Circulation

A personal view of the growth of ideas about the structure of the plasma membrane.

The control of ventricular rate plays an important role in the management of patients with atrial fibrillation, decreasing symptoms and improving cardiac function, exercise capacity, and quality of life. 1–3 Oral or intravenous agents are routinely administered to achieve adequate control of the ventricular rate by modulating atrioventricular nodal function. The systemic effects of calcium channel antagonists and -adrenergic receptor antagonists on blood pressure and other adverse effects, however, may limit use of these agents in some patients. In other patients, it may be difficult to achieve adequate rate control with the use of pharmacological agents. Article p 2383 In their article in this issue of Circulation, Sigg et al 4 describe the novel approach of delivering pharmacological agents via a luminal catheter secured to the region of the atrioventricular node. Using a steerable electrophysiological catheter, they locate the His bundle potential and the coronary sinus ostium and display these positions in 2 orthogonal planes. The luminal catheter is screwed into the myocardium, and third-degree atrioventricular block resulting from the injection of a 1-mg dose of acetylcholine is used to confirm the proper positioning of the luminal catheter. The authors demonstrate that varying degrees of atrioventricular nodal blockade may be achieved by continuous infusion of acetylcholine at rates between 10 and 200 g/min. In comparison, the intravenous injection of 1 mg acetylcholine did not cause atrioventricular block in any animal, demonstrating that a significant part of the effect of the direct luminal infusion was local. The authors provide histological evidence that the luminal catheter was positioned within or near the edge of the triangle of Koch, confirming the accuracy of the positioning method. In addition, no significant histological abnormalities were observed. This article by Sigg et al4 illustrates the potential for the local delivery of pharmacological therapy via an infusion catheter screwed into the atrioventricular nodal region. Their study serves as a “proof-of-principle” experiment for ability of this drug delivery system to have local electrophysiological effects without significant systemic effects. They demonstrate that it is possible to modulate the effect on atrioven

There is widespread recognition of the increasing challenge of conducting adequately powered clinical trials in cardiovascular medicine.1 Given the broadening gap between guideline-based recommendations and the level of evidence supported by trials, this matter is a central priority. Two fundamental properties characterize the contemporary assessment of cardiovascular clinical trials. First, they are generally designed to evaluate the time to first event between the study arms. Second, different clinical events, presumed to be related to the targeted disease of interest, are commonly combined to form a composite end point.2 This approach increases the number of events observed during follow-up, usually but not always enhancing the statistical power and efficiency of clinical trials (ie, reducing the number of patients required). Article see p 673 Despite these established analytic techniques, several potential liabilities exist. The first event within a composite end point may not reflect the most clinically important or relevant one. Thus, incorporating subsequent events seems rational to provide a more comprehensive perspective of disease burden or therapeutic efficacy. This would also be timely, given that the recognition of recurrent events has emerged as a matter of increasing interest to patients, healthcare investigators, providers, and payers. The interpretation of composite end points can be perplexing, particularly when the directions of the individual components differ.3 In this issue of Circulation , Kohli et al4 address recurrent multiple events in the recent Platelet Inhibition and Patient Outcomes (PLATO) trial. The PLATO trial definitively demonstrated a treatment benefit of ticagrelor compared with clopidogrel in the …

Physiological blood pressure (BP) fluctuations with frequencies >0.1 Hz can override renal blood flow autoregulation. The influence of such immediate changes in renal perfusion pressure (RPP) on daily BP regulation, eg, via shear stress-stimulated liberation of renal endothelial NO, however, is unknown. Thus, we studied the effects of such RPP oscillations on renal function and on systemic BP during the onset of renal hypertension. Seven beagles (randomly assigned to each of the following protocols) were chronically instrumented for the measurement of systemic BP, RPP, and renal excretory function. An inflatable cuff was used to reduce and to oscillate RPP over 24 hours in the freely moving dog. Reducing RPP to 87+/-2 mm Hg diminished excretion of sodium and water and doubled plasma renin activity (PRA, n=7, P<0. 01) but had no significant effect on urinary nitrate excretion (n=6), a marker of NO generation. Superimposing 0.1-Hz oscillations (+/-10 mm Hg) onto the reduced RPP blunted hypertension, returned fluid excretion almost to control levels, and doubled renal sodium elimination. Nitrate excretion peaked at 8 hours, only to return to control values shortly thereafter. PRA, conversely, was significantly reduced during the last third of the experimental protocols. BP fluctuations transiently stimulate NO liberation and induce a reduction in PRA, which enhances 24-hour sodium and water excretion and markedly attenuates the acute development of renovascular hypertension.

