Cardiovascular Autonomic Abnormalities Research Articles

Objective Hemodynamic Cardiovascular Autonomic Abnormalities in Post-Acute Sequelae of COVID-19.

Many COVID-19 patients are left with symptoms several months after resolution of the acute illness; this syndrome is known as post-acute sequalae of COVID-19 (PASC). We aimed to determine the prevalence of objective hemodynamic cardiovascular autonomic abnormalities (CAA), explore sex differences, and assess the prevalence of CAA among hospitalized vs nonhospitalized patients with PASC. Patients with PASC (n= 70; female [F]= 56; 42 years of age; 95% confidence interval [CI], 40-48) completed standard autonomic tests, including an active stand test 399 days (338, 455) after their COVID-19 infection. Clinical autonomic abnormalities were evaluated. Most patients with PASC met the criteria for at least 1 CAA (51; 73%; F= 43). The postural orthostatic tachycardia syndrome hemodynamic (POTSHR) criterion of a heart rate increase of > 30 beats per minute within 5 to 10 minutes of standing was seen in 21 patients (30%; F= 20; P= 0.037 [by sex]). The initial orthostatic hypotension hemodynamic (IOH40) criterion of a transient systolic blood pressure change of > 40 mm Hg in the first 15 seconds of standing was seen in 43 (61%) patients and equally among female and male patients (63% vs 57%; P= 0.7). Only 9 (13%) patients were hospitalized; hospitalized vs nonhospitalized patients had similar frequencies of abnormalities (67% vs 74%; P= 0.7). Patients with PASC have evidence of CAA, most commonly IOH40, which will be missed unless an active stand test is used. Female patients have increased frequency of POTSHR, but IOH40 is equally prevalent between sexes. Finally, even nonhospitalized "mild" infections can result in long-term CAAs.

Coexistence of fibromyalgia syndrome and inflammatory rheumatic diseases, and autonomic cardiovascular system involvement in fibromyalgia syndrome.

The spectrum of symptoms represented by fibromyalgia syndrome (FMS) has a profound effect on daily activities and impairs the quality of life. A considerable proportion of patients with inflammatory rheumatic diseases (IRDs) fulfill the FMS criteria, which can complicate the diagnosis, treatment, and follow-ups of IRD. In addition, the coexistence of FMS may cause unnecessary laboratory and radiological assessments. Several mechanisms have been proposed that may have a role in the etiopathogenesis of FMS, one of which is autonomic dysregulation. In studies evaluating cardiac autonomic dysfunction based on heart rate variability (HRV), there has been found to be a decrease in HRV and dominance of the sympathetic nervous system. Autonomic reactivity reflects modulations of several functions to overcome the existing state and conditions. Blunted autonomic reactivity has been found in some FMS patients, which makes it difficult for these patients to respond appropriately to unexpected stress sources that occur during daily living activities. Baroreceptor signals have an inhibitory influence on the central nervous system, and these impulses cause pain suppression. From this perspective, there are studies that have suggested the involvement of diminished baroreflex sensitivity in the etiology of FMS. The risk of endothelial dysfunction and increased arterial stiffness have been shown to occur in FMS patients due to autonomic dysfunction, sympathetic nervous system dominance, chronic stress, and pain. There is also evidence linking FMS with the risk of atrial and ventricular arrhythmias. Considering all these cardiovascular autonomic dysfunctions, tests that can confirm abnormalities should be performed when suspicion arises. There is a need for specific pharmacological and non-pharmacological treatment alternatives to be identified for subgroups of patients with cardiovascular system abnormalities. Key points • The frequency of FMS accompanying inflammatory rheumatic diseases is considerable and this coexistence leads to troubles in evaluating treatment response and determining appropriate medical treatment options in inflammatory rheumatic diseases. • Various cardiovascular autonomic abnormalities have been described in FMS patients. Among these, the most emphasized are autonomic dysfunction, the disruption of the balance between the sympathetic-parasympathetic nervous systems, blunted autonomic reactivity to acute stress, changes in baroreflex sensitivity, increased arterial stiffness, and electrophysiological alterations. • Autonomic cardiovascular dysfunction may be involved in the complex etiopathogenesis of the fibromyalgia syndrome and may trigger at least some symptoms.

