Circadian rhythm and sudden death in heart failure: results from Prospective Randomized Amlodipine Survival Trial

OBJECTIVE: The purpose of this study was to address the timing of sudden death in advanced heart failure patients. BACKGROUND: Sudden death is a catastrophic event in cardiovascular disease. It has a circadian pattern prominent in the early AM, which has been thought to be due to a surge of sympathetic stimulation. We postulated that the distribution of events in advanced heart failure, with chronic sympathetic activation, would be more uniform implicating other potential mechanisms. METHODS: We analyzed data from Prospective Randomized Amlodipine Survival Trial (PRAISE). Sudden deaths were analyzed by time of death in 4-h and 1-h blocks for uniformity of distribution in the entire cohort, and in the prespecified ischemic and nonischemic stratum. Further analyses were undertaken in the treatment groups of amlodipine and placebo, and among those receiving background therapy of aspirin and warfarin. RESULTS: Sudden deaths in the overall cohort showed a nonuniform distribution with a PM peak but not an AM peak. The ischemic stratum also showed a PM peak, but sudden deaths within the nonischemic stratum were uniformly distributed. Neither amlodipine treatment nor aspirin or warfarin use altered the distribution. CONCLUSIONS: Sudden death in advanced heart failure did not show an AM peak, suggesting that circadian sympathetic activation did not strongly influence these events. The PM peak noted is likely complex in origin and was not affected by antiischemic or antithrombotic medications.     

Improved survival in patients with nonischemic advanced heart failure and syncope treated with an implantable cardioverter-defibrillator

The purpose of this study was to assess whether in patients with syncope and heart failure due to nonischemic cardiomyopathy, treatment with an implantable cardioverter-defibrillator (ICD) compared with conventional medical therapy is associated with a reduction in sudden death and total mortality. Patients with advanced heart failure who have syncope have been shown to be at high risk for sudden death. Further risk stratification has been difficult in patients with nonischemic cardiomyopathy in whom inducibility on electrophysiologic study is not predictive of future risk. Of 639 consecutive patients with nonischemic cardiomyopathy referred for heart transplantation, 147 patients with history of syncope and no prior history of sustained ventricular tachycardia or cardiac arrest were identified. Outcomes were compared for the 25 patients managed with an ICD and 122 patients managed with conventional medical therapy. There were no differences in the baseline variables in the 2 groups of patients, including age, ejection fraction, and medical treatments for heart failure, but patients receiving an ICD were more likely to have had nonsustained ventricular tachycardia (56% vs. 15%, p = 0.001). During a mean follow-up of 22 months, there were 31 deaths, 18 sudden, in patients treated with conventional therapy, whereas there were 2 deaths, none sudden, in patients treated with an ICD. An appropriate shock occurred in 40% of the ICD patients. Actuarial survival at 2 years was 84.9% with ICD therapy and 66.9% with conventional therapy (p = 0.04). Thus, in patients with nonischemic cardiomyopathy and syncope, therapy with an ICD is associated with a reduction in sudden death and an improvement in overall survival.     

Stratification of the Risk of Sudden Death in Nonischemic Heart Failure

Despite significant therapeutic advancements, heart failure remains a highly prevalent clinical condition associated with significant morbidity and mortality. In 30%-40% patients, the etiology of heart failure is nonischemic. The implantable cardioverter-defibrillator (ICD) is capable of preventing sudden death and decreasing total mortality in patients with nonischemic heart failure. However, a significant number of patients receiving ICD do not receive any kind of therapy during follow-up. Moreover, considering the situation in Brazil and several other countries, ICD cannot be implanted in all patients with nonischemic heart failure. Therefore, there is an urgent need to identify patients at an increased risk of sudden death because these would benefit more than patients at a lower risk, despite the presence of heart failure in both risk groups. In this study, the authors review the primary available methods for the stratification of the risk of sudden death in patients with nonischemic heart failure.     

