Improved Outcomes in Hemodialysis/Hemodiafiltration Treatments Applying Exercise and Physiological Monitoring Techniques: Preliminary Results Del Angel Francisco Lopez,M Miguel Cadena,Mendez Danilo,Azpiroz Leehan Joaquin,Martinez Fabiola,Rock Emilio Sacristan,Moron M Andres,A Gerardo Rosas,Fonseca A Angel,Karla Quevedo G,De la Rosa Ana M Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference End-stage renal disease affects millions of people worldwide, and the only definitive solutions are renal transplants that are not widely available. Temporary solutions are renal replacement therapies such as peritoneal dialysis, hemodialysis and hemodiafiltration. These therapies as they are applied today are just partial measures and have many drawbacks and complications such as high mortality rates and high costs due to the use of supplemental drugs and emergency room visits. Many enhancements to the therapies have been published, but they are not applied consistently in real world practice. Our work presents the results from the systematic application of several techniques to provide individualized therapies that can minimize the drawbacks and improve patient outcomes. This approach is based on the use of exercise, analysis of cardiovascular parameters, such as heart-rate variability, body composition and dry weight measurements through the use of bioimpedance and real-time monitoring of energy expenditure and nutrition intradialytically in order to provide individualized and dynamically variable therapies. Results show that patients can lead long, productive lives while maintaining a quality of life equivalent to that of a renal transplant. 10.1109/EMBC.2019.8856363
    Hemodialysis Procedure-Associated Autonomic Imbalance and Cardiac Arrhythmias: Insights From Continuous 14-Day ECG Monitoring. Rogovoy Nichole M,Howell Stacey J,Lee Tiffany L,Hamilton Christopher,Perez-Alday Erick A,Kabir Muammar M,Zhang Yanwei,Kim Esther D,Fitzpatrick Jessica,Monroy-Trujillo Jose M,Estrella Michelle M,Sozio Stephen M,Jaar Bernard G,Parekh Rulan S,Tereshchenko Larisa G Journal of the American Heart Association Background In patients with end-stage kidney disease, sudden cardiac death is more frequent after a long interdialytic interval, within 6 hours after the end of a hemodialysis session. We hypothesized that the occurrence of paroxysmal arrhythmias is associated with changes in heart rate and heart rate variability in different phases of hemodialysis. Methods and Results We conducted a prospective ancillary study of the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease cohort. Continuous ECG monitoring was performed using an ECG patch, and short-term heart rate variability was measured for 3 minutes every hour (by root mean square of the successive normal-to-normal intervals, spectral analysis, Poincaré plot, and entropy), up to 300 hours. Out of enrolled participants (n=28; age 54±13 years; 57% men; 96% black; 33% with a history of cardiovascular disease; left ventricular ejection fraction 70±9%), arrhythmias were detected in 13 (46%). Nonsustained ventricular tachycardia occurred more frequently during/posthemodialysis than pre-/between hemodialysis (63% versus 37%, =0.015). In adjusted for cardiovascular disease time-series analysis, nonsustained ventricular tachycardia was preceded by a sudden heart rate increase (by 11.2 [95% CI 10.1-12.3] beats per minute; <0.0001). During every-other-day dialysis, root mean square of the successive normal-to-normal intervals had a significant circadian pattern (Mesor 10.6 [ 95% CI 0.9-11.2] ms; amplitude 1.5 [95% CI 1.0-3.1] ms; peak at 02:01 [95% CI 20:22-03:16] am; <0.0001), which was replaced by a steady worsening on the second day without dialysis (root mean square of the successive normal-to-normal intervals -1.41 [95% CI -1.67 to -1.15] ms/24 h; <0.0001). Conclusions Sudden increase in heart rate during/posthemodialysis is associated with nonsustained ventricular tachycardia. Every-other-day hemodialysis preserves circadian rhythm, but a second day without dialysis is characterized by parasympathetic withdrawal. 10.1161/JAHA.119.013748
    Prognostic value of heart rate variability in patients with end-stage renal disease on chronic haemodialysis. Fukuta Hidekatsu,Hayano Junichiro,Ishihara Shinji,Sakata Seiichiro,Mukai Seiji,Ohte Nobuyuki,Ojika Kazuhito,Yagi Keiko,Matsumoto Hiroko,Sohmiya Sinken,Kimura Genjiro Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association BACKGROUND:Although decreased heart rate variability (HRV) is an independent predictor of death in various populations, its prognostic value in patients with end-stage renal disease on chronic haemodialysis is unknown. METHODS:We prospectively studied 120 chronic haemodialysis patients (age 61+/-11 years; males 51%; diabetics 38%; duration of haemodialysis therapy 50+/-114 months) who underwent 24 h electrocardiography at baseline for analysis of time- and frequency-domain HRV. RESULTS:All HRV measures in the patients were significantly reduced compared with those obtained from 62 age-matched healthy subjects. During a follow-up period of 26+/-10 months, 21 patients died (17.5%); 10 from cardiac causes and 11 from non-cardiac causes (seven fatal strokes and four other causes). A Cox proportional hazards model revealed that, of the HRV measures, decreases in the triangular index (TI), very-low-frequency (0.0033-0.04 Hz) power, ultra-low-frequency (<0.0033 Hz) power (ULF) and the ratio of low-frequency (0.04-0.15 Hz) power to high-frequency (0.15-0.4 Hz) power had significant predictive value for cardiac death. None of the HRV measures, however, had predictive value for non-cardiac death, including stroke death. Even after adjustment for other univariate predictors including age, diabetes, serum albumin and coronary artery disease, the predictive value of decreased TI and ULF remained significant-adjusted relative risk (95% confidence interval) per 1 SD decrement of TI and ULF, 3.28 (1.08-9.95) and 1.92 (1.01-3.67), respectively. CONCLUSIONS:Decreases in some HRV measures, particularly those reflecting long-term variability, are independent predictors of cardiac death in chronic haemodialysis patients. 10.1093/ndt/18.2.318
    Visit-to-visit variability of blood pressure and death, end-stage renal disease, and cardiovascular events in patients with chronic kidney disease. Chang Tara I,Tabada Grace H,Yang Jingrong,Tan Thida C,Go Alan S Journal of hypertension OBJECTIVES:Visit-to-visit variability of blood pressure (VVV of BP) is an important independent risk factor for premature death and cardiovascular events, but relatively little is known about this phenomenon in patients with chronic kidney disease (CKD) not yet on dialysis. METHODS:We conducted a retrospective study in a community-based cohort of 114 900 adults with CKD stages 3-4 (estimated glomerular filtration rate 15-59 ml/min per 1.73 m). We hypothesized that VVV of BP would be independently associated with higher risks of death, incident treated end-stage renal disease, and cardiovascular events. We defined systolic VVV of BP using three metrics: coefficient of variation, standard deviation of the mean SBP, and average real variability. RESULTS:The highest versus the lowest quintile of the coefficient of variation was associated with higher adjusted rates of death (hazard ratio 1.22; 95% confidence interval 1.11-1.34) and hemorrhagic stroke (hazard ratio 1.91; confidence interval 1.36-2.68). VVV of BP was inconsistently associated with heart failure, and was not significantly associated with acute coronary syndrome and ischemic stroke. Results were similar when using the other two metrics of VVV of BP. VVV of BP had inconsistent associations with end-stage renal disease, perhaps because of the relatively low incidences of this outcome. CONCLUSION:Higher VVV of BP is independently associated with higher rates of death and hemorrhagic stroke in patients with moderate to advanced CKD not yet on dialysis. 10.1097/HJH.0000000000000779
    The effect of n-3 fatty acids on heart rate variability in patients treated with chronic hemodialysis. Svensson My,Schmidt Erik B,Jørgensen Kaj A,Christensen Jeppe H Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation OBJECTIVE:The aim of the present study was to address the effect of n-3 polyunsaturated fatty acids (PUFAs) on heart rate variability (HRV) in patients treated with chronic hemodialysis. DESIGN:We performed a randomized, placebo-controlled intervention trial. SETTING:The study took place at two hospital-based dialysis centers. PATIENTS:Thirty patients with documented cardiovascular disease who were treated with hemodialysis for at least 6 months were included. INTERVENTION:Treatment consisted of 1.7 g of n-3 PUFA or a control treatment (olive oil). MAIN OUTCOME MEASURE:The outcome measure was 24-hour Holter recordings with time domain HRV measurements at baseline and after 3 months of treatment. Blood samples were obtained to assess the content of n-3 PUFA in serum phospholipids before and after treatment. RESULTS:n-3 PUFA did not significantly affect time domain parameters of HRV, compared with a control group. CONCLUSION:We conclude that treatment with n-3 PUFA does not increase HRV in patients treated with chronic hemodialysis, a result that may have been compromised by a small sample size. 10.1053/j.jrn.2007.02.004