Cardiovascular autonomic dysfunction, altered sleep architecture, and muscle overactivity during nocturnal sleep in pediatric patients with narcolepsy type 1.

Arterial blood pressure (ABP) decreases during sleep compared with wakefulness and this change is blunted in mouse models of and adult patients with narcolepsy type 1 (NT1). We tested whether: (1) pediatric patients with NT1 have similar cardiovascular autonomic abnormalities during nocturnal sleep; and (2) these abnormalities can be linked to hypocretin-1 cerebrospinal fluid concentration (CSF HCRT-1), sleep architecture, or muscle activity. Laboratory polysomnographic studies were performed in 27 consecutive drug-naïve NT1 children or adolescents and in 19 matched controls. Nocturnal sleep architecture and submentalis (SM), tibialis anterior (TA), and hand extensor (HE) electromyographic (EMG) activity were analyzed. Cardiovascular autonomic function was assessed through the analysis of pulse transit time (PTT) and heart period (HP). PTT showed reduced lengthening during total sleep and REM sleep compared with nocturnal wakefulness in NT1 patients than in controls, whereas HP did not. NT1 patients had altered sleep architecture, higher SM EMG during REM sleep, and higher TA and HE EMG during N1-N3 and REM sleep when compared with controls. PTT alterations found in NT1 patients were more severe in subjects with lower CSF HRCT-1, but did not cluster or correlate with sleep architecture alterations or muscle overactivity during sleep. Our results suggest that pediatric NT1 patients close to disease onset have impaired capability to modulate ABP as a function of nocturnal wake-sleep transitions, possibly as a direct consequence of hypocretin neuron loss. The relevance of this finding for cardiovascular risk later in life remains to be determined.

Exercise tolerance in obstructive sleep apnea-hypopnea (OSAH), before and after CPAP treatment: Effects of autonomic dysfunction improvement

BackgroundObstructive sleep apnea hypopnea (OSAH) is associated with decreased exercise tolerance and autonomic abnormalities and represents a risk for cardiovascular diseases. The aim of the study was to evaluate the effects of CPAP on cardiovascular autonomic abnormalities and exercise performance in patients with OSAH without changes in lifestyle and body weight during treatment. MethodsTwelve overweight subjects with OSAH underwent anthropometric measures, autonomic cardiovascular and incremental symptom-limited cardio-respiratory exercise tests before and after two months of treatment with CPAP. ResultsLower frequency component of power spectrum of heart rate variability (59.5±24.2 msec2 vs 43.2±25.9 msec2; p<0.05) and improvements of maximal workload (99.3±13.5 vs 108.3±16.8%pred.; p<0.05) and peak oxygen consumption (95.3±7.6 vs 105.5±7.9%pred.; p<0.05) were observed in these patients after CPAP, being their BMI unchanged. ConclusionsCPAP-induced decrease of sympathetic hyperactivity is associated with better tolerance to the effort in OSAH patients that did not change their BMI and lifestyle, suggesting that OSAH limits per se the exercise capacity.

Association of Resting Heart Rate and Blood Pressure in Late Adolescence With Subsequent Mental Disorders

