Abstract
Background: Autonomic malfunction is linked to elevated cardiovascular morbidity and mortality. Various patient characteristics can alter the cardiac autonomic function therefore, using a prospective observational study, we aimed to assess the effects of different clinical and angiographic factors of coronary artery disease (CAD) patients on the cardiac autonomic function evaluated by heart rate variability (HRV) measurement. Methods and Patients: 100 patients undergoing coronary angiography when clinically indicated were enrolled. A short-term 5-minute HRV measurement was performed by CheckMyheart™ handheld HRV device manufactured by DailyCare BioMedical Inc, Taiwan. HRV data were fed to CheckMyheart™ 5-min HRV analysis software and interpreted based on the standard methods for HRV measurement as discussed in the Task Force of the European Society of Cardiology (ESC) and The North American Society of Pacing and Electrophysiology (NAPSE). Coronary angiography was done with an emphasis on SYNTAX (SX) score calculation. Results: The mean age of the recruited patients was 56.89±10.75 years with 85% of them were males and the mean SX score 13.11±8.52. Multivariate regression analysis of the different patient clinical and angiographic characteristics affecting HRV showed that CAD type either single or multi-vessel and SX score were the major independent variables affecting HRV in patients with CAD. Conclusion: The complexity of CAD measured by SX score was the main independent predictor affecting the cardiac autonomic function estimated by HRV measurement.
Keywords: Coronary artery disease, heart rate variability, cardiac autonomic function, SYNTAX score
Introduction
Cardiac autonomic dysfunction is usually linked to an increased cardiovascular morbidity and mortality risk [1]. Previous studies confirmed that low heart rate variability (HRV) is an independent risk factor for sudden cardiac death (SCD) in coronary artery disease (CAD) [2], previous myocardial infarction (MI) [3], and congestive heart failure patients [4]. It is also an independent predictor of increased cardiovascular risk in diabetic and hypertensive patients [5,6]. CAD and exercise-induced angina are linked to a state of sympathetic overstimulation [7], Myocardial ischemia is the stimulus of that state of sympathetic overstimulation. HRV measurement is a non-invasive method that can reflect the activity of the autonomic nervous system (ANS) and detect any imbalance between its components (sympathetic and parasympathetic systems) [8,9]. While SYNTAX (SX) Score is one of the models which was designed to quantify the anatomical complexity of coronary lesions in patients with left main or three-vessel disease CAD and it is now well established to be an independent predictor of long-term major adverse car-diovascular and cerebrovascular events (MACCE) (Death, Myocardial infarction, Revascularization and Cerebrovascular accidents) in patients treated with PCI [10-14].
Several patient characteristics can affect the cardiac autonomic function therefore, this study aimed to determine the effects of different clinical and angiographic factors assessed by SX Score measurement on the cardiac autonomic function evaluated by HRV assessment among CAD patients.
Patients and methods
Study population
The study was designed as a single-center prospective cohort study included 100 patients.
Inclusion criteria
Clinical indication for coronary angiography (CA): 1. Subjective symptoms of ischemia or post-acute coronary syndrome (ACS). 2. Objective evidence of ischemia by a stress test or a viability study.
Exclusion criteria
1. Subjects with contraindication to receive contrast media. 2. Patients who have atrial fibrillation, multiple premature beats, or receiving anti-arrhythmic drugs for any indication. 3. Patients who had previous percutaneous coronary interventions (PCI) or Coronary Artery Bypass Graft (CABG).
Informed consent was acquired from all patients. The ethical committee of the hospital approved the study protocol.
Clinical evaluation
Full history, clinical examination, routine laboratory investigations including (hemoglobin %, creatinine level), a standard 12 lead electrocardiogram (ECG), and a 2D transthoracic echocardiography (TTE) were acquired from all patients.
Coronary angiographic data
Coronary angiographic data was recorded with emphasis on CAD type whether single or multiple CAD and SYNTAX (SX) score calculation using SX score calculator software.
