Faculty Bibliography

AIMS: OAT randomised patients with an occluded infarct artery three to 28 days after myocardial infarction (MI). The study demonstrated that PCI did not reduce the occurrence of the primary composite endpoint of death, re-MI, and New York Heart Association class IV heart failure in comparison with patients assigned to optimal medical therapy alone (MED). In view of prior literature in similar cohorts showing fewer sudden cardiac deaths and less left ventricular (LV) remodelling, but excess re-MI with PCI, causes of death were analysed in more detail. METHODS AND RESULTS: Stepwise Cox regression was used to examine baseline variables associated with causes of death. The immediate and primary cause of death did not differ between 1,101 PCI and 1,100 MED patients. One-year cardiovascular death rates were 3.8% for the PCI group, and 3.7% for the MED group, and 0.9% per year for the next four years in both groups. Five of six cases of cardiac rupture occurred in patients undergoing PCI. CONCLUSIONS: In stable post-MI patients with occlusion of the infarct-related artery, PCI did not change the rate or cause of death. The observation that the majority of cardiac ruptures occurred in patients undergoing PCI deserves further investigation

BACKGROUND: Little is known about predictors of survival in patients with persistent shock following acute myocardial infarction (MI) despite a patent infarct artery. METHODS: We examined data from TRIUMPH, a multicenter randomized clinical trial of the nitric oxide synthase inhibitor, L-N(G)-monomethyl-arginine, in patients with persistent vasopressor-dependent cardiogenic shock complicating acute MI at least 1 hour after established infarct-related artery patency. Patients who died within 30 days were compared with those who survived. Continuous variables were assessed using the Wilcoxon rank sum and categorical variables using the chi(2) test. Prespecified baseline variables were included in a multivariable logistic regression model to predict mortality. A second model incorporating baseline vasopressors and dosages and a third model including change in systolic blood pressure at 2 hours were also developed. Bootstrapping was used to assess the stability of model variables. RESULTS: Of 396 patients, 180 (45.5%) died within 30 days. Systolic blood pressure (SBP), measured on vasopressor support, and creatinine clearance were significant predictors of mortality in all models. The number of vasopressors and norepinephrine dose were also predictors of mortality in the second model, but the latter was no longer significant when change in SBP at 2 hours was added as a covariate in the third model. CONCLUSIONS: The SBP, creatinine clearance, and number of vasopressors are significant predictors of mortality in patients with persistent vasopressor-dependent cardiogenic shock following acute MI despite a patent infarct artery. These prognostic variables may be useful for risk-stratification and in selecting patients for investigation of additional therapies

BACKGROUND: Women with non-ST-segment elevation myocardial infarction (NSTEMI) who undergo coronary angiography have no obstructive coronary lesions more often than men. Sex-specific characteristics and outcomes of patients without obstructive coronary artery disease (CAD) have not been described previously. METHODS: Using data from NSTEMI patients enrolled in CRUSADE from 2001 to 2005, we evaluated differences in clinical features and in-hospital outcomes between men and women with no obstructive CAD. RESULTS: After excluding patients with missing catheterization and sex data (n = 1,494), previous coronary artery bypass grafting or percutaneous coronary intervention (47,907), catheterization contraindications (n = 6,588), and missing obstructive CAD status (n = 1,565), there were 55,514 patients (68.4%) with NSTE acute coronary syndromes (ACS) who underwent angiography (among women, 62.1% [21,294/34,290], and among men, 73% [34,220/46,875]; P < .001). Among these, a total of 5,538 patients (10.0%) had nonnonobstructive CAD-15.1% (3,221/21,294) of women and 6.8% (2,317/34,220) of men (P < .0001). In patients without obstructive CAD, women were as likely as men to have MI (troponin elevation in 89% vs 87%, P = .37). Women and men were equally likely to have larger troponin elevations (58.9% vs 58.6% with troponin >5x upper limit of normal, P = .69, respectively). In NSTEMI patients without obstructive CAD, in-hospital death (0.6% women vs 0.7% men) and cardiogenic shock (1.0% women vs 0.7% men) were infrequent. CONCLUSIONS: Among NSTE ACS patients undergoing coronary angiography, absence of obstructive CAD is more common in women than men. Although nonobstructive CAD was twice as common among women with NSTEMI, sex differences in characteristics and outcomes were similar to those found with obstructive CAD. Unadjusted in-hospital outcomes of NSTEMI patients with nonobstructive CAD are favorable in both sexes. Whether the underlying pathophysiology of NSTE ACS without documentation of obstructive CAD is different between women and men requires further study

BACKGROUND: The Occluded Artery Trial (OAT) was a 2,201-patient randomized clinical trial comparing routine stent-based percutaneous coronary intervention (PCI) versus optimal medical therapy alone in stable myocardial infarction (MI) survivors with persistent infarct-related artery occlusion identified day 3 to 28 post MI. Intent-to-treat analysis showed no difference between strategies with respect to the incidence of new class IV congestive heart failure, MI, or death. The influence of PCI failure, procedural hazard, and crossover on trial results has not been reported. METHODS: Study angiograms were analyzed and adjudicated centrally. Factors associated with PCI failure were examined. Time-to-event analysis using the OAT primary outcome was performed by PCI success status. Landmark analysis (up to and beyond 30 days) partitioned early hazard versus late outcome according to treatment received. RESULTS: Percutaneous coronary intervention was adjudicated successful in >87%. Percutaneous coronary intervention failure rates were similar in US and non-US sites, and did not significantly influence outcome at 60 months (hazard ratio for success vs fail 0.79, 99% CI 0.45-1.40, P = .29). Partitioning of early procedural hazard revealed no late benefit for PCI (hazard ratio for PCI success vs medical therapy alone 1.06, 99% CI 0.75-1.50, P = .66). CONCLUSIONS: Percutaneous coronary intervention failure and complication rates in the OAT were low. Neither PCI failure nor early procedural hazard substantively influenced the primary trial results