Differences in cardiovascular autonomic activity between individuals with psychiatric disorders and healthy controls have been observed, but whether cardiovascular autonomic abnormalities are associated with subsequent psychiatric disorders is unknown. To investigate whether differences in cardiac autonomic function as indexed by resting heart rate and blood pressure are associated with psychiatric disorders during the lifetime of men in Sweden. We conducted a longitudinal register-based study of Swedish men whose resting heart rate (n = 1 039 443) and blood pressure (n = 1 555 979) were measured at military conscription at a mean (SD) age of 18.3 (0.6) years during the period from 1969 to 2010, with register-based follow-up data available until the end of 2013. Analyses were performed from November 18, 2015, to June 9, 2016. Dates of inpatient/outpatient diagnoses of anxiety disorders, obsessive-compulsive disorder, posttraumatic stress disorder, depressive disorders, bipolar disorder, schizophrenia, and substance use disorders and convictions for violent crimes, between 1973 and 2013, were obtained from nationwide registers. Adjustments were made for height, weight, body mass index, cardiorespiratory fitness, cognitive ability, and socioeconomic covariates. After adjustment for covariates, Cox regression models with up to 45 years of follow-up data showed that men (mean [SD] age of 18.3 [0.6] years at conscription) with resting heart rates above 82 beats per minute had a 69% (95% CI, 46%-94%) increased risk for obsessive-compulsive disorder, a 21% (95% CI, 11%-33%) increased risk for schizophrenia, and an 18% (95% CI, 13%-22%) increased risk for anxiety disorders compared with men with resting heart rates below 62 beats per minute. Similar associations were observed with systolic/diastolic blood pressure. In contrast, lower resting heart rate and lower systolic blood pressure were associated with substance use disorders and violent criminality. Our results suggest that for men, differences in heart rate and blood pressure in late adolescence are associated with lifetime major psychiatric disorders, with higher levels associated with obsessive-compulsive disorder, schizophrenia, and anxiety disorders and lower levels associated with substance use disorders and violent behavior. Differences in autonomic nervous system functioning may predate or represent an early marker of psychiatric disorders.

Autonomic Nervous System Dysfunction in Patients With Parkinson Disease Having Depression.

Both depression and cardiovascular autonomic dysfunctions, such as orthostatic hypotension, supine hypertension, and the absence of normal nocturnal blood pressure (BP) fall ("nondipping"), occur relatively commonly in Parkinson disease (PD); however, the relationship between depression and cardiovascular autonomic abnormalities has not been established. In this study, we sought to determine whether the cardiovascular autonomic abnormalities found in PD are associated with depression. Among 129 nondemented, levodopa-naive patients with mild PD, 44 had depression. Orthostatic vital signs and ambulatory 24-hour BP monitoring were recorded, and geriatric depressive scales were obtained in all patients. Associations between orthostatic hypotension, supine hypertension, nocturnal hypertension, nondipping, and depression were analyzed. The ratio of the standard deviation of 24-hour heart rate to that of systolic BP (SBP) was utilized as an index of baroreflex-cardiovagal function. Depression was associated with orthostatic hypotension, and patients with depression had higher SBP change during orthostasis and attenuated cardiovagal dysfunction as observed during ambulatory BP monitoring. Across individuals, values for orthostatic changes in BP were correlated with values for geriatric depressive scale. Depression is associated with neurocirculatory abnormalities-especially orthostatic hypotension-in early PD. Although the association does not imply causation, this result suggests that depression in PD might be associated with functional impairment of the autonomic nervous system and its pathologic substrate.

A study of orthostatic hypotension, heart rate variability and baroreflex sensitivity in late-life depression

BackgroundTo determine if subjects with late-life depression have significant cardiovascular autonomic abnormalities (orthostatic blood pressure drop, heart rate variability and baroreflex sensitivity). MethodsA case–control study, in secondary care facilities, of forty two older (>60years) individuals with lifetime history of major depression and 31 age and sex matched comparison subjects. Autonomic function was assessed by measuring postural blood pressure, heart rate variability and baroreflex sensitivity using non-invasive beat-to-beat blood pressure and continuous ECG monitoring (Task Force® Monitor, CNSystems, Graz, Austria). The main outcome measures were maximal reduction in systolic blood pressure with active stand, low frequency and high frequency heart rate variability and baroreflex sensitivity using the sequence method. ResultsParticipants with depression had a significantly larger drop in systolic blood pressure on standing from a supine position. Depression was an independent predictor for developing systolic orthostatic hypotension. Depressed participants also had lower low frequency heart rate variability and lower baroreflex sensitivity. LimitationsThis was a cross-sectional and observational study; longitudinal effects or causality cannot be inferred from the findings and we could not distinguish state from trait related changes. ConclusionsLate-life depression has been associated with vascular disease but previous studies examining vascular risk factors have been inconsistent. Brain MRI white matter hyperintensities are ischemic and increased in late-life depression and associated with orthostatic blood pressure drops in animals. The presence of autonomic abnormalities in late-life depression may partly explain these inconsistencies and be associated with the development of brain white matter hyperintensities.

