Is Baseline Autonomic Tone Associated with New Onset Atrial Fibrillation?: Insights from the Framingham Heart Study

Background: Recent reports have indicated that autonomic tone fluctuations measured by heart rate variability (HRV) precede episodes of paroxysmal atrial fibrillation (AF). Little is known about the impact of baseline autonomic tone and the development of new onset AF in a population‐based cohort. The purpose of this study was to assess the role of HRV as a predictor of new onset AF. Method: Ambulatory ECG recordings obtained from the Framingham Heart Study subjects attending a routine examination were processed for HRV. The HRV variables analyzed included standard deviation of normal R‐R intervals (SDNN), low frequency power (LF), high frequency power (HF), and LF/HF ratio. There were 1434 women and 1142 men (54 ± 14.1 years) eligible for the study. Results: In 12 years of follow‐up, 65 women and 67 men had new onset AF. The study had 80% power to detect a hazard ratio (HR) of 1.3 per standard deviation (SD) decrement in HRV. A one SD decrement in log LF/HF was associated with increased risk of developing AF (HR = 1.23; 95% confidence intervals (CI) = 1.06–1.44) in age‐ and sex‐adjusted models; the association was no longer significant (HR = 1.15; 95% CI = 0.98–1.35) after adjusting for potential confounders. Conclusion: Autonomic dysregulation at baseline, as reflected by an altered HRV is associated with risk of AF; however, this association does not persist after adjusting for potential confounders. Much of the apparent association between HRV and AF is mediated by traditional risk factors.     

Autonomic Markers as Predictors of Nonfatal Acute Coronary Events after Myocardial Infarction

Background: Autonomic markers, such as heart rate variability (HRV), heart rate turbulence (HRT), and baroreflex sensitivity (BRS) provide information on the risk of all‐cause mortality after an acute myocardial infarction (AMI), but their value in predicting nonfatal cardiac events is not well known. Methods: A consecutive series of 675 patients with an AMI were followed up to 30 months. At baseline, the patients underwent a 24‐hour Holter recording, and assessment of BRS using phenylephrine test. Several parameters of HRV and HRT were determined. Results: After the follow‐up, 98 patients (15%) had a nonfatal acute coronary event. Among the studied variables, the short‐term scaling exponent alpha1 (P = 0.002), power‐law slope beta (P = 0.008), low‐frequency component of HRV power spectrum (P < 0.001), turbulence slope (P < 0.001), and BRS (P < 0.001) had the strongest association with the occurrence of nonfatal acute coronary events in univariate comparisons. After adjustment with relevant clinical variables (such as age, gender, ejection fraction, functional class, medication, diabetes) in the Cox proportional hazards model, alpha1 and beta remained as statistically significant predictors of nonfatal acute coronary events (HR = 2.0 [1.2–3.2, 95% CIs, P = 0.006] for alpha1 ≤ 1.025), (HR = 1.9 [1.2–3.1, P = 0.008] for beta ≤–1.507). Conclusion: Several autonomic markers provide information on the risk of recurrent nonfatal coronary events after an AMI. Altered fractal heart rate behavior seems to be the strongest independent predictor of such events.     

Influence of Heavy Cigarette Smoking on Heart Rate Variability and Heart Rate Turbulence Parameters

Background: Cigarette smoking increases the risk of cardiovascular events related with several mechanisms. The most suggested mechanism is increased activity of sympathetic nervous system. Heart rate variability (HRV) and heart rate turbulence (HRT) has been shown to be independent and powerful predictors of mortality in a specific group of cardiac patients. The goal of this study was to assess the effect of heavy cigarette smoking on cardiac autonomic function using HRV and HRT analyses. Methods: Heavy cigarette smoking was defined as more than 20 cigarettes smoked per day. Heavy cigarette smokers, 69 subjects and nonsmokers 74 subjects (control group) were enrolled in this study. HRV and HRT analyses [turbulence onset (TO) and turbulence slope (TS)] were assessed from 24‐hour Holter recordings. Results: The values of TO were significantly higher in heavy cigarette smokers than control group (?1.150 ± 4.007 vs ?2.454 ± 2.796, P = 0.025, respectively), but values of TS were not statistically different between two groups (10.352 ± 7.670 vs 9.613 ± 7.245, P = 0.555, respectively). Also, the number of patients who had abnormal TO was significantly higher in heavy cigarette smokers than control group (23 vs 10, P = 0.006). TO was correlated with the number of cigarettes smoked per day (r = 0.235, P = 0.004). While LF and LF/HF ratio were significantly higher, standard deviation of all NN intervals (SDNN), standard deviation of the 5‐minute mean RR intervals (SDANN), root mean square of successive differences (RMSSD), and high‐frequency (HF) values were significantly lower in heavy smokers. While, there was significant correlation between TO and SDNN, SDANN, RMSSD, LF, and high frequency (HF), only HF was correlated with TS. Conclusion: Heavy cigarette smoking has negative effect on autonomic function. HRT is an appropriate noninvasive method to evaluate the effect of cigarette on autonomic function. Simultaneous abnormal HRT and HRV values may explain increased cardiovascular event risk in heavy cigarette smokers.     