Inherited ventricular arrhythmias and sudden death in German shepherd dogs

Objectives. This report describes a unique group of German shepherd dogs with inherited ventricular arrhythmias and sudden death. Before death, these dogs have no evidence of cardiovascular failure.Background. There are few spontaneous animal models of sudden death that permit intensive investigation.Methods. To determine the temporal evolution of ventricular arrhythmias and to characterize ihe syndrome of sudden cardiac death in these dogs, 24-h ambulatory electrocardiographic (ECG) monitoring, echocardiograms, electrophysiologic testing and breeding studies were conducted.Results. The 24-h ambulatory ECGs from dogs that died showed frequent ventricular arrhythmias with rapid polymorphic ventricular tachycardia (rates > 480 beats/min). Affected dogs had a window of vulnerability for arrhythmias, with the highest incidence and severity of arrhythmias between 20 to 30 and 40 to 50 weeks of age. Affected dogs that died did not have prolongation of the QT interval over a spectrum of heart rates compared with unaffected dogs. The clinical arrhythmia was not induced in dogs during programmed electrical stimulation. Severely affected dogs monitored > 5 years did not develop any evidence of heart failure or cardiomyopathy, and no histopathologic abnormalities existed. Seventeen dogs died suddenly (age 4 to 30 months) and were either 1) found dead at first observation in the morning (n = 8), 2) observed to die during sleep (n = 4), 3) observed to die while resting after exercise (n = 3), or 4) observed to die during exercise (n = 2). All sudden deaths occurred between the end of September and April, with most (n = 11) during January and February.Conclusions. The cause of the inherited severe ventricular arrhythmias and sudden death in these young German shepherd dogs is still undetermined. A purely arrhythmic disorder is supported by the lack of cardiac pathology. Moreover, the window of vulnerability to ventricular arrhythmias and the age and circumstances of death invite speculation about the role of the autonomic nervous system.     

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.     

Circadian variation of malignant ventricular arrhythmias in patients with ischemic and nonischemic heart disease after cardioverter defibrillator implantation. European 7219 Jewel Investigators.

OBJECTIVES: The purpose of this study was to examine the circadian variation of ventricular arrhythmias detected by an implantable cardioverter defibrillator in patients with and without ischemic heart disease. BACKGROUND: Previous studies have shown a circadian variation of ventricular arrhythmias, sudden death and myocardial infarction with a peak occurrence in the morning hours. The circadian pattern, which is similar for both arrhythmic and ischemic events, suggests that ischemia may play a critical role in the genesis of ventricular arrhythmias and sudden death. We hypothesized that, if ischemia plays an important role in the triggering of ventricular arrhythmias, the circadian pattern should be different in patients with ischemic heart disease compared with patients with nonischemic heart disease. METHODS: The circadian variation of ventricular arrhythmias recorded by an implantable cardioverter defibrillator was studied in 310 patients during a mean follow-up of 181 +/- 163 days. Two hundred four patients had a history of ischemic heart disease and 106 patients had nonischemic heart disease. The times of the episodes of ventricular arrhythmias were retrieved from the data log of each device during follow-up, and the circadian pattern was compared between the two groups. RESULTS: During follow-up, 1,061 episodes of ventricular arrhythmias were recorded by the device in the 310 patients. Six hundred eighty-two episodes occurred in the group of patients with ischemic heart disease and 379 occurred in the nonischemic heart disease group. The circadian variation of the episodes showed a typical pattern with a morning and afternoon peak in both groups of patients with ischemic and nonischemic heart disease, but there was no significant difference between the two groups. CONCLUSIONS: The circadian rhythm of ventricular arrhythmias in patients with ischemic heart disease is similar to patients with nonischemic heart disease, suggesting that the trigger mechanisms of the initiation of ventricular tachyarrhythmias may be similar, irrespective of the underlying heart disease.     

Variation circadienne et hebdomadaire de la mort subite d'origine cardiaque : registre autopsique du nord de la Tunisie