Heart rate variability measurement
5-minute (short-term) HRV assessment was done before CA using CheckMyheart™ handheld HRV device manufactured by DailyCare BioMedical Inc, Taiwan. Data were fed to CheckMyheart™ 5-min HRV analysis software using the standard methods for HRV measurement based on the Task Force of the ESC and the NASPE with an emphasis on HRV time-domain parameters (mean time, SDNN, and RMSSD) (illustrated in Table 1A) and HRV frequency-domain parameters (low frequency (LF), high frequency (HF) and LF/HF ratio) (illustrated in Table 1B).
Table 1A.
Summary of the used time-domain measures of HRV
| Variable | Unit | Description |
|---|---|---|
| Mean time | ms | Time average of RR interval |
| SDNN | ms | Standard deviation of all normal to normal (NN) intervals |
| RMSSD | ms | Square root of the mean of the sum of the square of differences between adjacent NN interval |
Ms = millisecond.
Table 1B.
Summary of the used frequency-domain measures of HRV
| Variable | Units | Description | Frequency range |
|---|---|---|---|
| LF | ms2 | Low-frequency power | 0.04-0.15 Hz |
| HF | ms2 | High-frequency power | 0.15-0.4 Hz |
| LF/HF | Ratio between low to high-frequency power |
ms2 = millisecond square.
Statistical analysis of the data
Statistical analysis was done using IBM SPSS software package version 20.0. (Armonk, NY: IBM Corp). Number and percent were used to describe qualitative data. Mean and standard deviation (SD) were used to describe quantitative data. A significant level was set at 5% (p-value ≤0.05).
Statistical tests used: 1. Chi-square test for categorical variables comparing different groups. 2. Fisher’s Exact correction for chi-square if >20% of the cells have expected count <5. 3. Mann-Whitney test for abnormally distributed quantitative variables comparing two groups. 4. Kruskal Wallis test for abnormally distributed quantitative variables comparing between more than two groups. 5. Wilcoxon signed ranks test for abnormally distributed quantitative variables, to compare two periods. 6. Friedman test for abnormally distributed quantitative variables, to compare between more than two periods or stages. Spearman coefficient to correlate between two distributed abnormally quantitative variables. 7. Multivariate logistic regression analysis to detect the most independent/affecting factors for HRV parameters.
Results
Baseline patient demographic and clinical data
The mean age of the enrolled patients was 56.89±10.75 years, 85% of them were males. (Demographic and clinical data illustrated in Table 2).
Table 2.
Baseline patient demographic, clinical, and angiographic data (n=100)
| 1. Demographic data | |
| Age (years) | 56.89±10.75 |
| Male Sex | 85 (85%) |
| 2. Risk Factors | |
| Diabetes Mellitus | 41 (41%) |
| Hypertension | 47 (47%) |
| Smoking | 79 (79%) |
| Family history of CAD | 11 (11%) |
| Dyslipidemia | 8 (8%) |
| Others | 4 (4%) |
| 3. Indication For Coronary Angiography | |
| Typical ischemic symptoms | 6 (6%) |
| Positive stress test | 8 (8%) |
| Post-ACS | 86 (86%) |
| 4. Clinical Data | |
| Mean heart rate (beats/minute) | 77.95±11.79 |
| Mean LVEF (%) | 54.03±11.08 |
| 5. Coronary Angiographic Data | |
| Single-Vessel CAD | 58 (58%) |
| Mean SX score | 13.11±8.52 |
| TIMI III distal flow | 65 (65%) |
Results are shown in % and numbers of patients.
Coronary angiographic data
Multi-vessel CAD was encountered in 42 (42%) patients while single-vessel CAD was found in 58 (58%) patients with a mean SX score of 13.11±8.52 (illustrated in Table 2).
HRV parameters
The relation between HRV time and frequency domain parameters and different patient characteristics was illustrated in Tables 3, 4.
Table 3.