Effects of Hormone Replacement Therapy on Heart Rate Variability in Postmenopausal Women

Background: Hormone replacement therapy (HRT) is associated with reduced cardiovascular risk, but the underlying mechanism(s) are not fully understood. This study investigated the effects of a 6‐month course of HRT on cardiac autonomic function parameters assessed by heart rate variability (HRV) in postmenopausal women. Methods: Forty‐six healthy postmenopausal women (age 48 ± 5, range 40–60) with normal baseline electrocardiogram and negative exercise testing were enrolled. HRT, which was either 0.625 mg/day conjugated equine estrogen (CEE) plus 2.5 mg/day medroxyprogesterone acetate or 0.625 mg/day CEE alone were administered depending on hysterectomy status. Power spectral analysis of HRV was performed to calculate the low frequency component in absolute (LF) and normalized units (LF nu), high frequency component in absolute (HF), and normalized units (HF nu), and the LF/HF ratio. The standard deviation of RR intervals (SDNN) was calculated from the time series of RR intervals. Results: A 6‐month course of HRT did not significantly alter resting heart rate (P > 0.05). The LF/HF ratio and LF nu significantly decreased after HRT (P = 0.022 and P = 0.032), whereas a significant increase was noted in the HF component of HRV (P = 0.043), indicating an improvement in cardiac autonomic function. The SDNN value, which was 28.8 ± 11.8 ms before HRT significantly increased to 35.4 ± 16.7 ms after 6 months (P = 0.011). Conclusion: Our results indicate that a 6‐month course of HRT may significantly improve cardiac autonomic function parameters, a finding that could at least partly explain the potential cardiopro‐tective effect(s) of HRT. A.N.E. 2001;6(4):280–284     

Heart rate variability and heart rate turbulence in hypothyroidism before and after treatment

Background: Cardiac autonomic dysfunction may develop in patients with clinical or subclinical thyroid hormone deficiency. Heart rate variability (HRV) and heart rate turbulence (HRT) are used for evaluating changes in cardiac autonomic functions and also used to provide risk stratification in cardiac and noncardiac diseases. The aim of this study is to evaluate cardiac autonomic functions before and 6 months after thyroid replacement therapy in patients with thyroid hormone deficiency. Methods: Forty hypothyroid patients (mean age 48 ± 13, four male) and 31 healthy controls (mean age 51 ± 12, three male) were included in the study. Twenty‐four hour ambulatory electrocardiogram recordings were taken using Pathfinder Software Version V8.255 (Reynolds Medical). The time domain parameters of HRV analysis were performed using the Heart Rate Variability Software (version 4.2.0, Norav Medical Ltd, Israel). HRT parameters, Turbulence Onset (TO), and Turbulence Slope (TS) were calculated with HRT! View Version 0.60‐0.1 software. Results: HRV and HRT parameters were decreased in the patient group (SDNN; P < 0.001, SDANN; P < 0.009, RMSSD; P = 0.049, TO; P = 0.035, TS; P < 0.001). After 6 months of thyroid replacement therapy, there were no significant changes observed in either HRV or HRT. Conclusions: Hypothyroidism may cause cardiac autonomic dysfunction. Treating hypothyroidism with L‐thyroxine therapy does not effectively restore cardiac autonomic function. HRV and HRT can be used as to help monitor cardiovascular‐related risk in this population. Ann Noninvasive Electrocardiol 2011;16(4):344–350     

Predictors of Long‐Term Risk for Heart Failure Hospitalization after Acute Myocardial Infarction

