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1.  Effects of timing, location and definition of reinfarction on mortality in patients with totally occluded infarct related arteries late after myocardial infarction 
Structured Abstract
The Occluded Artery Trial (OAT) randomized stable patients (n=2,201) >24 hours (calendar days 3–28) after myocardial infarction (MI) with totally occluded infarct-related arteries (IRA), to percutaneous coronary intervention (PCI) with optimal medical therapy, or optimal medical therapy alone (MED). PCI had no impact on the composite of death, reinfarction, or class IV heart failure over extended follow-up of up to 9 years. We evaluated the impact of early and late reinfarction and definition of MI on subsequent mortality.
Methods and Results
Reinfarction was adjudicated according to an adaptation of the 2007 universal definition of MI and the OAT definition (≥2 of the following - symptoms, EKG and biomarkers). Cox regression models were used to analyze the effect of post-randomization reinfarction and baseline variables on time to death.
After adjustment for baseline characteristics the 169 (PCI: n=95; MED: n=74) patients who developed reinfarction by the universal definition had a 4.15-fold (95% CI 3.03–5.69, p<0.001) increased risk of death compared to patients without reinfarction. This risk was similar for both treatment groups (interaction p=0.26) and when MI was defined by the stricter OAT criteria. Reinfarctions occurring within 6 months of randomization had similar impact on mortality as reinfarctions occurring later, and the impact of reinfarction due to the same IRA and a different epicardial vessel was similar.
For stable post-MI patients with totally occluded infarct arteries, reinfarction significantly independently increased the risk of death regardless of the initial management strategy (PCI vs. MED), reinfarction definition, location and early or late occurrence.
PMCID: PMC4067126  PMID: 24726166
Reinfarction; late revascularization; myocardial infarction; mortality
2.  Comparative Definitions for Moderate-Severe Ischemia in Stress Nuclear, Echocardiography, and Magnetic Resonance Imaging 
JACC. Cardiovascular imaging  2014;7(6):593-604.
The lack of standardized reporting of the magnitude of ischemia on noninvasive imaging contributes to variability in translating the severity of ischemia across stress imaging modalities. We identified the risk of coronary artery disease (CAD) death or myocardial infarction (MI) associated with ≥10% ischemic myocardium on stress nuclear imaging as the risk threshold for stress echocardiography and cardiac magnetic resonance. A narrative review revealed that ≥10% ischemic myocardium on stress nuclear imaging was associated with a median rate of CAD death or MI of 4.9%/year (interquartile range: 3.75% to 5.3%). For stress echocardiography, ≥3 newly dysfunctional segments portend a median rate of CAD death or MI of 4.5%/year (interquartile range: 3.8% to 5.9%). Although imprecisely delineated, moderate-severe ischemia on cardiac magnetic resonance may be indicated by ≥4 of 32 stress perfusion defects or ≥3 dobutamine-induced dysfunctional segments. Risk-based thresholds can define equivalent amounts of ischemia across the stress imaging modalities, which will help to translate a common understanding of patient risk on which to guide subsequent management decisions.
PMCID: PMC4128344  PMID: 24925328
cardiac imaging; ischemia; prognosis
3.  Reinfarction Following PCI or Medical Management using the Universal Definition in Patients With Total Occlusion After Myocardial Infarction: Results from Long Term Follow up of the OAT Cohort 
American heart journal  2012;163(4):563-571.
The Occluded Artery Trial (OAT) randomized 2201 patients with a totally occluded infarct-related artery on days 3–28 (>24 hours) following myocardial infarction (MI) to percutaneous coronary intervention (PCI) or medical treatment (MED). There was no difference in the primary endpoint of death, reinfarction or heart failure at 2.9 year or 6-year mean follow-up. However in patients randomized to PCI there was a trend for an increase in reinfarction.
We analyzed the characteristics and types of reinfarction according to the universal definition. Independent predictors of reinfarction were determined using Cox proportional hazard models with follow up to 9 years.
There were 169 reinfarctions; 9.4% PCI vs 8.0% MED, HR 1.31, 95% CI 0.97 −1.77, p=0.08. Spontaneous reinfarction (type 1) occurred with similar frequency in the groups; 4.9% PCI vs 6.7% MED, HR 0.78, 95% CI 0.53 – 1.15, p=0.21. Rates of type 2 (secondary) and 3 (sudden death) MI were similar in both groups. There was an increase in type 4a reinfarctions (related to protocol or repeat PCI), 0.8% PCI vs 0.1% MED, p=0.01 and type 4b reinfarctions (stent thrombosis); 2.7% PCI vs 0.6% MED, p<0.001.
