose; p.o.); 2) MAC28 (40 mg/kg; p.o.); 3) metformin (300 mg/kg; p.o.; a positive control), the ND-fed rats received a vehicle (NDV). Rats were received their treatment for 4 weeks. Then, LV function and heart rate variability (HRV) were examined, and the heart was removed to determinecardiac malondialdehyde (MDA), cardiac inflammation (TNF-α) and mitochondrial function. Results HFD-induced prediabetes, together with depressed HRV and %LV ejection fraction (LVEF) (Fig. 1A). Moreover, cardiac oxidative stress and inflammation overproduction, and cardiac mitochondrial dysfunction was also observed, shown by elevated cardiac MDA, cardiac TNF-α protein levels, and mitochondrial ROS levels, mitochondrial depolarization and swelling (Fig. 1B). Notably, treatment with MAC28 effectively improved HRV and %LVEF and HRV (Fig. 1A), compared to HFDV group. Moreover, MAC28 significantly reduced cardiac MDA levels, cardiac TNF-α protein levels and cardiac mitochondrial dysfunction in HFD-induced prediabetic rats (Fig. 1B). These beneficial effects were also observed in metformin-treated rats (Fig. 1A, B). Conclusion MAC28 exerts cardioprotection in prediabetic rats by reducing cardiac oxidative stress, inflammation, and mitochondrial dysfunction, leading to restoring LV function. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the Thailand Science Research and Innovation

Predicting efficacy of combined assessment with fragmented QRS and severely depressed heart rate variability on outcome of patients with acute myocardial infarction

The association between fragmented QRS (fQRS) and autonomic nervous dysfunction, and major adverse cardiovascular events (MACE) is not fully clear in patients with acute myocardial infarction (AMI). This study aimed to observe whether combined assessment with fQRS and cardiac autonomic nervous function could enhance the predicting efficacy on outcome in AMI patients. A total of 153 consecutive hospitalized AMI patients were included in this retrospective study. Patients were divided into non-fQRS (nfQRS) group and fQRS group according to 12-lead electrocardiogram, into sHRV [severely depressed heart rate variability (HRV): standard deviation of NN intervals (SDNN) < 100 ms and very low frequency (VLF) < 26.7 ms] group and nsHRV (non-severely depressed HRV) group according to 24 h Holter monitoring, and into non-MACE (nMACE) group and MACE group according to 12 months’ follow-up results. The incidence of sHRV was significantly higher in the fQRS group than in the nfQRS group (71.9 vs. 39.3%, p < 0.05). The incidences of MACE were 7.4, 22.2, 25.7 and 56.5%, respectively, in nsHRV + nfQRS group, nsHRV + fQRS group, sHRV + nfQRS group and sHRV + fQRS group (p < 0.05). Multivariable Cox regression analysis showed that patients in the sHRV + fQRS group had a sixfold higher risk of MACE compared to patients in the nsHRV + nfQRS group (HR = 6.228, 95% CI 1.849–20.984, p = 0.003). The predicting sensitivity and specificity on MACE were 81.4 and 58.2% by sHRV, 69.8 and 69.1% by fQRS in these AMI patients. The specificity (81.8%) was the highest with the combination of sHRV and fQRS. Adding sHRV and fQRS to clinical data offered incremental prognostic value. Present results indicate that fQRS is closely related to sHRV, suggesting significant impairment of sympathetic nerve function in AMI patients with fQRS. Combined assessment with fQRS and sHRV enhances the predicting efficacy on outcome in AMI patients.

Describing heart rate variability in patients with chronic atrial fibrillation during hospitalization for COVID-19.