    Exploring the complexity: the interplay between the angiotensin-converting enzyme insertion/deletion polymorphism and the sympathetic response to hemodialysis. Ribas Ribeiro Larissa,Flores de Oliveira Jacqueline,Bueno Orcy Rafael,Castilho Barros Carlos,Damé Hense Jessica,Santos Fernando,Irigoyen Maria Claudia,Gonzalez Maria Cristina,Oses Jean Pierre,Böhlke Maristela American journal of physiology. Heart and circulatory physiology Patients on hemodialysis (HD) are at increased risk for arrhythmias and sudden cardiac death. Autonomic nervous system (ANS) dysfunction seems to participate in the arrhythmogenic process. Genetic factors have an impact on ANS modulation, but the specific role of the insertion/deletion (I/D) polymorphism in the gene for angiotensin-converting enzyme (ACE) has not been investigated. Since the D allele increases gene expression, it is a candidate polymorphism to interact with the ANS. The aim of the present study was to compare the behavior of heart rate variability (HRV) during HD, as a surrogate for ANS response to stressors, between the ACE genotypes. In a sample of patients with chronic kidney disease I/D ACE genotypes were assessed with PCR and HRV was measured before, in the second hour, and after a HD session. HRV parameters in the time and frequency domains were analyzed by repeated-measures mixed models according to the time of measurement and ACE polymorphism. HRV parameters in the frequency domain presented significantly different variations during the HD session between patients with or without the D allele. Only patients with the II genotype presented an increase in low-frequency normalized units and in the low frequency-to-high frequency ratio throughout HD. Patients with the II genotype seemed to have a more physiological response to the volemic and electrolytic changes that occur during HD, with greater sympathetic activation than patients with ID and DD genotypes. NEW & NOTEWORTHY Adding to the effort to understand the complexity of cardiovascular system regulation, we have found that the autonomic nervous system response to the acute volume removal during hemodialysis may be different between angiotensin-converting enzyme insertion/deletion polymorphisms. To our knowledge, this is the first time that this specific interaction was analyzed during a volume removal intervention. 10.1152/ajpheart.00162.2018
    Cardiac autonomic dysfunction in hemodialysis patients: The value of heart rate turbulence. Celik Atac,Melek Mehmet,Yuksel Seref,Onrat Ersel,Avsar Alaettin Hemodialysis international. International Symposium on Home Hemodialysis Patients with end-stage renal disease (ESRD) are likely to have cardiac autonomic dysfunction, which is related with an increased risk of sudden death. The aim of this study is to detect cardiac autonomic dysfunction in patients with ESRD and to evaluate the possible acute effects of hemodialysis (HD) on cardiac autonomic functions measured by heart rate variability (HRV) and heart rate turbulence (HRT). Thirty-one (mean age 50 ± 13 years, 15 males) with ESRD on regular HD program and 31 healthy volunteers (mean age 51 ± 12 years, 15 males) were included in the study. Twenty-four-hour ambulatory electrocardiogram recordings were taken from the subjects before and after HD and from the control group. Heart rate variability and HRT parameters were calculated from these recordings. All of the HRV and HRT parameters were found to be significantly blunted in patients in comparison with healthy individuals. There were significant differences in HRV after HD, but similar differences were not observed in HRT parameters. Cardiac autonomic functions were significantly altered in patients with ESRD. Heart rate turbulence parameters seemed to be less affected from HD and may be more useful in the evaluation of cardiac autonomic functions in the ESRD population. 10.1111/j.1542-4758.2011.00529.x
    Effect of plasma sodium concentration on blood pressure regulators during hemodialysis: a randomized crossover study. Ettema Esmée M,Kuipers Johanna,van Faassen Martijn,Groen Henk,van Roon Arie M,Lefrandt Joop D,Westerhuis Ralf,Kema Ido P,van Goor Harry,Gansevoort Ron T,Gaillard Carlo A J M,Franssen Casper F M BMC nephrology BACKGROUND:Intradialytic hypotension is a common complication of hemodialysis. The Hemocontrol biofeedback system, improving intradialytic hemodynamic stability, is associated with an initial transient increase in plasma sodium levels. Increases in sodium could affect blood pressure regulators. METHODS:We investigated whether Hemocontrol dialysis affects vasopressin and copeptin levels, endothelial function, and sympathetic activity in twenty-nine chronic hemodialysis patients. Each patient underwent one standard hemodialysis and one Hemocontrol hemodialysis. Plasma sodium, osmolality, nitrite and nitrate (NOx), endothelin-1, angiopoietins-1 and 2, and methemoglobin as measures of endothelial function, plasma catecholamines as indices of sympathetic activity and plasma vasopressin and copeptin levels were measured six times during each modality. Blood pressure, heart rate, blood volume, and heart rate variability were repeatedly monitored. Generalized Estimating Equations was used to compare the course of the parameters during the two treatment modalities. RESULTS:Plasma sodium and osmolality were significantly higher during the first two hours of Hemocontrol hemodialysis. Overall, mean arterial pressure (MAP) was higher during Hemocontrol dialysis. Neither the measures of endothelial function and sympathetic activity nor copeptin levels differed between the two dialysis modalities. In contrast, plasma vasopressin levels were significantly higher during the first half of Hemocontrol dialysis. The intradialytic course of vasopressin was associated with the course of MAP. CONCLUSIONS:A transient intradialytic increase in plasma sodium did not affect indices of endothelial function or sympathetic activity compared with standard hemodialysis, but coincided with higher plasma vasopressin levels. The beneficial effect of higher intradialytic sodium levels on hemodynamic stability might be mediated by vasopressin. TRIAL REGISTRATION:ClinicalTrials.gov. Identifier: NCT03578510 . Date of registration: July 5th, 2018. Retrospectively registered. 10.1186/s12882-018-0997-z
    Reliability analysis of the heart autonomic control parameters during hemodialysis sessions. da Silva Débora Martins,Macedo Murilo Carneiro,Lemos Lucas Brasileiro,Vieira Fernando Costa,Pirôpo Uanderson Silva,Andrade Helder Brito,Wessel Niels,Pereira Rafael Biomedizinische Technik. Biomedical engineering The study of heart autonomic control (HAC) in patients with chronic kidney disease (CKD) undergoing dialysis treatment has been carried out, however, there are no studies reporting the reliability of measurements of HAC parameters involving the mentioned samples and conditions. The reliability of many HAC parameters was evaluated from patients with CKD during two sessions of hemodialysis. The successive R-R intervals were recorded during two sessions of hemodialysis from 14 CKD patients that were undergoing dialysis for at least 6 months and with no history of recurrent hypotensive events. HAC parameters were obtained with time and frequency domain analysis, as well as with nonlinear methods. The reliability was measured with the intraclass correlation coefficient (ICC). The results showed excellent reliability (ICC=0.90-0.98) for most heart rate variability (HRV) parameters, especially the parameters obtained in the time domain [square root of the mean squared differences between successive R-R intervals (RMSSD), percentage of adjacent R-R intervals that differ by more than 50 ms (pNN50), mean of the 5-min standard deviations of R-R intervals (SDNNi), and triangular index] and with non-linear methods [standard deviation of the instantaneous variability beat-to-beat (SD1), standard deviation in long-term continuous R-R intervals (SD2), detrended fluctuation analysis (DFA) α1 and α2, approximate and sample entropies, and correlation dimension (D2): ICC=0.86-0.96]. Among the parameters obtained in the frequency domain (normalized magnitude from the spectrum of low-frequency components (LFnu), normalized magnitude from the spectrum of high-frequency components (HFnu), and LF/HF ratio), the LF/HF ratio showed better reliability (ICC=0.96 vs. ICC=0.70). Measurements of HAC parameters have excellent test-retest reliability for the studied samples and conditions. 10.1515/bmt-2015-0239
