Implantable defibrillators for the prevention of mortality in patients with nonischemic cardiomyopathy: a meta-analysis of randomized controlled trials

Context  Implantable cardioverter defibrillator (ICD) therapy is effective in primary and secondary prevention of sudden cardiac death among patients with prior myocardial infarction and depressed ejection fraction. However, conclusive evidence of survival benefit in patients with nonischemic cardiomyopathy (NICM) is still lacking. Objective  To determine whether ICD therapy reduces all-cause mortality in patients with NICM. Data Sources  MEDLINE (1966-2004), EMBASE (1991-2004), the Cochrane Central Register of Controlled Trials (through first quarter, 2004), reports presented at scientific meetings (2003-2004), and bibliographic review of secondary sources. Search terms included defibrillator, randomized controlled trials, clinical trials, andsudden death. Study Selection  Eligible studies were prospective randomized controlled trials of ICD or combined cardiac resynchronization therapy and defibrillator (CRT-D) vs medical therapy enrolling at least some individuals with NICM and reporting all-cause mortality as an outcome. Of 675 potentially relevant articles screened initially, 8 reports of randomized trials enrolling a total of 2146 patients with NICM were included. Data Extraction  Included studies were reviewed to determine the number of patients randomized, mean duration of follow-up, primary end point, mortality of ICD cohort, and mortality of control cohort. Data Synthesis  Five primary prevention trials enrolling 1854 patients with NICM were identified; pooled analysis suggested a significant reduction in total mortality among patients randomized to ICD or CRT-D vs medical therapy (risk ratio [RR], 0.69; 95% confidence interval [CI], 0.55-0.87; P = .002). Mortality reduction remained significant even after elimination of CRT-D trials. Two of the 3 secondary prevention trials presented subgroup estimates for ICD efficacy in NICM. Pooled analysis of these secondary prevention trials (n = 256 patients with NICM) indicated an equivalent but nonsignificant mortality reduction with ICD therapy (RR, 0.69; 95% CI, 0.39-1.24; P = .22). Analysis of all 7 trials combined demonstrated a statistically significant 31% overall reduction in mortality with ICD therapy (RR, 0.69; 95% CI, 0.56-0.86; P = .002). Conclusion  ICD therapy appears to significantly reduce mortality in selected patients with NICM.      

Predicting mortality among patients hospitalized for heart failure: derivation and validation of a clinical model

Context  A predictive model of mortality in heart failure may be useful for clinicians to improve communication with and care of hospitalized patients. Objectives  To identify predictors of mortality and to develop and to validate a model using information available at hospital presentation. Design, Setting, and Participants  Retrospective study of 4031 community-based patients presenting with heart failure at multiple hospitals in Ontario, Canada (2624 patients in the derivation cohort from 1999-2001 and 1407 patients in the validation cohort from 1997-1999), who had been identitifed as part of the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) study. Main Outcome Measures  All-cause 30-day and 1-year mortality. Results  The mortality rates for the derivation cohort and validation cohort, respectively, were 8.9% and 8.2% in hospital, 10.7% and 10.4% at 30 days, and 32.9% and 30.5% at 1 year. Multivariable predictors of mortality at both 30 days and 1 year included older age, lower systolic blood pressure, higher respiratory rate, higher urea nitrogen level (all P<.001), and hyponatremia (P<.01). Comorbid conditions associated with mortality included cerebrovascular disease (30-day mortality odds ratio [OR], 1.43; 95% confidence interval [CI], 1.03-1.98; P = .03), chronic obstructive pulmonary disease (OR, 1.66; 95% CI, 1.22-2.27; P = .002), hepatic cirrhosis (OR, 3.22; 95% CI, 1.08-9.65; P = .04), dementia (OR, 2.54; 95% CI, 1.77-3.65; P<.001), and cancer (OR, 1.86; 95% CI, 1.28-2.70; P = .001). A risk index stratified the risk of death and identified low- and high-risk individuals. Patients with very low-risk scores (60) had a mortality rate of 0.4% at 30 days and 7.8% at 1 year. Patients with very high-risk scores (>150) had a mortality rate of 59.0% at 30 days and 78.8% at 1 year. Patients with higher 1-year risk scores had reduced survival at all times up to 1 year (log-rank, P<.001). For the derivation cohort, the area under the receiver operating characteristic curve for the model was 0.80 for 30-day mortality and 0.77 for 1-year mortality. Predicted mortality rates in the validation cohort closely matched observed rates across the entire spectrum of risk. Conclusions  Among community-based heart failure patients, factors identifiable within hours of hospital presentation predicted mortality risk at 30 days and 1 year. The externally validated predictive index may assist clinicians in estimating heart failure mortality risk and in providing quantitative guidance for decision making in heart failure care.      