IntroductionSeveral studies have suggested a circadian and septadian pattern of incidence of sudden cardiac death with a morning peak and a Monday peak.ObjectiveTo analyze the circadian and septadian pattern of occurrence of sudden cardiac death in the eight northern Tunisian governorates.MethodsWe prospectively collected epidemiological and autopsy data of sudden cardiac death victims occurring in the northern region of Tunisia between January 2013 and December 2019.ResultsThe population included 1834 men (79.6%) and 468 women (20.4%) with a mean age of 56.5 ± 14 years. Smoking (53.9%) was the most prevalent cardiovascular risk factor. One-fifth (20.9%) of victims had known heart disease, and 3% had a family history of sudden death.ischemic heart disease was the leading cause of sudden death (46.8% of cases). One- fourth (25.7%) of autopsies were negative.Analysis of the circadian pattern of occurrence of sudden cardiac death identified a peak (36.1%, p < 0.001) between midnight and 6 am. This nocturnal excess mortality was significant (p < 0.001) and independent of sex (34.1 % in men and 43.8 % in women) and cause of death (39.3 % of cases of sudden ischemic death and 33.3 % of cases of nonischemic death).Moreover, there was a significant septadian variability in the occurrence of sudden death (p: 0.0015), with a peak on Friday (15.8 %, p: 0.042).ConclusionThis study showed a peak of sudden death between midnight and 6 am, and on Fridays, confirming the modification of the classic circadian and septadian pattern of sudden death occurrence. These results may help optimize the deployment of emergency mobile teams and structures during the most vulnerable periods.     

Prophylactic Implantation of Cardioverter Defibrillators in Idiopathic Nonischemic Cardiomyopathy for the Primary Prevention of Death: A Narrative Review

Implantable cardioverter defibrillator (ICD) therapy reduces sudden cardiac death rates and reduces mortality in patients with ischemic heart disease and low ejection fractions. One‐third of the deaths in patients with nonischemic cardiomyopathy are sudden. However, the efficacy of ICDs in the primary prevention of death in these patients is less clear. The most common cause of mortality in patients treated with ICDs is heart failure progression. ICD shocks can cause direct myocardial injury, fibrosis, inflammation, and adverse psychological outcomes, and these changes may contribute to the ventricular dysfunction in patients who already have a significantly depressed ejection fraction. We have reviewed the published randomized controlled trials and meta‐analysis of prophylactic ICD therapy in the primary prevention of death in patients with nonischemic cardiomyopathy. The individual randomized controlled trials do not report a statistically significant reduction of mortality unless the ICD treatment is added to cardiac resynchronization therapy, but the meta‐analysis did show a significant mortality reduction and favored ICD therapy in these patients. Medical management of many study participants was suboptimal, at least based on current guidelines. The patients with non‐ischemic cardiomyopathy have good outcomes with medical therapy, and ICD therapy in this relatively low‐risk population needs better selection criteria. Copyright © 2010 Wiley Periodicals, Inc.     

Prevalence and incidence of arrhythmias and sudden death in heart failure

Patients with heart failure are prone to a variety of arrhythmias, symptomatic and asymptomatic, that are prognostically significant and have an important bearing on the management of these patients. However there are some inherent problems in assessing the frequency of these arrhythmias within a large patient population, due to a lack of uniformity in defining heart failure and the transient nature of these rhythms. Patients with heart failure commonly die suddenly. The causes of these deaths are difficult to ascertain accurately and are often presumed arrhythmic. With the advent of effective interventions to prevent sudden death, accurately defining the causal relationship between the arrhythmias and sudden death has assumed great importance to appropriately target therapy. Several attempts have been made to predict such deaths on the basis of non-invasive and invasive diagnostic investigations with variable success. In this article we review the incidence and prevalence of atrial and ventricular arrhythmias and sudden deaths in epidemiological studies, surveys and randomised control trials of patients with heart failure. We discuss the prognostic significance of these arrhythmias, the inherent problems in their diagnosis and whether their presence predicts the risk of sudden deaths and the mode of such deaths in the heart failure population. The role of various investigations in risk stratification of sudden death has also been discussed     

Association of low serum levels of apolipoprotein A-I with adverse outcomes in patients with nonischemic heart failure

BackgroundThere is extensive evidence that low serum levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apoA-I) predict a worse prognosis in patients with ischemic heart disease. This study examined whether apoA-I levels may also provide prognostic information in patients with nonischemic heart failure.Methods and ResultsA prospective follow-up study was performed in 117 consecutive patients with nonischemic heart failure for a period of ≤36 months until the first occurrence of 1 of the following clinical events: all-cause death, cardiac death, and hospitalization with worsening heart failure. Serum levels of apoA-I were measured by immunoturbidimetry. A clinical event occurred during follow-up in 28 (24%) patients. A multivariate Cox proportional hazards analysis showed that lower apoA-I levels (<103 mg/dL: determined by a receiver-operating characteristic analysis) were significantly associated with an adverse outcome that was independent of creatinine clearance, HDL cholesterol levels, and brain natriuretic peptide levels. ApoA-I was inversely correlated with levels of C-reactive protein and fibrinogen, known inflammatory predictors of poor prognosis in heart failure.ConclusionsLow levels of apoA-I are independently associated with an adverse prognosis in patients with nonischemic heart failure. ApoA-I may play a beneficial role in nonischemic heart failure partly through an anti-inflammatory action.     