    Predictors of heart rate variability and its prognostic significance in chronic kidney disease. Chandra Preeti,Sands Robin L,Gillespie Brenda W,Levin Nathan W,Kotanko Peter,Kiser Margaret,Finkelstein Fredric,Hinderliter Alan,Pop-Busui Rodica,Rajagopalan Sanjay,Saran Rajiv Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association BACKGROUND:Heart rate variability (HRV), a noninvasive measure of autonomic dysfunction and a risk factor for cardiovascular disease (CVD), has not been systematically studied in nondialysis chronic kidney disease (CKD). METHODS:HRV was assessed using 24-h Holter monitoring in 305 subjects from the Renal Research Institute-CKD Study, a four-center prospective cohort of CKD (Stages 3-5). Multiple linear regression was used to assess predictors of HRV (both time and frequency domain) and Cox regression used to predict outcomes of CVD, composite of CVD/death and end-stage renal disease (ESRD). RESULTS:A total of 47 CVD, 67 ESRD and 24 death events occurred over a median follow-up of 2.7 years. Lower HRV was significantly associated with older age, female gender, diabetes, higher heart rate, C-reactive protein and phosphorus, lower serum albumin and Stage 5 CKD. Lower HRV (mostly frequency domain) was significantly associated with higher risk of CVD and the composite end point of CVD or death. Significantly, lower HRV (frequency domain) was associated with higher risk of progression to ESRD, although this effect was relatively weaker. CONCLUSIONS:This study draws attention to the importance of HRV as a relatively under recognized predictor of adverse cardiovascular and renal outcomes in patients with nondialysis CKD. Whether interventions that improve HRV will improve these outcomes in this high-risk population deserves further study. 10.1093/ndt/gfr340
    Association between autonomic nervous dysfunction and cellular inflammation in end-stage renal disease. Seibert Eric,Zohles Kristina,Ulrich Christof,Kluttig Alexander,Nuding Sebastian,Kors Jan A,Swenne Cees A,Werdan Karl,Fiedler Roman,Girndt Matthias BMC cardiovascular disorders BACKGROUND:Alterations in autonomic nervous function are common in hemodialysis (HD) patients. Sympathetic as well as parasympathetic activation may be associated with immune and inflammatory responses. We intended to confirm a role of autonomous dysregulation for inflammation in HD patients. METHODS:30 HD patients (including 15 diabetics) and 15 healthy controls were studied for heart rate variability (HRV) using 5 min ECG recordings. Heart rate variability was estimated by time-domain parameters (the standard deviation of the RR intervals (SDNN) and the percentage of pairs of adjacent RR intervals differing by >50 ms (pNN50)) and frequency-domain-analysis (high- and low-frequency variation of RR intervals, HF and LF). Inflammation was detected as serum C-reactive Protein (CRP), IL-6 and circulating monocyte subpopulation numbers. Immune cells were characterized by ACh receptor expression. RESULTS:Patients differed from controls in terms of age (68.0 [14.8] yrs vs. 58.0 [13.0] yrs, p < 0.001; Median [IQR]) and sex. However, HRV parameters were different in controls and HD patients (SDNN controls 34.0 [14.0] ms, HD patients 15.5 [14.8] ms, p < 0.01). This finding was not restricted to patients with diabetes mellitus (diab), although diabetes is an important cause of autonomous dysfunction (SDNN, diab 13.0 [14.0] ms, non-diab 18.0 [15.3] ms, p = 0.8). LF and HF were reduced by the same magnitude to 1/3 of those in controls. Patients suffered from chronic inflammation (CRP 9.4 [12.9] mg/l, controls 1.6 [2.4] mg/l, p < 0.001) and expanded proinflammatory monocyte subpopulations (CD14++/CD16+ cells: patients 41 [27]/μl, controls 24 [18]/μl, p < 0.01). ECG parameters did not correlate with inflammation in patients, but monocyte ACh receptor expression was enhanced, indicating potentially elevated responsiveness of this cell type to parasympathetic regulation. CONCLUSIONS:HD patients have strongly impaired HRV. Chronic inflammation is not related to autonomous dysfunction, although monocytes express the ACh receptor at enhanced density making them potentially more sensitive to parasympathetic effects. TRIAL REGISTRATION:This study was listed with ClinicalTrials.gov ( NCT00878033 ). 10.1186/s12872-016-0385-1
    Reproducibility of Heart Rate Variability Revealed by Repeated Measurements during and after Hemodialysis. Deussing Kerstin,Wendt Ralph,Burger Ronald,Gollasch Maik,Beige Joachim Blood purification BACKGROUND/AIMS:Trajectory of heart rate variability (HRV) represents a noninvasive real-time measure of autonomous nervous system (ANS) and carries the capability of providing new insights into the hemodynamic compensation reserve during hemodialysis (HD). However, studies on HRV reproducibility during HD are scarce and did not refer to different reading periods. In this observational study, we aimed to establish the best suited and most reliable and reproducible HRV index in routine HD treatments including different reading rates. METHODS:HRV was characterized by standardized mathematical variation expressions of R/R' intervals: SD of all R/R' intervals (ms), square root of the root mean square of the sum of all differences between adjacent R/R' intervals (ms), percentage of consecutive R/R' intervals that differ by >50 ms (%), low-frequency spectral analysis HRV (LF, expressing sympathetic activity), and high-frequency HRV (HF, expressing parasympathetic activity). To compare robustness of these HRV indices during HD procedures, we compared HRV indices means between different HD sessions and controlled for association with clinical parameters. RESULTS:In 72 HD treatments of 34 patients, we detected the highest reproducibility (89%) of HRV measures when analyzing the low-frequency to high-frequency (LF/HF) ratio in long-term (3 h) readings. Long-term LF/HF was able to discriminate -between patients with and without heart failure NYHA classes ≥3 (p = 0.009) and type 2 diabetes (p = 0.023). We were unable to study relationships between ANS and intradialytic complications because they did not appear in our cohort. Short-term readings of HRV indices did not show any significance of pattern change during HD. CONCLUSION:In summary, our data provide evidence for high robustness of long-term LF/HF in analyzing HRV in HD patients using future automated monitoring systems. For short-term analysis, mathematical real-time analysis must evolve. 10.1159/000504525
    Heart rate variability (HRV) in kidney failure: measurement and consequences of reduced HRV. Ranpuria Reena,Hall Martica,Chan Chris T,Unruh Mark Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association A common cause of death in end-stage renal disease (ESRD) patients on dialysis is sudden cardiac death (SCD). Compared to the general population, the percentage of cardiovascular deaths that are attributed to SCD is higher in patients treated by dialysis. While coronary artery disease (CAD) is the predominant cause of SCD in dialysis patients, reduced heart rate variability (HRV) may play a role in the higher risk of SCD among other risk factors. HRV refers to beat-to-beat alterations in heart rate as measured by periodic variation in the R-R interval. HRV provides a non-invasive method for investigating autonomic input into the heart. It quantifies the amount by which the R-R interval or heart rate changes from one cardiac cycle to the next. The autonomic nervous system transmits impulses from the central nervous system to peripheral organs and is responsible for controlling the heart rate, blood pressure and respiratory activity. In normal individuals, without cardiac disease, the heart rate has a high degree of beat-to-beat variability. HRV fluctuates with respiration: it increases with inspiration and decreases with expiration and is primarily mediated by parasympathetic activity. HRV has been used to evaluate and quantify the cardiac risk associated with a variety of conditions including cardiac disorders, stroke, multiple sclerosis and diabetes. In this narrative review, we will examine the association between HRV and SCD. This report explains the measurement of HRV and the consequences of reduced HRV in the general population and dialysis patients. Lastly, this review will outline the possible use of HRV as a clinical predictor for SCD in the dialysis population. The current understanding of SCD based on HRV findings among the ESRD population support the use of more aggressive treatment of CAD; greater use of angiotensin converting enzyme inhibitor (ACE-i)/angiotensin receptor blockers (ARBs) and beta-blockers and more frequent and/or nocturnal haemodialysis to improve the survival of a patient with kidney failure. 10.1093/ndt/gfm634