Multivariate predictors of reinfarction were history of PCI prior to study entry (p=0.001), diabetes (p=0.005), and absence of new Q waves with the index infarction (p=0.01).
There was a trend for reMI to be more frequent with PCI. Opening an occluded infarct-related artery in stable patients late post-MI exposes them to a risk of subsequent reinfarction related to reocclusion and stent thrombosis.
PMCID: PMC4238915  PMID: 22520521
reinfarction; universal definition; occluded infarct artery
American heart journal  2010;160(3):443-450.
Early revascularization (ERV) is beneficial in the management of CS complicating myocardial infarction. The severity of CS varies widely, and identification of independent risk factors for outcome is needed. The effect of ERV on mortality in different risk strata is also unknown. We created a severity scoring system for cardiogenic shock (CS) and used it to examine the potential benefit of ERV in different risk strata using data from the SHOCK Trial and Registry.
Data from 1217 patients (294 from the randomized trial and 923 from the registry) with CS due to pump failure were included in a Stage 1 severity scoring system using clinical variables. A Stage 2 scoring system was developed using data from 872 patients who had invasive hemodynamic measurements. The outcome was in-hospital mortality at 30 days.
In-hospital mortality at 30 days was 57%. Multivariable modeling identified eight risk factors (Stage 1): age, shock on admission, clinical evidence of end-organ hypoperfusion, anoxic brain damage, systolic BP, prior CABG, non-inferior MI, and creatinine≥1.9 mg/dl (c-statistic=0.74). Mortality ranged from 22–88% by score category. ERV benefit was greatest in moderate-to-high-risk patients (p=0.02). The Stage 2 model based on patients with pulmonary artery catheterization included age, end-organ hypoperfusion, anoxic brain damage, stroke work and LVEF<28% (c-statistic=0.76). In this cohort the effect of ERV did not vary by risk stratum.
Simple clinical predictors provide good discrimination of mortality risk in CS complicating MI. ERV is associated with improved survival across a broad range of risk strata.
PMCID: PMC4229030  PMID: 20826251
cardiogenic shock; myocardial infarction; risk assessment
5.  Early revascularization is beneficial across all ages and a wide spectrum of cardiogenic shock severity: A pooled analysis of trials 
Acute cardiac care  2011;13(1):14-20.
A pooled analysis in cardiogenic shock due to acute coronary syndromes is desirable to assess the effect of early revascularization (ERV) across all ages and a wide spectrum of disease severity.
Only two randomized controlled trials (RCT), i.e. SMASH and SHOCK, met the inclusion criteria and were combined for a pooled analysis using individual patient data (n = 348).
SMASH patients (n = 54, 16%) had more severe disease than SHOCK patients (n = 294, 84%). After adjustment for age, anoxic brain damage, non-inferior myocardial infarction, prior coronary artery bypass graft surgery, renal failure, systolic blood pressure, and selection for coronary angiography, one-year mortality was similar (relative risk SHOCK versus SMASH 0.87, 95% CI: 0.61–1.25). Relative risk of one-year death for ERV versus initial medical stabilization was 0.82 (95% CI: 0.70–0.96). There was no significant difference in the treatment effect by age (≤75 years relative risk at one year 0.79, 95% CI: 0.63–0.99; >75 years relative risk at one year 0.93, 95% CI: 0.56–1.53; interaction P = 0.10).
Only two RCT have been published emphasizing the difficulty of enrolling critically ill patients. Despite large differences in shock severity, ERV benefit is similar across all ages and not significantly different for the elderly.