Blood lead levels above 0.48 micromol/L (10 microg/dL) in adults have been associated with increased risk of cardiovascular, cancer, and all-cause mortality. The objective of the present study was to determine the association between blood lead levels below 0.48 micromol/L and mortality in the general US population. Blood lead levels were measured in a nationally representative sample of 13,946 adult participants of the Third National Health and Nutrition Examination Survey recruited in 1988 to 1994 and followed up for up to 12 years for all-cause and cause-specific mortality. The geometric mean blood lead level in study participants was 0.12 micromol/L (2.58 microg/dL). After multivariate adjustment, the hazard ratios (95% CI) for comparisons of participants in the highest tertile of blood lead (> or = 0.17 micromol/L [> or = 3.62 microg/dL]) with those in the lowest tertile (< 0.09 micromol/L [< 1.94 microg/dL]) were 1.25 (1.04 to 1.51; P(trend) across tertiles = 0.002) for all-cause mortality and 1.55 (1.08 to 2.24; P(trend) across tertiles = 0.003) for cardiovascular mortality. Blood lead level was significantly associated with both myocardial infarction and stroke mortality, and the association was evident at levels > 0.10 micromol/L (> or = 2 microg/dL). There was no association between blood lead and cancer mortality in this range of exposure. The association between blood lead levels and increased all-cause and cardiovascular mortality was observed at substantially lower blood lead levels than previously reported. Despite the marked decrease in blood lead levels over the past 3 decades, environmental lead exposures remain a significant determinant of cardiovascular mortality in the general population, constituting a major public health problem.

Because most cardiac arrests occur at home, widespread training is needed to increase the incidence of cardiopulmonary resuscitation (CPR) by lay persons. The aim of this study was to evaluate the effect of mass distribution of CPR instructional materials among schoolchildren. We distributed 35,002 resuscitation manikins to pupils (12 to 14 years of age) at 806 primary schools. Using the enclosed 24-minute instructional DVD, they trained in CPR and subsequently used the kit to train family and friends (second tier). They completed a questionnaire on who had trained in CPR using the kit. Teachers also were asked to evaluate the project. The incidence of bystander CPR in out-of-hospital cardiac arrest in the months following the project was compared with the previous year. In total, 6947 questionnaires (19.8%) were returned. The 6947 kits had been used to train 17,140 from the second tier (mean, 2.5 persons per pupil; 95% confidence interval, 2.4 to 2.5). The teachers had used a mean of 64 minutes (95% confidence interval, 60 to 68) for preparation and a mean of 13 minutes (95% confidence interval, 11 to 15) to tidy up. Incidence of bystander CPR in the months after the project did not increase significantly compared with the previous year (25.0% versus 27.9%; P=0.16). CPR training can be disseminated in a population by distributing personal resuscitation manikins among children in primary schools. The teachers felt able to easily facilitate CPR training. The incidence of bystander CPR did not increase significantly in the months following the project.