    Detection of autonomic dysfunction in hemodialysis patients using the exercise treadmill test: the role of the chronotropic index, heart rate recovery, and R-R variability. Carreira Maria Angela M Q,Nogueira André B,Pena Felipe M,Kiuchi Marcio G,Rodrigues Ronaldo C,Rodrigues Rodrigo R,Matos Jorge P S,Lugon Jocemir R PloS one OBJECTIVE:To evaluate the ability of different parameters of exercise treadmill test to detect autonomic dysfunction in hemodialysis patients. METHODS:Cross-sectional study involving hemodialysis patients and a control group. Clinical examination, blood sampling, echocardiogram, 24-hour Holter, and exercise treadmill test were performed. A ramp treadmill protocol symptom-limited with active recovery was employed. RESULTS:Forty-one hemodialysis patients and 41 controls concluded the study. There was significant difference between hemodialysis patients and controls in autonomic function parameters in 24h-Holter and exercise treadmill test. Probability of having autonomic dysfunction in hemodialysis patients compared to controls was 29.7 at the exercise treadmill test and 13.0 in the 24-hour Holter. Chronotropic index, heart rate recovery at the 1st min, and SDNN at exercise were used to develop an autonomic dysfunction score to grade autonomic dysfunction, in which, 83% of hemodialysis patients reached a scoring ≥2 in contrast to 20% of controls. Hemodialysis was independently associated with either altered chronotropic index or autonomic dysfunction scoring ≥2 in every tested model (OR=50.1, P=0.003; and OR=270.9, P=0.002, respectively, model 5). CONCLUSION:The exercise treadmill test was feasible and useful to diagnose of the autonomic dysfunction in hemodialysis patients. Chronotropic index and autonomic dysfunction scoring ≥2 were the most effective parameters to differentiate between hemodialysis patients and controls suggesting that these variables portrays the best ability to detect autonomic dysfunction in this setting. 10.1371/journal.pone.0128123
    Heart Rate Variability Change Before and After Hemodialysis is Associated with Overall and Cardiovascular Mortality in Hemodialysis. Chen Szu-Chia,Huang Jiun-Chi,Tsai Yi-Chun,Hsiu-Chin Mai R N,Jui-Hsin Chen R N,Kuo Po-Lin,Chang Jer-Ming,Hwang Shang-Jyh,Chen Hung-Chun Scientific reports Low heart rate variability (HRV) has been recognized to correlate with adverse cardiovascular (CV) outcomes in hemodialysis (HD) patients. It has been reported that HRV might be improved after HD, but whether the improved HRV after HD predicts a better CV prognosis remains to be determined. This study examined the ability of the change in HRV before and after HD in predicting overall and CV mortality in HD patients. This study enrolled 182 patients under maintenance HD. HRV was examined to assess changes before and after HD. The change in HRV (ΔHRV) was defined as post-HD HRV minus pre-HD HRV. During a median follow-up period of 35.2 months, 29 deaths (15.9%) were recorded. Multivariate analysis showed that decreased ΔLF% was associated with increased overall (hazard ratios [HR], 0.978; 95% confidence interval [CI], 0.961-0.996; p = 0.019) and CV mortality (HR, 0.941; 95% CI, 0.914-0.970; p < 0.001), respectively. Moreover, adding ΔLF% to a clinical model provided an additional benefit in the prediction of overall (p = 0.002) and CV mortality (p < 0.001). HRV change before and after HD (ΔHRV) is an useful clinical marker, and it is stronger than HRV before HD in predicting overall and CV mortality. 10.1038/srep20597
    A Walking Intervention to Increase Weekly Steps in Dialysis Patients: A Pilot Randomized Controlled Trial. Sheshadri Anoop,Kittiskulnam Piyawan,Lazar Ann A,Johansen Kirsten L American journal of kidney diseases : the official journal of the National Kidney Foundation RATIONALE & OBJECTIVE:Patients receiving dialysis report very low physical activity. We implemented a pilot trial to assess the feasibility of a pedometer-based intervention to gather preliminary evidence about its impact on physical activity, symptoms, and surrogates of cardiovascular risk. STUDY DESIGN:Pilot randomized controlled trial. SETTING & PARTICIPANTS:60 dialysis patients from San Francisco dialysis clinics. INTERVENTION:Participants were randomly assigned 1:1 to receiving pedometers with weekly step goals or usual care for 3 months. OUTCOMES:The primary outcome was step counts, measured using pedometers. Secondary outcomes included physical performance using the Short Physical Performance Battery, the Physical Function and Vitality scales of the 36-Item Short Form Health Survey, the Dialysis Symptoms Index, and the Center for Epidemiologic Studies-Depression Scale, with endothelial function as a secondary and heart rate variability as an exploratory surrogate measure of cardiovascular risk. Targeted enrollment was 50% and targeted completion was 85%. RESULTS:49% of approached patients were enrolled, and 92% completed the study. After 3 months, patients randomly assigned to the intervention (n=30) increased their average daily steps by 2,256 (95% CI, 978-3,537) more than the 30 controls (P<0.001). Heart rate variability (standard deviation of N-N intervals) increased by 14.94 (95% CI, 0.31-33.56) millisecondsin the intervention group as compared with controls (P = 0.05). There were no statistically significant differences across intervention groups in symptoms, physical performance, or endothelial function. Participants in the intervention group reverted to baseline steps during the postintervention follow-up. LIMITATIONS:The Northern California study setting may limit generalizability. Walking does not capture the full spectrum of physical activity. CONCLUSIONS:A short-term pedometer-based intervention led to increased step counts in dialysis patients, but the increase was not sustained. Pedometer-based interventions are feasible for dialysis patients, but future studies are needed to address whether more prolonged interventions can improve physical function or symptoms. FUNDING:Supported by grants from the American Kidney Fund, National Institutes of Health-National Institute of Diabetes and Digestive and Kidney Diseases, and International Society of Nephrology. TRIAL REGISTRATION:Registered at ClinicalTrials.gov with study identifier NCT02623348. 10.1053/j.ajkd.2019.07.026
    Heart Rate Variability Correlates to Functional Aerobic Impairment in Hemodialysis Patients. Carreira Maria Angela Magalhães de Queiroz,Nogueira André Barros,Pena Felipe Montes,Kiuchi Marcio Galindo,Rodrigues Ronaldo Campos,Rodrigues Rodrigo da Rocha,Matos Jorge Paulo Strogoff de,Lugon Jocemir Ronaldo Arquivos brasileiros de cardiologia BACKGROUND:Autonomic dysfunction (AD) is highly prevalent in hemodialysis (HD) patients and has been implicated in their increased risk of cardiovascular mortality. OBJECTIVE:To correlate heart rate variability (HRV) during exercise treadmill test (ETT) with the values obtained when measuring functional aerobic impairment (FAI) in HD patients and controls. METHODS:Cross-sectional study involving HD patients and a control group. Clinical examination, blood sampling, transthoracic echocardiogram, 24-hour Holter, and ETT were performed. A symptom-limited ramp treadmill protocol with active recovery was employed. Heart rate variability was evaluated in time domain at exercise and recovery periods. RESULTS:Forty-one HD patients and 41 controls concluded the study. HD patients had higher FAI and lower HRV than controls (p<0.001 for both). A correlation was found between exercise HRV (SDNN) and FAI in both groups. This association was independent of age, sex, smoking, body mass index, diabetes, and clonidine or beta-blocker use, but not of hemoglobin levels. CONCLUSION:No association was found between FAI and HRV on 24-hour Holter or at the recovery period of ETT. Of note, exercise HRV was inversely correlated with FAI in HD patients and controls. 10.5935/abc.20150039
    Link between Peripheral Artery Disease and Heart Rate Variability in Hemodialysis Patients. Chen Szu-Chia,Chen Chien-Fu,Huang Jiun-Chi,Lee Mei-Yueh,Chen Jui-Hsin,Chang Jer-Ming,Hwang Shang-Jyh,Chen Hung-Chun PloS one Peripheral artery disease (PAD) and low heart rate variability (HRV) are highly prevalent in hemodialysis patients, and both are associated with increased cardiovascular morbidity and mortality. This study aims to examine the suggested relationship between PAD and HRV, and the relationship of parameters before and after hemodialysis. This study enrolled 161 maintenance hemodialysis patients. PAD was defined as ABI < 0.9 in either leg. HRV was performed to assess changes before and after hemodialysis. The change in HRV (△HRV) was defined as post-hemodialysis HRV minus pre-hemodialysis HRV. Patients' clinical parameters were collected from the dialysis records. All HRV parameters except high frequency (HF) % were lower in patients with PAD than patients without PAD, though not achieving significant level. In patients without PAD, HF (P = 0.013), low frequency (LF) % (P = 0.028) and LF/HF (P = 0.034) were significantly elevated after hemodialysis, whereas no significant HRV parameters change was noted in patients with PAD. Serum intact parathyroid hormone was independently associated with △HF (β = -0.970, P = 0.032) and △LF% (β = -12.609, P = 0.049). Uric acid level (β = -0.154, P = 0.027) was negatively associated with △LF/HF in patients without PAD. Our results demonstrated that some of the HRV parameters were significantly increased after hemodialysis in patients without PAD, but not in patients with PAD, reflecting a state of impaired sympatho-vagal equilibrium. Severity of secondary hyperparathyroidism and hyperuricemia contributed to lesser HRV parameters increase after hemodialysis in patients without PAD. 10.1371/journal.pone.0120459