Relation between the mean value of HRV time-domain parameters and different patient characteristics
| Patient characteristics | Number of patients | Mean Time (ms) | U | P | SDNN (ms) | U | P | RMSSD (ms) | U | P |
|---|---|---|---|---|---|---|---|---|---|---|
| Gender | ||||||||||
| Male | 85 | 685.01±47.60 | 614.0 | 0.820 | 11.94±3.32 | 609.50 | 0.787 | 7.12±1.95 | 603.0 | 0.738 |
| Female | 15 | 685.67±43.62 | 11.63±3.66 | 7.45±2.63 | ||||||
| Age (years) | ||||||||||
| <65 | 76 | 695.14±44.03 | 382.50* | <0.001* | 12.60±3.29 | 447.50* | <0.001* | 7.41±2.07 | 640.0* | 0.028* |
| ≥ 65 | 24 | 653.33±41.54 | 9.67±2.51 | 6.39±1.83 | ||||||
| HTN | ||||||||||
| No | 53 | 692.57±36.80 | 1067.5 | 0.218 | 12.35±3.02 | 1037.0 | 0.149 | 7.60±1.83 | 891.0* | 0.014* |
| Yes | 47 | 676.70±55.23 | 11.38±3.67 | 6.68±2.19 | ||||||
| DM | ||||||||||
| No | 59 | 698.39±36.35 | 757.0* | <0.001* | 12.77±3.17 | 768.0* | 0.002* | 7.60±1.91 | 823.50* | 0.007* |
| Yes | 41 | 666.0±53.62 | 10.64±3.26 | 6.55±2.11 | ||||||
| FH | ||||||||||
| No | 89 | 686.42±46.04 | 444.0 | 0.616 | 11.96±3.27 | 403.50 | 0.343 | 7.25±2.03 | 388.0 | 0.262 |
| Yes | 11 | 674.55±53.9 | 11.39±4.16 | 6.48±2.20 | ||||||
| Smoking | ||||||||||
| No | 21 | 681.43±51.68 | 788.0 | 0.725 | 11.43±3.60 | 512.0 | 0.516 | 7.13±2.56 | 797.50 | 0.786 |
| Yes | 79 | 686.09±45.75 | 12.02±3.30 | 7.18±1.91 | ||||||
| Dyslipidemia | ||||||||||
| No | 92 | 685.50±45.98 | 366.50 | 0.985 | 11.90±3.24 | 329.0 | 0.620 | 7.16±2.03 | 341.0 | 0.731 |
| Yes | 8 | 680.63±59.07 | 11.8± 4.78 | 7.25±2.46 | ||||||
| LVEF | ||||||||||
| ≤45 | 34 | 662.79±50.17 | 681.0* | 0.001* | 10.88±3.24 | 842.0* | 0.041* | 6.34±1.71 | 709.0* | 0.003* |
| >45 | 66 | 696.6±40.82 | 12.42±3.32 | 7.59±2.09 | ||||||
| ACS | 86 | 683.27±48.39 | 9.30± 2.13 | 7.14±2.07 | ||||||
| Non-ACS | 14 | 696.43±34.94 | 527.50 | 0.459 | 11.82±2.77 | 596.0 | 0.952 | 7.36±1.98 | 564.50 | 0.709 |
| Type of CAD | ||||||||||
| MVD | 42 | 650.26±39.31 | 289.0* | <0.001* | 9.30±2.13 | 259.50* | <0.001* | 5.60±1.64 | 299.0* | <0.001 |
| SVD | 58 | 710.34±33.95 | 13.78±2.78 | 8.30±1.50 | ||||||
| TIMI | ||||||||||
| 0 + I | 27 | 670.19±38.24 | 695.0* | 0.024* | 10.93±2.99 | 4.0 | 0.133 | 6.58±1.83 | 759.0 | 0.078 |
| II + III | 73 | 690.63±48.70 | 12.25±3.43 | 7.38±2.10 | ||||||
| Drug history (Beta-blockers) | ||||||||||
| No | 17 | 694.41±36.09 | 647.50 | 0.594 | 11.74±2.69 | 685.50 | 0.854 | 7.35±2.0 | 659.0 | 0.668 |
| Yes | 83 | 683.2±48.69 | 11.93±3.49 | 7.13±2.07 |
U, P: U and P values for Mann Whitney test for comparing between the two groups.
Statistically significant at P≤0.05.
Table 4.
