Prognostic Value of Heart Rate Variability in Time Domain Analysis in Congestive Heart Failure

AIMS: Analysis of heart rate variability is a noninvasive tool that allows to study autonomic control of the heart. Several studies have shown disturbed heart rate variability in patients with chronic heart failure (CHF). We sought to assess the prognostic value of time domain measures of heart rate variability in CHF. METHODS AND RESULTS: We prospectively enrolled 190 patients with CHF in sinus rhythm, mean age 61+/-12 years, 109 (57.4 %) in NYHA class II and 81 (42.6 %) in class III or IV, mean cardiothoracic ratio 57.6+/-6.4 % and mean left ventricular ejection fraction 28.2+/-8.8 %, 85 (45 %) with ischemic and 105 (55 %) with idiopathic dilated cardiomyopathy. Time domain measures of heart rate variability were obtained from 24 h Holter ECG recordings. During follow-up (22+/-18 months), 55 patients died. In multivariate analysis, independent predictors for all-cause mortality were: ischemic 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). CONCLUSIONS: Depressed heart rate variability has independent prognostic value in patients with CHF.     

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.     

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.     

QT interval dispersion as a predictor of arrhythmic events in congestive heart failure: Importance of aetiology

Aims Identification of patients with congestive heart failure atrisk of sudden death remains problematic and few data are availableon the prognostic implications of QT dispersion. We sought toassess the predictive value of QT dispersion for arrhythmicevents in heart failure secondary to dilated cardiomyopathyor ischaemic heart disease. Methods and Results Twelve-lead ECGs calculated for QT dispersion, 24h Holter ECGsand signal-averaged ECGs were prospectively recorded in 205heart failure patients in sinus rhythm. The 86 patients withischaemic heart disease and the 119 with dilated cardiomyopathywere not significantly different as regards NYHA grades (51vs 49% in grades III–IV), cardiothoracic ratio (57±7vs 57±6%) and ejection fraction (28±8 vs 29±9%).The mean QT dispersion (66±29 vs 65±27ms), thefrequency of non-sustained ventricular tachycardia (37 vs 38%)and ventricular late potentials (41 vs 40%) were not significantlydifferent in patients with ischaemic or dilated cardiomyop-athy.QT dispersion was not significantly related to other arrhythmogenicmarkers. During follow-up (24±16 months), 66 patientsdied, 22 of them died suddenly and seven presented a spontaneoussustained ventricular tachycardia. In patients with dilatedcardiomyopathy, in multivariate analysis, only a QT dispersion>80ms was an independent predictor of sudden death (RR: 4·9,95% CI 1·4–16·8,P<0·02) and arrhythmicevents (RR: 4·5, 95% CI 1·5–13·5,P<0·01).In patients with ischaemic heart disease, no studied parameterwas found significantly related to sudden death or arrhythmicevents. Conclusion: In congestive heart failure, abnormal QT dispersion can identifypatients with dilated cardiomyopathy who are at high risk ofarrhythmic events.     

Effect of quinapril on blood pressure and heart rate in congestive heart failure.

The effect of quinapril on blood pressure (BP), heart rate (HR) and their variabilities in 12 patients with severe congestive heart failure (New York Heart Association class III and IV) was assessed using ambulatory electrocardiographic and intraarterial monitoring. Mean +/- standard deviation daytime BP was 122/75 +/- 20/15 mm Hg at baseline and 113/70 +/- 13/16 mm Hg after 16 weeks of therapy with quinapril (p greater than 0.05 for systolic and diastolic BP); mean nighttime BP was 114/69 +/- 19/14 mm Hg at baseline and 107/69 +/- 15/14 mm Hg with quinapril (p greater than 0.05 for systolic and diastolic BP). Mean daytime HR was unchanged but nighttime HR was reduced from 77 +/- 11 to 71 +/- 10 beats/min, p = 0.02. HR variability (difference between the 75th and 25th percentiles of the frequency distribution of RR intervals) increased from 91 +/- 34 to 134 +/- 47 ms, p = 0.008. The variability of successive differences between RR intervals also increased significantly (75th to 25th percentile = 17 +/- 4 ms at baseline and 31 +/- 26 ms with quinapril, p = 0.02). Long-term quinapril caused clinically unimportant decreases in BP in patients with severe congestive heart failure. An increase in vagal activity caused by the reduction in circulating angiotensin II may account for the effect of converting enzyme inhibition on HR and its variability.     