Background: Data on the value of baseline brain natriuretic peptide (BNP) and autonomic markers in predicting heart failure (HF) hospitalization after an acute myocardial infarction (AMI) are limited. Methods: A consecutive series of patients with AMI without a previous history of HF (n = 569) were followed up for 8 years. At baseline, the patients had a blood sample for determination of BNP, a 24‐hour Holter recording for evaluating heart rate variability (HRV) and heart rate turbulence (HRT), and an assessment of baroreflex sensitivity (BRS) using phenylephrine test. Results: During the follow‐up, 79 (14%) patients were hospitalized due to HF. Increased baseline BNP, decreased HRV, HRT, and BRS had a significant association with HF hospitalization in univariate comparisons (P < 0.001 for all). After adjusting with all the relevant clinical parameters, BNP, HRV, and HRT still significantly predicted HF hospitalization (P < 0.001 for BNP and for the short‐term scaling exponent α₁, P < 0.01 for turbulence slope). In the receiver operator characteristics curve analysis, the area under the curve for BNP was 0.77, for the short‐term scaling exponent α₁ 0.69, for turbulence slope 0.71, and for BNP/standard deviation of all N‐N intervals ratio 0.80. Conclusion: Baseline increased BNP and impaired autonomic function after AMI yield significant information on the long‐term risk for HF hospitalization. Ann Noninvasive Electrocardiol 2010;15(3):250–258     

Short‐Period Heart Rate Variability in the General Population as Compared to Patients with Acute Myocardial Infarction from the Same Source Population

Background: Our aim was to compare the distribution and determinants of heart rate variability (HRV) measures in a middle‐aged population with patients of the same sex and age after an acute myocardial infarction (AMI), and to show, whether HRV values defined as abnormal from the general population are indicative for a worse prognosis even in AMI patients. Methods: HRV was studied in a random sample of 149 middle‐aged men and 137 women from the general population (45–65 years) as well as 129 consecutive AMI patients (25–74 years). Spectral analysis was used to compute low frequency (LF), high frequency (HF), and total frequency power. To the AMI population of age 45–65 years (N = 85) a sample out of the general population was matched by age and sex by 2:1 matching (N = 149). All AMI patients were followed for a median of 43 months (range 1–47) for death or malignant arrhythmia. Results: All measures of HRV were significantly and substantially lower in AMI patients than the general population (P < 0.001). Expression in relative terms revealed that the proportionate contributions of HF and LF to total power were significantly different in the two populations with relatively lower LF power in AMI patients (P < 0.01). The negative correlation with heart rate and HRV measures was significantly more pronounced in AMI patients (P < 0.01). The 2.5th percentile of the LF power distribution in the general population (3.08 ln ms²) corresponds to the 25th percentile in the AMI population. Subjects of the whole AMI population with values below this LF cutpoint revealed a significant increased risk of death or malignant arrhythmia during follow‐up (odds ratio 5.1; 95% confidence interval: 1.3; 23). Conclusions: AMI patients had strongly diminished HRV compared to the general population. The relatively lower LF power indicates an alteration of the sympathico‐vagal balance, and the significantly stronger correlation of heart rate with HRV may be indicative for a more pronounced effect of sympathetic activation on autonomic modulation in the case of myocardial infarction. Finally, a value below the 2.5th percentile of the population LF power distribution may identify subjects at risk and warrant further testing.     

Heart rate turbulence can predict cardiac mortality following myocardial infarction in patients with diabetes mellitus

Heart Rate Turbulence in Post‐MI Patients With DM. Background: Previous studies have described the clinical utility of heart rate turbulence (HRT) as an autonomic predictor in risk‐stratifying patients after myocardial infarction (MI). Some reports showed that diabetes mellitus (DM) affects the prognostic value of autonomic markers. We assessed the utility of HRT as a risk marker in post‐MI patients with DM and without DM. Methods: We prospectively enrolled 231 consecutive DM patients and 300 non‐DM patients after acute MI. HRT was measured using an algorithm based on 24‐hour Holter electrocardiograms (ECGs), assessing 2 parameters: turbulence onset (TO) and turbulence slope (TS). HRT was considered positive when both TO ≥0% and TS ≤2.5 ms/R‐R interval were met. The endpoint was defined as cardiac mortality. Results: Of patients with DM, 9 patients (4%) were not utilized for HRT assessment because of frequent ventricular contractions or presence of atrial fibrillation. Forty‐two of 222 patients (19%) were HRT positive. During follow‐up of 876 ± 424 days, 26 patients (22%) reached the endpoint. Several factors including left ventricular ejection fraction (LVEF), renal dysfunction, documentation of nonsustained ventricular tachycardia (VT), and a HRT‐positive outcome had significant association with the endpoint. Multivariate analysis determined that renal dysfunction and a positive HRT outcome had significant value with a hazard ratio (HR) of 4.7 (95%CI, 1.9–11.5; P = 0.0008) and 3.5 (95%CI, 1.4–8.8; P = 0.007), respectively. In non‐DM patients, only a positive HRT outcome had significant value. Conclusions: This study reveals that HRT detected by 24‐hour Holter ECG can predict cardiac mortality in post‐MI patients whether DM is present or not. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1135‐1140, October 2011)     

