Depressed Heart Rate Variability as an Independent Predictor of Death in Chronic Congestive Heart Failure Secondary to Ischemic or Idiopathic Dilated Cardiomyopathy

After acute myocardial infarction, depressed heart rate variability (HRV) has been proven to be a powerful independent predictor of a poor outcome. Although patients with chronic congestive heart failure (CHF) have also markedly impaired HRV, the prognostic value of HRV analysis in these patients remains unknown. The aim of this study was to investigate whether HRV parameters could predict survival in 102 consecutive patients with moderate to severe CHF (90 men, mean age 58 years, New York Heart Association [NYHA] class II to IV, CHF due to idiopathic dilated cardiomyopathy in 24 patients and ischemic heart disease in 78 patients, ejection fraction [EF], 26%; peak oxygen consumption, 16.9 ml/kg/min) after exclusion of patients in atrial fibrilation with diabetes or with chronic renal failure. In the prognostic analysis (Cox proportional-hazards model, Kaplan-Meier survival analysis), the following factors were investigated: age, CHF etiology, NYHA class, EF, peak oxygen consumption, presence of ventricular tachycardia on Holter monitoring, and HRV measures derived from 24-hour electrocardiography monitoring, calculated in the time (standard deviation of all normal RR intervals [SDNN], standard deviation of 5-minute RR intervals [SDANN], mean of all 5-minute standard deviations of RR intervals [SD], root-mean-square of difference of successive RR intervals [rMSSD], and percentage of adjacent RR intervals >50 ms different [pNN50]) and frequency domain (total power [TP], power within low-frequency band [LF], and power within high-frequency band [HF]). During follow-up of 584 ± 405 days (365 days in all who survived), 19 patients (19%) died (mean time to death: 307 ± 315 days, range 3 to 989). Cox's univariate analysis identified the following factors to be predictors of death: NYHA (p = 0.003), peak oxygen consumption (p = 0.01), EF (p = 0.02), ventricular tachycardia on Holter monitoring (p = 0.05), and among HRV measures: SDNN (p = 0.004), SDANN (p = 0.003), SD (p = 0.02), and LF (p = 0.003). In multivariate analysis, HRV parameters (SDNN, SDANN, LF) were found to predict survival independently of NYHA functional class, EF, peak oxygen consumption, and ventricular tachycardia on Holter monitoring. The Kaplan-Meier survival curves revealed SDNN <100 ms to be a useful risk factor; 1-year survival in patients with SDNN <100 ms was 78% when compared with 95% in those with SDNN >100 ms (p = 0.008). The coexistence of SDNN <100 ms and a peak oxygen consumption <14 ml/kg/min allowed identification of a group of 18 patients with a particularly poor prognosis (1-year survival 63% vs 94% in the remaining patients, p <0.001). We conclude that depressed HRV on 24-hour ambulatory electrocardiography monitoring is an independent risk factor for a poor prognosis in patients with CHF. Whether analysis of HRV could be recommended in the risk stratification for better management of patients with CHF needs further investigation.

In 102 consecutive patients with stable chronic congestive heart failure and sinus rhythm, several heart rate variability measures derived from 24-hour electrocardiographic recording were significant prognostic risk markers, independent of clinical variables (New York Heart Association class, peak oxygen consumption, left ventricular ejection fraction). The coexistence of the standard deviation of all normal RR intervals <100 ms and peak oxygen consumption <14 ml/kg/min had the worst prognosis, and it is concluded that heart rate variability analysis is useful for noninvasive heart transplant assessment.     

Depressed low frequency power of heart rate variability as an independent predictor of sudden death in chronic heart failure.