Heart rate variability in patients with diabetes mellitus, ischemic heart disease, and congestive heart failure.

The prognosis of patients with heart disease and prediction of sudden cardiac death can be assessed through heart rate variability, an indirect measure of abnormal autonomic control. The authors have evaluated the heart rate variability by 24-hour ambulatory electrocardiographic monitoring in 25 diabetic patients, 19 ischemic heart disease patients, 18 congestive heart failure patients, and 10 normal subjects. Thirteen diabetic patients had autonomic neuropathy and 12 patients did not. Heart rate variability index (mean SD) in patients with diabetes mellitus, ischemic heart disease, and congestive heart failure was significantly lower (34.5 +/- 12.6 ms, 43.7 +/- 15.4 ms, and 34.6 +/- 15.8 ms vs 65.6 +/- 16.7 ms, p less than 0.05) than that of normal subjects. Mean SD was significantly lower in patients with autonomic neuropathy as compared to patients without autonomic neuropathy (26.4 +/- 6.5 ms vs 44.2 +/- 11.0 ms, p less than 0.05) mean SD as compared to survivors: 49 +/- 7 ms in patients with mild ischemic heart disease, 48 +/- 15 ms in patients with severe ischemic heart disease, and 23 +/- 7 ms in patients who died. Similarly, the mean SD in 4 congestive heart failure patients who died was lower significantly (p less than 0.05) than in those who survived (19.0 +/- 5.6 ms vs 40.0 +/- 14.5 ms). Among congestive heart failure patients, clinical improvement by therapy was associated with a significant increase in mean SD. When the mean SD of 30 ms was used as the cutoff point for detection of autonomic dysfunction or patient death, specificity exceeded 90% and sensitivity was 75%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular critical event pathways for the progression of heart failure; a report from the ATLAS study.

AIMS: To determine the sequence of critical cardiovascular events in the progression of heart failure, and whether aetiology or high-dose vs low-dose lisinopril affected these pathways. METHODS AND RESULTS: This was a post-hoc investigation of the ATLAS database, which comprised 3164 patients with chronic heart failure, randomized to low- (2.5-5.0 mg. day(-1)) or high-dose (32.5-35.0 mg. day(-1)) lisinopril, followed up for a median of 46 months. Two-thirds (64.3%) of patients had heart failure attributed to ischaemic heart disease. During the study, most patients (61.1%) had at least one cardiovascular hospitalization and 42.5% of all patients died: most deaths (88.2%) were cardiovascular. Nearly half (49.7%) of the cardiovascular deaths were considered sudden and 45.2% of cardiovascular deaths occurred as the first cardiovascular event. A third (30.2%) of deaths resulted from heart failure and were generally preceded by hospitalization, either for heart failure (85.5%), myocardial ischaemic events (21.7%) or arrhythmias (18.0%). Compared with low-dose, high-dose lisinopril was associated with a lower risk of death or hospitalization for any reason (P=0.002) and death or hospitalization with worsening heart failure (P<0.001). High-dose lisinopril delayed the time to all-cause mortality and hospitalization for chronic heart failure by 7.1 months. CONCLUSIONS: Vascular and arrhythmic events may not only be important precipitants of sudden death, but were also seen to contribute to the progression of heart failure. A reduction in vascular events, as well as benefits on ventricular remodelling, could account for the decrease in death or hospitalization with high-dose lisinopril.     