Global risk scores and exercise testing for predicting all-cause mortality in a preventive medicine program

Context  The usefulness of exercise stress test results and global cardiovascular risk systems for predicting all-cause mortality in asymptomatic individuals seen in clinical settings is unclear. Objectives  To determine the validity for prediction of all-cause mortality of the Framingham Risk Score and of a recently described European global scoring system Systematic Coronary Risk Evaluation (SCORE) for cardiovascular mortality among asymptomatic individuals evaluated in a clinical setting and to determine the potential prognostic value of exercise stress testing once these baseline risks are known. Design, Setting, and Participants  Prospective cohort study of 3554 asymptomatic adults between the ages of 50 and 75 years who underwent exercise stress testing as part of an executive health program between October 1990 and December 2002; participants were followed up for a mean of 8 years. Main Outcome Measures  Global risk based on the Framingham Risk Score and the European SCORE. Prospectively recorded exercise stress test result abnormalities included impaired physical fitness, abnormal heart rate recovery, ventricular ectopy, and ST-segment abnormalities. The primary end point was all-cause mortality. Results  There were 114 deaths. The c-index, which corresponds to receiver operating characteristic curve values, and the Akaike Information Criteria found that the European SCORE was superior to the Framingham Risk Score in estimating global mortality risk. In a multivariable model, independent predictors of death were a higher SCORE (for 1% predicted increase in absolute risk, relative risk [RR], 1.07; 95% confidence interval [CI], 1.04-1.09; P<.001), impaired functional capacity (RR, 2.95; 95% CI, 1.98-4.39; P<.001), and an abnormal heart rate recovery (RR, 1.59; 95%, 1.04-2.41; P = .03). ST-segment depression did not predict mortality. Among patients in the highest tertile from the SCORE, an abnormal exercise stress test result, defined as either impaired functional capacity or an abnormal heart rate recovery, identified a mortality risk of more than 1% per year. Conclusion  Exercise stress testing when combined with the European global risk SCORE may be useful for stratifying risk in asymptomatic individuals in a comprehensive executive health screening program.      

Association of socioeconomic status with functional capacity, heart rate recovery, and all-cause mortality

Context  Lower socioeconomic status (SES) confers heightened cardiovascular risk and mortality, although the mediating pathways are unclear. Objective  To evaluate the extent to which exercise physiologic characteristics account for the association between lower SES and mortality. Design, Setting, and Participants  Prospective cohort study of 30 043 consecutive patients living in 7 counties in northeast Ohio referred between 1990 and 2002 for symptom-limited stress testing for evaluation of known or suspected coronary artery disease. Follow-up for mortality continued through February 2004. Main Outcome Measures  Estimated functional capacity in metabolic equivalents and heart rate recovery, physiologic characteristics that are determined directly from exercise; testing and all-cause mortality during a median follow-up of 6.5 years. Results  Multivariable models adjusting for demographics, insurance status, smoking status, and clinical confounders demonstrated a strong association between a composite SES score based on census block data and functional capacity (adjusted odds ratio comparing 25th with 75th percentile values, 1.72; 95% confidence interval [CI], 1.56-1.89; P<.001) as well as heart rate recovery (adjusted odds ratio comparing 25th with 75th percentile values, 1.18; 95% CI, 1.07-1.30; P<.001). There were 2174 deaths, with mortality risk increasing from 5% to 10% as SES decreased by quartile (P<.001). Cox proportional hazards models that included all confounding variables except exercise physiologic characteristics demonstrated increased mortality as SES decreased (adjusted hazard ratio comparing 25th with 75th percentile values, 1.32; 95% CI, 1.22-1.42; P<.001). After further adding functional capacity and heart rate recovery, the magnitude of this relationship was reduced (comparing 25th with 75th percentile values; adjusted hazard ratio, 1.17; 95% CI, 1.08-1.26; P<.001), with these variables explaining 47% of the association. Conclusions  Impaired functional capacity and abnormal heart rate recovery were strongly associated with lower SES and accounted for a major proportion of the correlation between SES and mortality. Efforts to modify these clinical features among patients with low SES may narrow disparities in mortality.      