AIMS: Identification of patients with chronic heart failure at risk for sudden death remains difficult. We sought to assess the prognostic value for all-cause and sudden death of time and frequency domain measures of heart rate variability in chronic heart failure. METHODS AND RESULTS: We prospectively enrolled 190 patients with chronic heart failure in sinus rhythm, mean age 61+/-12 years, 109 (57.4%) in NYHA class II and 81 (42.6%) in classes III or IV, mean cardiothoracic ratio 57.6+/-6.4% and mean left ventricular ejection fraction 28.2+/-8.8%, 85 (45%) with ischaemic and 105 (55%) with idiopathic dilated cardiomyopathy. Time and frequency domain measures of heart rate variability were obtained from 24 h Holter ECG recordings, spectral measures were averaged for calculation of daytime (1000h-1900h) and night-time (2300h-0600h) values. During follow-up (22+/-18 months), 55 patients died, 21 of them suddenly and two presented with a syncopal spontaneous sustained ventricular tachycardia. In multivariate analysis, independent predictors for all-cause mortality were: ischaemic heart disease, cardiothoracic ratio > or =60% and standard deviation of all normal RR intervals <67 ms (RR = 2.5, 95% CI 1.5-4.2). Independent predictors of sudden death were: ischaemic heart disease and daytime low frequency power <3.3 ln (ms(2)) (RR = 2.8, 95% CI 1.2-8.6). CONCLUSION: Depressed heart rate variability has independent prognostic value in patients with chronic heart failure; spectral analysis identifies an increased risk for sudden death in these patients.     

Fractal analysis and time- and frequency-domain measures of heart rate variability as predictors of mortality in patients with heart failure

Time-domain measures of heart rate (HR) variability provide prognostic information among patients with congestive heart failure (CHF). The prognostic power of spectral and fractal analytic methods of HR variability has not been studied in the patients with chronic CHF. The aim of this study was to assess whether traditional and fractal analytic methods of HR variability predict mortality among a population of patients with CHF. The standard deviation of RR intervals, HR variability index, frequency-domain indexes, and the short-term fractal scaling exponent of RR intervals were studied from 24-hour Holter recordings in 499 patients with CHF and left ventricular ejection fraction < or =35%. During a mean follow-up of 665 +/- 374 days, 210 deaths (42%) occurred in this population. Conventional and fractal HR variability indexes predicted mortality by univariate analysis. For example, a short-term fractal scaling exponent <0.90 had a risk ratio (RR) of 1.9 (95% confidence interval [CI] 1.4 to 2.5) and the SD of all RR intervals <80 ms had an RR of 1.7 (95% CI 1.2 to 2.1). After adjusting for age, functional class, medication, and left ventricular ejection fraction in the multivariate proportional-hazards analysis, the reduced short-term fractal exponent remained the independent predictor of mortality, RR 1.4 (95% CI 1.0 to 1.9; p <0.05). All HR variability indexes were more significant univariate predictors of mortality in functional class II than in class III or IV. Among patients with moderate heart failure, HR variability measurements provide prognostic information, but all HR variability indexes fail to provide independent prognostic information in patients with the most severe functional impairment.     

Heart Rate Variability in Chronic Heart Failure and Its Role in Prognosis of the Disease

Aim. To assess role of 24 hour heart rate variability (HRV) for prognosis of patients with chronic heart failure (CHF) and systolic dysfunction in the era of wide use of b-adrenoblockers. Material. Patients (n=135) with symptomatic CHF and ischemic (68%) or nonischemic cardiomyopathy (32%) with systolic left ventricular (LV) dysfunction and sinus rhythm (age 52+/-11.9 years; 42, 40 and 18% with NYHA class II, III and IV, respectively; mean LV ejection fraction 30.1+/-6.7%) At study entry 89 and 78% of patients received angiotensin converting enzyme inhibitors and b-adrenoblockers, respectively. Methods. Holter ECG monitoring with HRV temporal and spectral analysis. Results. During average follow-up of 2.4 years 60 patients (44.4%) died of cardiac causes (92.3% of all deaths). Other deaths were due to surgical pathology (n=1) and stroke (n=2). All standard HRV values with the exception of high frequency power were lowered, this lowering correlated with functional severity of heart failure. According to multifactorial analysis the following characteristics were independent predictors of all cause death: NYHA class III-IV (RR=1.9, 95% confidence interval 1.1-9.6, p=0.002), and SDNN value 90 ms (RR=1.5, 95% confidence interval 1.2-2.5, p=0.001). Conclusion. In CHF parameters of HRV are lowered compared to normal values and correlate with functional heart failure severity. NYHA class III-IV and lowered HRV (SDNN 90 ms) allow to identify patients with high risk of death.     

