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Determinants of cardiac autonomic dysfunction in ESRD.

ABSTRACT: Cardiovascular events are common in patients with ESRD. Whether sympathetic overactivity or vagal withdrawal contribute to cardiovascular events is unclear. We determined the general prevalence and clinical correlates of heart rate variability in patients on hemodialysis.We collected baseline information on demographics, clinical conditions, laboratory values, medications, physical performance, left ventricular mass (LVM), and 24-hour Holter monitoring on 239 subjects enrolled in the Frequent Hemodialysis Network Daily Trial.The mean R-R interval was 812 ± 217 ms. The SD of R-R intervals was 79.1 ± 40.3 ms. Spectral power analyses showed low-frequency (sympathetic modulation of heart rate) and high-frequency power (HF; vagal modulation of heart rate) to be 106.0 (interquartile range, 48.0 to 204 ms(2)) and 42.4 ms(2) (interquartile range, 29.4 to 56.3 ms(2)), respectively. LVM was inversely correlated with log HF (-0.02 [-0.0035; -0.0043]) and the R-R interval (-1.00 [-1.96; -0.032]). Physical performance was associated with mean R-R intervals (1.98 [0.09; 3.87]) and SD of R-R intervals (0.58 [0.049; 1.10]). After adjustment for age, race, ESRD vintage, diabetes, and physical performance, the relationship between log HF and LVM (per 10 g) remained significant (-0.025 [-0.042; -0.0085]).Holter findings in patients on hemodialysis are characterized by sympathetic overactivity and vagal withdrawal and are associated with higher LVM and impaired physical performance. Understanding the spectrum of autonomic heart rate modulation and its determinants could help to guide preventive and therapeutic strategies.

SUBMITTER: Chan CT

PROVIDER: S-EPMC2974383 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Determinants of cardiac autonomic dysfunction in ESRD.

Chan Christopher T CT Levin Nathan W NW Chertow Glenn M GM Larive Brett B Schulman Gerald G Kotanko Peter P

Clinical journal of the American Society of Nephrology : CJASN 20100708 10

<h4>Background and objectives</h4>Cardiovascular events are common in patients with ESRD. Whether sympathetic overactivity or vagal withdrawal contribute to cardiovascular events is unclear. We determined the general prevalence and clinical correlates of heart rate variability in patients on hemodialysis.<h4>Design, setting, participants, & measurements</h4>We collected baseline information on demographics, clinical conditions, laboratory values, medications, physical performance, left ventricul ...[more]

PMID: 20616163

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Project description:Molecular mechanisms linking autonomic dysfunction with poorer clinical outcomes in critical illness remain unclear. We hypothesized that baroreflex dysfunction alone is sufficient to cause cardiac impairment through neurohormonal activation of (nicotinamide adenine dinucleotide phosphate oxidase dependent) oxidative stress resulting in increased expression of G-protein-coupled receptor kinase 2, a key negative regulator of cardiac function.Laboratory/clinical investigations.University laboratory/medical centers.Adult rats; wild-type/nicotinamide adenine dinucleotide phosphate oxidase subunit-2-deficient mice; elective surgical patients.Cardiac performance was assessed by transthoracic echocardiography following experimental baroreflex dysfunction (sino-aortic denervation) in rats and mice. Immunoblots assessed G-protein-coupled receptor recycling proteins expression in rodent cardiomyocytes and patient mononuclear leukocytes. In surgical patients, heart rate recovery after cardiopulmonary exercise testing, time/frequency measures of parasympathetic variables were related to the presence/absence of baroreflex dysfunction (defined by spontaneous baroreflex sensitivity of <6?ms mm Hg). The associations of baroreflex dysfunction with intraoperative cardiac function and outcomes were assessed.Experimental baroreflex dysfunction in rats and mice resulted in impaired cardiac contractility and upregulation of G-protein-coupled receptor kinase 2 expression. In mice, genetic deficiency of gp91 nicotinamide adenine dinucleotide phosphate oxidase subunit-2 prevented upregulation of G-protein-coupled receptor kinase 2 expression in conditions of baroreflex dysfunction and preserved cardiac function. Baroreflex dysfunction was present in 81 of 249 patients (32.5%) and was characterized by lower parasympathetic tone and increased G-protein-coupled receptor kinase 2 expression in mononuclear leukocytes. Baroreflex dysfunction in patients was also associated with impaired intraoperative cardiac contractility. Critical illness and mortality were more frequent in surgical patients with baroreflex dysfunction (relative risk, 1.66 [95% CI, 1.16-2.39]; p = 0.006).Reduced baroreflex sensitivity is associated with nicotinamide adenine dinucleotide phosphate oxidase subunit-2-mediated upregulation of G-protein-coupled receptor kinase 2 expression in cardiomyocytes and impaired cardiac contractility. Autonomic dysfunction predisposes patients to the development of critical illness and increases mortality.