PMCID: PMC4224032  PMID: 21244231
Shock; cardiogenic; meta-analysis; myocardial revascularization; age factors; comorbidity
6.  Cardiogenic SHOCK Without Flow-Limiting Angiographic Coronary Artery Disease – (From The SHOCK Trial And Registry) 
Myocardial infarction (MI) often develops when thrombosis occurs at lesions which have not previously been flow-limiting. However, the development of cardiogenic shock complicating acute myocardial infarction in such circumstances has received little attention. We studied the characteristics of 15 patients with cardiogenic shock who had no flow-limiting angiographic stenosis compared to 767 patients with at least one stenosis, who were enrolled in the SHOCK Trial and Registry. Compared to patients with at least one flow-limiting stenosis, patients with no flow-limiting stenosis were less likely to have pulmonary edema on chest x-ray (29% v 62%, P=0.008), and to have white ethnicity (53% v 82%, P = 0.011), and had lower median highest creatine kinase levels (702 v 2731 u/l; P = 0.018). For SHOCK Trial patients 1-year survival was 49% for patients with at least one flow-limiting stenosis and 71% for those with no flow-limiting stenosis (P= 0.268).
PMCID: PMC4060258  PMID: 19576316
no flow-limiting stenosis; myocardial infarction; cardiogenic shock
7.  Outcome following Surgery and Percutaneous Intervention for Cardiogenic Shock and Left Main Disease 
The Annals of thoracic surgery  2008;86(1):29-34.
The ideal revascularization strategy (bypass surgery vs. percutaneous coronary intervention [PCI]) for patients with cardiogenic shock in the setting of left main coronary artery (LMCA) disease is unknown.
The Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock Trial and Registry included 164 patients with LMCA disease who underwent revascularization. Although the standard of care at the time and the trial protocol recommended bypass surgery for patients with LMCA disease, the revascularization strategy (79 bypass surgery and 85 PCI) was individualized for each patient by site investigators.
The median time from myocardial infarction to revascularization was 24.3 hours (interquartile range, 8.7 to 82.5 hours) in the surgical group and 7.4 hours (interquartile range, 3.7 to 19.5 hours) in the PCI group (p <0.05). Overall 30-day survival with surgery in this setting was 569% (95% confidence interval (0.43, 0.69) and was significantly superior to the 21% (95% confidence interval (0.09, 0.35) in the PCI group (p <0.01). When the LMCA was the infarct-related artery, the 30-day survival rate was 40% in the surgical group (n=6) and 16% in the PCI group (n=15) (p=0.03). Bypass surgery [hazard ratio 0.41, 95% confidence interval (0.22, 0.77), p=0.006) and age [per 10 years, hazard ratio 1.04, 95% confidence interval (1.01-1.08); p=0.02] were independently associated with 30-day survival.
Bypass surgery appeared to provide a survival advantage over PCI at 30-day follow up in patients with LMCA disease. The impact of current PCI strategies on this subgroup is undetermined.
PMCID: PMC4056020  PMID: 18573394
Coronary artery bypass grafts; Myocardial infarction
8.  Revascularization for Silent Ischemia? Another Piece of the Puzzle 
PMCID: PMC3712878  PMID: 23500294
9.  Infarct Artery Distribution and Clinical Outcomes in Occluded Artery Trial Subjects Presenting with Non ST elevation Myocardial Infarction (From the Long Term Follow-up of the Occluded Artery Trial) 
The American journal of cardiology  2013;111(7):930-935.
We hypothesized that the insensitivity of the electrocardiogram (ECG) in identifying acute circumflex occlusion would result in differences in the distribution of the infarct related artery (IRA) between patients with non ST elevation myocardial infarction (NSTEMI) and ST elevation myocardial infarction (STEMI) enrolled in the Occluded Artery Trial. We also sought to evaluate the impact of percutaneous intervention to the IRA on clinical outcomes for patients with NSTEMI. Overall NSTEMI subjects comprised 13% (n=283) of the trial population. The circumflex IRA was overrepresented in the NSTEMI group compared to patients enrolled with STEMI (42.5 vs. 11.2%; p<0.0001). The 7 year clinical outcomes for NSTEMI patients randomized to percutaneous intervention and optimal medical therapy versus optimal medical therapy alone were similar for the primary composite of Death, MI and Class IV Congestive Heart Failure (CHF) (22.3 vs. 20.23%, p=0.51, HR 1.20; 0.59-2.43); as well as the individual endpoints of Death (13.8 vs. 17.0%, p=0.51, HR 0.81;0.36-1.85); MI (6.1 vs. 5.1%, p=0.84, HR=1.11; 0.28-4.41); Class IV CHF (6.7 vs. 6.0%, p=0.45, HR 1.50;0.37-6.02). There was no interaction between MI type by ECG and treatment effect (p= NS). In conclusion the occluded circumflex IRA is overrepresented in the NSTEMI population. Consistent with the overall trial results, stable patients with NSTEMI and a totally occluded IRA did not benefit from randomization to PCI.