Prognostic value of non-sustained ventricular tachycardia and the potential role of amiodarone treatment in hypertrophic cardiomyopathy: assessment in an unselected non-referral based patient population

Background—Amiodarone has been reported to reduce the likelihood of sudden death in patients with hypertrophic cardiomyopathy (HCM). However, data regarding the clinical course in HCM have traditionally come from selected referral populations biased toward assessment of high risk patients.
Aims—To evaluate antiarrhythmic treatment for sudden death in an HCM population not subject to tertiary referral bias, closely resembling the true disease state present in the community.
Methods—Cardiovascular mortality was assessed in relation to the occurrence of non-sustained ventricular tachycardia (NSVT) on 24 or 48 hour ambulatory Holter recording, a finding previously regarded as a marker for sudden death, particularly when the arrhythmia was frequent, repetitive or prolonged. 167 consecutive patients were analysed by multiple Holter ECG recordings (mean (SD) 157 (129) hours) and followed for a mean of 10 (5) years. Only patients with multiple repetitive NSVT were treated with amiodarone, and in relatively low doses (220 (44) mg/day).
Results—Nine HCM related deaths occurred: 8 were the consequence of congestive heart failure, but only 1 was sudden and unexpected. Three groups of patients were segregated based on their NSVT profile: group 1 (n = 39), multiple ( 2 runs) and repetitive bursts (on 2 Holters) of NSVT, or prolonged runs of ventricular tachycardia, included 4 deaths due to heart failure; group 2 (n = 38), isolated infrequent bursts of NSVT, included 1 sudden death; group 3 (n = 90), without NSVT, included 4 heart failure deaths. Kaplan-Meier survival analysis showed no significant differences in survival between the three groups throughout follow up.
Conclusions—In an unselected patient population with HCM, isolated, non-repetitive bursts of NSVT were not associated with adverse prognosis and so this arrhythmia does not appear to justify chronic antiarrhythmic treatment. Amiodarone, administered in relatively low doses, did not carry an independent and additive risk for cardiac mortality. Amiodarone may have contributed to the absence of sudden cardiac death in patients believed to be at higher risk because of multiple repetitive NSVT.

Keywords: hypertrophic cardiomyopathy; ventricular tachycardia; amiodarone     

Predictive power of increased heart rate versus depressed left ventricular ejection fraction and heart rate variability for risk stratification after myocardial infarction: Results of a two-year follow-up study

Objectives. The aim of this study was to compare the predictive value of mean RR interval assessed from predischarge Holter recordings with that of heart rate variability and left ventricular ejection fraction for risk stratification after myocardial infarction.Background. Heart rate variability is a powerful tool for risk stratification after myocardial infarction. Although heart rate variability is related to heart rate, little is known of the prognostic value of 24-h mean heart rate.Methods. A total of 579 patients surviving the acute phase of myocardial infarction were followed up for at least 2 years. Predischarge heart rate variability, 24-h mean RR interval and left ventricular ejection fraction were analyzed.Results. During the first 2 years of follow-up, there were 54 deaths, 42 of which were cardiac (26 sudden). Shorter mean RR interval was a better predictor of all-cause mortality as well as cardiac and sudden death than depressed left ventricular ejection fraction. Depressed heart rate variability predicted the risk of death better than mean RR interval for sensitivities <40%. For sensitivities ≥40%, mean RR interval was as powerful as heart rate variability. All three variables performed equally well in predicting nonsudden cardiac death. For cardiac death prediction, a left ventricular ejection fraction <35% had a 40% sensitivity, 78% specificity and 14% positive predictive accuracy; a mean RR interval <700 ms had a 45% sensitivity, 85% specificity and 20% positive predictive accuracy; and a heart rate variability <17 U had a 40% sensitivity, 86% specificity and 20% positive predictive accuracy.Conclusions. Predischarge 24-h mean heart rate is a strong predictor of mortality after myocardial infarction that can compete with left ventricular ejection fraction and heart rate variability.     