Measures of heart period variability as predictors of mortality in hospitalized patients with decompensated congestive heart failure

Depressed heart rate variability (HRV) is a powerful independent predictor of a poor outcome in patients with chronic and stable congestive heart failure (CHF). However, the prognostic value of HRV analysis in patients hospitalized for decompensated CHF is not known. The aim of this study was to investigate whether HRV parameters obtained during admission for decompensated CHF could predict survival after hospital discharge. We studied 199 patients (131 men, aged 60 +/- 14 years) with a previous diagnosis of New York Heart Association class III or IV CHF who were admitted to the hospital for decompensated CHF. Twenty-four-hour Holter recordings were obtained on admission, and measures of HRV were calculated in the time and frequency domain. During a mean follow-up of 312 +/- 150 days, 40 patients (21.1%) died. Kaplan-Meier analysis indicated that patients with SD of the RR intervals over a 24-hour period (p = 0.027), SD of all 5-minute mean RR intervals (p = 0.043), total power (p = 0.022), and ultra-low-frequency power (p = 0.008) in the lower tertile were at a higher risk of death. In a multivariate Cox regression model, the same indexes in the lower tertile were independent predictors of mortality: SD of the RR intervals over a 24-hour period (risk ratio [RR] 2.2, 95% confidence interval [CI] 1.05 to 4.3, p = 0.036), SD of all 5-minute mean RR intervals (RR 2.1, 95% CI 1.05 to 4.2, p = 0.04), total power (RR 2.2, 95% CI 1.08 to 4.2, p = 0.03), and ultra-low-frequency power (RR 2.6, 95% CI 1.3 to 5.3, p = 0.007). Therefore, the severity of autonomic perturbations during hospital admission for CHF decompensation, as reflected by measures of overall HRV, can predict survival after hospital discharge. Together with previous studies, our findings suggest that indexes of overall HRV provide useful prognostic information in the full spectrum of CHF severity.     

Prognostic significance of circadian variability of RR and QT intervals and QT dynamicity in patients with chronic heart failure

BACKGROUND: In patients with chronic heart failure (CHF), circadian variability of RR and QT intervals may be altered because of neurohumoral activation and functional and structural remodeling of the heart. OBJECTIVE: The aim of this study was to evaluate the prognostic significance of circadian variability of the RR and QT intervals and QT dynamicity (QT/RR slope) in CHF patients. METHODS: We prospectively enrolled 121 patients with stable CHF in sinus rhythm (age 67 +/- 14 years, mean +/- SD; range 34 to 87 years). The RR, QT, and rate-corrected QT (QTc) intervals and the QT/RR slope measured from 24-hour Holter electrocardiogram were fitted by cosine curves. RESULTS: During the follow-up period of 34 +/- 17 months, 40 (33%) patients died of cardiac causes, 10 of which were sudden. All patients showed significant circadian rhythms in the RR, QT, and QTc intervals and the QT/RR slope by cosine-curve fitting. In addition to the expected higher heart rate, longer QT interval, and steeper QT/RR slope, we found that patient who died of cardiac causes had reduced circadian variability of QT interval (10 +/- 10 ms vs 21 +/- 13 ms) and a later maximum RR interval (4.1 +/- 0.9 AM vs 2.3 +/- 2.1 AM) compared with survivors, among many other statistically significant circadian parameter differences. These 2 parameters were independent predictors of cardiac death in multivariate Cox proportional hazards regression analysis. CONCLUSION: Circadian variability analyses of Holter-derived RR and QT intervals may provide prognostic information beyond that provided by 24-hour averages of these parameters.     