The relationship between QT intervals and mortality in ambulant patients with chronic heart failure. The united kingdom heart failure evaluation and assessment of risk trial (UK-HEART)

Aims: Mortality in patients with heart failure remains high and is difficult to predict. QT interval parameters on a 12-lead ECG have been shown to predict arrhythmic events in patients with a variety of myocardial diseases. There is some, but not consistent, evidence that QT interval parameters may act as predictors of mortality, in particular sudden death, in patients with heart failure. In an adequately powered prospective study we have studied QT interval parameters in patients with stable chronic heart failure in order to determine whether they are predictive of all-cause mortality or mode of death. Methods and Results: Five hundred and fifty-four ambulant outpatients with chronic heart failure were recruited. A 12-lead ECG, chest radiograph, echocardiogram, 24 h ambulatory electrocardiogram and serum for biochemical analysis were obtained at baseline. Patients were followed for 471+/-168 days. QT intervals were measured in all leads blinded to patient's characteristics and outcome, were corrected for heart rate, and the maximum QT intervals, and QT dispersion (range of QT intervals) were determined. The same parameters were determined for JT intervals. The primary end-point was all-cause mortality, secondary end-points were sudden cardiac death and death due to progressive heart failure. Multivariate analysis with the Cox's proportional hazards model was used to determine which variables were independently related to outcome.Four hundred and ninety-five patients had analysable ECGs at study entry and of these 71 died during follow-up. The heart rate corrected QT dispersion and maximum QT interval were significant univariate predictors of all-cause mortality (P=0.026 and <0.0001 respectively), and also of sudden death and progressive heart failure death, but were not related to outcome in the multivariate analysis. The independent predictors of all-cause mortality were cardiothoracic ratio (P=0.0003), creatinine (P=0.0009), heart rate (P=0.007), echocardiographically derived left ventricular end-diastolic dimension (P=0.007) and ventricular couplets on 24 h electrocardiographic monitoring (P=0.015).Conclusion: In an adequately powered prospective study none of the QT or JT parameters were shown to be independent predictors of outcome in patients with mild to moderate congestive heart failure. These variables do not therefore add to the prognostic information which can be gained from simple radiographic, biochemical, echocardiographic and Holter data in this group of patients.     

Prognostic value of heart rate variability for sudden death and major arrhythmic events in patients with idiopathic dilated cardiomyopathy

OBJECTIVE: This study was designed to evaluate the prognostic value of heart rate variability for sudden death, resuscitated ventricular fibrillation or sustained ventricular tachycardia in patients with idiopathic dilated cardiomyopathy. BACKGROUND: Previous studies have shown that heart rate variability could predict arrhythmic events and sudden death in postinfarction patients, but the prognostic value of heart rate variability for arrhythmic events or sudden death in patients with idiopathic dilated cardiomyopathy has not been established. METHODS: Time and frequency domain analysis of heart rate variability on 24-h electrocardiographic (ECG) recording was assessed in 116 patients with idiopathic dilated cardiomyopathy (91 men, aged 51+/-12 years, left ventricular ejection fraction 34+/-12%). RESULTS: Mean follow-up (+/-SD) was 53+/-39 months. Sixteen patients reached one of the defined study end-points (sudden death, resuscitated ventricular fibrillation or sustained ventricular tachycardia) during follow-up. Using multivariate analysis, only reduced standard deviation of all normal-to-normal intervals (SDNN) (p = 0.02) and ventricular tachycardia during 24-h ECG recording (p = 0.02) predicted sudden death and/or arrhythmic events. For SDNN, a cutoff level of 100 ms seemed the best for the risk stratification. CONCLUSIONS: Decrease in heart rate variability is an independent predictor of arrhythmic events and sudden death in idiopathic dilated cardiomyopathy, whether the mechanism of sudden death is ventricular tachyarrhythmia or not.     