To the Editor: Is headache a cause or a consequence of hypertension? This apparently simple dilemma has not been answered over the last 100 years. All previous studies addressing this issue had important limitations, which left this as a medical impasse. The same seems to occur in a recent publication by Law et al1 in Circulation . After a judicious selection of 94 randomized trials with 4 classes of blood pressure–lowering drugs at fixed doses, the authors concluded that all classes reduce the prevalence of headache by one third, suggesting that high blood pressure is a cause of headache. Despite the robust study design, important points remain to be mentioned. First, the observation that blood pressure–lowering drugs prevent migraine is a well-established characteristic of many classes of antihypertensive drugs.2 Therefore, it is very likely that people in the interventional arm of the study would have fewer headaches than those in placebo arm. Second, none of the selected studies were designed to specifically evaluate the relationship between …

There are few published data on risk factors for stroke in patients with non-ST-elevation acute coronary syndrome (ACS). We investigated prognostic factors for stroke in 2 large cohorts of patients from the Organization to Assess Strategies for Ischemic Syndromes (OASIS) registry (8010) and the OASIS-2 trial (10 141). A total of 18 151 patients with non-ST-elevation ACS were enrolled in the OASIS program. Data from these 2 studies were pooled (a test for heterogeneity was nonsignificant, P=0.34). Overall, 238 patients (1.3%) had a stroke over a 6-month follow-up. Those who experienced stroke had a 4-fold increase in 6-month mortality (27.0% versus 6.3%, P<0.001). A Cox multivariate regression analysis identified CABG surgery as the most important predictor of stroke (hazard ratio [HR], 4.6), followed by history of stroke (HR, 2.3), diabetes mellitus (HR, 1.7), older age (HR, 1.6 per 10-year increase), higher heart rate (HR, 1.1 per 10-bpm increase), and on-site catheterization facility (HR, 1.4). There was no significant excess in stroke in patients undergoing percutaneous coronary intervention (P=0.21). Patients who underwent early CABG surgery were at a substantially increased risk compared with those who had later CABG (3.3% versus 1.6%; HR, 2.1; P=0.003) or who had no surgery (3.3% versus 1.1%; HR, 3.95; P=0.0001). In this large cohort of patients with ACS, stroke was an uncommon but serious event associated with high mortality. The performance of early CABG surgery was a powerful independent predictor of stroke.

Previous studies have suggested that there is an increase in cardiac events in the morning. Fewer data relate cardiac events to months of the year and season. We analyzed all monthly death certificate data from Los Angeles County, California, for death caused by coronary artery disease from 1985 through 1996 (n=222 265). The mean number of deaths was highest in December at 1808 and January at 1925; the lowest rates were in June, July, August, and September at 1402, 1424, 1418, and 1371, respectively. December and January had significantly higher rates than would be expected from a uniform distribution of monthly deaths (P=0.00001). The percent of yearly coronary deaths was defined by the quadratic U-shaped equation [percent=13.1198-1.5238(month)+0. 0952(month(2)), where January=1, February=2, etc]. When monthly deaths were plotted by year, there was a decrease from 1985 through 1996. Monthly mortality correlated inversely with temperature. During the months with the highest frequency of death (December, January), however, there was an increase in deaths that peaked around the holiday season and then fell, which could not be explained solely on the basis of the daily temperature change. Even in the mild climate of Los Angeles County, there are seasonal variations in the development of coronary artery death, with approximately 33% more deaths occurring in December and January than in June through September. Although cooler temperatures may play a role, other factors such as overindulgence or the stress of the holidays might also contribute to excess deaths during these peak times.

Uncertainty exists over whether blood pressure-lowering drugs prevent headache. A meta-analysis was carried out of the 94 randomized placebo-controlled trials of 4 different classes of blood pressure-lowering drugs (thiazides, beta-blockers, ACE inhibitors, and angiotensin II receptor antagonists) in fixed doses in which data on headache were reported. There were 17,641 participants who were allocated blood pressure-lowering drugs and 6603 who were allocated placebo. Treatment lowered systolic and diastolic blood pressures by 9.4 and 5.5 mm Hg, respectively, on average. One third fewer people on average reported headache in the treated groups (8.0%) than the placebo groups (12.4%) (odds ratio, 0.67; 95% CI, 0.61 to 0.74; P<0.001). About 1 in 30 treated persons benefited by having headache prevented. The prevalence of headache was reduced (P<0.001) in trials of each of the 4 classes of drugs. Our results show that blood pressure-lowering drugs prevent a significant proportion of headaches. That this effect is seen with pharmacologically unrelated classes of drugs indicates that it is likely to be due to the reduction in blood pressure per se, the only recognized action that the drugs have in common. This in turn indicates that high blood pressure is a cause of headache, but this conclusion is not supported by observational studies of blood pressure and headache. The uncertainty over whether high blood pressure causes headache does not, however, detract from the practical benefits of the use of blood pressure-lowering drugs in preventing headaches and cardiovascular disease.