Heart rate variability in dilated cardiomyopathy

Chronic heart failure is associated with excessive neurohormonal activation. Analysis of heart rate variability is considered a valid technique for assessment of the autonomic balance of the heart. Twenty symptomatic patients of dilated cardiomyopathy in NYHA class II-IV symptomatic status and as many normal controls were subjected to 24 hours Holter monitoring to assess the heart rate variability with both time domain and frequency domain analysis. Age of the patients ranged from 12 to 67 years (mean +/- SD 38.6 +/- 7 years), the male-female ratio was 4:1. The left ventricular ejection fraction of the patients was between 18-42 percent (mean +/- SD 30.2 +/- 9%) and all received diuretics, digoxin and angiotensin-converting enzyme inhibitors. Heart rate variability parameters measured included mean heart rate with standard deviation, hourly heart rate with SD and the mean of all normal RR intervals from the 24-hour recording. Time domain measures calculated were SD of all normal RR intervals, SD of 5 minute mean RR intervals and root mean square of difference of successive RR intervals. Using spectral plots, frequency domain subsets of low frequency and high frequency were analysed and expressed in normalised units. Total power was also measured. In the dilated cardiomyopathy patients, mean 24-hour heart rate in beats per minute was significantly higher in comparison to controls (82 +/- 13 vs 72 +/- 8; p < 0.001) whereas mean hourly heart rate with standard deviation (msec) was significantly lower (97 +/- 41 vs 232 +/- 25; p < 0.001), SD of all normal RR intervals (msec) was 85.5 +/- 26.3 vs 139.4 +/- 16.9 in controls (p < 0.001), SD of 5 minute mean RR intervals (msec) was also significantly less in patients in comparison to controls (75.8 +/- 39.6 vs 130.8 +/- 20.3; p < 0.001). However, although root mean square of difference of successive RR intervals (msec) was reduced in patients (30.1 +/- 9.3 vs 37.3 +/- 11.7; p < 0.05), the difference was non-significant. Low frequency power (0.05-0.15 Hz) (normalised units) was reduced in the dilated cardiomyopathy group (0.0721 +/- 0.003 vs 0.136 +/- 0.047 in the control group; p < 0.001). High frequency power (0.35-0.50 Hz) (normalised units) (0.08 +/- 0.05 in patients vs 0.09 +/- 0.02 in controls; p > 0.1) and total power frequency (0.02-0.50 Hz) (normalised units) (0.34 +/- 0.05 in patients vs 0.35 +/- 0.12 in controls; p > 0.1) was non-significantly different in the two groups. Regression analysis showed a significant decrease in SD of all normal RR intervals, SD of 5 minute mean RR intervals, low frequency, high frequency, total power and a non-significant decrease in root mean square of difference of successive RR intervals with a decrease in ejection fraction percent whereas there was a significant decrease in SD of all normal RR intervals, SD of 5 minute mean RR intervals, low frequency and total power and a less significant decrease in root mean square of difference of successive RR intervals and high frequency power with an increase in NYHA class. At 6 months duration, 6 patients were lost to follow-up, 3 patients were readmitted (2 for congestive cardiac failure, one of paroxysmal supraventricular tachycardia). One patient who was NYHA class IV at baseline was readmitted for congestive cardiac failure and showed much lower heart rate variability parameters compared to the average of the patients. We conclude that in symptomatic dilated cardiomyopathy patients, heart rate variability parameters are significantly reduced in comparison to control subjects.     

Heart rate variability enhances the prognostic value of established parameters in patients with congestive heart failure

This prospective study evaluated whether heart rate variability (HRV) assessed from Holter ECG has prognostic value in addition to established parameters in patients with congestive heart failure (CHF). The study included 222 patients with CHF due to dilated or ischemic cardiomyopathy (left ventricular ejection fraction LVEF 21+/-1%; mean+/-SEM). During a mean follow-up of 15+/-1 months, 38 (17%) patients died and 45 (20%) were hospitalized due to worsening of CHF. The HRV parameter SDNN (standard deviation of all intervals between normal beats) was significantly lower in non-surviving or hospitalized than in event-free patients (118+/-6 vs 142+/-5 ms), as were LVEF (18+/-1 vs 23+/-1%), and peak oxygen uptake during exercise (peak VO(2)) (12.8+/-0.5 vs 15.6+/-0.5 ml/min/kg). While each of these parameters was a risk predictor in univariate analysis, multivariate analysis revealed that HRV provides both independent and additional prognostic information with respect to the risk 'cardiac mortality or deterioration of CHF'. It is concluded that the determination of HRV enhances the prognostic power given by the most widely used parameters LVEF and peak VO(2) in the prediction of mortality or deterioration of CHF and thus enables to improve risk stratification.     