IntroductionMyriad cardiovascular manifestations have been reported with COVID‐19. We previously reported that failure of PR interval shortening with increasing heart rate (HR) in patients with COVID‐19 is associated with adverse outcomes. Here, we report on heart rate variability (HRV) and clinical outcomes in patients with chronic atrial fibrillation (cAF) hospitalized for COVID‐19.MethodsA retrospective review of admitted COVID‐19 patients with cAF between 1 March 2020 to 30 June 2020 was performed. HRV in cAF was compared during pre‐COVID‐19 and COVID‐19 admissions; we selected pre‐COVID‐19 ECGs with HRs that were within 10 beats per minute of the COVID‐19 ECGs. Mean HR and each RR interval were recorded. Time‐domain measurements of HR variability were then calculated (SDSD, RMSSD, pNN50). Clinical outcomes during COVID‐19 were correlated to indices of HRV.ResultsA total of 184 ECGs (95 pre‐COVID‐19, 89 COVID‐19) from 38 cAF in‐patients were included. Mean age 78.6 ± 11.4 years, male 44.7%. The mean number of ECGs analyzed per patient pre‐COVID‐19 was 2.50 and during COVID‐19 was 2.34. Comparing pre‐COVID‐19 versus COVID‐19 ECGs showed: mean HR (95.9 ± 24.3 vs. 101.6 ± 22.8 BPM; P = .10), SDSD (109.0 ± 50.6 vs. 90.3 ± 37.2 ms; P < .01), RMSSD (184.1 ± 80.4 vs. 147.3 ± 59.8 ms; P < .01), pNN50 (73.8 ± 16.3 vs. 65.6 ± 16.6%; P < .01). Patients who had a smaller pNN50 during a COVID‐19 admission had increased mortality (50.0% vs. 14.3%; log‐rank test P = .02).ConclusionIn patients with cAF, the HRV was reduced during COVID‐19 compared with prior illnesses at similar average heart rates. Patients with the most depressed HRV as measured by pNN50 had an associated increase in mortality compared with patients whose HRV was preserved.

Abstract 14712: Cardiometabolic Differences Between Male and Female Obese-insulin Resistant Rats Following Sex Hormone Deprivation

Introduction: Male gender and menopause increase the risk for cardiovascular incidence. However, less is known about gender differences in cardiometabolic disorders, particularly under obese-insulin resistant and sex hormone-deprived conditions. Hypothesis: Male have worse cardiometabolic disorders than female under obese-insulin resistant and sex hormone-deprived conditions. Methods: Adult Wistar rats of both sexes (n=20) were randomly assigned into four groups (n = 5/group): male normal diet sham (M-NDS), male high fat-diet with orchiectomy (M-HFO), female normal diet sham (F-NDS) and female high fat-diet with ovariectomy (F-HFO). Rats were fed either a normal diet (19.77% of energy fat) or a high-fat diet (57.60% of energy fat) for 12 weeks following the induction of sex hormone deprivation by either bilateral orchiectomy or ovariectomy. Temporal determinations of metabolic parameters, heart rate variability (HRV), left ventricular (LV) function, and cardiac mitochondrial function at 4, 8, and 12 weeks were done after starting each feeding program. Results: Insulin resistance was initially observed after 8 weeks of high-fat diet consumption in both M-HFO and F-HFO groups. In addition, M-HFO had depressed HRV, impaired LV performance indicated by decreased ejection fraction (%EF) and cardiac mitochondrial dysfunction indicated by increased mitochondrial ROS level, depolarization and swelling, as early as week 4, whereas F-HFO exhibited them at week 8 or 12. Moreover, at week 12, M-HFO have worse cardiometabolic disorders than F-HFO, particularly %EF and HRV. Conclusions: Under sex hormone-deprived condition, male are generally more susceptible to cardiometabolic disorders and cardiac mitochondrial dysfunction, especially in the presence of obese-insulin resistant condition.