Acute renal failure in critically ill patients: a multinational, multicenter study

Context  Although acute renal failure (ARF) is believed to be common in the setting of critical illness and is associated with a high risk of death, little is known about its epidemiology and outcome or how these vary in different regions of the world. Objectives  To determine the period prevalence of ARF in intensive care unit (ICU) patients in multiple countries; to characterize differences in etiology, illness severity, and clinical practice; and to determine the impact of these differences on patient outcomes. Design, Setting, and Patients  Prospective observational study of ICU patients who either were treated with renal replacement therapy (RRT) or fulfilled at least 1 of the predefined criteria for ARF from September 2000 to December 2001 at 54 hospitals in 23 countries. Main Outcome Measures  Occurrence of ARF, factors contributing to etiology, illness severity, treatment, need for renal support after hospital discharge, and hospital mortality. Results  Of 29 269 critically ill patients admitted during the study period, 1738 (5.7%; 95% confidence interval [CI], 5.5%-6.0%) had ARF during their ICU stay, including 1260 who were treated with RRT. The most common contributing factor to ARF was septic shock (47.5%; 95% CI, 45.2%-49.5%). Approximately 30% of patients had preadmission renal dysfunction. Overall hospital mortality was 60.3% (95% CI, 58.0%-62.6%). Dialysis dependence at hospital discharge was 13.8% (95% CI, 11.2%-16.3%) for survivors. Independent risk factors for hospital mortality included use of vasopressors (odds ratio [OR], 1.95; 95% CI, 1.50-2.55; P<.001), mechanical ventilation (OR, 2.11; 95% CI, 1.58-2.82; P<.001), septic shock (OR, 1.36; 95% CI, 1.03-1.79; P = .03), cardiogenic shock (OR, 1.41; 95% CI, 1.05-1.90; P = .02), and hepatorenal syndrome (OR, 1.87; 95% CI, 1.07-3.28; P = .03). Conclusion  In this multinational study, the period prevalence of ARF requiring RRT in the ICU was between 5% and 6% and was associated with a high hospital mortality rate.      

Impact of the pulmonary artery catheter in critically ill patients: meta-analysis of randomized clinical trials

Context  Randomized clinical trials (RCTs) evaluating the pulmonary artery catheter (PAC) have been limited by small sample size. Some nonrandomized studies suggest that PAC use is associated with increased morbidity and mortality. Objective  To estimate the impact of the PAC device in critically ill patients. Data Sources  MEDLINE (1985-2005), the Cochrane Controlled Trials Registry (1988-2005), the National Institutes of Health ClinicalTrials.gov database, and the US Food and Drug Administration Web site for RCTs in which patients were randomly assigned to PAC or no PAC were searched. Results from the ESCAPE trial of patients with severe heart failure were also included. Search terms included pulmonary artery catheter, right heart catheter, catheter, and Swan-Ganz. Study Selection  Eligible studies included patients who were undergoing surgery, in the intensive care unit (ICU), admitted with advanced heart failure, or diagnosed with acute respiratory distress syndrome and/or sepsis; and studies that reported death and the number of days hospitalized or the number of days in the ICU as outcome measures. Data Extraction  Information on eligibility criteria, baseline characteristics, interventions, outcomes, and methodological quality was extracted by 2 reviewers. Disagreements were resolved by consensus. Data Synthesis  In 13 RCTs, 5051 patients were randomized. Hemodynamic goals and treatment strategies varied among trials. A random-effects model was used to estimate the odds ratios (ORs) for death, number of days hospitalized, and use of inotropes and intravenous vasodilators. The combined OR for mortality was 1.04 (95% confidence interval [CI], 0.90-1.20; P = .59). The difference in the mean number of days hospitalized for PAC minus the mean for no PAC was 0.11 (95% CI, –0.51 to 0.74; P = .73). Use of the PAC was associated with a higher use of inotropes (OR, 1.58; 95% CI, 1.19-2.12; P = .002) and intravenous vasodilators (OR, 2.35; 95% CI, 1.75-3.15; P<.001). Conclusions  In critically ill patients, use of the PAC neither increased overall mortality or days in hospital nor conferred benefit. Despite almost 20 years of RCTs, a clear strategy leading to improved survival with the PAC has not been devised. The neutrality of the PAC for clinical outcomes may result from the absence of effective evidence-based treatments to use in combination with PAC information across the spectrum of critically ill patients.      