Effects of Carvedilol on Heart Rate Dynamics in Patients with Congestive Heart Failure

Background: Patients with congestive heart failure (CHF) have alterations in the traditional and nonlinear indices of heart rate (HR) dynamics, which have been associated with an increased risk of mortality. This study was designed to test the effects of carvedilol, a nonselective beta‐blocker with alpha‐1 blocking properties, on HR dynamics in patients with CHF. Methods: We studied 15 patients with CHF secondary to ischemic or idiopathic cardiomyopathy who met the following inclusion criteria: NYHA functional class II‐III, optimal conventional medical therapy, normal sinus rhythm, left ventricular ejection fraction (LVEF) of < 40%, and resting systolic blood pressure greater than 100 mmHg. The 6‐minute corridor walk test, estimation of LVEF, and 24‐hour Holter recording were performed at baseline and after 12 weeks of therapy with carvedilol. Traditional time and frequency domain measures and short‐term fractal scaling exponent of HR dynamics were analyzed. Results: After 12 weeks of therapy with carvedilol, the mean LVEF improved significantly (from 0.27 ± 0.08 to 0.38 ± 0.08, P < 0.001). The average HR decreased significantly (from 86 ± 11 to 70 ± 8 beats/min, P < 0.001). The mean distance traveled in the 6‐minute walk test increased significantly (from 177 ± 44 to 273 ± 55 m, P < 0.01). The frequency‐domain indices (HF and LF), the time domain indices (rMSSD and PNN5), and the short‐term fractal scaling exponent increased significantly. The scaling exponent increased particularly among the patients with the lowest initial values (< 1.0), and the change in the fractal scaling exponent correlated with the change in ejection fraction (r = 0.63, P < 0.01). Conclusion: Carvedilol improves time and frequency domain indices of HR variability and corrects the altered scaling properties of HR dynamics in patients with CHF. It also improves LVEF and functional capacity. These specific changes in HR behavior caused by carvedilol treatment may reflect the normalization of impaired cardiovascular neural regulation of patients with CHF. A.N.E. 2002;7(2):133–138     

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     

Chronic heart failure in the very elderly: clinical status, survival, and prognostic factors in 188 patients more than 70 years old.

BACKGROUND: Chronic heart failure (CHF) is a frequent disease with a dismal prognosis, but little is known about survival in the very elderly. There are no data on the prognostic value of cardiopulmonary exercise testing in this population. We aimed to assess exercise capacity, survival, and prognostic parameters in elderly patients with CHF. METHODS: We evaluated 188 patients with CHF >70 years old (mean 77 +/- 4 years, range 70-94 years) seen at our heart failure clinic between March 1992 and June 1998. A cardiopulmonary exercise test was performed in 102 patients (peak VO2 15.3 +/- 4.7, VE/VCO2 slope 39.6 +/- 15.01). All patients were followed up for at least 12 months. The prognostic end point of the study was all-cause mortality. RESULTS: At the end of follow-up (16 +/- 10 mo, range 12-41 mo), 67 patients (35.6%) had died (1-year mortality rate 26% [95% confidence interval 20-32]). In univariate analysis New York Heart Association class (NYHA) (relative risk [RR] = 2.56, P <.0001), VE/VCO2 (RR = 1.041, P <.0001), peak VO2 (RR = 0.87, P =.0007), and fractional shortening (RR = 0.95, P <.0001) predicted mortality. Peak VO2 predicted mortality independently of age, NYHA class, and left ventricular ejection fraction. A subgroup of 12 patients with dynamic left ventricular outflow tract obstruction during stress had an excellent outcome, with a 100% survival at the end of follow-up (mean 16 +/- 7 mo, range 12-39 mo). CONCLUSIONS: The prognosis in elderly patients with CHF is poor. Valid exercise testing results can be obtained in more than 50% of elderly patients with CHF. NYHA class and peak VO2 are the strongest prognostic factors in this population.     

Comparison of different methods for assessing sympathovagal balance in chronic congestive heart failure secondary to coronary artery disease.