Novel measures of heart rate variability predict cardiovascular mortality in older adults independent of traditional cardiovascular risk factors: the Cardiovascular Health Study (CHS)

Background: It is unknown whether abnormal heart rate turbulence (HRT) and abnormal fractal properties of heart rate variability identify older adults at increased risk of cardiovascular death (CVdth). Methods: Data from 1,172 community‐dwelling adults, ages 72 ± 5 (65–93) years, who participated in the Cardiovascular Health Study (CHS), a study of risk factors for CV disease in people ≥65 years. HRT and the short‐term fractal scaling exponent (DFA1) derived from 24‐hour Holter recordings. HRT categorized as: normal (turbulence slope [TS] and turbulence onset [TO] normal) or abnormal (TS and/or TO abnormal). DFA1 categorized as low (≤1) or high (>1). Cox regression analyses stratified by Framingham Risk Score (FRS) strata (low = <10, mid = 10–20, and high >20) and adjusted for prevalent clinical cardiovascular disease (CVD), diabetes, and quartiles of ventricular premature beat counts (VPCs). Results: CVdths (N = 172) occurred over a median follow‐up of 12.3 years. Within each FRS stratum, low DFA1 + abnormal HRT predicted risk of CVdth (RR = 7.7 for low FRS; 3.6, mid FRS; 2.8, high FRS). Among high FRS stratum participants, low DFA1 alone also predicted CVdth (RR = 2.0). VPCs in the highest quartile predicted CVdth, but only in the high FRS group. Clinical CV disease predicted CVdth at each FRS stratum (RR = 2.9, low; 2.6, mid; and 1.9, high). Diabetes predicted CVdth in the highest FRS group only (RR = 2.2). Conclusions: The combination of low DFA1 + abnormal HRT is a strong risk factor for CVdth among older adults even after adjustment for conventional CVD risk measures and the presence of CVD.     

Heart rate variability measures during sinus rhythm predict cycle length entropy during atrial fibrillation

Introduction: Several noninvasive measures of cardiac risk such as heart rate variability (HRV) cannot be used in patients with atrial fibrillation (AF). One promising exception is the measure of ventricular cycle length entropy (VCLE) where initial data suggest that a reduction in VCLE portends an increased risk of cardiac death in patients with chronic AF. In this study, we hypothesized that measures of short‐term HRV during sinus rhythm would correlate with measures of cycle length entropy during paroxysms of AF. Methods: We tested 25 Holter recordings of paroxysmal AF from the Physionet AF Prediction Database. We calculated HRV parameters including standard deviation of all NN intervals (SDNN), the root mean square root of the differences between adjacent NN intervals (RMSSD), standard deviation of 5‐minute averages of NN intervals (SDANN), percentage of adjacent NN interval differences >50 ms (pNN50), and interbeat correlation coefficient (ICC) from 30 minutes of normal sinus rhythm, and entropy measures (the Shannon Informational Entropy [ShEn] and Average of Approximate Entropy [ApEn]) from 5 minutes of AF that occurred during the same 24‐hour monitor. Pairwise correlations were used to assess associations, as regression residuals were normally distributed. Results: The mean entropy measures during AF were: ShEn: 4.78 ± 0.82, ApEn: 0.198 ± 0.21. When assessed during the 30 minutes immediately preceding AF onset, ICC showed a significant negative correlation with both ShEn (r =–0.65, P < 0.001) and ApEn (r =–0.60, P < 0.01). RMSSD also correlated with both ShEn (r = 0.41, P = 0.04) and ApEn (r = 0.39, P = 0.05), but other HRV measures showed no correlation with VCLE during AF. Conclusion: Reductions in RMSSD or increases in ICC, two short‐term HRV measures that are known to reflect parasympathetic function in sinus rhythm, are correlated with reductions in the entropy of ventricular response intervals during AF. Our findings suggest that entropy during AF may be modulated, in part, by vagal innervation.     

