Introduction: Decreased heart rate variability (HRV) in patients with end stage renal disease (ESRD) undergoing hemodialysis is predictive of cardiac death, especially due to sudden death. Objective: To evaluate the effects of aerobic training during hemodialysis on HRV and left ventricular function in ESRD patients. Methods: Twenty two patients were randomized into two groups: exercise (n = 11; 49.6 ± 10.6 years; 4 men) and control (n = 11; 43.5 ± 12.8; 4 men). Patients assigned to the exercise group were submitted to aerobic training, performed during the first two hours of hemodialysis, three times weekly, for 12 weeks. HRV and left ventricular function were assessed by 24 hours Holter monitoring and echocardiography, respectively. Results: After 12 weeks of protocol, no significant differences were observed in time and frequency domains measures of HRV in both groups. The ejection fraction improved non-significantly in exercise group (67.5 ± 12.6% vs. 70.4 ± 12%) and decreased non-significantly in control group (73.6 ± 8.4% vs. 71.4 ± 7.6%). Conclusion: A 12-week aerobic training program performed during hemodialysis did not modify HRV and did not significantly improve the left ventricular function.
Descriptors: exercise, renal dialysis, heart rate, ventricular function, left.
Introdução: Pacientes com doença renal crônica (DRC) sob tratamento hemodialítico apresentam diminuição da variabilidade da frequência cardíaca (VFC) que representa um fator de risco independente para a mortalidade cardíaca, especialmente a morte súbita. Objetivo: Avaliar o efeito do exercício aeróbico, realizado durante as sessões de hemodiálise, na VFC e na função ventricular esquerda de pacientes portadores de DRC. Métodos: Foram avaliados 22 pacientes randomizados em dois grupos: exercício (n = 11; 49,6 ± 10,6 anos; 4 homens) e controle (n = 11; 43,5 ± 12,8; 4 homens). Os pacientes do grupoexercício foram submetidos a três sessões semanais de exercício aeróbico, realizado nas duas horas iniciais da hemodiálise, durante 12 semanas. Para a análise da VFC e da função ventricular esquerda, todos os pacientes foram submetidos aos exames de Holter de 24 horas e ecocardiograma, respectivamente. Resultados: Após 12 semanas de protocolo, não foi observada diferença significante em nenhum dos parâmetros da VFC nos domínios do tempo e da frequência em ambos os grupos. A fração de ejeção aumentou de modo não significante nos pacientes do grupo-exercício (67,5 ± 12,6% vs. 70,4 ± 12%) e diminuiu não significantemente nos pacientes do grupo-controle (73,6 ± 8,4% vs. 71,4 ± 7,6%). Conclusão: A realização de 12 semanas de exercício aeróbico, durante as sessões de hemodiálise, não modificou a VFC e não promoveu melhora significante na função ventricular esquerda.
Descritores: exercício, diálise renal, frequência cardíaca, função ventricular esquerda.
The high mortality rate among patients with chronic kidney disease (CKD) undergoing hemodialysis is mainly associated with a high prevalence of cardiovascular diseases, such as coronary artery disease, arterial hypertension, left ventricular hypertrophy, and heart failure.1 Another relevant cardiovascular event in those patients is the occurrence of cardiac arrhythmias, which represent the major cause of sudden death.2
The development of cardiac arrhythmias in patients with CKD is associated with autonomic dysfunction evidenced by the reduction in heart rate variability (HRV).3 In addition, the reduction in HRV represents an independent risk factor for cardiac mortality in those patients.4,5
Thus, strategies, such as exercise training, have been implemented aiming at reducing cardiovascular mortality due to an increase in HRV and improvement of the left ventricular function, specially in the population with heart disease.6,7 However, only a few studies have assessed the effect of an exercise training program on those cardiovascular parameters in patients with CKD undergoing hemodialysis.8-11
This study aimed at assessing the effects of guided aerobic training during hemodialysis sessions on HRV and left ventricular function of patients with CKD.
The sample comprised patients with CKD undergoing hemodialysis at the Nephrology Service of the Hospital Universitário of the Universidade Federal de Juiz de Fora, state of Minas Gerais, three times a week, in a total of 12 hours per week, for at least six months. During hemodialysis sessions, polysulfone membrane and bath with the following characteristics were used: sodium, 138.0 mEq/L; potassium, 2.0 mEq/L; calcium, 2.5 mEq/L; magnesium, 1.0 mEq/L; chloride, 108.5 mEq/L; acetate, 3.0 mEq/L; bicarbonate, 32.0 mEq/L. Adult patients, of both sexes, who did not exercise on a regular basis for at least six months were included.