Twenty-five patients (aged 62 +/- 2 years) with stable, moderate to severe ischemic congestive heart failure (CHF) (New York Heart Association class II/III: 15/10; ejection fraction 21.6 +/- 2%; and peak oxygen uptake 13.6 +/- 0.7 ml/kg/min) were studied to evaluate the ability of different methods to characterize autonomic tone in chronic CHF. Sympathovagal balance was assessed by: (1) heart rate variability in the time domain, assessed by the SD of RR intervals; (2) heart rate variability in the frequency domain, assessed by low- (0.03 to 0.14 Hz) and high- (0.18 to 0.40 Hz) frequency components of heart rate variability by autoregressive power spectral analysis; (3) 24-hour, daytime and nighttime heart rate; (4) submaximal heart rate during upright bicycle exercise, with respiratory gas analysis to obtain peak oxygen uptake; and (5) radiolabeled norepinephrine spillover. These methods did not correlate, with the exception of day and nighttime heart rate (r = 0.74; p < 0.001) and the expected inverse correlation between low and high frequency (r = -0.92; p < 0.001). No method correlated significantly with peak oxygen uptake, exercise tolerance or ejection fraction. After 8 weeks of physical training at home, all methods showed improvement in autonomic balance: increases in SD of RR intervals (+21%; p < 0.02) and high frequency (+41%; p < 0.007), and decreases in low frequency (-19%; p < 0.002), low-/high-frequency ratio (-48%; p < 0.03), norepinephrine spillover (-28.9%; p < 0.03), 24-hour heart rate (-2.7%; p < 0.005) and submaximal heart rate (-10.8%; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Heart rate turbulence and left ventricular ejection fraction in Chagas disease.

AIMS: Chagas disease patients often present premature ventricular complexes (PVCs), depression of left ventricular ejection fraction (LVEF) and autonomic dysfunction, which is generally evaluated by heart rate variability (HRV) analysis. As frequent PVCs may complicate HRV computation, we measured heart rate turbulence (HRT) and evaluated the correlation between ejection fraction and HRT or HRV in Chagas disease. METHODS: We studied 30 patients (47+/-11 years, 20 men) with Chagas cardiomyopathy and left ventricular dilatation who underwent clinical evaluation, ejection fraction (EF: 45+/-14%) determination and 24-h Holter monitoring (median PVC=1781). In all patients, the standard deviation of normal RR intervals (SDNN), the square root of the mean square differences of successive RR intervals (RMSSD) and values of turbulence onset (TO) and turbulence slope (TS) were calculated. RESULTS: HRT indices were independent of mean RR interval and presented high correlation with EF: TO (-0.11+/-0.01%, r=-0.60, P<0.001) and TS (5.8+/-3.7 ms/RR-interval, r=0.73, P<0.001). Of HRV parameters, only SDNN, corrected for mean RR interval, showed a weak but not significant correlation with EF (r=0.41). The comparison of HRT/EF and HRV/EF correlation coefficients, indicated the presence of a significant difference (P=0.017). CONCLUSIONS: HRT indices appear to correlate better with EF than SDNN in Chagas disease. Thus, an analysis based on heart rate transient adaptation seems to perform better than HRV in detecting the autonomic alterations that parallel left ventricular dysfunction in Chagas disease patients. The high number of PVCs observed in these patients further support the use of HRT methodology.     

Interleukin-6 levels are inversely correlated with heart rate variability in patients with decompensated heart failure

INTRODUCTION: Increased local and systemic elaboration of cytokines have an important role in the pathogenesis of congestive heart failure (CHF) through diverse mechanisms. Because cytokines are known to act at the neuronal level in both the peripheral and central nervous system, we sought to determine whether increased cytokine levels are associated with the autonomic dysfunction that characterizes CHF. METHODS AND RESULTS: We studied 64 patients admitted for decompensated CHF (mean age 59+/-12 years). Autonomic function was assessed using time- and frequency-domain heart rate variability (HRV) measures, obtained from 24-hour Holter recordings. In addition, norepinephrine, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured in all patients. TNF-alpha levels did not correlate with any of the HRV measures. IL-6 inversely correlated with the time-domain parameters of standard deviation of RR intervals (SDNN) (r = -0.36, P = 0.004) and standard deviation of all 5-minute mean RR intervals (SDANN) (r = -0.39, P = 0.001), and with the frequency-domain parameters of total power (TP) (r = -0.37, P = 0.003) and ultralow-frequency (ULF) power (r = -0.43, P = 0.001). No correlation was found between IL-6 and indices of parasympathetic modulation. Using multiple linear regression models, adjusting for clinical variables and drug therapies, the strong inverse relationship between IL-6 and SDNN (P = 0.006), SDANN (P = 0.001), TP (P = 0.04), and ULF power (P = 0.0007) persisted. CONCLUSION: Reduction of long-term HRV indices is associated with increased levels of IL-6 in patients with decompensated heart failure. The ability of long-term HRV parameters to better reflect activation of diverse hormonal systems may explain their greater prognostic power for risk stratification in patients with CHF.     