Relation between the mean value of HRV frequency-domain parameters and different patient characteristics
| Patient characteristics | Number of patients | LF | U | P | HF | U | P | LF/HF | U | P |
|---|---|---|---|---|---|---|---|---|---|---|
| Gender | ||||||||||
| Male | 85 | 42.0±6.53 | 578.0 | 0.565 | 11.60±3.38 | 597.50 | 0.699 | 3.79±0.72 | 597.50 | 0.698 |
| Female | 15 | 43.53±8.41 | 11.93±4.18 | 3.88±0.76 | ||||||
| Age (years) | ||||||||||
| <65 | 76 | 43.13±6.76 | 599.0* | 0.011* | 12.09±3.55 | 606.0* | 0.013* | 3.73±0.72 | 650.0* | 0.033* |
| ≥ 65 | 24 | 39.38±6.29 | 10.26±2.95 | 4.01±0.71 | ||||||
| HTN | ||||||||||
| No | 53 | 43.24±6.32 | 1015.50 | 0.111 | 12.36±3.15 | 950.0* | 0.041* | 3.62±0.61 | 885.0* | 0.012* |
| Yes | 47 | 41.10±7.23 | 10.84±3.70 | 4.01±0.79 | ||||||
| DM | ||||||||||
| No | 59 | 43.68±6.40 | 836.0* | 0.009* | 12.44±3.20 | 820.0* | 0.006* | 3.62±0.61 | 810.50* | 0.005* |
| Yes | 41 | 40.15±6.93 | 10.52±3.60 | 4.06±0.80 | ||||||
| FH | ||||||||||
| No | 89 | 42.54±6.87 | 366.50 | 0.174 | 11.85±3.49 | 342.0 | 0.104 | 3.75±0.71 | 300.50* | 0.036* |
| Yes | 11 | 39.68±6.03 | 10.0±3.15 | 4.18±0.77 | ||||||
| Smoking | ||||||||||
| No | 21 | 42.48±8.25 | 822.0 | 0.949 | 11.57±4.04 | 827.0 | 0.983 | 3.92±0.78 | 749.50 | 0.496 |
| Yes | 79 | 42.16±6.44 | 11.67±3.36 | 3.77±0.71 | ||||||
| Dyslipidemia | ||||||||||
| No | 92 | 42.30±6.84 | 340.50 | 0.726 | 11.72±3.47 | 333.0 | 0.656 | 3.78±0.71 | 284.0 | 0.283 |
| Yes | 8 | 41.38±6.84 | 10.90±3.81 | 4.06±0.84 | ||||||
| LVEF | ||||||||||
| ≤45 | 34 | 39.38±6.25 | 707.0* | 0.002* | 10.87±3.33 | 895.0 | 0.098 | 3.81±0.78 | 1084.0 | 0.781 |
| >45 | 66 | 43.70±6.67 | 12.05±3.52 | 3.80±0.70 | ||||||
| ACS | 86 | 42.15±6.88 | 550.0 | 0.605 | 11.72±3.56 | 559.50 | 0.672 | 3.78±0.73 | 512.50 | 0.371 |
| Non-ACS | 14 | 42.75±6.59 | 11.21±3.12 | 3.95±0.73 | ||||||
| Type of CAD | ||||||||||
| MVD | 42 | 36.76±5.12 | 222.0* | <0.001* | 8.48±2.37 | 113.50* | <0.001* | 4.46±0.64 | 108.0* | <0.001* |
| SVD | 58 | 46.19±4.88 | 13.95±2.07 | 3.32±0.27 | ||||||
| TIMI | ||||||||||
| 0 + I | 27 | 39.76±5.94 | 731.0* | 0.048* | 10.89±3.19 | 818.0 | 0.193 | 3.81±0.73 | 964.50 | 0.870 |
| II + III | 73 | 43.14±6.93 | 11.93±3.57 | 3.79±0.73 | ||||||
| Drug history (Beta-blockers) | ||||||||||
| No | 17 | 43.09±6.49 | 626.0 | 0.465 | 11.50±3.14 | 686.50 | 0.861 | 3.88±0.69 | 634.0 | 0.509 |
| Yes | 83 | 42.05±6.90 | 11.68±3.57 | 3.78±0.73 |
U, P: U and P values for Mann Whitney test for comparing between the two groups.