The exclusion criteria were as follows: diabetes mellitus; unstable angina; uncontrolled arterial hypertension [systolic blood pressure (SBP) > 200 mm Hg and/or diastolic blood pressure (DBP) > 120 mm Hg]; use of antiarrhythmic drugs; severe pneumopathies; acute systemic infection; severe renal osteodystrophy; and disabling neurological and muscle-skeletal disorders.
The study project was approved by the Committee on Ethics in Research of the Universidade Federal de Juiz de Fora and all patients who agreed to participate in the study provided written informed consent.
Initially, the patients included in the study were randomized into an exercise and a control group. Patients in the exercise group underwent three sessions of aerobic exercise per week, performed during hemodialysis sessions, for 12 weeks, while patients in the control group remained in the usual dialytic treatment.
At baseline and after 12 weeks in the study, all patients underwent Holter monitoring and echocardiography, conducted by examiners who did not know about the groups. In addition, a blood sample was also collected.
Holter monitoring and heart rate variability assessment
Holter monitoring was performed for 24 hours, in the interdialytic period, by use of a digital Holter monitor (DMS 300-7, Compact Flash Card Holter Recorder, DMS, Nevada, USA). The data stored were processed by use of the Cardio Scan 8.0 software to assess HRV. Abnormal beats and artifact areas were automatically and manually identified and excluded from analysis. Heart rate variability was assessed in the time and frequency domains.
For analysis in the time domain, normal R-R intervals were called iNN. To assess HRV in the time domain and based on iNN, the following parameters were obtained by use of statistical methods: mean of the standard deviations of iNN every five minutes (SDNN index); root of the mean squared difference of successive iNN (RMSSD); and percentage of successive iNN with a difference in duration greater than 50 ms (pNN50).12
When assessing HRV in the frequency domain, a low frequency (LF) band (between 0.04 and 0.15 Hz) and a high frequency (HF) band (between 0.15 and 0.40 Hz) were used. The LF/HF ratio was obtained.12
Beta-blockers were suspended four days before Holter monitoring.
M mode and two-dimensional echocardiography was performed in the interdialytic period by a single cardiologist, with the Doppler technique (VIVID 3 - GE Healthcare, Milwaukee, Wisconsin, USA). Anatomical and functional data were obtained at rest by use of a 3.5-MHz linear transducer, placed on the third or fourth left intercostal space. Measures were obtained and analyzed according to the guidelines of the American Society of Echocardiography.13
Left ventricular mass index was obtained by correcting left ventricular mass to body surface.14,15 The geometrical classification of the left ventricle was based on the assessment of left ventricular mass and relative wall thickness.15 The following indices were measured for assessing left ventricular function: end diastolic volume; end systolic volume; systolic volume; and ejection fraction.
The following values were assessed: hemoglobin (g/ dL); hemodialysis efficiency index (Kt/V); creatinine (mg/dL); phosphorus (mg/dL); potassium (mEq/L); calcium (mg/dL); and albumin (g/dL). Blood samples were collected before the hemodialysis session, with no indication of fasting.
Supervised aerobic training was performed within the first two hours of hemodialysis, and lasted, on average, one hour. The training comprised three steps: warm up; conditioning; and cool down. A horizontal electromagnetic cycle ergometer (Movement, BM 4000, Brudden Equipamentos Ltda, São Paulo, Brazil) was used for aerobic exercise training.
Warm up comprised stretching the lower limbs for approximately 10 minutes, and aerobic exercise training with low load (4.9 N.m) and at low rotation (up to 35 rpm) for five minutes. Conditioning consisted of aerobic exercise training for up to 35 minutes. The duration of exercise training was individualized according to the response of the patients: they started training for a period of time with which they felt comfortable and were encouraged to increase the length of training session to complete 35 minutes. Load was assigned according to the tolerance of each patient, who was instructed to maintain a constant rotation throughout the entire aerobic exercise training. The intensity of the training was determined by the Borg-modified scale, in which patients had to remain between four and six.16 Cool down consisted in one to three minutes of aerobic exercise with a 4.9 N.m load and at low rotation.
Arterial blood pressure was monitored at rest, every five minutes during conditioning, and after cool down. Heart rate was continuously monitored by use of a cardiofrequencemetre (Polar F1, Polar Electro Oy, Kempele, Finland).