PMCID: PMC3619220  PMID: 23351464
Coronary artery disease; Myocardial Infarction; Percutaneous coronary intervention; Prognosis
10.  Outcomes among non-ST-segment elevation acute coronary syndromes patients with no angiographically obstructive coronary artery disease: observations from 37,101 patients 
Limited data exist concerning outcomes of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) with no angiographically obstructive coronary artery disease (non-obstructive CAD). We assessed the frequency of clinical outcomes among patients with non-obstructive CAD compared with obstructive CAD.
Methods and results:
We pooled data from eight NSTE ACS randomized clinical trials from 1994 to 2008, including 37,101 patients who underwent coronary angiography. The primary outcome was 30-day death or myocardial infarction (MI). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for 30-day death or MI for non-obstructive versus obstructive CAD were generated for each trial. Summary ORs (95% CIs) across trials were generated using random effects models. Overall, 3550 patients (9.6%) had non-obstructive CAD. They were younger, more were female, and fewer had diabetes mellitus, previous MI or prior percutaneous coronary intervention than patients with obstructive CAD. Thirty-day death or MI was less frequent among patients with non-obstructive CAD (2.2%) versus obstructive CAD (13.3%) (ORadj 0.15; 95% CI, 0.11–0.20); 30-day death or spontaneous MI and six-month mortality were also less frequent among patients with non-obstructive CAD (ORadj 0.19 (0.14–0.25) and 0.37 (0.28–0.49), respectively).
Among patients with NSTE ACS, one in 10 had non-obstructive CAD. Death or MI occurred in 2.2% of these patients by 30 days. Compared with patients with obstructive CAD, the rate of major cardiac events was lower in patients with non-obstructive CAD but was not negligible, prompting the need to better understand management strategies for this group.
PMCID: PMC3932771  PMID: 24562802
Acute coronary syndromes; angiography; atherosclerosis; coronary disease; infarction
11.  Serious Infection Following Acute Myocardial Infarction: Incidence, Clinical Features, and Outcomes 
JACC. Cardiovascular interventions  2012;5(7):10.1016/j.jcin.2012.03.018.
Little is known about the incidence, location, etiologic organisms, and outcomes of infection in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI).
To address this knowledge gap using the database of the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial. We also assessed the association between serious infections and 90-day death or death/MI.
We analyzed data from 5745 STEMI patients enrolled in the APEX-AMI trial. Detailed information on infection was collected on all patients. We describe characteristics of patients according to infection and details of infection. Cox proportional hazards models were used to assess 90-day outcomes among patients with and without infections after adjusting for associated clinical variables and using infection as a time-dependent covariate.
Overall, 138 patients developed a serious infection (2.4%), most of whom presented with a single-site infection. The median (25th, 75th percentile) time until diagnosis of infection was 3 (1, 6) days. The most commonly identified organism was Staphylococcus aureus, and the main location of infection was the bloodstream. These patients had more comorbidities and lower procedural success at index PCI than those without infections. Serious infection was associated with significantly higher rates of 90-day death (adjusted hazard ratio [HR] 5.6; 95% confidence interval [CI] 3.8-8.4) and death or MI (adjusted HR 4.9; 95% CI 3.4-7.1).
Infections complicating the course of patients with STEMI are uncommon but associated with markedly worse 90-day clinical outcomes. Mechanisms for early identification of these high-risk patients, as well as design of strategies to reduce their risk of infection, are warranted.
PMCID: PMC3883036  PMID: 22814783
ST-segment elevation myocardial infarction; percutaneous coronary intervention; infection; outcomes
12.  Heart Failure in post MI patients with persistent IRA occlusion: Prevalence, Risk Factors, and the Long-term Effect of PCI in the Occluded Artery Trial (OAT) 
Journal of cardiac failure  2012;18(11):813-821.
The incidence and predictors of heart failure (HF) post myocardial infarction (MI) with modern post-MI treatment have not been well characterized.