Interval hypoxic training improves autonomic cardiovascular and respiratory control in patients with mild chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is associated with cardiac autonomic nervous system dysregulation. This study evaluates the effects of interval hypoxic training on cardiovascular and respiratory control in patients with mild COPD. In 18 eucapnic normoxic mild COPD patients (age 51.7 +/- 2.4 years, mean +/- SEM), randomly assigned to either training or placebo group, and 14 age-matched healthy controls (47.7 +/- 2.8 years), we monitored end-tidal carbon dioxide, airway flow, arterial oxygen saturation, electrocardiogram, and continuous noninvasive blood pressure at rest, during progressive hypercapnic hyperoxia and isocapnic hypoxia to compare baroreflex sensitivity to hypoxia and hypercapnia before and after 3 weeks of hypoxic training. In double-blind fashion, both groups received 15 sessions of passive intermittent hypoxia (training group) or normoxia (placebo group). For the hypoxia group, each session consisted of three to five hypoxic (15-12% oxygen) periods (3-5 min) with 3-min normoxic intervals. The placebo group inhaled normoxic air. Before training, COPD patients showed depressed baroreflex sensitivity, as compared with healthy individuals, without evident chemoreflex abnormalities. After training, in contrast to placebo group, the training group showed increased (P < 0.05) baroreflex sensitivity up to normal levels and selectively increased hypercapnic ventilatory response (P < 0.05), without changes in hypoxic ventilatory response. Eucapnic normoxic mild COPD patients already showed signs of cardiovascular autonomic abnormalities at baseline, which normalized with hypoxic training. If confirmed in more severe patients, interval hypoxic training may be a therapeutic strategy to rebalance early autonomic dysfunction in COPD patients.

Autonomic nervous system abnormalities in spinocerebellar ataxia type 2: A cardiovascular neurophysiologic study

Autonomic nervous system dysfunction is part of the spinocerebellar ataxia (SCA) clinical picture, but few data are available on this topic. The present study is aimed to report a detailed investigation of autonomic nervous system in patients with molecular diagnosis of SCA type 2, one of the most frequent forms and the commonest in Italy. Nine patients with a mild to moderate form of SCA2 underwent a questionnaire about dysautonomic symptoms and a complete cardiovascular neurophysiologic evaluation of both sympathetic and parasympathetic system, comprising head-up tilt, standing, isometric hand grip, cold pressure, mental arithmetic, Valsalva manoeuvre, deep breathing, and hyperventilation tests. An echocardiographic study and Holter-ECG recording were also performed. All patients complained dysautonomic problems regarding urinary tract, cardiovascular system, or gastrointestinal dysfunction. The neurophysiologic study showed both sympathetic and parasympathetic involvement, with highly variable degree and pattern of dysautonomia. The present study results show that the autonomic dysfunction is common in SCA2 representing a significant component of the complex picture of the disease. We found a wide spectrum of cardiovascular autonomic abnormalities, without a typical pattern of dysfunction and without correlation with clinical variables.