Abdominal adiposity is a growing clinical and public health problem. It is not known whether it is similarly associated with cardiovascular disease (CVD) and diabetes mellitus in different regions around the world, and thus whether measurement of waist circumference (WC) in addition to body mass index (BMI) is useful in primary care practice. Randomly chosen primary care physicians in 63 countries recruited consecutive patients aged 18 to 80 years on 2 prespecified half days. WC and BMI were measured and the presence of CVD and diabetes mellitus recorded. Of the patients who consulted the primary care physicians, 97% agreed to participate in the present study. Overall, 24% of 69,409 men and 27% of 98,750 women were obese (BMI > or = 30 kg/m2). A further 40% and 30% of men and women, respectively, were overweight (BMI 25 to 30 kg/m2). Increased WC (> 102 for men and > 88 cm for women) was recorded in 29% and 48%, CVD in 16% and 13%, and diabetes mellitus in 13% and 11% of men and women, respectively. A statistically significant graded increase existed in the frequency of CVD and diabetes mellitus with both BMI and WC, with a stronger relationship for WC than for BMI across regions for both genders. This relationship between WC, CVD, and particularly diabetes mellitus was seen even in lean patients (BMI < 25 kg/m2). Among men and women who consulted primary care physicians, BMI and particularly WC were both strongly linked to CVD and especially to diabetes mellitus. Strategies to address this global problem are required to prevent an epidemic of these major causes of morbidity and mortality.

C-reactive protein (CRP) is a heritable marker of chronic inflammation that is strongly associated with cardiovascular disease. We sought to identify genetic variants that are associated with CRP levels. We performed a genome-wide association analysis of CRP in 66 185 participants from 15 population-based studies. We sought replication for the genome-wide significant and suggestive loci in a replication panel comprising 16 540 individuals from 10 independent studies. We found 18 genome-wide significant loci, and we provided evidence of replication for 8 of them. Our results confirm 7 previously known loci and introduce 11 novel loci that are implicated in pathways related to the metabolic syndrome (APOC1, HNF1A, LEPR, GCKR, HNF4A, and PTPN2) or the immune system (CRP, IL6R, NLRP3, IL1F10, and IRF1) or that reside in regions previously not known to play a role in chronic inflammation (PPP1R3B, SALL1, PABPC4, ASCL1, RORA, and BCL7B). We found a significant interaction of body mass index with LEPR (P<2.9×10(-6)). A weighted genetic risk score that was developed to summarize the effect of risk alleles was strongly associated with CRP levels and explained ≈5% of the trait variance; however, there was no evidence for these genetic variants explaining the association of CRP with coronary heart disease. We identified 18 loci that were associated with CRP levels. Our study highlights immune response and metabolic regulatory pathways involved in the regulation of chronic inflammation.