CONTEXT: Conflicting information exists about whether sex differences modulate short-term mortality following acute coronary syndromes (ACS). OBJECTIVES: To investigate the relationship between sex and 30-day mortality in ACS, and to determine whether this relationship was modified by clinical syndrome or coronary anatomy using a large database across the spectrum of ACS and adjusting for potentially confounding clinical covariates. DESIGN, SETTING, AND PARTICIPANTS: A convenience sample of patients pooled from 11 independent, international, randomized ACS clinical trials between 1993 and 2006 whose databases are maintained at the Duke Clinical Research Institute, Durham, North Carolina. Of 136 247 patients, 38 048 (28%) were women; 102 004 (26% women) with ST-segment elevation myocardial infarction (STEMI), 14 466 (29% women) with non-STEMI (NSTEMI), and 19 777 (40% women) with unstable angina. MAIN OUTCOME MEASURE: Thirty-day mortality following ACS. RESULTS: Thirty-day mortality was 9.6% in women and 5.3% in men (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.83-2.00). After multivariable adjustment, mortality was not significantly different between women and men (adjusted OR, 1.06; 95% CI, 0.99-1.15). A significant sex by type of ACS interaction was demonstrated (P < .001). In STEMI, 30-day mortality was higher among women (adjusted OR, 1.15; 95% CI, 1.06-1.24), whereas in NSTEMI (adjusted OR, 0.77; 95% CI, 0.63-0.95) and unstable angina, mortality was lower among women (adjusted OR, 0.55; 95% CI, 0.43-0.70). In a cohort of 35 128 patients with angiographic data, women more often had nonobstructive (15% vs 8%) and less often had 2-vessel (25% vs 28%) and 3-vessel (23% vs 26%) coronary disease, regardless of ACS type. After additional adjustment for angiographic disease severity, 30-day mortality among women was not significantly different than men, regardless of ACS type. The relationship between sex and 30-day mortality was similar across the levels of angiographic disease severity (P for interaction = .70). CONCLUSIONS: Sex-based differences existed in 30-day mortality among patients with ACS and vary depending on clinical presentation. However, these differences appear to be largely explained by clinical differences at presentation and severity of angiographically documented disease

AIMS: To assess the incidence and timing of atrial fibrillation (AF), describe antithrombotic therapy use, and evaluate the association of AF with 90 day mortality and other secondary clinical outcomes. METHODS AND RESULTS: We studied 5745 ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention (PCI) in APEX-AMI. Approximately 11% had AF during hospitalization. Atrial fibrillation prevalence at baseline and at discharge was 4.8% [confidence interval (CI) 4.3-5.4%] and 2.5% (CI 2.1-2.9%), respectively. The proportion of 5466 patients without AF at baseline who developed new onset AF was 6.3% (CI 5.6-6.9%). This corresponded to 9.3 cases of new onset AF/1000 patient days at risk. New onset AF was independently associated with 90 day mortality [adjusted hazard ratio (HR) 1.81; 95% CI 1.06-3.09; P = 0.029] after accounting for baseline covariates and in-hospital procedures and complications. New onset AF was associated with shock (adjusted HR 3.81; 95% CI 1.88-7.70; P = 0.0002), congestive heart failure (adjusted HR 2.66; 95% CI 1.74-4.06; P < 0.0001), and stroke (adjusted HR 2.98; 95% CI 1.47-6.04; P = 0.0024) in models accounting for baseline covariates. Of AF patients, 55% did not receive oral anticoagulation therapy at discharge. Among patients with coronary stents, 5.1% were discharged on triple therapy. Patients at highest risk of stroke (CHADS(2) score > or =2) were least likely to receive oral anticoagulation at discharge (39%). Warfarin use in patients with AF at discharge (43.4%) was associated with lower rates of 90 day mortality and stroke. CONCLUSION: Atrial fibrillation prevalence at baseline and at discharge was 4.8 and 2.5%, respectively. The proportion of patients who developed new onset AF was 6.3%. New onset AF was independently associated with 90 day mortality and was a marker of adverse outcomes in patients undergoing primary PCI

Myocardial infarction often develops when thrombosis occurs at lesions that have not previously been flow limiting. However, the development of cardiogenic shock complicating acute myocardial infarction in such circumstances has received little attention. The characteristics of 15 patients with cardiogenic shock who had no flow-limiting angiographic stenoses were compared with those of 767 patients with > or =1 stenosis who were enrolled in the Should We Emergently Revascularize Occluded Coronary Arteries for Cardiogenic Shock (SHOCK) trial and registry. Compared with patients with > or =1 flow-limiting stenosis, patients with no flow-limiting stenoses were less likely to have pulmonary edema on chest x-ray (29% vs 62%, p = 0.008) and to be white (53% vs 82%, p = 0.011), and they had lower median highest creatine kinase levels (702 vs 2,731 U/L, p = 0.018). For SHOCK trial patients, 1-year survival was 49% for patients with > or =1 flow-limiting stenosis and 71% for those with no flow-limiting stenoses (p = 0.268). In conclusion, patients with cardiogenic shock without flow-limiting stenosis have different characteristics, and potentially disease mechanisms, and they do not require revascularization