Statistically significant at P≤0.05.
The correlation between HRV time domain parameters and patient characteristics revealed that there was a statistically significant positive correlation between mean time, SDNN, and RMSSD and LVEF (r=0.370, P=0.001), (r=0.282, P=0.004), and (r=0.288, P=0.004) respectively while there was a statistically significant negative correlation between them and SX score as well as age (r=-0.686, P=0.001), (r=-0.435, P=0.001), (r=-0.637, P=0.001), (r=-0.416, P=0.001) (r=-0.673, P=0.001) and (r=-0.233, P=0.019) respectively (illustrated in Table 5).
Table 5.
Correlation between different HRV time-domain parameters and patient characteristics (n=100)
| Patient Characteristics | Mean time | SDNN | RMSSD | |||
|---|---|---|---|---|---|---|
|
|
|
|
||||
| rs | p | rs | p | rs | P | |
| Age (years) | -0.435* | <0.001* | -0.416* | <0.001* | -0.233* | 0.019* |
| LVEF | 0.370* | <0.001* | 0.282* | 0.004* | 0.288* | 0.004* |
| SYNTAX score | -0.686* | <0.001* | -0.637* | <0.001* | -0.673* | <0.001* |
| TIMI flow | 0.151 | 0.133 | 0.085 | 0.398 | 0.121 | 0.229 |
rs: Spearman coefficient.
Statistically significant at P≤0.05.
While the correlation between HRV frequency domain parameters and patient characteristics showed that there was a statistically significant negative correlation between LF and HF with SX score and age (r=-0.709, P=0.001), (r=-0.251, P=0.012) and (r=-0.699, P≤0.001), (r=-0.259, P=0.009) respectively while there was a statistically significant positive correlation between LF/HF ratio with SX score and age (r=0.630, P≤0.001), (r=0.227, P=0.023) (illustrated in Table 6).
Table 6.
Correlation between different HRV frequency-domain parameters and patient characteristics (n=100)
| Patient Characteristics | LF | HF | LF/HF | |||
|---|---|---|---|---|---|---|
|
|
|
|
||||
| rs | p | rs | p | rs | p | |
| Age (years) | -0.251* | 0.012* | -0.259* | 0.009* | 0.227* | 0.023* |
| LVEF | 0.288* | 0.004* | 0.154 | 0.127 | 0.008 | 0.935 |
| SYNTAX score | -0.709 | <0.001* | -0.699* | <0.001* | 0.630* | <0.001* |
| TIMI flow | 0.122 | 0.227 | 0.042 | 0.680 | 0.071 | 0.483 |
rs: Spearman coefficient.
Statistically significant at P≤0.05.
Multivariate regression analysis of patient factors affecting mean time, SDNN, and RMSSD revealed that age, LVEF, CAD type, and SX score were the most powerful independent factors that affect the HRV time-domain parameters (illustrated in Table 7).
Table 7.