    Heart rate variability during hemodialysis is an indicator for long-term vascular access survival in uremic patients. Huang Ya-Ting,Chang Yu-Ming,Chen I-Ling,Yang Chuan-Lan,Leu Show-Chin,Su Hung-Li,Kao Jsun-Liang,Tsai Shih-Ching,Jhen Rong-Na,Tang Woung-Ru,Shiao Chih-Chung, PloS one BACKGROUND:Vascular access (VA) is the lifeline of hemodialysis patients. Although the autonomic nervous system might be associated with VA failure (VAF), it has never been addressed in previous studies. This study aimed to evaluate the predictive values of the heart rate variability (HRV) indices for long-term VA outcomes. METHODS:This retrospective study was conducted using a prospectively established cohort enrolling 175 adult chronic hemodialysis patients (100 women, mean age 65.1 ± 12.9 years) from June 2010 to August 2010. Each participant received a series of HRV measurements at enrollment. After a 60-month follow-up period, we retrospectively reviewed all events and therapeutic procedures of the VAs which existed at the enrollment and during the follow-up period. RESULTS:During the 60-month follow-up period, 37 (26.8%) had VAF but 138 (73.2%) didn't. The values of most HRV indices were statistically increased during hemodialysis since initiation in the non-VAF group, but not in the VAF group. Among all participants, the independent indicators for VAF included higher normalized high-frequency (nHF) activity [hazard ratio (HR) 1.04, p = 0.005], lower low-frequency/high-frequency (LF/HF) ratio (HR 0.80, p = 0.015), experience of urokinase therapy (HR 11.18, p = 0.002), percutaneous transluminal angioplasty (HR 2.88, p = 0.003) and surgical thrombectomy (HR 2.36, p = 0.035), as well as higher baseline serum creatinine (HR 1.07, p = 0.027) and potassium level (HR 1.58, p = 0.037). In subgroup analysis, a lower sympathetic activity indicated by lower LF/HF ratio was an independent indicator for VAF (HR 0.61, p = 0.03) for tunneled cuffed catheter, but conversely played a protective role against VAF (HR 1.27, p = 0.002) for arteriovenous fistula. CONCLUSIONS:HRV is a useful tool for predicting long-term VAF among hemodialysis patients. 10.1371/journal.pone.0172212
    The forgotten role of central volume in low frequency oscillations of heart rate variability. Ferrario Manuela,Moissl Ulrich,Garzotto Francesco,Cruz Dinna N,Tetta Ciro,Signorini Maria G,Ronco Claudio,Grassmann Aileen,Cerutti Sergio,Guzzetti Stefano PloS one The hypothesis that central volume plays a key role in the source of low frequency (LF) oscillations of heart rate variability (HRV) was tested in a population of end stage renal disease patients undergoing conventional hemodialysis (HD) treatment, and thus subject to large fluid shifts and sympathetic activation. Fluid overload (FO) in 58 chronic HD patients was assessed by whole body bioimpedance measurements before the midweek HD session. Heart Rate Variability (HRV) was measured using 24-hour Holter electrocardiogram recordings starting before the same HD treatment. Time domain and frequency domain analyses were performed on HRV signals. Patients were retrospectively classified in three groups according to tertiles of FO normalized to the extracellular water (FO/ECW%). These groups were also compared after stratification by diabetes mellitus. Patients with the low to medium hydration status before the treatment (i.e. 1st and 2nd FO/ECW% tertiles) showed a significant increase in LF power during last 30 min of HD compared to dialysis begin, while no significant change in LF power was seen in the third group (i.e. those with high pre-treatment hydration values). In conclusion, several mechanisms can generate LF oscillations in the cardiovascular system, including baroreflex feedback loops and central oscillators. However, the current results emphasize the role played by the central volume in determining the power of LF oscillations. 10.1371/journal.pone.0120167
    Heart Rhythm Complexity Predicts Long-Term Cardiovascular Outcomes in Peritoneal Dialysis Patients: A Prospective Cohort Study. Tsai Cheng-Hsuan,Huang Jenq-Wen,Lin Chen,Ma Hsi-Pin,Lo Men-Tzung,Liu Li-Yu Daisy,Lin Lian-Yu,Lin Chih-Ting,Hung Chi-Sheng,Peng Chung-Kang,Lin Yen-Hung Journal of the American Heart Association Background Cardiovascular disease is the leading cause of morbidity and mortality in patients with end-stage renal disease. Heart rhythm complexity analysis has been shown to be useful in predicting outcomes in various diseases; however, data on patients with end-stage renal disease are limited. In this study, we analyzed the association between heart rhythm complexity and long-term cardiovascular outcomes in patients with end-stage renal disease receiving peritoneal dialysis. Methods and Results We prospectively enrolled 133 patients receiving peritoneal dialysis and analyzed linear heart rate variability and heart rhythm complexity variables including detrended fluctuation analysis (DFA) and multiscale entropy. The primary outcome was cardiovascular mortality, and the secondary outcome was the occurrence of major adverse cardiovascular events. After a median of 6.37 years of follow-up, 21 patients (22%) died from cardiovascular causes. These patients had a significantly lower low-frequency band of heart rate variability, low/high-frequency band ratio, total power band of heart rate variability, heart rate turbulence slope, deceleration capacity, short-term DFA (DFAα1); and multiscale entropy slopes 1 to 5, scale 5, area 1 to 5, and area 6 to 20 compared with the patients who did not die from cardiovascular causes. Time-dependent receiver operating characteristic curve analysis showed that DFAα1 had the greatest discriminatory power for cardiovascular mortality (area under the curve: 0.763) and major adverse cardiovascular events (area under the curve: 0.730). The best cutoff value for DFAα1 was 0.98 to predict both cardiovascular mortality and major adverse cardiovascular events. Multivariate Cox regression analysis showed that DFAα1 (hazard ratio: 0.076; 95% CI, 0.016-0.366; =0.001) and area 1 to 5 (hazard ratio: 0.645; 95% CI, 0.447-0.930; =0.019) were significantly associated with cardiovascular mortality. Conclusions Heart rhythm complexity appears to be a promising noninvasive tool to predict long-term cardiovascular outcomes in patients receiving peritoneal dialysis. 10.1161/JAHA.119.013036
    Impact of metabolic syndrome and its components on heart rate variability during hemodialysis: a cross-sectional study. Chang Yu-Ming,Shiao Chih-Chung,Huang Ya-Ting,Chen I-Ling,Yang Chuan-Lan,Leu Show-Chin,Su Hung-Li,Kao Jsun-Liang,Tsai Shih-Ching,Jhen Rong-Na,Uen Ching-Cherng, Cardiovascular diabetology BACKGROUND:Both uremia and metabolic syndrome (MetS) affect heart rate variability (HRV) which is a risk factor of poor prognoses. The aim of this study was to evaluate the impact of MetS on HRV among chronic hemodialysis patients. METHODS:This cross-sectional study was carried out in a teaching hospital in Northern Taiwan from June to August, 2010. Adult patients on chronic hemodialysis without active medical conditions were enrolled. HRV were measured for 4 times on the index hemodialysis day (HRV-0, -1, -2, and -3 at before, initial, middle, and late phases of hemodialysis, respectively), and the baseline demographic data and clinical parameters during the hemodialysis session were documented. Then we evaluated the impacts of MetS and its five components on HRV. RESULTS:One hundred and seventy-five patients (100 women, mean age 65.1 ± 12.9 years) were enrolled and included those with MetS (n = 91, 52 %) and without MetS (n = 84, 48 %). The patients with MetS(+) had significantly lower very low frequency, total power, and variance in HRV-0, total power and variance in HRV-2, and variance in HRV-3. (all p ≦ 0.05) When using the individual components of MetS to evaluate the impacts on HRV indices, the fasting plasma glucose (FPG) criterion significantly affected most indices of HRV while other four components including "waist circumference", "triglycerides", "blood pressure", and "high-density lipoprotein" criteria exhibited little impacts on HRV. FPG criterion carried the most powerful influence on cardiac ANS, which was even higher than that of MetS. The HRV of patients with FPG(+) increased initially during the hemodialysis, but turned to decrease dramatically at the late phase of hemodialysis. CONCLUSIONS:The impact of FPG(+) outstood the influence of uremic autonomic dysfunction, and FPG criterion was the most important one among all the components of MetS to influence HRV. These results underscored the importance of interpretation and management for abnormal glucose metabolism. 10.1186/s12933-016-0328-2
    Electrocardiogram abnormalities and heart rate variability in predicting mortality and cardiovascular events among hemodialyzed patients. Badarau Silvia,Siriopol Dimitrie,Drugus Daniela,Dumea Raluca,Hogas Simona,Blaj Mihaela,Voroneanu Luminita,Gramaticu Angelica,Petris Antoniu,Burlacu Alexandru,Covic Adrian International urology and nephrology PURPOSE:The aim of the study was to evaluate the correlation between electrocardiographic parameters and heart rate variability with cardiovascular events and mortality among chronic hemodialysis patients. METHODS:In this prospective study, we enrolled 116 asymptomatic patients in whom we performed ambulatory 24-h electrocardiographic Holter monitoring and before and after hemodialysis electrocardiographs. We measured the interval (PR, QRS, QTc, QTc dispersion) differences on the surface electrocardiographs and obtained frequency-domain measures from Holter monitoring (VLF, LF, HF and the LF/HF ratio). RESULTS:During the follow-up period, 13 participants died (11.2 %) and 16 (13.8 %) patients experienced a cardiovascular event. The pre-post-dialysis difference in QTc interval was the best predictor for cardiovascular events (95 % CI 0.453-0.786), while pre-dialysis QRS interval was the predictor for all-cause mortality (95 % CI 1.134-3.136). Also, both outcomes were predicted by pre-post-dialysis difference in PR interval and VLF. CONCLUSIONS:Interval changes during hemodialysis are predictive for cardiovascular events and mortality. Autonomic dysfunction and changes in PR should be monitored routinely, particularly in patients with suspected coronary artery disease. 10.1007/s11255-015-1063-4