Impaired baroreflex function in temporal lobe epilepsy

Changes of cardiovascular function are frequent in temporal lobe epilepsy (TLE). The baroreflex - the most important reflex for cardiovascular stability - has not been studied systematically in TLE. We evaluated cardiovascular variability and baroreflex function in TLE. In 22 TLE patients and 20 controls, we continuously monitored heart rate (HR) and blood pressure (BP). Time-domain parameters were derived from recordings at rest and from standard cardiovascular reflex tests. Spectral analysis determined sympathetic and parasympathetic modulation of HR and BP in the low (LF-power) and high frequency range (HF-power). We calculated the relative LF- and HF-powers of HR in relation to the sum of LF- and HF-powers. LF/HF-ratio of HR was assessed as a parameter of sympatheticovagal balance. LF-transfer function gain between BP and HR determined baroreflex function.Time-domain parameters did not differ between TLE patients and controls. Spectral analysis showed decreased absolute LF- and HF-powers but increased relative LF-power and LF/HF-ratio of HR in TLE. LF-transfer function gain between BP and HR was reduced in TLE (p<0.05). The reduction of absolute LF- and HF-powers indicates decreased total autonomic variability in TLE. However, increased relative LF-power and LF/HF-ratio of HR in TLE show a relative increase of sympathetic tone. Most importantly, we demonstrate an impaired baroreflex function in TLE. These cardiovascular autonomic abnormalities may contribute to cardiac arrhythmia in TLE.

Autonomic nervous system function in multiple sclerosis

Autonomic dysfunction causes significant disability in patients with multiple sclerosis (MS). Abnormalities of bladder, bowel and sexual function have been well documented in previous studies but cardiovascular and sudomotor autonomic changes have been less frequently reported. The present study has documented autonomic symptoms and results of cardiovascular and sudomotor autonomic function tests in 63 MS patients and correlated these changes with the clinical features of MS. Autonomic symptoms were common in MS patients, the most common being disorders of micturition, impotence, sudomotor and gastrointestinal disturbances, which were associated with increased MS severity. There was no significant association between autonomic symptoms and abnormalities of autonomic investigations. Abnormalities of one or more autonomic function tests, not including those of bladder, gastrointestinal or sexual dysfunction, were present in more than one half of the MS patients. Autonomic dysfunction, defined as abnormalities in two or more tests, was found in 18% of patients and was associated with increased MS severity. Postural hypotension was very uncommon. Parasympathetic cardiovascular autonomic abnormalities occurred in 16% of patients and were associated with increased MS severity. Sympathetic cardiovascular abnormalities were present in 13% of patients and showed no significant association with MS severity. The sympathetic skin response(SSR) was abnormal in nearly one half of the patients and also showed no significant association with MS severity. There was a variable and heterogenous pattern of autonomic test abnormalities found in the MS patients, which were of minor clinical significance except for postural hypotension. Cardiovascular and sudomotor autonomic abnormalities in MS patients are likely to be due to plaques distributed throughout the brainstem and spinal cord affecting anatomically widespread autonomic regulatory areas and their connections.

Cardiovascular autonomic dysregulation and fatigue in multiple sclerosis.

Both cardiovascular disturbances and fatigue are frequent in multiple sclerosis (MS). We investigated their relationship in 84 MS patients (mean age 39.9 +/- 8.9 years) using five established autonomic tests and three different fatigue questionnaires. 64.2% of the patients were categorised as being fatigued Fatigue perception was weakly related to EDSS. Moderate cardiovascular disturbances were found in 16.6% of the patients, and 10.7% had severe cardiovascular autonomic abnormalities. Cardiovascular dysfunction was slightly related to age and to EDSS. In 19.4% of all patients signs of autonomic failure and fatigue were co-existent Using correlation analysis, we found only weakly significant correlation coefficients between some single autonomic test parameters and fatigue scores, which were confounded by age effects. The analysis of dichotomised data revealed slightly significant differences in fatigue experience between patients with and without abnormalities regarding the handgrip test and the Valsalva reaction. Thus, autonomic disturbances might contribute to fatigue symptoms in a MS subgroup, but the overall influence of the autonomic cardiovascular regulation towards fatigue experience seems to be of minor relevance.