Methods and Results
2201 stable patients with persistent infarct related artery occlusion > 24 hours after MI with left ventricular ejection fraction <50% and/or proximal coronary artery occlusion were randomized to percutaneous intervention plus optimal medical therapy (PCI) or optimal medical therapy (MED) alone. Centrally adjudicated HF hospitalizations for NYHA III/IV HF and mortality were determined in patients with and without baseline HF, defined as a history of HF, Killip Class > I at index MI, rales, S3 gallop, NYHA II at randomization, or NYHA > I prior to index MI. Long-term follow-up data were used to determine 7-year life-table estimated event rates and hazard ratios.
There were 150 adjudicated HF hospitalizations during a mean follow-up of 6 years with no difference between the randomized groups (7.4% PCI vs. 7.5% MED, p=0.97). Adjudicated HF hospitalization was associated with subsequent death (44.0% vs. 13.1%, HR 3.31, 99% CI 2.21–4.92, p<0.001). Baseline HF (present in 32% of patients) increased the risk of adjudicated HF hospitalization (13.6% vs. 4.7%, HR 3.43, 99% CI 2.23–5.26, p<0.001) and death (24.7% vs. 10.8%, HR 2.31, 99% CI 1.71–3.10, p<0.001).
In the overall OAT population, adjudicated HF hospitalizations occurred in 7.5% of subjects and were associated with increased risk of subsequent death. Baseline or prior HF was common in the OAT population and was associated with increased risk of hospitalization and death.
PMCID: PMC3518044  PMID: 23141853
Heart Failure; Myocardial Infarction; Occlusion; Revascularization
13.  Impact of percutaneous coronary intervention on biomarker levels in patients in the subacute phase following myocardial infarction: the Occluded Artery Trial (OAT) biomarker ancillary study 
The purpose of the Occluded Artery Trial (OAT) Biomarker substudy was to evaluate the impact of infarct related artery (IRA) revascularization on serial levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and dynamics of other biomarkers related to left ventricular remodeling, fibrosis and angiogenesis.
Patients were eligible for OAT-Biomarker based on the main OAT criteria. Of 70 patients (age 60.8 ± 8.8, 25% women) enrolled in the substudy, 37 were randomized to percutaneous coronary intervention (PCI) and 33 to optimal medical therapy alone. Baseline serum samples were obtained prior to OAT randomization with follow up samples taken at one year. The primary outcome was percent change of NT-proBNP from baseline to 1 year. The secondary outcomes were respective changes of matrix metalloproteinases (MMP) 2 and 9, tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), Vascular Endothelial Growth Factor (VEGF), and Galectin-3.
Paired (baseline and one-year) serum samples were obtained in 62 subjects. Baseline median NT-proBNP level was 944.8 (455.3, 1533) ng/L and decreased by 69% during follow-up (p < 0.0001). Baseline MMP-2 and TIMP-2 levels increased significantly from baseline to follow-up (p = 0.034, and p = 0.027 respectively), while MMP-9 level decreased from baseline (p = 0.038). Levels of VEGF and Galectin-3 remained stable at one year (p = NS for both). No impact of IRA revascularization on any biomarker dynamics were noted.
There were significant changes in measured biomarkers related to LV remodeling, stress, and fibrosis following MI between 0 and 12 month. Establishing infarct vessel patency utilizing stenting 24 hours-28 days post MI did not however influence the biomarkers’ release.
PMCID: PMC3871016  PMID: 24156746
Acute coronary syndrome; Percutaneous coronary intervention; Biomarkers; Heart failure; Remodeling
14.  Effect of Late Revascularization of a Totally Occluded Coronary Artery After Myocardial Infarction on Mortality Rates in Patients with Renal Impairment 
The American journal of cardiology  2012;110(7):954-960.
Renal dysfunction is an independent predictor of cardiovascular events and a negative prognostic indicator after myocardial infarction (MI). Randomized data comparing percutaneous coronary intervention (PCI) to medical therapy in MI patients with renal insufficiency are needed. The Occluded Artery Trial (OAT) compared optimal medical therapy alone to PCI with optimal medical therapy in 2201 high risk patients with an occluded infarct artery >24 hours post-MI with serum creatinine ≤2.5 mg/dl. The primary endpoint was a composite of death, MI, and class IV heart failure (HF). Analyses were carried out utilizing estimated glomerular filtration rates (eGFR) as a continuous variable and by eGFR categories. Long term follow up data (maximum 9 years) were used for this analysis. Lower eGFR (ml/min/1.73m2) was associated with development of the primary outcome (6-year life-table rate 16.9% in eGFR>90; 19.2% in eGFR 60–89; 34.9% in eGFR<60; p-value <0.0001), death, and class IV HF, with no difference in rates of reinfarction. On multivariable analysis, eGFR was an independent predictor of death and HF. There was no effect of treatment assignment on the primary endpoint regardless of eGFR, and there was no significant interaction between eGFR and treatment assignment on any outcome. In conclusion, lower eGFR at enrollment was independently associated with death and HF in OAT participants. Despite this increased risk, the lack of benefit from PCI in the overall trial was also seen in patients with renal dysfunction and persistent occlusion of the infarct artery in the subacute phase post MI.