The criteria for interrupting aerobic exercise included intense physical fatigue, chest pain, dizziness, paleness, lipothymia, tachycardia, hypotension, and lower limb fatigue.
When patients had a change in blood pressure (SBP > 180 mm Hg and/or DBP > 110 mm Hg), interdialytic weight gain greater than 5 kg, difficulty in vascular access, or any significant complain (pain, dyspnea) before exercise training, they could not exercise on that day or while such changes persisted.
Data were expressed as mean ± standard deviation or median (interquartile range), when appropriate. For comparing initial and final values in each group, paired t test and Wilcoxon test were used for parametric and nonparametric data, respectively. For comparing the groups, non-paired t test or Mann- Whitney test were used, when appropriate.
Difference was considered statistically significant when p value was lower than 0.05. All analyses were performed in the SPSS 13.0 for Windows program (SPSS Inc, Chicago, USA).
Characteristics of the patients
Of the 81 patients on chronic hemodialysis, 28 met the inclusion criteria and agreed to participate in the study. Of those, 22 patients completed the study, 11 in each group (Figure 1). As shown in Table 1, no significant difference was observed in the clinical and demographic characteristics and medications between the groups assessed.
Figure 1. Flowchart of patients throughout the protocol.
After 12 weeks following the protocol, a significant difference was observed in neither dry weight (exercise group: 59 ± 4.6 kg vs
. 59.1 ± 4.4 kg; control group 59.7 ± 15.3 kg vs
. 59.6 ± 15.4 kg) nor interdialytic weight gain (exercise group: 1.9 ± 0.8 kg vs
. 2.2 ± 0.9 kg; control group 1.7 ± 0.6 kg vs
. 1.6 ± 0.8 kg). Similarly, the anti-hypertensive drugs and phosphorus binders were maintained in both groups.Aerobic exercise
Adherence to exercise training during the 12 weeks was 75.3 ± 15.2%, and no significant clinical complication was observed during training. The major causes for skipping training were report of pain and fatigue, in addition to pre-dialysis arterial hypotension.Heart rate variability
After 12 weeks following the protocol, no significant difference was observed in the HRV parameters in the time and frequency domains in both groups (Table 2).Echocardiographic data
At baseline and at the end of 12 weeks of training, no significant difference was observed in the echocardiographic variables between the exercise and control groups. Most patients had concentric left ventricular hypertrophy (seven in the exercise group and eight in the control group), while concentric remodeling was identified in the others.
After the aerobic training period, no echocardiographic parameter showed a significant increase (Table 3). The ejection fraction increased in seven of the 11 patients of the exercise group and decreased in most patients of the control group (Figure 2).
Figure 2. Individual data of ejection fraction obtained on echocardiography at baseline and end of the 12 weeks in the exercise and control groups.
After 12 weeks following the protocol, a significant increase in potassium was observed in both groups, and in creatinine and albumin in the control group (Table 4).DISCUSSION
The present study showed that 12 weeks of supervised aerobic training during hemodialysis sessions neither modified HRV nor significantly improved left ventricular function.
The HRV analysis is a non-invasive investigative method to assess the autonomic modulation exerted on the sinus node and has been described as one of the most sensitive techniques for diagnosing autonomic dysfunction.3,12,17,18 The HRV reduction in patients with CKD is considered a risk factor for the occurrence of cardiac arrhythmias, and is associated with a higher cardiovascular mortality.4,5 Cashion et al.19, assessing hemodialysis patients by use of 24-hour Holter to study HRV in the time and frequency domains for a period of two years, have reported that the reduction in the SDNN, LF, and LF/HF parameters predicted cardiovascular death, especially sudden death. In that population, the reduction in HRV associated with injury to the parasympathetic system due to the structural impairment of arteries or the functional alterations of the autonomic nervous system secondary to uremic toxins.18-20
The increase in HRV in patients with CKD has been observed with kidney transplantation and the practice of exercise programs.10,11,21,22 The present study did not show an increase in the HRV assessed in the time and frequency domains after 12 weeks of aerobic training. That finding is likely to be associated with the exercise training period. Contrarily, Deligiannis et al.10, submitting 30 patients with CKD undergoing hemodialysis to 24 weeks of exercise during the interdialytic period, have reported a significant increase in HRV assessed on 24-hour Holter. In another study, those same authors applied 40 weeks of aerobic exercise and strength training during hemodialysis sessions and have also reported an improvement in HRV.11 However, the training time seems to relate to an improvement in HRV in patients with CKD.