Current knowledge of prevalence, incidence, and survival in thoracic aortic diseases (aneurysm and dissection) is based on small studies from a dated era of treatment and diagnostic procedures. The objective of the present study was to reappraise epidemiology and long-term outcomes in subjects with thoracic aortic disease in a large contemporary population. All subjects with thoracic aortic aneurysm or dissection identified in Swedish national healthcare registers from 1987 to 2002 were included in the present study. Of 14,229 individuals with thoracic aortic disease, 11,039 (78%) were diagnosed before death. Incidence of thoracic aortic disease rose by 52% in men and by 28% in women to reach 16.3 per 100,000 per year and 9.1 per 100,000 per year, respectively. Operations increased 7-fold in men and 15-fold in women over time. Of the 2455 patients who underwent operation, 389 (16%) died within 30 days, with older age and thoracic aortic rupture as risk factors. In Cox analysis, increasing age was the only variable associated with long-term mortality. Both short- and long-term mortality improved over time. In patients who underwent operation, actuarial survival (95% CI) at 1, 5, and 10 years was 92% (91% to 93%), 77% (75% to 80%), and 57% (53% to 61%), respectively. The cumulative incidence of thoracic aortic reoperations was 7.8% at 10 years. The prevalence and incidence of thoracic aortic disease was higher than previously reported and increasing. The annual number of operations increased substantially. Surgical (30-day) and long-term survival improved significantly over time to form a growing cohort of patients needing counseling, management decisions, operations, and extended postoperative surveillance.

The AFFIRM Study showed that treatment of patients with atrial fibrillation and a high risk for stroke or death with a rhythm-control strategy offered no survival advantage over a rate-control strategy in an intention-to-treat analysis. This article reports an "on-treatment" analysis of the relationship of survival to cardiac rhythm and treatment as they changed over time. Modeling techniques were used to determine the relationships among survival, baseline clinical variables, and time-dependent variables. The following baseline variables were significantly associated with an increased risk of death: increasing age, coronary artery disease, congestive heart failure, diabetes, stroke or transient ischemic attack, smoking, left ventricular dysfunction, and mitral regurgitation. Among the time-dependent variables, the presence of sinus rhythm (SR) was associated with a lower risk of death, as was warfarin use. Antiarrhythmic drugs (AADs) were associated with increased mortality only after adjustment for the presence of SR. Consistent with the original intention-to-treat analysis, AADs were no longer associated with mortality when SR was removed from the model. Warfarin use improves survival. SR is either an important determinant of survival or a marker for other factors associated with survival that were not recorded, determined, or included in the survival model. Currently available AADs are not associated with improved survival, which suggests that any beneficial antiarrhythmic effects of AADs are offset by their adverse effects. If an effective method for maintaining SR with fewer adverse effects were available, it might be beneficial.

Intermittent claudication due to peripheral arterial occlusive disease (PAOD) is a common cause of pain and disability in the middle-aged. Clinical trials of the potent vasodilator prostaglandin E1 have been disappointing. This is the first report of a controlled clinical trial of AS-0:3, a novel prodrug of prostaglandin E1 incorporated into lipid microspheres that has been developed to improve delivery of the active compound to blood vessel walls. Eighty patients with stenosis or occlusion, symptoms of intermittent claudication, and maximum walking distance of > or = 30 and < or = 300 m on a standard treadmill test were randomized to placebo or one of three dosage regimens of AS-013. Drug was administered by intravenous injection 5 d/wk for 4 weeks. Treadmill tests and other assessments were completed at weeks 0, 4, and 8. A statistically significant increase in maximum walking distance was observed at 4 weeks (for placebo: median, 4.5 m; interquartile range [IQR], 20; for active treatment: median, 28.0 m; IQR, 81; P < .01, Mann-Whitney test). A similar response was seen at 8 weeks (for placebo; median, -11.2 m; IQR, 35; for active treatment: median, 35 m; IQR, 68; P < .01, Mann-Whitney test). Dose-related improvements in pain-free walking distance and quality of life were observed. No serious safety issues were noted. These promising clinical data indicate that AS-013, a new prodrug of prostaglandin E1, could provide an effective and acceptable treatment for patients with intermittent claudication. Studies to investigate the optimal dosing regimen, duration of clinical benefit, and effects in more severe forms of peripheral arterial disease are warranted.