Predicting death due to progressive heart failure in patients with mild-to-moderate chronic heart failure

OBJECTIVES: The aim of this study was to explore the value of noninvasive predictors of death/mode of death in ambulant outpatients with chronic heart failure (HF). BACKGROUND: Mortality in chronic HF remains high, with a significant number of patients dying of progressive disease. Identification of these patients is important. METHODS: We recruited 553 ambulant outpatients age 63 +/- 10 years with symptoms of chronic HF (New York Heart Association functional class, 2.3 +/- 0.5) and objective evidence of left ventricular dysfunction (ejection fraction <45%, cardiothoracic ratio >0.55, or pulmonary edema on chest radiograph). After 2,365 patient-years of follow-up, 201 patients had died, with 76 events due to progressive HF. RESULTS: Independent predictors of all-cause mortality assessed with the Cox proportional hazards model were as follows: a low standard deviation of all normal-to-normal RR intervals (SDNN); lower serum sodium and higher creatinine levels; higher cardiothoracic ratio; nonsustained ventricular tachycardia; higher left ventricular end-systolic diameter; left ventricular hypertrophy; and increasing age. Independent predictors of death specific to progressive HF were SDNN, serum sodium and creatinine levels. The hazard ratio of progressive HF death for a 10% decrease in SDNN was 1.06 (95% confidence interval [CI], 1.01 to 1.12); for a 2 mmol/l decrease in serum sodium, 1.22 (95% CI, 1.08 to 1.38); and for a 10 micromol/l increase in serum creatinine, 1.14 (95% CI, 1.09 to 1.19) (all p < 0.01). CONCLUSIONS: In ambulant outpatients with chronic HF, low serum sodium and SDNN and high serum creatinine identify patients at increased risk of death due to progressive HF.     

Prognostic value of heart rate variability in patients with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) have been reported to display impaired heart rate variability, although little is known regarding its prognostic value. By using fast Fourier transformation of 24-hour Holter recordings in 73 HCM patients at a stable clinical condition, we computed 4 spectral components: very low frequency, low frequency, high frequency, and total power. During 28 months, 7 HCM patients experienced death or acquired hospitalization for heart failure. Sudden death did not occurred. High frequency component was lower in HCM patients with cardiac events than that in patients without cardiac events (3.78 +/- 0.66 vs. 4.43 +/- 0.92 In(ms(2)), P =.045). There were no significant differences in other heart rate variability variables between HCM patients with and without cardiac events. In multivariate analysis, high frequency component remained to be an independent predictor of cardiac events (relative risk=0.10, 95% CI 0.01-0.73, P =.023). Heart rate variability analysis is predictive of heart failure in our cohort of HCM patients, whereas its predictive value of sudden death remains unclear.     

Comparison of verapamil versus felodipine on heart rate variability in hypertensive patients.

OBJECTIVE: We evaluated the effect of two calcium channel blockers, verapamil and felodipine, on heart rate variability in hypertensive patients. DESIGN: Time and frequency domain measures of heart rate variability were obtained from 24 h Holter recording in 25 previously untreated hypertensive patients without left ventricular hypertrophy, before and after 3 months of verapamil slow-release treatment (240 mg once daily) or felodipine extended-release treatment (10 mg once daily). RESULTS: Blood pressure values decreased with both drugs. Measures of heart rate variability, comparable at baseline in the two groups, were unchanged after felodipine. After verapamil, the average RR interval, the square root of the mean of the squared differences between all adjacent normal RR intervals (r-MSSD) and the percentage of differences between all adjacent normal RR intervals > 50 ms (pNN50), measures of vagal modulation of heart rate, increased (from 735 +/- 67 to 827 +/- 84 ms, P < 0.001; from 30 +/- 10 to 44 +/- 15 ms, P < 0.001; and from 3 +/- 2 to 7 +/- 6%, P < 0.01, respectively) and were higher than after felodipine. The coefficient of variation, a measure that compensates for heart rate effects, increased only after verapamil (from 5.8 +/- 1.3% to 6.6 +/- 1.0%; P < 0.05). High frequency power and its coefficient of component variance, both representing the vagal modulation of heart rate, increased after verapamil (from 5.33 +/- 0.29 to 5.80 +/- 0.27 In units, P < 0.001 and from 1.9 +/- 0.3 to 2.2 +/- 0.25%; P < 0.05). Finally, the low to high frequency power ratio, an indicator of sympathovagal balance, with a high value suggesting a sympathetic predominance, decreased after verapamil (from 2.16 +/- 0.41 to 1.36 +/- 0.35; P < 0.001), confirming the improvement in vagal modulation of heart rate. CONCLUSION: In hypertensive patients, despite a comparable anti-hypertensive effect, verapamil, but not felodipine, has favourable effect on cardiac autonomic control.     