    Correlation between indexes of autonomic maneuvers and heart rate variability in hemodialysis patients. Vieira Carlos Felipe Delmondes,Lima Márcia Maria Oliveira,Costa Henrique Silveira,Diniz Karen Marina Alves,Guião João Paulo Lemos,Alves Frederico Lopes,Maciel Emílio Henrique,Brandao Vanessa Gomes,Figueiredo Pedro Henrique Scheidt Clinical autonomic research : official journal of the Clinical Autonomic Research Society PURPOSE:The autonomic maneuvers are simple methods to evaluate autonomic balance, but the association between autonomic maneuvers and heart rate variability (HRV) in hemodialysis patients remains unknown. This study aimed to evaluate the correlation between HRV and respiratory sinus arrhythmia (RSA) and Valsalva maneuver (VM) indexes in hemodialysis patients and to compare two methods for RSA indexes acquisitions. METHODS:Forty-eight volunteers on hemodialysis (66.7 % men) were evaluated by VM, RSA, and 24 h Holter monitoring. At the VM, the Valsalva index (VI) was the variable considered. In the RSA, the ratio and difference between the RR intervals of inspiratory and expiratory phase (E:I and E-I, respectively) were considered by traditional form (average of respiratory cycles) and independent respiratory cycles (E:Iindep and E-Iindep). The HRV indexes evaluated were standard deviation of all normal RR intervals (SDNN), standard deviation of sequential 5-min RR interval means (SDANN), root mean square of the successive differences (rMSSD) and percentage of adjacent RR intervals with difference of duration greater than 50 ms (pNN50). RESULTS:The SDNN, SDANN showed significant correlation with all classic indexes of RSA (E:I: r = 0.62, 0.55, respectively, E-I: r = 0.64, 0.57, respectively), E:Iindep (r = 0.59, 0.54, respectively), E-Iindep (r = 0.47, 0.43, respectively) and VI (r = 0.42, 0.34, respectively). Significant correlation of rMSSD with E:I (r = 0.37), E-I (r = 0.41) and E:Iindep (r = 0.34) was also observed. There was no association of any variable with pNN50. Have been show high values for all variables of independent cycles method (p < 0.05). CONCLUSION:The autonomic maneuvers, especially RSA, are useful methods to evaluate cardiac autonomic function in hemodialysis patients. The acquisition of the RSA index by independent cycles should not be used in this population. 10.1007/s10286-016-0351-0
    Prevalence of autonomic dysfunction among pre-dialysis chronic kidney disease patients in a tertiary hospital, South East Nigeria. Onodugo Obinna,Arodiwe Ejikeme,Okoye Julius,Ezeala Birinus,Onodugo Nkiru,Ulasi Ifeoma,Ijoma Chinwuba African health sciences Background:Autonomic dysfunction (AD) has been recognized as an important contributor to the poor outcome in chronic kidney disease (CKD) patients. Several studies have reported abnormalities in heart rate variability (HRV) among these patients. Objectives:To determine the prevalence of Autonomic Dysfunction (AD) in pre-dialysis Chronic Kidney Disease (CKD) patients in a tertiary hospital in South East Nigeria. Methods:A cross sectional study of eighty chronic kidney disease patients attending the renal unit out-patient in the University of Nigeria Teaching Hospital (UNTH) Enugu was carried out. Forty subjects, drawn randomly, who had no kidney disease served as control. Autonomic function was assessed with non - invasive cardiovascular tests including, measurement of resting tachycardia, orthostatic hypotension, heart rate response (HRR) to standing test, heart rate response to Vasalva manoeuvre and heart rate response to respiration. Results:With the battery of 5 tests used to assess AD, the frequency of autonomic dysfunction in pre-dialysis chronic kidney disease patients was 51.3% compared to 7.5% in the control group. Heart rate response to standing was the most sensitive test to detect AD in this group of subjects. Conclusion:AD is a common problem among pre-dialysis CKD patients in Nigeria. 10.4314/ahs.v18i4.14
    Non-Linear Heart Rate Variability Indices in the Frequent Hemodialysis Network Trials of Chronic Hemodialysis Patients. Ferrario Manuela,Raimann Jochen G,Larive Brett,Pierratos Andreas,Thijssen Stephan,Rajagopalan Sanjay,Greene Tom,Cerutti Sergio,Beck Gerald,Chan Christopher,Kotanko Peter, Blood purification BACKGROUND:Non-linear heart rate variability (HRV) indices were hypothesized to correlate with cardiac function, fluid overload and physical performance in hemodialysis patients. METHODS:Twenty-four-hour Holter electrocardiograms were recorded in patients enrolled in the Frequent Hemodialysis Network (FHN) Daily Dialysis Trial. Correlations between non-linear HRV indices and left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), extracellular volume (ECV)/total body water (TBW) ratio, the SF-36 Physical Health Composite (PHC) and Physical Functioning (PF) scores were tested. RESULTS:We studied 210 subjects (average age 49.8 ± 13.5 years, 62% men, 42% diabetics). In non-diabetic patients, multiscale entropy (MSE) slope sample entropy (SampEn) and approximate entropy (ApEn) correlated positively with LVEF, PF and PHC and inversely with LVEDV and ECV/TBW. Spectral power slope correlated positively with ECV/TBW (r = 0.27). Irregularity measures (MSE ApEn and MSE SampEn) correlated positively with LVEDV (r = 0.19 and 0.20). CONCLUSION:Non-linear HRV indices indicated an association between a deteriorated heart rate regulatory system and impaired cardiac function, fluid accumulation and poor physical condition. 10.1159/000381665
    Heart Rate Variability Predicts Major Adverse Cardiovascular Events and Hospitalization in Maintenance Hemodialysis Patients. Huang Jiun-Chi,Kuo I-Ching,Tsai Yi-Chun,Lee Jia-Jung,Lim Lee-Moay,Chen Szu-Chia,Chiu Yi-Wen,Chang Jer-Ming,Chen Hung-Hun Kidney & blood pressure research BACKGROUND/AIMS:Heart rate variability (HRV) has been linked to mortality in maintenance hemodialysis (HD) patients, but it is less clear whether HRV is associated with major adverse cardiovascular events (MACEs) and hospitalization. METHODS:This study enrolled 179 maintenance HD patients. HRV was measured to assess its prognostic significance in relation to MACEs and hospitalization. RESULTS:During the follow-up period of 33.3 ± 6.7 months, 36 (20.1%) patients had a MACE, and 98 (54.7%) experienced hospitalization. In multivariate adjusted Cox regression analysis, low very low frequency (VLF) power (hazard ratio [HR], 0.727; 95% confidence interval [CI], 0.624-0.848; p < 0.001), a history of coronary artery disease, high ultrafiltration rate, the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and the use of beta-blockers were all significantly associated with MACEs. Low VLF power (HR, 0.873; 95% CI, 0.785-0.971; p = 0.012), low serum albumin, low serum creatinine, low Kt/V levels, and high serum calcium-phosphorus product levels significantly predicted hospitalization in maintenance HD patients. CONCLUSIONS:Reduced VLF power is linked to an increased risk of MACEs and hospitalization in maintenance HD patients. Assessing cardiac autonomic function through HRV is of pivotal prognostic significance for this patient population. 10.1159/000469716
    Heart rate variability is an indicator for intradialytic hypotension among chronic hemodialysis patients. Chang Yu-Ming,Shiao Chih-Chung,Chang Kuo-Chi,Chen I-Ling,Yang Chuan-Lan,Leu Show-Chin,Su Hung-Li,Kao Jsun-Liang,Tsai Shih-Ching,Jhen Rong-Na Clinical and experimental nephrology BACKGROUND:Intradialytic hypotension (IDH) carries adverse impact. Heart rate variability (HRV) represents autonomic cardiac regulation which influences intradialytic blood pressure. We aimed to evaluate the association between IDH and HRV. METHODS:This prospective study was carried out in a teaching hospital in Taiwan from June to August 2010. Adult patients on chronic hemodialysis without active medical conditions were enrolled and received HRV measurements for 4 times (before and during an index hemodialysis session). Patients were categorized by the changes of systolic blood pressure during the index hemodialysis into Group 1 (elevation >20 mmHg), Group 2 (decrease >20 mmHg), and Group 3 (others). Then we compared HRV indices among the three groups, and determined the indicators for IDH. RESULTS:One hundred and seventy-one patients (96 women, mean age 64.9 years) were enrolled and categorized into Group 1 (n = 47, 27.5 %), Group 2 (n = 45, 26.3 %) and Group 3 (n = 79, 46.2 %). Comparing with Group 1 and/or Group 3, Group 2 had significantly higher blood pressure at hemodialysis initiation (most p < 0.001) and statistically lower levels of HRV indices including variance, total power, very low-frequency, low-frequency and high-frequency since the middle phase of the hemodialysis. By logistic regression method, higher systemic blood pressure [odds ratio (OR) 1.048; p < 0.001], heart rate (OR 1.093; p = 0.021), low-frequency/high-frequency ratio (OR 1.715; p = 0.022), as well as lower variance (OR 0.639; p = 0.048) at hemodialysis initiation were independently associated with intradialytic blood pressure changes. CONCLUSIONS:HRV is a useful indicator for IDH among hemodialysis patients. 10.1007/s10157-015-1189-9