Positron-emission tomography (PET) tracers for myocardial perfusion are commonly labeled with short-lived isotopes that limit their widespread clinical use. 18F-BMS-747158-02 (18F-BMS) is a novel pyridaben derivative that was evaluated for assessment of myocardial perfusion by comparison with 13N-ammonia (13NH3) and with radioactive microspheres in a pig model. Fourteen pigs injected with 500 MBq of 13NH3 or 100 to 200 MBq of 18F-BMS underwent dynamic PET at rest and during pharmacological stress. In 8 of these pigs, 18F-BMS was injected during stress combined with transient, 2.5-minute constriction of the left anterior descending coronary artery. Radioactive microspheres were coinjected with 18F-BMS. Ratios of myocardial tracer uptake to surrounding tissues were determined, and myocardial blood flow was quantified by compartmental modeling. Both tracers showed high and homogeneous myocardial uptake. Compared with 13NH3, 18F-BMS showed higher activity ratios between myocardium and blood (rest 2.5 versus 4.1; stress 2.1 versus 5.8), liver (rest 1.2 versus 1.8; stress 0.7 versus 2.0), and lungs (rest 2.5 versus 4.2; stress 2.9 versus 6.4). Regional myocardial blood flow assessed with 18F-BMS PET showed good correlation (r=0.88, slope=0.84) and agreement (mean difference -0.10 [25th percentile -0.3, 75th percentile 0.1 mL x min(-1) x g(-1)]) with that measured with radioactive microspheres over a flow range from 0.1 to 3.0 mL x min(-1) x g(-1). The extent of defects induced by left anterior descending coronary artery constriction measured by 18F-BMS and microspheres also correlated closely (r=0.63, slope=1.1). 18F-BMS-747158-02 is a very attractive new PET perfusion tracer that allows quantitative assessment of regional myocardial perfusion over a wide flow range. The long half-life of 18F renders this tracer useful for clinical PET/CT applications in the workup of patients with suspected or proven coronary artery disease.

Endothelin (ET) is a potent vasoconstrictor, and its concentration is increased in patients with heart failure. The purpose of this study was to investigate the role of endothelin in heart failure by use of a rat model. Experiments were performed on rats at 1 through 16 weeks after sham operation or coronary artery ligation. Rats with left ventricular end-diastolic pressures > 15 mm Hg were considered to have chronic heart failure (CHF), while the others were considered to have uncomplicated myocardial infarction (MI). There were increased ET-1 concentrations in CHF rats at weeks 1 to 16 (Sham, 20 +/- 0.5 pg/mL, n = 45; CHF, 31 +/- 2 pg/mL, n = 50; P < .001) and transient increases in ET-3 concentrations at week 1 in both the MI and CHF groups. There were no significant increases in big ET-1 concentrations, suggesting an increased conversion of ET-1 from big ET-1 in the CHF group. At weeks 2 through 8, oral administration of the mixed (ETA and ETB) endothelin receptor antagonist bosentan significantly decreased mean arterial pressure in conscious CHF rats, an effect that increased over time. Furthermore, bosentan had an additive effect to the angiotensin-converting enzyme inhibitor cilazapril. Endothelin plays a role in the maintenance of blood pressure in CHF rats, as evidenced by the significant reduction in mean arterial pressure after oral administration of bosentan. Therefore, endothelin antagonists may be useful therapeutic agents in the treatment of CHF.

