Clinical significance of heart rate variability for the monitoring of cardiac autonomic neuropathy in end-stage renal disease patients

Highlights

• HRV in ESRD patients are lower than healthy controls.

• HRV correlates with diastolic dysfunctions in ESRD patients.

• HRV correlates with endothelial dysfunction and atherosclerosis.

Abstract

Background and aims

The aim of this study is to determine whether the measurement of continuous heart rate variability (HRV) is useful in the evaluation of cardiac autonomic neuropathy (CAN) in end-stage renal disease (ESRD) patients.

Methods and results

This cross-sectional study was performed at Seoul St. Mary's hospital between June 2017 and February 2018. Seventy-seven ESRD patients, and 29 healthy controls (HCs) were asked to wear a continuous ambulatory HRV monitor for 24 h. General cardiac function was evaluated using transthoracic echocardiogram (TTE), pulse wave velocity (PWV), coronary calcium scoring (CCS), and 24-h ambulatory blood pressure monitoring (ABPM). HRV parameters of ESRD patients and HCs, and the correlation of HRV parameters with cardiovascular screening methods were observed. All HRV parameters were significantly decreased in ESRD patients compared to HCs (P < 0.001). In the correlation analysis between TTE results and HRV parameters, 24-h standard deviation of all N–N intervals (24SDNN), 24-h standard deviation of sequential 5-min N–N interval means (24DANN) and Low Frequency Power/High Frequency Power (LF/HF) ratio showed negative correlations with E/e’, LAVI and TR velocity which are representative indices for the diastolic function of the heart (P < 0.05). HRV parameters showed negative correlations with baPWV, CCS, and 24-h ABPM results as well (P < 0.05). Hemoglobin and serum albumin showed positive correlations with HRV parameters, and glucose, BUN, creatinine, and iPTH levels showed negative correlations (P < 0.05).

Conclusion

Continuous HRV monitoring may be a useful tool for the evaluation of CAN in ESRD.

Introduction

The number of end-stage renal disease (ESRD) patients are increasing in Korea and internationally. The most common cause of mortality known in ESRD patients are cardiovascular events [1], and several risk factors such as uremia, increased inflammatory markers, vascular calcification, secondary hyperparathyroidism, and comorbidities such as diabetes and hypertension add to the risk [2]. Autonomic dysfunction, especially cardiac autonomic neuropathy (CAN) is also common among ESRD patients, and is a well-known risk factor for ventricular arrhythmia and sudden cardiac death in this patient group [3,4].

The autonomic nervous system has an essential role in controlling heart rate, blood pressure and respiratory function, and its dysfunction results in abnormal heart rate variability (HRV) [3,5]. HRV, which measures the variation of beat-to-beat intervals, is a non-invasive method for measuring autonomic input to the heart. Reduced HRV is known to be associated with higher risk of coronary heart disease and mortality in healthy subjects [6,7] as well as in those with chronic kidney disease (CKD) [8]. In addition, it was reported that reduced HRV or autonomic dysfunction is associated with reduced renal function in patients with CKD [4,9,10]. In the study by Chou et al. HRV decreased along with the severity of CKD, and low frequency power (LF)/high frequency power (HF) ratio was predictive of rapid CKD progression [11]. Furthermore, HRV was reported to predict hospitalization of CKD patients [12], and was linked with hyperphosphatemia in CKD patients [13].

However, results of previous studies are usually based on HRV measurement of shorter duration or have limitations in the method of HRV measurement. The results from the PREVEND study were based on 15-min pulse wave measurements [9], and the study by Brotman et al. measured HRV from 2-min beat-to-beat heart rate recordings [12]. Also, conventional Holter-based 24-h recordings are cumbersome for patients to carry and difficult for physicians to interpret due to background noise. Therefore, a more accessible ambulatory and continuous HRV measurement method is needed. In the study by Kim et al. the HRV of sixty-one young healthy subjects was monitored for 24–48 h using wearable devices including an R–R interval recorder and a customized electrocardiography electrode [14]. They observed the diurnal fluctuations of HRV, in real-time. Using this device, a more precise and longer duration HRV monitoring would be possible for CKD patients, with monitoring of both day and night HRV.

Therefore, the aim of our study was to investigate the continuous HRV pattern of ESRD patients in comparison with healthy subjects and also to observe whether HRV results correlate with results of well-known cardiovascular surveillance tools in ESRD patients using an ambulatory real time monitoring device.