PMCID: PMC3439588  PMID: 22728005
Myocardial Infarction; Stents and Kidney Disease
15.  Physical activity in patients with stable coronary heart disease: an international perspective 
European Heart Journal  2013;34(42):3286-3293.
Despite the known benefits of regular exercise, the reasons why many coronary heart disease (CHD) patients engage in little physical activity are not well understood. This study identifies factors associated with low activity levels in individuals with chronic CHD participating in the STABILITY study, a global clinical outcomes trial evaluating the lipoprotein phospholipaseA2 inhibitor darapladib.
Methods and results
Prior to randomization, 15 486 (97.8%) participants from 39 countries completed a lifestyle questionnaire. Total physical activity was estimated from individual subject self-reports of hours spend each week on mild, moderate, and vigorous exercise, corresponding approximately to 2, 4, and 8 METS, respectively. Multivariate logistic regression evaluated clinical and demographic variables for the lowest compared with higher overall exercise levels, and for individuals who decreased rather than maintained or increased activity since diagnosis of CHD. The least active 5280 subjects (34%) reported exercise of ≤24MET.h/week. A total of 7191 subjects (46%) reported less exercise compared with before diagnosis of CHD. The majority of participants were either ‘not limited’ or ‘limited a little’ walking 100 m (84%), climbing one flight of stairs (82%), or walking 1 km/½ mile (68%), and <10% were limited ‘a lot’ by dyspnoea or angina. Variables independently associated with both low physical activity and decreasing exercise after diagnosis of CHD included more co-morbid conditions, poorer general health, fewer years of education, race, and country (P < 0.001 for all).
In this international study, low physical activity was only partly explained by cardiovascular symptoms. Potentially modifiable societal and health system factors are important determinants of physical inactivity in patients with chronic CHD.
PMCID: PMC3819591  PMID: 24014220
Physical activity; Exercise; Coronary artery disease; Cardiac rehabilitation
16.  Impact of National Clinical Guideline Recommendations for Revascularization of Persistently Occluded Infarct-Related Arteries on Clinical Practice in the United States 
Archives of internal medicine  2011;171(18):1636-1643.
The Occluded Artery Trial (OAT) was a large, randomized controlled trial published in 2006 that demonstrated no benefit to routine percutaneous coronary intervention (PCI) of persistently totally occluded infarct-related arteries (IRA) identified a minimum of 24 hours (on calendar days 3–28) after myocardial infarction (MI). The purpose of this study was to determine the impact of OAT results and consequent change in guideline recommendations for PCI for treatment of persistently occluded IRAs.
We identified all patients enrolled in the CathPCI Registry, from 2005 to 2008, undergoing catheterization more than 24 hours after MI with a totally occluded native coronary artery and no major OAT exclusion criteria. We examined trends in monthly rates of PCI for occlusions after OAT publication and after guideline revisions. Because reporting of diagnostic catheterizations was not mandatory, we examined trends among hospitals in the highest quartile for reporting of diagnostic procedures.
A total of 28 780 patient visits from 896 hospitals were included. Overall, we found no significant decline in the adjusted monthly rate of PCI of occlusions after publication of OAT (odds ratio [OR], 0.997; 95% confidence interval [CI], 0.989–1.006) or after guideline revisions (OR, 1.007; 95% CI, 0.992–1.022). Among hospitals consistently reporting diagnostic catheterizations, there was no significant decline after OAT publication (OR, 1.018; 95% CI, 0.995–1.042), and there was a trend toward decline after guideline revisions (OR, 0.963; 95% CI, 0.920–1.000).