First documented rhythm and clinical outcome from in-hospital cardiac arrest among children and adults

Context  Cardiac arrests in adults are often due to ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT), which are associated with better outcomes than asystole or pulseless electrical activity (PEA). Cardiac arrests in children are typically asystole or PEA. Objective  To test the hypothesis that children have relatively fewer in-hospital cardiac arrests associated with VF or pulseless VT compared with adults and, therefore, worse survival outcomes. Design, Setting, and Patients  A prospective observational study from a multicenter registry (National Registry of Cardiopulmonary Resuscitation) of cardiac arrests in 253 US and Canadian hospitals between January 1, 2000, and March 30, 2004. A total of 36 902 adults (18 years) and 880 children (<18 years) with pulseless cardiac arrests requiring chest compressions, defibrillation, or both were assessed. Cardiac arrests occurring in the delivery department, neonatal intensive care unit, and in the out-of-hospital setting were excluded. Main Outcome Measure  Survival to hospital discharge. Results  The rate of survival to hospital discharge following pulseless cardiac arrest was higher in children than adults (27% [236/880] vs 18% [6485/36 902]; adjusted odds ratio [OR], 2.29; 95% confidence interval [CI], 1.95-2.68). Of these survivors, 65% (154/236) of children and 73% (4737/6485) of adults had good neurological outcome. The prevalence of VF or pulseless VT as the first documented pulseless rhythm was 14% (120/880) in children and 23% (8361/36 902) in adults (OR, 0.54; 95% CI, 0.44-0.65; P<.001). The prevalence of asystole was 40% (350) in children and 35% (13 024) in adults (OR, 1.20; 95% CI, 1.10-1.40; P = .006), whereas the prevalence of PEA was 24% (213) in children and 32% (11 963) in adults (OR, 0.67; 95% CI, 0.57-0.78; P<.001). After adjustment for differences in preexisting conditions, interventions in place at time of arrest, witnessed and/or monitored status, time to defibrillation of VF or pulseless VT, intensive care unit location of arrest, and duration of cardiopulmonary resuscitation, only first documented pulseless arrest rhythm remained significantly associated with differential survival to discharge (24% [135/563] in children vs 11% [2719/24 987] in adults with asystole and PEA; adjusted OR, 2.73; 95% CI, 2.23-3.32). Conclusions  In this multicenter registry of in-hospital cardiac arrest, the first documented pulseless arrest rhythm was typically asystole or PEA in both children and adults. Because of better survival after asystole and PEA, children had better outcomes than adults despite fewer cardiac arrests due to VF or pulseless VT.      

Trends in heart failure incidence and survival in a community-based population

Context  The epidemic of heart failure has yet to be fully investigated, and data on incidence, survival, and sex-specific temporal trends in community-based populations are limited. Objective  To test the hypothesis that the incidence of heart failure has declined and survival after heart failure diagnosis has improved over time but that secular trends have diverged by sex. Design, Setting, and Participants  Population-based cohort study using the resources of the Rochester Epidemiology Project conducted in Olmsted County, Minnesota. Patients were 4537 Olmsted County residents (57% women; mean [SD] age, 74 [14] years) with a diagnosis of heart failure between 1979 and 2000. Framingham criteria and clinical criteria were used to validate the diagnosis Main Outcome Measures  Incidence of heart failure and survival after heart failure diagnosis. Results  The incidence of heart failure was higher among men (378/100 000 persons; 95% confidence interval [CI], 361-395 for men; 289/100 000 persons; 95% CI, 277-300 for women) and did not change over time among men or women. After a mean follow-up of 4.2 years (range, 0-23.8 years), 3347 deaths occurred, including 1930 among women and 1417 among men. Survival after heart failure diagnosis was worse among men than women (relative risk, 1.33; 95% CI, 1.24-1.43) but overall improved over time (5-year age-adjusted survival, 43% in 1979-1984 vs 52% in 1996-2000, P<.001). However, men and younger persons experienced larger survival gains, contrasting with less or no improvement for women and elderly persons. Conclusion  In this community-based cohort, the incidence of heart failure has not declined during 2 decades, but survival after onset of heart failure has increased overall, with less improvement among women and elderly persons.      

Routine vs selective invasive strategies in patients with acute coronary syndromes: a collaborative meta-analysis of randomized trials