Despite remarkable advances in the treatment of acute myocardial infarction, substantial early patient mortality remains. Appropriate choices among alternative therapies and the use of clinical resources depend on an estimate of the patient's risk. Individual patients reflect a combination of clinical features that influence prognosis, and these factors must be appropriately weighted to produce an accurate assessment of risk. Prior studies to define prognosis either were performed before widespread use of thrombolysis or were limited in sample size or spectrum of data. Using the large population of the GUSTO-I trial, we performed a comprehensive analysis of relations between baseline clinical data and 30-day mortality and developed a multivariable statistical model for risk assessment in candidates for thrombolytic therapy. For the 41,021 patients enrolled in GUSTO-I, a randomized trial of four thrombolytic strategies, relations between clinical descriptors routinely collected at initial presentation, and death within 30 days (which occurred in 7% of the population) were examined with both univariable and multivariable analyses. Variables studied included demographics, history and risk factors, presenting characteristics, and treatment assignment. Risk modeling was performed with logistic multiple regression and validated with bootstrapping techniques. Multivariable analysis identified age as the most significant factor influencing 30-day mortality, with rates of 1.1% in the youngest decile (< 45 years) and 20.5% in patients > 75 (adjusted chi 2 = 717, P < .0001). Other factors most significantly associated with increased mortality were lower systolic blood pressure (chi 2 = 550, P < .0001), higher Killip class (chi 2 = 350, P < .0001), elevated heart rate (chi 2 = 275, P < .0001), and anterior infarction (chi 2 = 143, P < .0001). Together, these five characteristics contained 90% of the prognostic information in the baseline clinical data. Other significant though less important factors included previous myocardial infarction, height, time to treatment, diabetes, weight, smoking status, type of thrombolytic, previous bypass surgery, hypertension, and prior cerebrovascular disease. Combining prognostic variables through logistic regression, we produced a validated model that stratified patient risk and accurately estimated the likelihood of death. The clinical determinants of mortality in patients treated with thrombolytic therapy within 6 hours of symptom onset are multifactorial and the relations complex. Although a few variables contain most of the prognostic information, many others contribute additional independent prognostic information. Through consideration of multiple characteristics, including age, medical history, physiological significance of the infarction, and medical treatment, the prognosis of an individual patient can be accurately estimated.

regarding effect of coronary artery disease (CAD), heart failure (bothischemic and nonischemic), and atrial fibrillation (AF) on mortalityand readmission rates after noncardiac surgery. The well-writtenarticle attempts to identify perioperative risk factors beyond that ofthe well-known CAD by using a nested case-control study. However,a few interesting points arise from the analysis that we feel may bepertinent.First, patients with nonischemic heart failure had the highestunadjusted 30-day mortality and readmission rates for the cohort.This seems a little counterintuitive, because rates of mortality withnonischemic heart failure, especially after optimal therapy, havebeen reported to be lower than with ischemic heart failure.

The postoperative risks for patients with coronary artery disease (CAD) undergoing noncardiac surgery are well described. However, the risks of noncardiac surgery in patients with heart failure (HF) and atrial fibrillation (AF) are less well known. The purpose of this study is to compare the postoperative mortality of patients with HF, AF, or CAD undergoing major and minor noncardiac surgery. Population-based data were used to create 4 cohorts of consecutive patients with either nonischemic HF (NIHF; n=7700), ischemic HF (IHF; n=12 249), CAD (n=13 786), or AF (n=4312) who underwent noncardiac surgery between April 1, 1999, and September 31, 2006, in Alberta, Canada. The main outcome was 30-day postoperative mortality. The unadjusted 30-day postoperative mortality was 9.3% in NIHF, 9.2% in IHF, 2.9% in CAD, and 6.4% in AF (each versus CAD, P<0.0001). Among patients undergoing minor surgical procedures, the 30-day postoperative mortality was 8.5% in NIHF, 8.1% in IHF, 2.3% in CAD, and 5.7% in AF (P<0.0001). After multivariable adjustment, postoperative mortality remained higher in NIHF, IHF, and AF patients than in those with CAD (NIHF versus CAD: odds ratio 2.92; 95% confidence interval 2.44 to 3.48; IHF versus CAD: odds ratio 1.98; 95% confidence interval 1.70 to 2.31; AF versus CAD: odds ratio 1.69; 95% confidence interval 1.34 to 2.14). Although current perioperative risk prediction models place greater emphasis on CAD than HF or AF, patients with HF or AF have a significantly higher risk of postoperative mortality than patients with CAD, and even minor procedures carry a risk higher than previously appreciated.