These findings suggest that the results of OAT and consequent guideline revisions have not, to date, been fully incorporated into clinical practice in a large cross-section of hospitals in the United States.
PMCID: PMC3738051  PMID: 21747002
17.  Long-term outcomes after a strategy of percutaneous coronary intervention of the infarct-related artery with drug-eluting stents or bare metal stents vs medical therapy alone in the Occluded Artery Trial (OAT) 
American heart journal  2012;163(6):1011-1018.
The OAT, a randomized study of routine percutaneous coronary intervention or optimal medical therapy (MED) alone for the treatment of a totally occluded infarct-related artery in the subacute phase after myocardial infarction, showed similar rates of death, reinfarction and congestive heart failure (CHF) between study groups. Although most percutaneous coronary intervention patients were treated with bare metal stents (BMS), drug-eluting stents (DES) were also implanted in the latter part of the study. The aim of the study was to conduct an exploratory analysis of long-term outcomes for DES vs. BMS deployment vs. MED in the OAT.
Patients enrolled after February 2003 (when first DES was implanted) were followed (DES n = 79, BMS n = 393, MED n = 552) up to a maximum of 6 years (mean survivor follow-up 5.1 years).
The 6-year occurrence of the composite end point of death, reinfarction and class IV CHF was similar [20.4% of DES, 18.9% of BMS and 18.4% of MED (P = .66)] as were the rates of the components of the primary end point. During the follow-up period, 33.4% of DES, 44.4% of BMS and 48.1% of MED patients, developed angina (P = .037). The rate of revascularization during follow up was 11.3%, 20.5% and 22.5% among these groups, respectively (P = .045).
There is no suggestion of reduced long-term risk of death, reinfarction or class IV CHF with DES usage compared to BMS or medical treatment alone. An association between DES use and freedom from angina and revascularization relative to medical therapy is suggested.
PMCID: PMC3735135  PMID: 22709754
19.  Methods of creatine kinase-MB analysis to predict mortality in patients with myocardial infarction treated with reperfusion therapy 
Trials  2013;14:123.
Larger infarct size measured by creatine kinase (CK)-MB release is associated with higher mortality and has been used as an important surrogate endpoint in the evaluation of new treatments for ST-segment elevation myocardial infarction (STEMI). Traditional approaches to quantify infarct size include the observed CK-MB peak and calculated CK-MB area under the curve (AUC). We evaluated alternative approaches to quantifying infarct size using CK-MB values, and the relationship between infarct size and clinical outcomes.
Of 1,850 STEMI patients treated with reperfusion therapy in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) (percutaneous coronary intervention (PCI)-treated) and the COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) (fibrinolytic-treated) trials, 1,718 (92.9%) (COMMA, n = 868; COMPLY, n = 850) had at least five of nine protocol-required CK-MB measures. In addition to traditional methods, curve-fitting techniques were used to determine CK-MB AUC and estimated peak CK-MB. Cox proportional hazards modeling assessed the univariable associations between infarct size and mortality, and the composite of death, heart failure, shock and stroke at 90 days.
In COMPLY, CK-MB measures by all methods were significantly associated with higher mortality (hazard ratio range per 1,000 units increase: 1.09 to 1.13; hazard ratio range per 1 standard deviation increase: 1.41 to 1.62; P <0.01 for all analyses). In COMMA, the associations were similar but did not reach statistical significance. For the composite outcome of 90-day death, heart failure, shock and stroke, the associations with all CK-MB measures were statistically significant in both the COMMA and COMPLY trials.
Sophisticated curve modeling is an alternative to infarct-size quantification in STEMI patients, but it provides information similar to that of more traditional methods. Future studies will determine whether the same conclusion applies in circumstances other than STEMI, or to studies with different frequencies and patterns of CK-MB data collection.
PMCID: PMC3662641  PMID: 23782531
Creatine kinase-MB; Infarct size; ST-segment elevation myocardial infarction; Clinical outcomes
20.  Mechanisms of Myocardial Infarction in Women without Angiographically Obstructive Coronary Artery Disease 
Circulation  2011;124(13):1414-1425.
There is no angiographically demonstrable obstructive coronary artery disease (CAD) in a significant minority of patients with myocardial infarction (MI), particularly women. We sought to determine mechanism(s) of MI in this setting using multiple imaging techniques.