The choice of the 12-week training period of this study was due to the benefits observed in previous protocols developed in our center. One of such studies has assessed the effect of a 12-week intradialytic aerobic training in 14 patients with CKD. After the training period, the following was observed: a reduction in blood pressure assessed by use of 24-hour ambulatory blood pressure monitoring; improvement in the quality of life assessed by use of the SF-36 questionnaire; an increase in functional capacity assessed by use of the six-minute walking test; and improvement of anemia and Kt/V23. The present study has not shown a significant increase in hemoglobin and Kt/V after 12 weeks of aerobic training. The significant increase in potassium in both groups and in creatinine and albumin in the control group was not clinically relevant.
In addition to HRV, left ventricular function has also been assessed by use of resting echocardiography. Although no significant improvement has been observed in the ejection fraction after the training period, that parameter increased in seven of the 11 patients in the exercise group. The duration of training also seems to have influenced the improvement in left ventricular function. In accordance, Shalom et al.8 have reported that 12 weeks of exercise training were not accompanied by a significant improvement in left ventricular function. On the other hand, other protocols with longer training have shown a significant increase in ejection fraction.9,11 In one of such studies, the authors have assessed left ventricular function by use of resting and stress echocardiography of 16 hemodialysis patients with CKD undergoing a 24-week aerobic and strength training in the interdialytic period. After the training period, significant gains in the ejection fraction and systolic volume were observed on resting echocardiography; however, on stress echocardiography, significant increases were observed in the ejection fraction, systolic volume, and cardiac output. 9 That result has also been confirmed after 40 weeks of aerobic and strength training during hemodialysis sessions.11
The aerobic training applied during hemodialysis sessions for 12 weeks in this study did not cause a significant improvement in the cardiovascular parameters assessed. Patients with CKD undergoing an exercise program have shown central adaptations, such as improvement of the cardiac performance, and mainly an improvement in peripheral mechanisms, represented by strength and muscle resistance gains, in addition to neural adjustments evidenced by an increase in the nervous conduction velocity.24,25 Those data have been recently confirmed in a study developed by our group, in which, after 12 weeks of intradialytic aerobic training, a significant increase was observed in the kinetics of oxygen consumption.26 Thus, our data allow the speculation that the time of training used in the present study provided an improvement in peripheral mechanisms, although consistent benefits regarding central mechanisms have not been observed. The discrepancy between our findings and those in the literature allows suggesting that aerobic exercises for patients with CKD aiming at assessing HRV should be prescribed for periods longer than 12 weeks.CONCLUSION
Twelve weeks of supervised aerobic training during hemodialysis sessions have not modified HRV and have not promoted a significant improvement of left ventricular function. New protocols with longer training periods are required for assessing the effects of aerobic exercise in those cardiovascular parameters.ACKNOWLEDGMENTS
We thank the Fundação de Amparo à Pesquisa do Estado de Minas Gerais - FAPEMIG (APQ-02452- 09), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES, and the Fundação IMEPEN (Instituto Mineiro de Estudos e Pesquisas em Nefrologia) for financial support. We thank the cardiologist Paulo César Tostes for his support in Holter monitoring. We also thank the nephrologists, nurse team, and staff of the Hemodialysis Service of the HU-UFJF and Fundação IMEPEN for support during the study.REFERENCES
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1. Federal Institute of Education, Science and Technology of Southeast of Minas Gerais (Instituto Federal de Educação, Ciência e Tecnologia do Sudeste de Minas Gerais from Portuguese)
2. Department of Internal Medicine of the Universidade Federal de Juiz de Fora - UFJF
3. Escola Paulista de Medicina of the Universidade Federal de São Paulo
4. Physical therapy of the UFJF 5 Medical School of the UFJF
Dr. Maycon de Moura Reboredo
Rua José Lourenço Khelmer, 1300 - sobreloja, Bairro São Pedro
Juiz de Fora - Minas Gerais - Brasil. CEP: 36036-330
This study was conducted at the Universidade Federal de Juiz de Fora - Interdisciplinary Nucleus of Study and Research in Nephrology (NIEPEN)
Financial support: Fundação de Amparo à Pesquisa do Estado de Minas Gerais - FAPEMIG (APQ-02452-09), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES, and Fundação IMEPEN (Instituto Mineiro de Estudos e Pesquisas em Nefrologia)