The Significance of Heart Rate Turbulence in Predicting Major Cardiovascular Events in Patients after Myocardial Infarction Treated Invasively

Introduction: The role of heart rate turbulence (HRT) related to baroreflex sensitivity in predicting mortality after myocardial infarction (MI) has been confirmed by several investigators. However, the significance of HRT in predicting major adverse cardiovascular events (MACE) following acute MI is unknown. Purpose: To analyze the prognostic value of HRT and other independent risk factors associated with autonomic regulation of MACE. Methods: HRT was assessed based on 24‐hour Holter recordings in 500 patients (pts) with acute MI treated invasively (352 M, aged 60.58 years). Turbulence onset (TO,%), slope (TS, ms/RR interval) and timing (TT) were calculated. TO ≥ 0, TS ≤ 2.5 and TT ≥ 10 were considered abnormal; classic and own categories were defined. Time domain heart rate variability (HRV) parameters were also calculated. Within 30.1 ± 15.1 months of follow‐up, MACE occurred in 116 pts. Results: Abnormal TO, TS, and TT were significantly more frequent in patients with MACE (P < 0.05 for each parameter, classic and own categories). In long‐term follow‐up, the largest differences in MACE were observed in patients with own category comprising abnormal TO, TS, and TT. Combining HRT parameters with SDNN (total HRV index) augmented their predictive value. Independent risk factors for MACE were TT, SDNN and rMSSD (a parasympathetic activity index) (HR 2.44, 1.71 and 1.69 respectively; P < 0.05). Conclusion: Abnormal HRT distinguishes patients at risk of MACE after MI. Own category encompassing three abnormal HRT parameters best differentiates patients at risk of MACE. Turbulence timing is a strong independent risk factor for MACE following MI.     

Evaluation of Effects of Intra aortic Balloon Counterpulsation on Autonomic Nervous System Functions by Heart Rate Variability Analysis

Background: In patients with acute myocardial infarction (AMI), intraaortic balloon counterpulsation (IABC) may improve cardiac performance, decrease the incidence of recurrent ischemia, and improve survival. Although there have been several reports concerning circulatory maintenance with the IABC, response of the autonomic nervous system to these hemodynamic changes is not clear. Heart rate variability (HRV) analysis has been extensively used to evaluate autonomic modulation of sinus node and to identify patients at risk for an increased cardiac mortality. In this study, we evaluated effects of the IABC on autonomic nervous system functions by HRV analysis. Methods: The study group was composed of 32 consecutive patients (13 female, 19 male aged 61.8 ± 8.8 years) undergoing IABC. Transthoracic echocardiography and 1‐hour Holter recordings for HRV analysis in each IAB pumping mode were obtained. Results: The IABC improved left ventricular diastolic and systolic functions as well as caused an increase in SDNN1, PNN50(1), RMSSD1, and HF1 and a decrease in LF1, LF/HF1, mean heart rate, and the number of ventricular extrasystoles. The improvements in HRV parameters were correlated with some hemodynamic changes such as the increase in MAP and CO during counterpulsation. The only independent factors affecting in‐hospital mortality were the change in LF/HF1 ratio (ΔLF/HF1) and the change in the number of ventricular extrasystole (ΔVES). The decrease in LF/HF1 ≥4.9 decreased the mortality by 1.7‐folds (RR = 0.6, P = 0.04, 95% CI: 0.1–2.3). The decrease in VES ≥27/15 minutes resulted in mortality reduction by 16‐folds (RR = 0.06, P = 0.02, 95% CI: 0.01–0.4). Conclusions: As a result, the IABC, especially in 1:1 support, causes an increase in HRV, decrease in sympathetic overactivity, and improvement in sympathovagal balance besides the favorable hemodynamic changes, and these electrophysiologic changes may explain the role of the IABC in the treatment of ventricular arrhythmias.     

The Relationship between Heart Rate Variability and Heart Rate Turbulence Dynamics after Primary Coronary Angioplasty

Background: The application of heart rate turbulence (HRT) analysis for risk assessment after pharmacologically treated myocardial infarction (MI) was described in 1999. The aim of the present study was to evaluate the dynamics of HRT changes in long‐term observation after MI treated with primary coronary angioplasty (PTCA). Moreover, the usefulness was assessed of early postinfarction heart rate variability (HRV) analysis for predicting HRT dynamics. Methods: The study group consisted of 96 patients with MI treated with primary PTCA. Holter monitoring with HRV and HRT analysis was performed 3 days after the procedure and 1 year later. Results: Twelve months after primary PTCA, an improvement (Type I HRT dynamics) was noted in 51 patients, and the worsening of both the HRT parameters (Type II HRT dynamics) in 34 patients. Fourteen patients showed the worsening of only one HRT parameter (Type III HRT dynamics). The following HRV parameters recorded in early postinfarction Holter monitoring had a significant influence on the risk of Type II HRT dynamics: SDNN, RMSSD, Triangle Index and Δ LF/HF (mean day‐time LF/HF – mean night‐time LF/HF). Only the latter was found in the multivariate analysis as significantly connected with worsened HRT. During the follow‐up, SDNN and Triangular Index improved in all the patients. Conclusions: HRT after myocardial infarction treated with primary PTCA presents a significant dynamics, which is different than dynamics of HRV. An abnormal circadian pattern of autonomic activity is a finding that helps identify patients who need to have HRT analysis repeated during a long‐term follow‐up, due to the tendency for HRT to change with time toward the prognostically unfavorable values.     