冠心病和充血性心力衰竭患者的心率变异性

本文采用标准差法及心率变指数法分析了冠心病、充血性心力衰竭及正常人各５０例的心率变异性，结果发现冠心病及充血性心力衰竭者的心率变异值显著低于正常人。心衰组中，心衰程度越重者，心率弈异赵低。且心率变异与心胸比值及ＰＥＰ／ＬＶＥＴ呈负相关，与心脏指数呈正相关。急性心肌梗死者的心率变趔氏于陈旧性心肌梗死和心绞痛者。２４例心肌梗死者查心室晚电位，晚电位阳性者的心率变异值显著低于晚电位阴性者，提示两者结合可     

Effect of beta-blockade on heart rate variability in decompensated heart failure

BACKGROUND: One of the putative mechanisms for the salutary effects of beta-blockers in patients with congestive heart failure is their ability to improve autonomic dysfunction. However, patients with profound neurohumoral abnormalities derive little survival benefit from beta-blockers. The purpose of the current study was to evaluate the effect of beta-blockers on heart rate variability in decompensated heart failure. METHODS: Time and frequency domain heart rate variability indices were obtained from 24-h Holter recordings and compared to assess the role of beta-blockade in 199 patients (mean age 60+/-14 years [range 21 to 87]) with decompensated heart failure (New York Heart Association functional class III [66%] and IV [34%]). RESULTS: All heart rate variability indices were markedly suppressed but were substantially higher in patients who were on beta-blockers. Time domain measures of parasympathetic cardiac activity, the percentage of RR intervals with >50 ms variation (4.9+/-0.6 vs. 7.7+/-1.2%, P=0.006) and the square root of mean squared differences of successive RR intervals (22.7+/-2.0 vs. 31.6+/-4.1 ms, P=0.004), were higher in the beta-blocker group. Spectral analysis revealed that the total power and the ultra low frequency power were significantly higher in patients on beta-blockers (82% and 59%, respectively). The high frequency power, a spectral index of parasympathetic modulation, was 41% higher in the beta-blocker group (121+/-25 vs. 171+/-27 ms(2), P=0.02). Multiple linear regression, adjusted for clinical parameters and drug therapies, revealed a strong positive relationship between beta-blockade and higher values of time and frequency domain measures. The mean number of ventricular tachycardia episodes were significantly lower in patients on beta-blocker therapy (3.6+/-1.5 vs. 19.0+/-5.3, P=0.04). CONCLUSIONS: beta-blockers improve the impaired cardiac autonomic regulation during high sympathetic stress of decompensated heart failure.     

Decreased spontaneous heart rate variability in congestive heart failure

Heart rate (HR) variability is a noninvasive index of the neural activity of the heart. Although also dependent on the sympathetic activity of the heart, HR variability is mainly determined by the vagal outflow of the heart. Several HR abnormalities have been described in patients with congestive heart failure (CHF); however, there are no data on HR variability in CHF patients. In the present study HR variability was assessed in 20 CHF patients and 20 control subjects from 24-hour Holter tapes. HR variability was evaluated by calculating the mean hourly HR standard deviation and by analyzing the 24-hour RR histogram. Mean hourly HR standard deviation was markedly and significantly reduced in CHF patients both over the 24-hour period (97.5 +/- 41 vs 233.2 +/- 26 ms, p less than 0.001) as well as during most of the individual hours examined. The 24-hour RR histogram of CHF patients had a different shape and had a decreased variation compared to control subjects (total variability 356 +/- 102 vs 757 +/- 156 ms, p less than 0.001). Thus, CHF patients with depressed ejection fraction (less than 30%) have a low HR variability compared to normal individuals. This result can be interpreted as adjunctive evidence for decreased parasympathetic activity to the heart during CHF.     