Project description:BackgroundAutonomic nervous system dysfunction is implicated in the development of hypothalamic obesity. We investigated the relationship between hypothalamic involvement (HI), central obesity, and cardiac autonomic dysfunction by assessing heart rate variability (HRV) indices in patients with childhood-onset craniopharyngioma.MethodsA cross-sectional study of 48 patients (28 males, 10-30 years old) with hypothalamic damage after childhood-onset craniopharyngioma was performed. Postoperative HI was graded as mild (n = 19) or extensive (n = 29) on magnetic resonance imaging. Anthropometry, body composition and HRV indices including the standard deviation of all normal R-R intervals (SDNN) and total power (TP) as overall variability markers, root-mean square differences of successive R-R intervals (RMSSD) and high frequency (HF) as parasympathetic modulation markers, and low frequency (LF) as a sympathetic/sympathovagal modulation marker were measured.ResultsPatients with extensive HI had increased means of body mass index, waist circumference, and fat mass than those with mild HI (P < 0.05, for all). Centrally obese patients had a lower mean HF, a parasympathetic modulation marker, than centrally non-obese patients (P < 0.05). The extensive HI group had lower means of overall variability (SDNN and TP), parasympathetic modulation (HF), and sympathetic/sympathovagal modulation (LF) than the mild HI group (P < 0.05, for all). The interaction effect of HI and central obesity on HRV indices was not significant. In models adjusted for age, sex, and family history of cardiometabolic disease, the means of the overall variability indices (P < 0.05 for both SDNN and TP) and a sympathetic/sympathovagal modulation index (P < 0.05 for LF) were lower with extensive HI, without differences according to central obesity.ConclusionsThe reduced HRV indices with extensive HI suggests that hypothalamic damage may contribute to cardiac autonomic dysfunction, underscoring the importance of minimizing hypothalamic damage in patients with childhood-onset craniopharyngioma.

Project description:Type 1 diabetes mellitus (T1DM) has an important impact on morbidity and mortality because it may start early in life. Therefore, the early detection of cardiovascular autonomic neuropathy (DCAN) in T1DM patients is important to intervene quickly and prevent further deterioration. Traditional autonomic function tests detect abnormalities in severely symptomatic patients but they are difficult to be standardized, require the patient’s active participation and their sensitivity to the early disease is limited. In comparison, heart rate variability (HRV) is easier to be measured and standardized. Therefore, we aim to find the HRV indexes that better identify DCAN at an early stage in T1DM patients, and evaluate if HRV is a valid alternative to traditional tests. For this aim, we administered the SCOPA-AUT questionnaire on symptoms of autonomic dysfunction as well as deep breathing, Valsalva, handgrip, head-up tilt (HUT), and cold-pressor tests, to 52 T1DM patients and 27 controls. We calculated HRV indexes during supine rest (SUP) and HUT, assessing differences between groups and postures by a linear mixed-effect model for repeated measures. Receiver Operating Characteristic (ROC) analysis quantified how each HRV index and autonomic test distinguishes between patients and controls. We found that the SCOPA-AUT score was slightly but significantly (p < 0.05) greater in patients, indicating an early DCAN. T1DM patients preserved the HRV response to changing posture but in SUP they showed significantly lower standard deviation and vagal indexes of HRV than controls. The area under the ROC curve of these HRV indexes was not lower than 0.68. By contrast, traditional autonomic tests did not differ between groups. Therefore, early DCAN initially causes an impairment of the cardiac vagal control manifest in conditions of elevated vagal tone, as in SUP. Compensatory adjustments of the sympathetic control might explain the unaltered response to traditional autonomic tests. In conclusion, vagal HRV indexes in SUP help to identify early DCAN better than traditional tests, potentially allowing rapid interventions.

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Determinants of cardiac autonomic dysfunction in ESRD.

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Determinants of cardiac autonomic dysfunction in ESRD.

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