Serum matrix metalloproteinase-3 as a novel marker for risk stratification of patients with nonischemic dilated cardiomyopathy

BackgroundSelective induction of myocardial matrix metalloproteinases (MMPs) has been reported to occur in human nonischemic dilated cardiomyopathy (DCM). We aimed to evaluate the utility of serum MMPs for risk stratification of patients with DCM.Methods and ResultsWe measured serum levels of MMP-2, MMP-3, and MMP-9 using enzyme-linked immunosorbent assay in 71 patients with mild to moderate DCM (left ventricular ejection fraction = 28.3 ± 11.5%). The primary end point was the composite incidence of cardiac death and hospitalizations for worsening heart failure. During the follow-up period (mean, 28 ± 16 months), 19 patients had major cardiac events with sudden cardiac death in 6 cases and hospitalizations for worsening heart failure in 13 cases. Multivariate analysis revealed that MMP-3 and B-type natriuretic peptide were significant independent predictors of cardiac events in patients with DCM (hazard ratio 1.41, P = .012; hazard ratio 2.72, P = .048, respectively). According to the Kaplan-Meier analyses of cumulative cardiac event-free rates of the two groups that were based on the median levels of MMPs, the differences in the cardiac event-free curves were significant only for MMP-3 (P = .009). Moreover, patients with elevations of both MMP-3 and B-type natriuretic peptide were found to have the poorest prognosis.ConclusionOur results may address the utility of serum MMP-3 for risk stratification of patients with DCM.     

Epidemiology of sudden cardiac death in Spain]

Sudden cardiac death is a remarkable public health problem though its incidence in Spain is lower than in other industrialised countries. Approximately 12% of all natural deaths occur suddenly, and 88% of them are of cardiac origin. This is the form of death in more than 50% of coronary heart disease patients. Moreover, it is the first symptom in 19-26% of cases. This close relationship with coronary heart disease results in cardiovascular risk factors being also risk factors for sudden death. Several factors, such as physical activity or certain drugs may act as sudden death triggers. The more effective strategy addressed to sudden cardiac death prevention includes identification high-risk subgroups of patients (i.e. patients with previous coronary heart disease, heart failure, out-of-hospital sudden death survivors and patients who developed a ventricular fibrillation or tachycardia after a myocardial infarction) and development of efficacious therapeutic interventions. Given that most sudden death are related to coronary heart disease, those primary preventive measures directed to reduce the coronary heart disease incidence rates will also prevent sudden cardiac deaths in population. Finally, community programs directed to reduce the time to reach cardiac emergencies by trained personnel, and to train general population in cardio-respiratory reanimation have shown to be efficacious owing to the fact that most sudden cardiac deaths occur out of hospitals.     

Arrhythmias in Patients with Heart Failure

Opinion statement Both atrial and ventricular arrhythmias are very common in patients with congestive heart failure, and their presence is associated with symptoms, significant morbidity, and mortality. Studies have attempted to determine the prognostic significance of atrial and ventricular arrhythmias in patients with heart failure. Whether atrial fibrillation is an independent risk factor of mortality remains controversial. The presence of ventricular arrhythmias in patients with ischemic cardiomyopathy identifies patients at high risk for sudden death. However, in patients with nonischemic cardiomyopathy there is not a strong correlation between ventricular arrhythmias and increased risk for sudden death. Multiple trials using antiarrhythmic drugs, pharmacologic therapy, and implantable cardioverter defibrillators have been performed in an attempt to improve survival in patients 1) post-myocardial infarction; 2) with congestive heart failure, with and without nonsustained ventricular tachycardia; and 3) with sustained ventricular tachycardia and those who have survived an out-of-hospital cardiac arrest. The purpose of this article is to present an overview of arrhythmias in patients with heart failure and discuss the prevalence, prognostic significance, complications, mechanisms, and trials that have formed the current therapies presently used.     