QT dynamicity: a prognostic factor for sudden cardiac death in chronic heart failure

INTRODUCTION: The aim of this study was to determine whether impaired adaptation of the QT interval to changes in heart rate predicts sudden death in patients with chronic heart failure (CHF). METHODS: We prospectively included 175 CHF patients in sinus rhythm. QT dynamicity was evaluated by analyzing 24-h Holter recordings. The linear regression slope of QT interval measured to the apex and to the end of T wave plotted against RR intervals was calculated using a dedicated Holter algorithm. RESULTS: Mean follow-up was 29.9+/-17.9 months. There were 48 deaths, of which 21 were sudden. The actuarial 3-year mortality rates were 38.4% for overall mortality and 14.1% for sudden death. Of all the parameters, an increased QTe/RR slope (>0.28) was the strongest independent predictor of sudden death (relative risk 3.47, 95% confidence interval 1.43-8.40, p=0.006). CONCLUSION: Increased 24-h QTe dynamicity is independently predictive of sudden death among patients with heart failure. This simple parameter may help to stratify risk and select patients who may benefit from antiarrhythmic prophylaxis.     

Comparison of various methods of assessment of heart rate variability including simple cardiovascular reflex tests as predictors of sudden cardiac death after myocardial infarction.

Long term heart rate variability is used for prediction of sudden cardiac death (SD). There are simpler methods of assessment of autonomic cardiac control - registration of heart rate response to reflex tests and determination of heart rate variability (HRV) on short ECG recordins. Comparative value for prognosis of SD after myocardial infarction (MI) of these 3 techniques has not been studied yet. METHODS: Valsalva maneuver with calculation of Valsalva ratio (VR) and deep breath test with calculation of difference between average maximal and minimal HR during first minute of test (HR difference - HRD) were performed in 188 patients on days 4-11 of MI (68.1% men, age 34-75 years, 93.6% on beta-blockers, without heart failure NYHA IV on the day of tests). Time and frequency domain HRV measures were assessed during 15 min at bed rest and at Holter monitoring for median 24 h on the same day as reflex tests. RESULTS: During follow up for 2.1+/-0.8 years there were 9 sudden and 13 non-sudden cardiac deaths. ROC analysis was used to determine cut-off values of VR, HRD and HRV measures for dichotomization of patients into those with low- and high-risk of SD and these values were used in logistic regression analysis. The following parameters were univariate predictors of SD: obtained at reflex tests - VR <1.13 (OR 7.8, 95% CI 1.6-39.0; p=0.012), HRD <3.36 (OR 4.3, 95% CI 1.1-16.9; p=0.034); HRV parameters from 15 min ECG recordings - total frequency power <739 ms(2), VLF power <294 ms(2), LF power <197 ms(2) and LF/HF <1.5; HRV parameters from long term ECG recording - LF power <491 ms(2), LF/HF <1.4. At multivariate analysis only LF power for 15 min <197 ms(2) among HRV parameters remained independent predictor of SD (OR 24.2, 95% CI 2.4-245.5; p=0.007). Other predictors were clinical - VF during acute phase of MI (OR 94.7, 95% CI 4.2-2115.2; p=0.004) and history of MI (OR 8.4, 95% CI 1.4-48.5; p=0.017). CONCLUSION: In this population of patients without severe heart failure low LF power on 15 min resting ECG recordings on days 4-11 of MI was more powerful predictor of sudden cardiac death during subsequent 2 years than other HRV parameters including heart rate response to Valsalva maneuver and deep breath test.     