    Effects of daily hemodialysis on heart rate variability: results from the Frequent Hemodialysis Network (FHN) Daily Trial. Chan Christopher T,Chertow Glenn M,Daugirdas John T,Greene Tom H,Kotanko Peter,Larive Brett,Pierratos Andreas,Stokes John B, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association BACKGROUND:End-stage renal disease is associated with reduced heart rate variability (HRV), components of which generally are associated with advanced age, diabetes mellitus and left ventricular hypertrophy. We hypothesized that daily in-center hemodialysis (HD) would increase HRV. METHODS:The Frequent Hemodialysis Network (FHN) Daily Trial randomized 245 patients to receive 12 months of six versus three times per week in-center HD. Two hundred and seven patients had baseline Holter recordings. HRV measures were calculated from 24-h Holter electrocardiograms at both baseline and 12 months in 131 patients and included low-frequency power (LF, a measure of sympathetic modulation), high-frequency power (HF, a measure of parasympathetic modulation) and standard deviation (SD) of the R-R interval (SDNN, a measure of beat-to-beat variation). RESULTS:Baseline to Month 12 change in LF was augmented by 50% [95% confidence interval (95% CI) 6.1-112%, P =0.022] and LF + HF was augmented by 40% (95% CI 3.3-88.4%, P = 0.03) in patients assigned to daily hemodialysis (DHD) compared with conventional HD. Changes in HF and SDNN were similar between the randomized groups. The effects of DHD on LF were attenuated by advanced age and diabetes mellitus (predefined subgroups). Changes in HF (r = -0.20, P = 0.02) and SDNN (r = -0.18, P = 0.04) were inversely associated with changes in left ventricular mass (LVM). CONCLUSIONS:DHD increased the LF component of HRV. Reduction of LVM by DHD was associated with increased vagal modulation of heart rate (HF) and with increased beat-to-beat heart rate variation (SDNN), suggesting an important functional correlate to the structural effects of DHD on the heart in uremia. 10.1093/ndt/gft212
    Effects of Orthostatism and Hemodialysis on Mean Heart Period and Fractal Heart Rate Properties of Chronic Renal Failure Patients. Echeverría Juan C,Infante Oscar,Pérez-Grovas Héctor,González Hortensia,José Marco V,Lerma Claudia Artificial organs The aim of this work was to evaluate the short-term fractal index (α ) of heart rate variability (HRV) in chronic renal failure (CRF) patients by identifying the effects of orthostatism and hemodialysis (HD), and by evaluating the correlation between α and the mean RR interval from sinus beats (meanNN). HRV time series were derived from ECG data of 19 CRF patients and 20 age-matched healthy subjects obtained at supine and orthostatic positions (lasting 5 min each). Data from CRF patients were collected before and after HD. α was calculated from each time series and compared by analysis of variance. Pearson's correlations between meanNN and α were calculated using the data from both positions by considering three groups: healthy subjects, CRF before HD and CRF after HD. At supine position, α of CRF patients after HD (1.17 ± 0.30) was larger (P < 0.05) than in healthy subjects (0.89 ± 0.28) but not before HD (1.10 ± 0.34). α increased (P < 0.05) in response to orthostatism in healthy subjects (1.29 ± 0.26) and CRF patients after HD (1.34 ± 0.31), but not before HD (1.25 ± 0.37). Whereas α was correlated (P < 0.05) with the meanNN of healthy subjects (r = -0.562) and CRF patients after HD (r = -0.388), no significance in CRF patients before HD was identified (r = 0.003). Multiple regression analysis confirmed that α was mainly predicted by the orthostatic position (in all groups) and meanNN (healthy subjects and patients after HD), showing no association with the renal disease condition in itself. In conclusion, as in healthy subjects, α of CRF patients correlates with meanNN after HD (indicating a more irregular-like HRV behavior at slower heart rates). This suggests that CRF patients with stable blood pressure preserve a regulatory adaptability despite a shifted setting point of the heart period (i.e., higher heart rate) in comparison with healthy subjects. 10.1111/aor.12887
    Quantification of autonomic nervous activity by heart rate variability and approximate entropy in high ultrafiltration rate during hemodialysis. Tsuji Yoshihiro,Suzuki Naoki,Hitomi Yasumasa,Yoshida Toshiko,Mizuno-Matsumoto Yuko Clinical and experimental nephrology BACKGROUND:Few studies have focused on the imbalance of the autonomic nervous system in ultrafiltration rate (UFR) subjects without blood pressure variation during maintenance hemodialysis (HD), although the role of autonomic nervous system activation during HD has been proposed to be an important factor for the maintenance of blood pressure. METHODS:Variations over time in autonomic nervous activity due to differences in UFR were evaluated by measuring heart rate variability (HRV) and approximate entropy (ApEn) in 35 HD patients without blood pressure variations during HD session. The subjects were divided into 3 groups, those with UFR <10 ml/h/kg; ≥10 ml/h/kg but ≤15 ml/h/kg; and >15 ml/h/kg, and Holter ECG was recorded continuously during HD session using frequency analysis of RR intervals. High frequency (HF) and low frequency (LF) spectral components are found to be representative of the parasympathetic nervous system and sympathovagal balance, respectively, with the ratio of LF to HF of HRV providing a measure of sympathetic nervous system. RESULTS:In subjects with UFR >15 ml/h/kg, HF components were significantly lower, and LF/HF and ApEn values were significantly higher, in the latter half of an HD session than before starting HD. CONCLUSION:Removing water from these subjects would promote sustained sympathetic nervous overactivity. These findings indicate that the UFR during HD needs to be set at ≤15 ml/h/kg. 10.1007/s10157-016-1305-5
    Effects of stroke on changes in heart rate variability during hemodialysis. Huang Jiun-Chi,Chen Chien-Fu,Chang Chia-Chu,Chen Szu-Chia,Hsieh Ming-Chia,Hsieh Yao-Peng,Chen Hung-Chun BMC nephrology BACKGROUND:Stroke and low heart rate variability (HRV) are both associated with an unfavorable prognosis in hemodialysis patients. The relationship between stroke and changes in HRV during hemodialysis remains unclear. METHODS:This study measured differences between predialysis and postdialysis HRV (△HRV) in 182 maintenance hemodialysis patients, including 30 patients with stroke, to assess changes in HRV during hemodialysis, and also to compare results to 114 healthy controls. RESULTS:All predialysis HRV measurements had no differences between stroke patients and those without stroke, but were lower than healthy controls. Postdialysis very low frequency (VLF) (P < 0.001), low frequency (LF) (P = 0.001), total power (TP) (P < 0.001) and the LF/high frequency (HF) ratio (P < 0.001) increased significantly relative to predialysis values in patients without stroke, whereas postdialysis HRV did not increase in stroke patients. After multivariate adjustment, dialysis vintage was negatively associated with △VLF (β = -0.698, P = 0.046), △LF (β = -0.931, P = 0.009), and △TP (β = -0.887, P = 0.012) in patients without stroke. Serum intact parathyroid hormone (β = -0.707, P = 0.019) was negatively associated with △LF. Total cholesterol (β = -0.008, P = 0.001) and high sensitivity C-reactive protein (β = -0.474, P = 0.012) were inversely correlated with the △LF/HF ratio in patients without stroke. CONCLUSION:HRV in hemodialysis patients is lower than in the general population. Increase in △HRV was observed in hemodialysis patients without stroke but not in stroke patients. This result suggests suppressed autonomic nervous reactions against volume unloading during hemodialysis, which might contribute to unfavorable outcomes in hemodialysis patients but even more so in those with prior stroke. Nephrologists should notice the importance of △HRV especially in high-risk patients. 10.1186/s12882-017-0502-0