Coste-efectividad del desfibrilador automático implantable para la prevención primaria de la muerte súbita cardiaca

Introduction and objectiveImplantable cardioverter-defibrillators (ICD) are a cost-effective alternative for secondary prevention of sudden cardiac death, but their efficiency in primary prevention, especially among patients with nonischemic heart disease, is still uncertain.MethodsWe performed a cost-effectiveness analysis of ICD plus conventional medical treatment (CMT) vs CMT for primary prevention of cardiac arrhythmias from the perspective of the national health service. We simulated the course of the disease by using Markov models in patients with ischemic and nonischemic heart disease. The parameters of the model were based on the results obtained from a meta-analysis of clinical trials published between 1996 and 2018 comparing ICD plus CMT vs CMT, the safety results of the DANISH trial, and analysis of real-world clinical practice in a tertiary hospital.ResultsWe estimated that ICD reduced the likelihood of all-cause death in patients with ischemic heart disease (HR, 0.70; 95%CI, 0.58-0.85) and in those with nonischemic heart disease (HR, 0.79; 95%CI, 0.66–0.96). The incremental cost-effectiveness ratio (ICER) estimated with probabilistic analysis was €19 171/quality adjusted life year (QALY) in patients with ischemic heart disease and €31 084/QALY in those with nonischemic dilated myocardiopathy overall and €23 230/QALY in patients younger than 68 years.ConclusionsThe efficiency of single-lead ICD systems has improved in the last decade, and these devices are cost-effective in patients with ischemic and nonischemic left ventricular dysfunction younger than 68 years, assuming willingness to pay as €25 000/QALY. For older nonischemic patients, the ICER was around €30 000/QALY.Full English text available from:www.revespcardiol.org/en     

Effect on Mode of Death of Heart Failure Treatment Started with Bisoprolol Followed by Enalapril,Compared to the Opposite Order: Results of the Randomized CIBIS III Trial

Background: Mode of death in chronic heart failure (CHF) may be of relevance to choice of therapy for this condition. Sudden death is particularly common in patients with early and/or mild/moderate CHF. β‐Blockade may provide better protection against sudden death than ACE inhibition (ACEI) in this setting. Methods: We randomized 1010 patients with mild or moderate, stable CHF and left ventricular ejection fraction ≤35%, without ACEI, β‐blocker or angiotensin‐receptor‐blocker therapy, to either bisoprolol (n = 505) or enalapril (n = 505) for 6 months, followed by their combination for 6–24 months. The two strategies were blindly compared regarding adjudicated mode of death, including sudden death and progressive pump failure death. Results: During the monotherapy phase, 8 of 23 deaths in the bisoprolol‐first group were sudden, compared to 16 of 32 in the enalapril‐first group: hazard ratio (HR) for sudden death 0.50; 95% confidence interval (CI) 0.21–1.16; P= 0.107. At 1 year, 16 of 42 versus 29 of 60 deaths were sudden: HR 0.54; 95% CI 0.29–1.00; P= 0.049. At study end, 29 of 65 versus 34 of 73 deaths were sudden: HR 0.84; 95% CI 0.51–1.38; P= 0.487. Comparable figures for pump failure death were: monotherapy, 7 of 23 deaths versus 2 of 32: HR 3.43; 95% CI 0.71–16.53; P= 0.124, at 1 year, 13 of 42 versus 5 of 60: HR 2.57; 95% CI 0.92–7.20; P= 0.073, at study end, 17 of 65 versus 7 of 73: HR 2.39; 95% CI 0.99–5.75; P= 0.053. There were no significant between‐group differences in any other fatal events. Conclusion: Initiating therapy with bisoprolol compared to enalapril decreased the risk of sudden death during the first year in this mild systolic CHF cohort. This was somewhat offset by an increase in pump failure deaths in the bisoprolol‐first cohort.     

Predictors of sudden death and death from pump failure in congestive heart failure are different. Analysis of 24 h Holter monitoring,clinical variables,blood chemistry,exercise test and radionuclide angiography

One hundred and ninety consecutive patients discharged with congestive heart failure were examined with clinical evaluation, blood chemistry, 24 h Holter monitoring, exercise test and radionuclide angiography. Median left ventricular ejection fraction was 0.30, 46% were in New York Heart Association class II and 44% in III. Total mortality after 1 year was 21%, after 2 years 32%. Of 60 deaths, 33% were sudden and 49% due to pump failure. Multivariate analyses identified totally different risk factors for sudden death: ventricular tachycardia, s-sodium≤137 mmol/l, s-magnesium≤0.80 mmol/l, s-creatinine>121 μmol/l, and maximal change in heart rate during exercise≤35 min⁻¹, and for death from progressive pump failure: New York Heart Association class III+IV, Δheart rate over 24 h≤50 min⁻¹, low ejection fraction, high resting p-noradrenaline, s-urea>7.6 mmol/l, s-potassium<3,5 mmol/l, and maximal exercise duration≤4 min. In conclusion, this study demonstrated different risk factors for sudden death and for death from progressive pump failure.     