Initiating mechanisms of paroxysmal atrial fibrillation.

BACKGROUND: The understanding of the onset mechanisms of paroxysmal atrial fibrillation (AF) may help to develop preventive therapy. Specific heart rate (HR) patterns and autonomic changes immediately before the onset of paroxysmal AF are not fully investigated. We undertook the present study to assess HR and heart rate variability (HRV) changes before the onset of AF using 24-h Holter electrocardiographic analysis in patients without antiarrhythmic medication. METHODS AND RESULTS: In 27 patients, 48 episodes of AF, lasting more than 30s and preceded by sinus rhythm for more than 1h were analysed. The hour preceding AF was divided in 5- and 30 min blocks. HR was also analysed in the last 15 beats. In 21% of the episodes, HR decreased >or=5% in the last 5 min (defined as deceleration); it increased >or=5% in 37% (defined as acceleration). HR, standard deviation (SD) and SD corrected for RR interval changed significantly in the last 5 min in the total group. Acceleration and deceleration were already visible over 30-min blocks in both these subgroups; changes in SD were only seen in the accelerators. The number of atrial premature beats (PACs) increased before AF, most clearly in the accelerators. Spectral HRV analysis revealed no additional information. CONCLUSIONS: Changes in HR, SD, and an increased number of PACs herald AF from at least 30 min before onset, more pronounced in accelerators. Spectral HRV parameters are not useful to foresee AF onset. This has possible implications for device therapy.     

急性冠脉综合征患者窦性心率震荡变化特点及其与心率变异性的相关性研究

目的分析急性冠脉综合征（ACS）患者窦性心率震荡（HRT）指标变化特点及其与心率变异性（HRV）的相关性。方法应用相应的分析软件对与59名健康体检者和161例确诊为ACS的患者24h动态心电图检查结果进行分析,检测HRT参数震荡初始（TO）、震荡斜率（TS）和HRV时域指标24h正常RR间期标准差（SDNN）、全程相邻窦性R—R间期之差的均方根值（rMSSD）、相邻正常RR间期差值〉50ms的心搏数占总RR间期数的百分比（PNN50）。将ACS组分为不稳定型心绞痛（UAP）组和急性心肌梗死（AMI）组,比较HRT、HRV指标和HRT异常的发生率在各组间的差异,进一步探讨ACS患者HRT和HRV指标相关性。结果与健康对照组比较,UAP组及AMI组TO明显增高,TS显著降低（均P〈0．01）;UAP组及AMI组间TO和TS无显著差异。UAP组及AMI组HRT异常率较对照组显著升高（X^2=5．385,P〈0．05;r=9．227,P=0．01）。UAP组及AMI组HRV指标SDNN、rMSSD、PNN50较对照组显著降低（均P〈0．01）,AMI组SDNN较UAP组降低（P〈0．05）,rMSSD、PNN50差异无统计学意义。ACS患者的TO与SDNN呈负相关（r=-0．26,P=0．031）,与rMSSD、PNN50不相关,TS与SDNN、PNN50、RMSSD呈正相关,其中和SDNN的相关性最强（r=0．301,P=0．047）。结论HRT可作为ACS危险分层的一项新的心电学筛选指标。ACS患者HRT、HRV变化从不同方面反映心脏迷走神经的功能受损,二者互相联系又相互独立。     

Heart Rate Variability in Young Women with Polycystic Ovary Syndrome

Background: Limited data are available related to the effects of sex hormones on cardiac autonomic function. Few studies investigated the heart rate variability (HRV) parameters during regular menstrual cycle or in postmenopausal women using hormone replacement therapy, but the results were contradictory. The aim of the study was to compare the characteristics of the autonomic innervation of the heart in polycystic ovary syndrome (PCOS) patients with regularly cycling controls. Methods: Thirty PCOS patients and 30 healthy regularly cycling controls were included in the study. Groups were compared with respect to age and various cardiovascular risk factors. Characteristics of autonomic innervation of the heart were evaluated with HRV. Power spectral analysis of HRV was performed to calculate the low frequency peak (LF 0.04–0.15 Hz), high‐frequency peak (HF 0.15–0.40 Hz), LF in normalized unit (LF nu), HF in normalized unit (HF nu) and LF/HF ratio. Results: PCOS patients had adverse cardiovascular risk profile than controls. As the HRV parameters, PCOS patients had significantly higher LF nu (P = 0.005) and LF/HF ratio (P = 0.001) and significantly lower HF (P = 0.006) and HF nu (P < 0.001) compared to controls. Conclusion: Autonomic innervation of the heart can be affected in PCOS with increased sympathetic and decreased parasympathetic components of HRV. As a result, sympathetic to parasympathetic ratio may increase in PCOS. This finding should be confirmed with larger studies also evaluating the clinical implications of altered HRV parameters.     