Central Chemoreceptor Sensitivity Is Not Enhanced in Contemporary Patients With Chronic Systolic Heart Failure Receiving Optimal Treatment

Background

Clinical and prognostic consequences of enhanced central chemosensitivity in the contemporary optimally treated patients with chronic heart failure (CHF) are unknown.

Prognostic value of QT/RR slope in predicting mortality in patients with congestive heart failure

Introduction: Repolarization dynamics, reflecting adaptation of QT to changing heart rate, is considered a marker of unfavorable prognosis in patients with heart diseases. We aimed to evaluate the prognostic value of QT/RR slope in predicting total mortality (TM) and sudden death (SD) in patients with congestive heart failure (CHF). Methods and Results: In 651 sinus rhythm patients with CHF in NYHA class II–III enrolled in the MUSIC study, 24‐hour Holter monitoring was performed at enrollment to assess slope of the QTa/RR (QT apex) and QTe/RR (QTend) during the entire 24‐hour Holter recording and separately during day and night periods. Patients were followed for a median of 44 months, with the primary endpoint defined as TM and the secondary as SD. Analysis of repolarization dynamics was feasible in 542 patients (407M), mean age 63 years, 83% in NYHA class II, 49% with ischemic cardiomyopathy, with mean LVEF 37%. Mean value of QTa/RR slope was 0.172 and QTe/RR was 0.193. During the 44‐month follow‐up there were 119 deaths including 47 SD. Nonsurvivors were characterized by steeper QT/RR slopes. Increased QT/RR slopes during the daytime (>0.20 for QTa and >0.22 for QTe) were independently associated with increased TM in multivariate analysis after adjustment for clinical covariates with respective hazard ratios 1.57 and 1.58, P = 0.002. None of the dynamic repolarization parameters was associated with increased risk of SD in the entire population. Conclusions: Abnormal repolarization dynamics reflected as increased daytime QT/RR slopes is an independent risk stratifier of all‐cause mortality in patients with chronic heart failure     

Non-invasive blood pressure variability in chronic heart failure: characteristics and prognostic value

BACKGROUND: Short-term variability of blood pressure can be used as an index of sympathetic vascular modulation and has been studied in patients with hypertension. AIM: The aim of this study was to characterise blood pressure variability (BPV) and its prognostic value in patients with congestive heart failure. METHODS AND RESULTS: 104 patients with congestive heart failure due to ischemia (n = 104) or idiopathic cardiomyopathy (n = 50) in New York Heart Association (NYHA) class II (n = 50), III (n = 71), IV (n = 33), and 40 healthy subjects were studied. The mean ejection fraction was 0.33 +/- 0.10. Continuous non-invasive BP recordings were obtained for 3,600 seconds with a photoplethysmographic finger device in patients and control subjects at rest. Patients with chronic heart failure (CHF) had significantly less pronounced BPV than control subjects. Diastolic blood pressure (DBP) variability was related to left ventricular ejection and to peak oxygen uptake. BPV was not different in patients with ischemic or idiopathic CHF. During the mean follow up (+/- SD) of 565 +/- 215 days, 44 patients died (28.6%). All deaths were cardiac related. Cox's univariate analysis identified the following factors to be predictors of death: peak oxygen uptake (p = 0.01), ejection fraction (p = 0.008), and among BPV parameters: total spectral amplitude (TA) for DBP (p = 0.002), very low frequencies over total amplitude (VLF/TA) for DBP (p = 0.005) and for mean blood pressure (MBP) (p = 0.03), and very low over high frequencies ratio (VLF/HF) for DBP (p = 0.002). Multivariate analysis showed that BPV predicted survival independently of EF or peak VO2. Kaplan-Meier survival curves revealed that VLF/TA < 55% for DBP, MBP and SBP are useful risk factors. One-year survival in patients with VLF/TA < 55% of DBP was 53% compared with 95% in those with VLF/TA > 55% (p = 0.005). CONCLUSIONS: Decreased BPV in patients with CHF is related to left ventricular dysfunction. Analysis of BPV can identify patients with CHF who have an increased risk of cardiac death.