Cardiothoracic surgery after heart and heart-lung transplantation

OBJECTIVE: We sought to examine our management and the outcomes of cardiothoracic procedures after heart and heart lung transplantation. METHODS: We performed a retrospective review of cardiothoracic surgical procedures carried out between 1990 and 2004 in patients who had previously undergone heart or heart-lung transplantation at our institution. RESULTS: Twenty-one out of 340 patients (6.2 %) were identified. Cardiothoracic surgery was performed 44.4 +/- 33 months (range 1 - 115 months) after transplantation. Predominant types of surgery were coronary artery bypass grafting due to allograft vasculopathy (n = 5), aortic surgery due to acute dissection (n = 3), biventricular assist device implantation due to acute rejection (n = 1), tricuspid valve repair (n = 1), multiple cardiac surgical procedures including coronary artery bypass grafting, retransplantation, and tricuspid valve replacement (n = 2), explantation of a functionless heterotopic transplanted heart (n = 1). Lung surgery was performed in six patients due to pneumonia (n = 2), primary lung carcinoma (n = 3), lung torsion following heart-lung transplantation (n = 1). All patients underwent either lobectomy or segmental lung resection. Single lung retransplantation (n = 2) after prior heart-lung transplantation due to bronchiolitis obliterans was performed. In one patient a pneumonectomy (n = 1) due to severe chronic rejection of the contralateral lung was performed. Six subsequent deaths after cardiothoracic procedures were recorded after 1, 4, 78, 163, 205, and 730 days, respectively. Causes of death were advanced carcinoma (n = 1), multi-organ failure due to sepsis (n = 2), sudden heart death (n = 2), and advanced heart failure (n = 1). Fifteen out of 21 patients having undergone cardiothoracic procedures (71.4 %) survived the observation period of 56.6 +/- 34 months (range 1 - 114). CONCLUSIONS: Reasons for cardiothoracic procedures after prior heart or heart-lung transplantation were allograft vasculopathy, aortic dissections years after transplantation, chronic rejection, and either lung infections or malignancies. Surgical repair can be performed with an acceptable operative risk and good long-term survival rates.     

Subnormal heart period variability in heart failure: effect of cardiac transplantation

Heart period variability and arterial baroreceptor-cardiac reflex function were studied in cardiac transplant patients to determine if correction of heart failure restores parasympathetic control mechanisms toward normal. Heart period variability (standard deviation [SD] of 120 consecutive RR or PP intervals) was measured at supine rest in 34 patients with congestive heart failure (23 patients receiving diuretics, digoxin or vasodilators and 11 patients weaned from all medications), 30 cardiac transplant patients (both innervated recipient and denervated donor atrial rates) and 16 age-matched healthy control subjects. Arterial baroreflex gain was evaluated with intravenous bolus injections of phenylephrine in 22 transplant patients. Mean heart period variability (+/- SEM) was significantly lower (p less than 0.05) in the heart failure groups (22 +/- 3 ms for medicated and 17 +/- 3 ms for nonmedicated) than in the transplant patients (41 +/- 5 ms) or control subjects (58 +/- 5 ms). Heart period variability of the transplant patients was less than that of the control patients (p less than 0.05). A stepwise regression model revealed that heart period variability was inversely related to systolic arterial pressure and directly related to time after transplantation (R2 = 0.39; p = 0.03) in the transplant patients. Baroreflex gain of normotensive transplant patients was normal (11.7 +/- 1.0 ms/mm Hg) and correlated directly with heart period variability (r = 0.62; p less than 0.001). These data suggest that subnormal levels of cardiac parasympathetic activity at rest associated with congestive heart failure can be restored progressively toward normal by correction of congestive heart failure after cardiac transplantation. Post-transplant hypertension opposes this correction of baseline parasympathetic activity.     

Different spectral components of 24 h heart rate variability are related to different modes of death in chronic heart failure.