Multivariate linear analysis logistic regression of patient characteristics affecting HRV time-domain parameters
| A. Multivariate linear analysis logistic regression of patient characteristics affecting mean time | |||||
|
| |||||
| Patient characteristics | B | SE | Sig. | 95% CI | |
|
| |||||
| LL | UL | ||||
|
| |||||
| Age | -1.512 | 0.210 | <0.001* | -1.929 | -1.096 |
| DM | -3.505 | 4.758 | 0.463 | -12.954 | 5.944 |
| LVEF | 1.458 | 0.220 | <0.001* | 1.022 | 1.894 |
| Type of CAD | 32.184 | 5.821 | <0.001* | 20.624 | 43.744 |
| SYNTAX score | -2.275 | 0.390 | <0.001* | -3.050 | -1.500 |
| TIMI flow | -2.759 | 2.010 | 0.173 | -6.750 | 1.232 |
|
| |||||
| B. Multivariate linear analysis logistic regression of patient characteristics affecting SDNN | |||||
|
| |||||
| Patient characteristics | B | SE | Sig. | 95% CI | |
|
| |||||
| LL | UL | ||||
|
| |||||
| Age | -0.121 | 0.018 | <0.001* | -0.156 | -0.086 |
| DM | -0.236 | 0.397 | 0.554 | -1.023 | 0.552 |
| LVEF | 0.081 | 0.018 | <0.001* | 0.044 | 0.117 |
| Type of CAD | 3.102 | 0.470 | <0.001* | 2.170 | 4.035 |
| SYNTAX score | -0.097 | 0.030 | 0.001* | -0.156 | -0.039 |
|
| |||||
| C. Multivariate linear analysis logistic regression of patient characteristics affecting RMSSD | |||||
|
| |||||
| Patient characteristics | B | SE | Sig. | 95% CI | |
|
| |||||
| LL | UL | ||||
|
| |||||
| Age | -0.033 | 0.013 | 0.009* | -0.058 | -0.008 |
| DM | 0.228 | 0.301 | 0.450 | -0.369 | 0.826 |
| LVEF | 0.054 | 0.014 | <0.001* | 0.026 | 0.082 |
| Type of CAD | 1.891 | 0.336 | <0.001* | 1.223 | 2.559 |
| SYNTAX score | -0.064 | 0.022 | 0.004* | -0.107 | -0.021 |
B: Unstandardized Coefficients, OR: Odds ratio, CI: Confidence interval, LL: Lower limit, UL: Upper Limit.
Statistically significant at P≤0.05.
Multivariate regression analysis of patient factors affecting LF, HF, and LF/HF ratio revealed that CAD type and SX score were the most powerful independent factors affecting the HRV frequency-domain parameters (illustrated in Table 8).
Table 8.
Multivariate linear analysis logistic regression of patient characteristics affecting HRV frequency-domain parameters
| A. Multivariate linear analysis logistic regression of patient characteristics affecting LF | |||||
|
| |||||
| Patient Characteristics | B | SE | Sig. | 95% CI | |
|
| |||||
| LL | UL | ||||
|
| |||||
| Age | -0.119 | 0.039 | 0.003* | -0.195 | -0.042 |
| DM | 0.346 | 0.875 | 0.694 | -1.392 | 2.084 |
| LVEF | 0.130 | 0.040 | 0.002* | 0.050 | 0.210 |
| Type of CAD | 6.156 | 1.071 | <0.001* | 4.030 | 8.282 |
| TIMI (before) | -0.048 | 0.370 | 0.897 | -0.782 | 0.686 |
| SYNTAX score | -0.303 | 0.072 | <0.001* | -0.446 | -0.161 |
|
| |||||
| B. Multivariate linear analysis logistic regression of patient characteristics affecting HF | |||||
|
| |||||
| Patient Characteristics | B | SE | Sig. | 95% CI | |
|
| |||||
| LL | UL | ||||
|
| |||||
| Age | -0.052 | 0.018 | 0.004* | -0.087 | -0.016 |
| HTN | -0.083 | 0.403 | 0.837 | -0.883 | 0.717 |
| DM | 0.096 | 0.424 | 0.821 | -0.746 | 0.939 |
| Type of CAD | 3.723 | 0.467 | <0.001* | 2.795 | 4.651 |
| Syntax | -0.160 | 0.028 | <0.001* | -0.216 | -0.105 |
|
| |||||
| C. Multivariate linear analysis logistic regression of patient characteristics affecting HF/LF ratio | |||||
|
| |||||
| Patient Characteristics | B | SE | Sig. | 95% CI | |
|
| |||||
| LL | UL | ||||
|
| |||||
| Age | 0.006 | 0.004 | 0.132 | -0.002 | 0.014 |
| HTN | 0.091 | 0.086 | 0.296 | -0.081 | 0.262 |
| DM | 0.020 | 0.091 | 0.827 | -0.161 | 0.201 |
| FH | 0.054 | 0.135 | 0.690 | -0.214 | 0.322 |
| Type of CAD | -0.761 | 0.102 | <0.001* | -0.963 | -0.559 |
| Syntax | 0.032 | 0.006 | <0.001* | 0.020 | 0.044 |
B: Unstandardized Coefficients, OR: Odds ratio, CI: Confidence interval, LL: Lower limit, UL: Upper Limit.