The effect of comorbidity on the competing risk of sudden and nonsudden death in an ambulatory heart failure population

Background

Sudden death (SD) and non-sudden cardiac death are responsible for the majority of deaths in patients with heart failure. We sought to identify the influence of comorbid illness (Charlson Comorbidity Index [CCI]) on competing modes of death in heart failure.

Methods

A retrospective analysis of 824 patients followed in a tertiary care heart failure clinic was performed. We analyzed the cumulative incidence of sudden and nonsudden death. Competing risk regression was used to examine the association between medical comorbidities and mode of death. The outcomes of interest were overall mortality, SD, SD and/or appropriate implantable cardioverter-defibrillator therapy (ICD), and non-SD.

Results

Mean age of the study population was 64.1 ± 14.7 years, 68.6% were male, and mean ejection fraction was 32.8% ± 13.5%. Over a mean follow-up of 4.4 years, 229 patients (27.8%) died. SD accounted for 33 deaths (14.4%), whereas SD/appropriate ICD therapy occurred in 56 patients (24.5%). The risk of non-SD and total mortality increased (P < .0001) as the CCI increased, whereas the risk of SD decreased (P = .03). The cumulative incidence of SD, SD and/or ventricular tachycardia/fibrillation, and non-SD at 5 years was 5.6%, 9.1%, and 27.8%, respectively. In multivariate competing risk analysis, advancing age, New York Heart Association class, and a CCI >4 were significantly associated with non-SD.

Conclusion

Patients with heart failure with significant comorbidities are much more likely to sustain non-SD. These findings may have implications in optimal selection of patients with heart failure for interventions such as prophylactic ICD therapy.     

Evaluation of platelets in heart failure: is platelet activity related to etiology,functional class,or clinical outcomes?

Objectives We sought to determine whether platelet activity in patients with heart failure is related to an ischemic versus nonischemic etiologic condition, clinical disease severity, or adverse clinical outcomes. Background Platelet activity may affect outcome in patients with heart failure. A prospective evaluation of the relation of baseline platelet function to etiologic condition, New York Heart Association (NYHA) class, and clinical outcomes has not been previously reported. Methods Ninety-six consecutive outpatients with ambulatory heart failure with an ejection fraction <0.40 and NYHA Class II to IV symptoms who presented to the Duke Heart Failure Clinic and 14 healthy control subjects formed the study groups. Baseline characteristics and blood analyzed for thromboxane (Tx) B₂, 6-keto PGF_1α, platelet contractile force, adenosine diphosphate/collagen shear-induced closure time, whole blood aggregation and CD41, CD31, CD62p, and CD51/CD61 by flow cytometry were determined. Survival status and hospitalizations were determined in the heart failure patient cohort. Results The median age of patients was 65 years (22% female, 64% white). An ischemic etiologic condition was present in 61% of patients. The population had mild to moderate heart failure: NYHA class I (1%), II (41%), III (46%), and IV (12.5%) and severe ventricular dysfunction (median ejection fraction = 0.20). There were 39 clinical events (7 deaths, 3 cardiac transplants, 29 other first hospitalizations) in 305 median days of observation. Platelet activity, indicated by whole blood aggregation with 5 μmol adenosine diphosphate (P = .04) and Tx B₂ (P = .01), was higher in patients with heart failure. Whole blood aggregation was greater than the 90th percentile in 22% of patients with heart failure versus 7% of control subjects. Platelet function did not differ for any of the markers between the ischemic and nonischemic groups and was not affected by antecedent aspirin. There was no relation of NYHA class or the occurrence of events to platelet activity. Conclusion Platelet activity is heightened in 22% of outpatients with stable heart failure symptoms and is not affected by antecedent aspirin therapy. The degree of platelet activation is similar in ischemic and nonischemic patients with heart failure and is not related to clinical disease severity. Current methods to assess platelet activation do not appear to predict outcome. (Am Heart J 2002;143:1068-75.)