AIMS: To assess whether analysis of heart rate variability (HRV) from 24 h Holter recordings provides information about the mode of death (pump failure vs. sudden death) in chronic heart failure (CHF). METHODS AND RESULTS: We analysed 24 h HRV in 330 consecutive CHF patients in sinus rhythm. Indices derived from time domain, spectral domain, and fractal analyses of 24 h automatic HRV were evaluated. Data from clinical assessment, echocardiography, right heart catheterization, exercise test, blood biochemical examination, and arrhythmia pattern were analysed. Patients were followed up for 3 years. Two simple multivariable models, both including 24 h spectral indices, were able to identify patients at higher risk of progressive pump failure and sudden death, respectively. Depressed power of night-time HRV (< or = 509 ms(2)) below 0.04 Hz [very low frequency (VLF)], high pulmonary wedge pressure (PWP > or = 18 mm Hg) and low left ventricular ejection fraction (LVEF < or = 24%) were independently related to death for progressive pump failure, while the reduction of power between 0.04 and 0.15 Hz at night (LF < or = 20 ms(2)) and increased left ventricular end-systolic diameter (LVESD > or = 61 mm) were linked to sudden mortality. CONCLUSION: Automatic spectral analysis of 24 h HRV provides independent risk indices related to mode of death in sinus rhythm CHF patients.     

Effects of metoprolol CR/XL on mortality and hospitalizations in patients with heart failure and history of hypertension

BACKGROUND: We describe the effect of controlled-release/extended-release (CR/XL) metoprolol succinate once daily on mortality and hospitalizations among patients with a history of hypertension complicated by chronic systolic heart failure. METHODS AND RESULTS: We enrolled 3,991 patients with chronic heart failure of New York Heart Association functional class II-IV with an ejection fraction of < or = 0.40, stabilized with optimum standard therapy, in a double-blind randomized placebo-controlled study. A total of 1,747 patients (44%) had a history of hypertension; 871 were randomized to receive metoprolol CR/XL and 876 to receive placebo. Treatment with metoprolol CR/XL compared with placebo resulted in a significant reduction in total mortality (relative risk [RR], 0.61; 95% confidence interval [CI], 0.44-0.84; P =.0022), mainly because of reductions in sudden death (RR, 0.51; 95% CI, 0.33-0.79; P =.0022) and mortality from worsening heart failure (RR, 0.49; 95% CI, 0.25-0.99; P =.042). Total number of hospitalizations for worsening heart failure was reduced by 30% in the metoprolol CR/XL group compared with placebo (P =.015). Metoprolol CR/XL was well tolerated: 12% fewer patients withdrew from study medication (all-cause) compared with placebo (P =.048). CONCLUSIONS: A subgroup analysis of MERIT-HF shows that patients with heart failure and a history of hypertension received a similar benefit from metoprolol CR/XL treatment as all patients included in the total study.     

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)     

Circadian rhythm of heart rate variability in survivors of cardiac arrest.

Reduced heart rate (HR) variability is associated with increased risk of cardiac arrest in patients with coronary artery disease. In this study, the power spectral components of HR variability and their circadian pattern in 22 survivors of out-of-hospital cardiac arrest not associated with acute myocardial infarction were compared with those of 22 control patients matched with respect to age, sex, previous myocardial infarction, ejection fraction and number of diseased coronary arteries. Survivors of cardiac arrest had significantly lower 24-hour average standard deviation of RR intervals than control patients (29 +/- 10 vs 51 +/- 15 ms, p less than 0.001), and the 24-hour mean high frequency spectral area was also lower in survivors of cardiac arrest than in control patients (13 +/- 7 ms2 x 10 vs 28 +/- 14 ms2 x 10, p less than 0.01). In a single cosinor analysis, a significant circadian rhythm of HR variability was observed in both groups with the acrophase of standard deviation of RR intervals and high-frequency spectral area occurring between 3 and 6 A.M. which was followed by an abrupt decrease in HR variability after arousal. The amplitude of the circadian rhythm of HR variability did not differ between the groups. Thus, HR variability is reduced in survivors of cardiac arrest but its circadian rhythm is maintained so that a very low HR variability is observed in the morning after awakening, corresponding to the time period at which the incidence of sudden cardiac death is highest.