Statistically significant at P≤0.05.
Discussion
Our study included 100 patients undergoing CA with a broad spectrum of patient selection including patients with various indications for intervention such as patients with typical anginal symptoms or positive stress testing also, post-ACS patients either unstable angina or post-MI angina patients with or without a viability study. On the contrary to all previous studies [1], in our study, the complexity of CAD was quantified using SX score [15]. Multivariate linear regression analysis of the various patient factors that can affect HRV showed that the CAD type either single or multi-vessel and SX score were the main independent variables to affecting cardiac autonomic malfunction assessed by HRV parameters in CAD patients.
Previous studies addressed the link between CAD and autonomic dysfunction, Airaksinen et al [2], evaluated vagal cardiac function in CAD patients by measuring HRV range during deep breathing suggesting that CAD was associated with vagal cardiac function impairment independently of the NYHA class, medications, diseased coronary arteries location, previous MI, and left ventricular function indices. Hayano et al [16], analyzed the RR interval variability under controlled respiration in patients referred for CA demonstrating that CAD was associated with vagal dominant impairment in cardiac autonomic function and the reduction in the vagal cardiac function correlated with the angiographic severity independently from previous MI, diseased coronary artery location, and left ventricular function. Huikuri et al [17], proved that reduced autonomic responses to sleep-wake rhythm could suggest that the cardiac autonomic function modulation by central nervous system stimuli was impaired in CAD patients in comparison to age-matched individuals with no evidence of CAD. Wennerblom et al [18], investigated whether uncomplicated chronic CAD could cause changes in HRV and if so, whether the HRV pattern different from that was described in AMI patients. The study involved 65 patients with angina who had no previous MI or other diseases and not receiving drugs affecting sinus rhythm. Time and frequency-domains of HRV were measured and results were compared with 33 age-matched healthy subjects revealing that uncomplicated CAD even without previous AMI was associated with reduced HRV parameters. Kotecha et al [19], conducted (The Alternative Risk Markers in Coronary Artery Disease (ARM-CAD) study), a prospective multicenter observational study to assess the feasibility of a bedside (5-minute) HRV test to be used as a predictor of CAD presence recruiting 470 consecutive patients undergoing elective CA regardless the co-morbidities. The study concluded that lower HRV was highly predictive of angiographic CAD irrespective of other risk factors and it can be clinically used as a risk predictor for CAD in sinus rhythm patients. Simula et al [20], performed quantitative coronary angiography (QCA), myocardial Tc-99m sestamibi (MIBI) perfusion imaging, and HRV to study the correlation between cardiac autonomic function and the extent and distribution of coronary atherosclerosis in 30 asymptomatic patients with high familial risk of CAD yet no evident myocardial ischemia. The study concluded that the severity and extent of coronary atherosclerosis were related to a change in cardiac autonomic regulation to sympathetic predominance in patients without subjective or objective evidence of ischemia. Feng et al [21], assessed the correlation between CAD and cardiac autonomic dysfunction using HRV among 236 patients with stable angina. Unlike our study where the SX score was calculated, Gensini score was used to quantify CAD severity. The study concluded that HRV analysis among CAD patients may predict CAD severity, screening of high-risk population and determine prognosis. Li et al [22], studied if HRV could predict the presence of angiographic CAD beyond Framingham risk in 514 patients presenting with stable angina concluding that low HRV can be used as a predictive non-invasive method for CAD in patients with stable angina, independent from the traditional risk factors and Framingham risk.
Study limitations
Our study was a single-center prospective study that involved a relatively small number of patients.
Study recommendations
Large-scale studies are required to validate the patient characteristics linked to reduce HRV in CAD patients and to further confirm the usefulness of HRV as a prognostic factor for CAD patients.
Conclusion
In single-center prospective study studying the effects of different patient characteristics affecting cardiac autonomic dysfunction in CAD patients, the complexity of CAD measured by SX score was the main independent predictor affecting the cardiac autonomic function estimated by HRV measurement.
Disclosure of conflict of interest
None.
References
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