Differences in Heart Rate Dynamics Before the Spontaneous Onset of Long and Short Episodes of Paroxysmal Atrial Fibrillation

Background: Altered heart rate (HR) dynamics precede the spontaneous onset of atrial fibrillation (AF), but the factors related to the perpetuation and duration of paroxysmal AF episodes are not well established. This study was designed to test the hypothesis that HR dynamics preceding the onset of (AF) may influence the duration of AF. Methods: Traditional time and frequency domain HR variability indices, along with a short‐term fractal scaling exponent (α₁) and approximate entropy (ApEn), were analyzed in 20‐minute intervals before 92 episodes of spontaneous paroxysmal AF in 22 patients without structural heart disease. AF episodes were divided into two groups according to the duration of the arrhythmia episodes. Results: The high‐frequency (HF) spectral component in normalized units (nu) of heart rate variability was higher and low‐frequency (LF) component lower before long (> 200 s, n = 41) compared to short (< 200 s, n = 51) AF episodes (HF nu; 40.1 ± 14.8 vs 31.5 ± 16.4, P < 0.0001 and LF nu; 59.9 ± 14.8 vs 68.5 ± 16.4, P < 0.0001). Short‐term scaling exponent values also were lower before long compared to short AF episodes (e.g., α₁; 1.12 ± 0.21 vs 1.24 ± 0.23, P < 0.0001). Women had a larger number of long AF episodes than men, but the duration of AF was not related to any other clinical or demographic features or antiarrhythmic medication. Conclusion: Increased HF oscillations and decreased short‐term correlation properties of R‐R intervals, reflecting altered sympathovagal balance before the onset of AF, predispose to perpetuation of spontaneous arrhythmia episodes in patients with vulnerability to paroxysmal AF and without structural heart disease. A.N.E. 2001;6(2):134–142     

The Relationship Between Heart Rate Recovery and Heart Rate Variability in Coronary Artery Disease

Background: Reduced heart rate recovery (HRR) in coronary artery disease (CAD) is predictive of increased cardiovascular mortality and is related to reduced parasympathetic tonus. Objective: To investigate HRR and heart rate variability (HRV) measured at steady state condition and the relationship between these two parameters in CAD. Materials and Methods: In our study, we enrolled 33 (28 males, mean age 52.4 ± 9.6 years) patients with CAD who did not have heart failure, atrial fibrillation, pacemaker, and any disease state that could affect the autonomic functions and 38 age‐matched healthy subjects (21 males, mean age 48.3 ± 7.8 years). All the patients underwent submaximal treadmill exercise testing (Bruce protocol). HRR was calculated by subtracting the heart rate values at the 1st, 2nd, and 3rd minutes of the recovery phase from the peak heart rate (HRR₁, HRR₂, HRR₃). Before exercise testing, short‐term steady state HRV analyses of all subjects were obtained with the time‐ and frequency‐domain methods and were correlated to HRR. For frequency‐domain analysis, low‐frequency HRV (LF, 0.004–0.15 Hz), high‐frequency HRV (HF, 0.15–0.5 Hz), and LF/HF ratio were measured for 5 minutes in the morning. For time‐domain analysis, standard deviation of the normal‐to‐normal NN intervals (SDNN), square root of the mean squared differences of successive N‐N intervals (RMSSD), and proportion derived by dividing the number of interval differences of successive N‐N intervals greater than 50 ms by the total number of N‐N intervals (pNN50) were obtained. Only HRR₃ was used for the correlation analysis. Results: In CAD groups, the HF, an indicator of parasympathetic activation, was significantly reduced, whereas the LF and LF/HF values, which are indicators of sympathetic activity, were increased (P = 0.0001 for each parameter). The time‐domain parameters SDNN, RMSSD, and pNN50 were significantly reduced in the patient group (P = 0.0001, P = 0.009, and P = 0.0001, respectively). Similar to the HRV parameters, the HRR₁, HRR₂, and HRR₃ values were significantly reduced in the patient group (P = 0.0001 for each parameter). We observed a significant negative correlation between HRR₃ and LF (r =?0.67, P = 0.0001) and between HRR₃ and LF/HF (r =?0.62, P < 0.0001), while there was a significant positive correlation between HRR₃ and HF, SDNN, RMSSD, and pNN50 (r = 0.69, P = 0.0001; r = 0.41, P = 0.0001; r = 0.31, P = 0.008; and r = 0.44, P = 0.0001). Conclusions: HRR and HRV are significantly reduced in CAD. The reduction in HRR is parallel to the changes in HRV parameters. HRR, which can be measured easily in the recovery phase of exercise testing, can be used to detect the depression of parasympathetic tonus and to evaluate the basal autonomic balance in this patient group.     