    Abnormal nocturnal heart rate variability response among chronic kidney disease and dialysis patients during wakefulness and sleep. Roumelioti Maria-Eleni,Ranpuria Reena,Hall Martica,Hotchkiss John R,Chan Chris T,Unruh Mark L,Argyropoulos Christos Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association BACKGROUND:Dialysis patients and patients with chronic kidney disease (CKD) experience a substantial risk for abnormal autonomic function and abnormal heart rate variability (HRV). It remains unknown whether HRV changes across sleep stages in patients with different severity of CKD or dialysis dependency. We hypothesized that high-frequency (HF) HRV (vagal tone) will be attenuated from wakefulness to non-rapid eye movement (NREM) and then to rapid eye movement (REM) sleep in dialysis patients as compared to patients with CKD. METHODS:In-home polysomnography was performed in 95 patients with stages 4-5 CKD or end-stage renal disease (ESRD) on haemodialysis (HD) or peritoneal dialysis (PD). HRV was measured using fast Fourier transform of interbeat intervals during wakefulness and sleep. Low-frequency (LF) and HF intervals were generated. Natural logarithm HF (LNHF) and the logarithm LF/HF ratio (sympathovagal tone) were analysed by multivariable quantile regression and generalized estimating equations. RESULTS:Of the 95 patients, 63.2% (n = 60) was male, 35.8% (n = 34) was African American and 20.4% (n = 19) was diabetic. Average age was 51.6 ± 15.1 (range 19-82). HRV variables were significantly associated with diabetic status, higher periodic limb movement indices and lower bicarbonate levels. Patients with advanced CKD did not differ from dialysis patients in their inability to increase vagal tone during sleep. During wakefulness, female gender (P = 0.05) was associated with the increases in the vagal tone. CONCLUSIONS:Patients with CKD/ESRD exhibit dysregulation of the autonomic nervous system tone manifesting as a failure to increase HRV during wakefulness and sleep. Different patient characteristics are associated with changes in HRV at different sleep stages. 10.1093/ndt/gfq234
    Usefulness of measurement of heart rate variability by holter ECG in hemodialysis patients. Kida Nanami,Tsubakihara Yoshiharu,Kida Hirota,Ageta Shunro,Arai Makoto,Hamada Yoshinosuke,Matsuura Nariaki BMC nephrology BACKGROUND:Major adverse cardiac and cerebrovascular event (MACCE) is one of most common complications of hemodialysis patients. Heart rate variability (HRV) is the predictor of death in heart disease patients. However, there are no studies on the role of HRV in hemodialysis patients. METHODS:From September 2009 to March 2011, 24-h electrocardiography was performed in 101 hemodialysis patients. Standard deviation of sequential 5-minute N-N interval means (SDANN) and standard deviation of the N-N interval (SDNN) was examined by a 24-h ECG analysis. Patients were observed prospectively. The primary endpoints were incidence of MACCE and MACCE-free survival. RESULTS:We studied 90 hemodialysis patients (64 males, 63.4 ± 11.8 years old). During a follow-up period of 32.0 ± 11.7 months, 33 patients developed MACCE. 24-h ECG showed mean SDNN 93.4 ± 33.4 ms and mean SDANN 83.2 ± 31.3 ms. MACCE group showed significantly lower SDNN and SDANN than event-free group. In Kaplan-Meier analysis higher SDNN and SDANN group showed significantly higher event-free survival rate than lower group. Using a Cox proportional hazards model, SDNN was independent prognostic factor while SDANN or diabetic status was not significant. In diabetic cases, there were no differences in any factors for the incidence of MACCE between higher SDNN, SDANN groups and lower groups. On the other hand in non-diabetic cases, lower SDNN or SDANN group developed significantly higher MACCE than higher groups. CONCLUSION:Measurement of HRV by Holter ECG is useful to predict MACCE in hemodialysis patients, especially non-diabetic group. 10.1186/s12882-016-0423-3
    Associations of parathyroid hormone levels and mineral parameters with heart rate variability in patients with end-stage renal disease. Zhang Lei,Yang Shaoyan,Chen Jianling,Ma Jinling,Ren Yueqin International urology and nephrology PURPOSE:Parathormone (PTH) is a very potent uraemic toxin, which affects calcium/phosphate homeostasis in patients with end-stage renal disease (ESRD). It also plays the role in uraemic autonomic neuropathy. The aim of the study was to investigate the relationship between elevated PTH levels and cardiac autonomic neuropathy assessed by frequency-domain measures of heart rate variability. METHODS:24-h ECG was performed in 106 ESRD patients and 65 healthy controls. Very-low-frequency (VLF), low-frequency (LF) and high-frequency (HF) bands were computed. LF/HF ratio was calculated. RESULTS:We found that most heart rate variability indices were lower in ESRD patients than in healthy controls. Variables including demographics (age, sex, body mass index, dialysis vintage, systolic pressure, and diastolic pressure), laboratory values (Hb, Hct, glucose, Alb, and triglyceride), and bone metabolism panel (Ca, P, ALP, and iPTH) were selected as independent variables in the multivariable models. In multivariate analysis, serum intact PTH (iPTH) was correlated with mean normal-to-normal R-R intervals, mean heart rate, and VLF, serum calcium was correlated with standard deviation of 5-min average of normal R-R intervals (SDANN), and serum phosphorus was correlated with VLF and LF/HF. Serum iPTH was independently correlated with mean normal-to-normal R-R intervals (NN), mean HR, and VLF. Serum Ca was independently correlated with SDANN, and serum P was independently correlated with VLF and LF/HF. The results remained significant after the adjustment for iPTH. CONCLUSIONS:In conclusion, high PTH levels and disorders of mineral metabolism are associated with decreased heart rate variability in ESRD patients. 10.1007/s11255-017-1513-2
    Heart rate variability as a predictor of rapid renal function deterioration in chronic kidney disease patients. Chou Yu-Hsiang,Huang Wei-Lieh,Chang Chin-Hao,Yang Cheryl C H,Kuo Terry B J,Lin Shuei-Liong,Chiang Wen-Chih,Chu Tzong-Shinn Nephrology (Carlton, Vic.) AIM:Autonomic dysfunction contributes to cardiovascular morbidity/mortality and can be evaluated with heart rate variability (HRV). This study is to evaluate the prognostic significance of HRV on renal function in non-dialysis chronic kidney disease (CKD) patients. METHODS:We enrolled 326 non-dialysis CKD patients in this prospective observational study. The median follow-up period was 2.02 years. Five-minutes of electrocardiography recordings obtained at enrolment were reprocessed to assess HRV. Five frequency-domain measures and one time-domain measures were obtained. Rapid CKD progression was defined as annual estimated glomerular filtration rate (eGFR) loss over 30% per year or eGFR decline rate over 3 mL/min per 1.73 m per year. The prevalence of abnormal HRV, associated factors of HRV and impact of HRV on the risk of CKD progression were analyzed. RESULTS:The abnormality of HRV increased along with the severity of CKD. In patients with stage 5 CKD, the proportion of abnormal ln(low frequency power) (LF), ln(high frequency power) (HF), lnLF/HF were 69.5, 52.8 and 50%, respectively. Associated factors of HRV included advanced CKD, diabetes mellitus, serum albumin, severe proteinuria, Beck Anxiety Inventory score, erythropoietin use, renin-angiotensin system inhibitors and heart failure. Multivariate logistic regression model analysis revealed lower lnLF/HF, hypertension and severe proteinuria were the risk factors of rapid CKD progression. CONCLUSION:The prevalence of autonomic dysfunction measured by HRV among each stage CKD patients is different. Most patients in advanced CKD stage have reduced values of HRV parameters. The estimation of lnLF/HF also provided prognostic information on CKD progression in addition to classical risk factors. 10.1111/nep.13514
    Short-term heart rate variability as a predictor of long-term survival in patients with chronic hemodialysis: A prospective cohort study. Kuo George,Chen Szi-Wen,Huang Jeng-Yi,Wu Chao-Yi,Fu Chung-Ming,Chang Chih-Hsiang,Liu Su-Hsun,Chan Yi-Hsin,Wu I-Wen,Yang Huang-Yu Journal of the Formosan Medical Association = Taiwan yi zhi BACKGROUND:Heart rate variability (HRV), a non-invasive measurement of the sympathetic-vagal balance, has been demonstrated as a predictor of long-term survival in various patient populations. However, its predictive value in patients with end-stage renal disease (ESRD) has not been evaluated in a long-term follow-up study. METHODS:Prospective data collected for 41 patients with chronic hemodialysis (age 59 ± 10 years, men 51.3%, diabetes mellitus 31%, and duration of dialysis 64 ± 50 months) who underwent a 5-minute electrocardiogram (ECG) recording as a baseline for frequency domain HRV analysis. RESULTS:During a median follow-up of 150.2 months from 2003 to 2014, 15 (35.7%) patients died (3 due to cardiac causes and 12 due to non-cardiac causes). The Cox proportional hazards model suggested that the low frequency versus high frequency signal (LF/HF) of a high ratio for the HRV and diabetes mellitus were two independent predictors of mortality (hazard ratios 3.028 and 3.494; p = 0.033 and 0.022, respectively). Less reduction in MAP during dialysis showed borderline significance of long-term survival than those with larger drop (p = 0.058). CONCLUSION:A short ECG recording and an analysis of the frequency domain of the HRV is clinically predictive of the long-term survival of patients with chronic hemodialysis. 10.1016/j.jfma.2018.09.006