Context  Patients with unstable angina or non–ST-segment elevation myocardial infarction (NSTEMI) can be cared for with a routine invasive strategy involving coronary angiography and revascularization or more conservatively with a selective invasive strategy in which only those with recurrent or inducible ischemia are referred for acute intervention. Objective  To conduct a meta-analysis that compares benefits and risks of routine invasive vs selective invasive strategies. Data Sources  Randomized controlled trials identified through search of MEDLINE and the Cochrane databases (1970 through June 2004) and hand searching of cross-references from original articles and reviews. Study Selection  Trials were included that involved patients with unstable angina or NSTEMI who received a routine invasive or a selective invasive strategy. Data Extraction  Major outcomes of death and myocardial infarction (MI) occurring from initial hospitalization to the end of follow-up were extracted from published results of eligible trials. Data Synthesis  A total of 7 trials (N = 9212 patients) were eligible. Overall, death or MI was reduced from 663 (14.4%) of 4604 patients in the selective invasive group to 561 (12.2%) of 4608 patients in the routine invasive group (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.72-0.93; P = .001). There was a nonsignificant trend toward fewer deaths (6.0% vs 5.5%; OR, 0.92; 95% CI, 0.77-1.09; P = .33) and a significant reduction in MI alone (9.4% vs 7.3%; OR, 0.75; 95% CI, 0.65-0.88; P<.001). Higher-risk patients with elevated cardiac biomarker levels at baseline benefited more from routine intervention, with no significant benefit observed in lower-risk patients with negative baseline marker levels. During the initial hospitalization, a routine invasive strategy was associated with a significantly higher early mortality (1.1% vs 1.8% for selective vs routine, respectively; OR, 1.60; 95% CI, 1.14-2.25; P = .007) and the composite of death or MI (3.8% vs 5.2%; OR, 1.36; 95% CI, 1.12-1.66; P = .002). But after discharge, the routine invasive strategy was associated with fewer subsequent deaths (4.9% vs 3.8%; OR, 0.76; 95% CI, 0.62-0.94; P = .01) and the composite of death or MI (11.0% vs 7.4%; OR, 0.64; 95% CI, 0.56-0.75; P<.001). At the end of follow-up, there was a 33% reduction in severe angina (14.0% vs 11.2%; OR, 0.77; 95% CI, 0.68-0.87; P<.001) and a 34% reduction in rehospitalization (41.3% vs 32.5%; OR, 0.66; 95% CI, 0.60-0.72; P<.001) with a routine invasive strategy. Conclusions  A routine invasive strategy exceeded a selective invasive strategy in reducing MI, severe angina, and rehospitalization over a mean follow-up of 17 months. But routine intervention was associated with a higher early mortality hazard and a trend toward a mortality reduction at follow-up. Future strategies should explore ways to minimize the early hazard and enhance later benefits by focusing on higher-risk patients and optimizing timing of intervention and use of proven therapies.      

Contemporary clinical profile and outcome of prosthetic valve endocarditis

Context  Prosthetic valve endocarditis (PVE) is associated with significant mortality and morbidity. The contemporary clinical profile and outcome of PVE are not well defined. Objectives  To describe the prevalence, clinical characteristics, and outcome of PVE, with attention to health care–associated infection, and to determine prognostic factors associated with in-hospital mortality. Design, Setting, and Participants  Prospective, observational cohort study conducted at 61 medical centers in 28 countries, including 556 patients with definite PVE as defined by Duke University diagnostic criteria who were enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to August 2005. Main Outcome Measure  In-hospital mortality. Results  Definite PVE was present in 556 (20.1%) of 2670 patients with infective endocarditis. Staphylococcus aureus was the most common causative organism (128 patients [23.0%]), followed by coagulase-negative staphylococci (94 patients [16.9%]). Health care–associated PVE was present in 203 (36.5%) of the overall cohort. Seventy-one percent of health care–associated PVE occurred within the first year of valve implantation, and the majority of cases were diagnosed after the early (60-day) period. Surgery was performed in 272 (48.9%) patients during the index hospitalization. In-hospital death occurred in 127 (22.8%) patients and was predicted by older age, health care–associated infection (62/203 [30.5%]; adjusted odds ratio [OR], 1.62; 95% confidence interval [CI], 1.08-2.44; P = .02), S aureus infection (44/128 [34.4%]; adjusted OR, 1.73; 95% CI, 1.01-2.95; P = .05), and complications of PVE, including heart failure (60/183 [32.8%]; adjusted OR, 2.33; 95% CI, 1.62-3.34; P<.001), stroke (34/101 [33.7%]; adjusted OR, 2.25; 95% CI, 1.25-4.03; P = .007), intracardiac abscess (47/144 [32.6%]; adjusted OR, 1.86; 95% CI, 1.10-3.15; P = .02), and persistent bacteremia (27/49 [55.1%]; adjusted OR, 4.29; 95% CI, 1.99-9.22; P<.001). Conclusions  Prosthetic valve endocarditis accounts for a high percentage of all cases of infective endocarditis in many regions of the world. Staphylococcus aureus is now the leading cause of PVE. Health care–associated infection significantly influences the clinical characteristics and outcome of PVE. Complications of PVE strongly predict in-hospital mortality, which remains high despite prompt diagnosis and the frequent use of surgical intervention.