Abstract 15180: Myeloid Differentiation Factor 2 Inhibitor Improves Left Ventricular Function And Heart Rate Variability Via Attenuating Cardiac Mitochondrial Dysfunction In Pre-diabetic Rats

Introduction: Systemic inflammation is known as a key mediator of left ventricular (LV) dysfunction in pre-diabetic models including obese-insulin resistance. In obese rats, lipopolysaccharide activates myeloid differentiation factor 2 (MD2)/toll-like receptor 4 complex, leading to systemic inflammation. Previously, MD2 inhibitor L6H21 (20 mg/kg) was shown to effectively reduce systemic inflammation in obese mice. However, its potential benefits on the heart and the underlying mechanisms in pre-diabetic obese-insulin resistant rats are unknown. Hypothesis: L6H21 exerts cardiometabolic protection in pre-diabetic rats by improving LV function and heart rate variability (HRV) via reducing cardiac mitochondrial dysfunction. Methods: Male Wistar rats were fed either a normal diet (n=8) or high-fat diet (HFD, n=40) for 12 weeks. In HFD group, rats were divided into 5 groups (n=8/group): 1) vehicle (1% Na-carboxymethyl cellulose), 2) metformin (300 mg/kg, positive control), 3-5) L6H21 at 10, 20, and 40 mg/kg. After 4 weeks of treatments, LV function and HRV were examined. Heart tissue was assessed for mitochondrial function. Results: Pre-diabetic rats had impaired glucose tolerance, depressed HRV, and decreased LV ejection fraction (LVEF), indicating cardiac autonomic imbalance and LV dysfunction. Cardiac mitochondrial dysfunction was also observed, shown by increased mitochondrial ROS levels, mitochondrial depolarization, and mitochondrial swelling. Although L6H21 at 20 and 40 mg/kg improved insulin sensitivity, cardiac autonomic balance, LV function, and mitochondrial function, L6H21 at 40 mg/kg exerted the highest cardioprotective effects, compared to metformin, in pre-diabetic rats by restoring LV function, HRV, and cardiac mitochondrial function (Fig) . Conclusions: L6H21 exerted cardiometabolic protection in pre-diabetic rats by improving insulin sensitivity and cardiac mitochondrial function, leading to restoring LV function.

Early rehabilitation after stroke: relationship between the heart rate variability and functional outcome.

AimsImpaired autonomic nervous system regulation is frequently observed in patients with stroke. The aim of this prospective study was to evaluate the impact of cardiac autonomic tone on functional outcome after the early post‐stroke rehabilitation.Methods and resultsOne hundred and three consecutive patients (67 ± 11 years, body mass index (BMI) 27.1 ± 5.4 kg/m2, 64% men) with ischaemic (84% of patients) and haemorrhagic stroke were studied. Depressed heart rate variability (HRV), as a surrogate marker of increased sympathetic tone, was defined by the standard deviation of NN intervals < 100 ms and HRV triangular index ≤ 20 assessed from a 24 h Holter electrocardiogram at admission to rehabilitation (23 ± 16 days after stroke). Twenty‐two per cent of patients had depressed HRV at baseline and were comparable with patients with normal HRV with regard to their functional [Barthel Index (BI), modified Rankin Scale (mRS), and Rivermead Motor Assessment (RMA)] and biochemical status. After a 4‐week follow‐up, 70% of patients with depressed HRV showed a cumulative functional disability, defined by mRS ≥ 4, BI ≤ 70, and RMA ≤ 5, in contrast to patients with normal HRV (35%, P = 0.003). Patients with depressed HRV showed a worse functional status by BI (−16%, P < 0.001), RMA (−12%, P < 0.05), and mRS (+16%, P < 0.01), compared with patients with normal HRV. Cumulative functional disability was associated with depressed HRV (odds ratio 4.25, 95% confidence interval 1.56–11.54, P < 0.005) after adjustment for age, sex, and body mass index (odds ratio 4.6, 95% confidence interval 1.42–14.97, P < 0.05).ConclusionsThe presence of autonomic cardiovascular dysregulation in patients with subacute stroke was associated with adverse functional outcome after the early post‐stroke rehabilitation.