Relationship of abnormal heart rate turbulence and elevated CRP to cardiac mortality in low, intermediate, and high-risk older adults

HRT and CRP for Mortality Risk in Elderly. Introduction: We examined whether heart rate turbulence (HRT) and C‐reactive protein (CRP) add to traditional risk factors for cardiac mortality in older adults at low, intermediate, and high risk. Methods and Results: One thousand two hundred and seventy‐two individuals, age ≥65 years, with 24‐hour Holter recordings were studied. HRT, which quantifies heart rate response to ventricular premature contractions, was categorized as: both turbulence onset (TO) and turbulence slope (TS) normal; TO abnormal; TS abnormal; or both abnormal. Independent risks for cardiac mortality associated with HRT or, for comparison, elevated CRP (>3.0 mg/L), were calculated using Cox regression analysis adjusted for traditional cardiovascular disease risk factors and stratified by the presence of no, isolated subclinical (i.e., intermediate risk) or clinical cardiovascular disease. Having TS + TO abnormal compared to both normal was associated with cardiac mortality in the low‐risk group [HR 7.9, 95% confidence interval (CI) 2.8–22.5, (P < 0.001)]. In the high and intermediate risk groups, abnormal TS and TS + TO ([HR 2.2, 95% CI 1.5–4.0, P = 0.016] and [HR 2.7, 95% CI 1.2–5.9, P = 0.012]), respectively, were also significantly associated with cardiac mortality. In contrast, elevated CRP was associated with increased cardiac mortality risk only in low‐risk individuals [HR 2.5, 95% CI 1.3–5.1, P = 0.009]. Among low risk, the c‐statistic was 0.706 for the base model, 0.725 for the base model with CRP, and 0.767 for the base model with HRT. Conclusions: Abnormal HRT independently adds to risk stratification of low, intermediate and high‐risk individuals, but HRT and CRP appear to both add to stratification of those considered low risk . (J Cardiovasc Electrophysiol, Vol. 22, pp. 122‐127, February 2011)     

Heart Rate Turbulence for Prediction of Heart Transplantation and Mortality in Chronic Heart Failure

Background: Previous studies have shown conflicting results about the value of heart rate turbulence (HRT) for risk stratification of patients (pts) with chronic heart failure (CHF). We prospectively evaluated the relation between HRT and progression toward end‐stage heart failure or all‐cause mortality in patients with CHF. Methods: HRT was assessed from 24‐hour Holter recordings in 110 pts with CHF (54 in NYHA class II, 56 in class III–IV; left ventricular ejection fraction (LVEF) 30%± 10%) on optimal pharmacotherapy and quantified as turbulence onset (TO,%), turbulence slope (TS, ms/RR interval), and turbulence timing (beginning of RR sequence for calculation of TS, TT). TO ≥ 0%, TS ≤ 2.5 ms/RR, and TT >10 were considered abnormal. End point was development of end‐stage CHF requiring heart transplantation (OHT) or all‐cause mortality. Results: During a follow‐up of 5.8 ± 1.3 years, 24 pts died and 10 required OHT. TO, TS, TT, and both (TO and TS) were abnormal in 35%, 50%, 30%, and 25% of all patients, respectively. Patients with at least one relatively preserved HRT parameter (TO, TS, or TT) (n = 98) had 5‐year event‐free rate of 83% compared to 33% of those in whom all three parameters were abnormal (n = 12). In multivariate Cox regression analysis, the most powerful predictor of end point events was heart rate variability (SDNN < 70 ms, hazard ratio (HR) 9.41, P < 0.001), followed by LVEF ≤ 35% (HR 6.23), TT ≥ 10 (HR 3.14), and TO ≥ 0 (HR 2.54, P < 0.05). Conclusion : In patients with CHF on optimal pharmacotherapy, HRT can help to predict those at risk for progression toward OHT or death of all causes. Ann Noninvasive Electrocardiol 2010;15(3):230–237