Methods and Results
Women with MI were enrolled prospectively, prior to angiography if possible. Women with ≥50% angiographic stenosis or use of vasospastic agents were excluded. Intravascular ultrasound (IVUS) was performed during angiography and cardiac magnetic resonance imaging (CMR) within one week. Fifty women (age 57±13 years) had median peak troponin 1.60 ng/ml; 11 had ST elevation. Median diameter stenosis of the worst lesion was 20% by angiography; 15 patients (30%) had normal angiograms. Plaque disruption was observed in 16/42 patients (38%) undergoing IVUS. There were abnormal myocardial CMR findings in 26/44 patients (59%) undergoing CMR: late gadolinium enhancement (LGE) in 17 and T2 signal hyperintensity indicating edema in 9 additional patients. The most common LGE pattern was ischemic (transmural/subendocardial). Non-ischemic LGE patterns (midmyocardial/subepicardial) were also observed. LGE was infrequent with plaque disruption but T2 signal hyperintensity was common with plaque disruption.
Plaque rupture and ulceration are common in women with MI without angiographically demonstrable obstructive CAD. LGE is also common in this cohort of women, with an ischemic pattern of injury most evident. Vasospasm and embolism are possible mechanisms of ischemic LGE without plaque disruption. IVUS and CMR provide complementary mechanistic insights in female MI patients without obstructive CAD and may be useful in identifying potential etiologies and therapies.
PMCID: PMC3619391  PMID: 21900087
myocardial infarction; magnetic resonance imaging; coronary disease; imaging
21.  Comparison of Late Results of Percutaneous Coronary Intervention Among Stable Patients ≤ 65 vs. >65 Years of Age With An Occluded Infarct Related Artery (From The Occluded Artery Trial) 
The American Journal of Cardiology  2011;109(5):614-619.
While opening an occluded infarct-related artery (IRA) > 24 hours post myocardial infarction in stable patients in the Occluded Artery Trial (OAT) did not reduce events over 7 years, there was a suggestion that effect of treatment may differ by patient age. Baseline characteristics and outcomes by treatment with percutaneous coronary intervention (PCI) vs. optimal medical therapy (MED) alone were compared by pre-specified stratification at age 65. P<0.01 was pre-specified as significant for OAT secondary analyses. The primary outcome was death, myocardial infarction or Class IV heart failure. Patients > 65 years of age (n=641) were more likely to be female, non-smokers, and to have hypertension, lower estimated glomerular filtration rate and multivessel disease compared to younger patients (age ≤ 65, n=1560), p<0.001. There was no significant observed interaction between treatment assignment and age for the primary outcome after adjustment (p=0.1) and there was no difference between PCI and MED observed in either age group. At 7 year follow-up, younger patients tended to have angina more often compared to the older group (H.R. 1.21, 99% CI: 1.00–1.46, p=0.01). The 7-year composite primary outcome was more common in older patients (p<0.001), and age remained significant after co-variate adjustment (H.R. 1.42, 99% CI: 1.09–1.84). The rate of early PCI complications was low in both age groups. The trend toward a differential effect of PCI in the young vs. the old for the primary outcome was likely driven by measured and unmeasured confounders, and by chance. PCI reduces angina to a similar degree in the young and old. There is no indication for routine PCI to open a persistently occluded IRA in stable patients post-MI regardless of age.
PMCID: PMC3288611  PMID: 22172242
Elderly; PCI; Age; occlusion
22.  Relationship of Female Sex to Outcomes after Myocardial Infarction with Persistent Total Occlusion of the Infarct Artery: Analysis of the Occluded Artery Trial 
American Heart Journal  2012;163(3):462-469.
Long-term follow-up (up to 9 years) from the Occluded Artery Trial (OAT) allows for examination of sex differences in outcomes and the effect of PCI in a relatively homogeneous cohort of MI survivors.
OAT randomized 484 (22%) women and 1717 men to PCI of the occluded infarct-related artery vs. medical therapy alone >24 hours post-MI. There was no benefit of PCI on the composite of death, MI and class IV heart failure. We analyzed outcomes by sex and investigated for sex-based trial selection bias using a concurrent registry.
Women were older and more likely to have LAD infarct-related artery, diabetes and hypertension, history of heart failure and rales at randomization, but less likely to smoke. The proportion and characteristics of women enrolled in the trial and the registry were similar, including LVEF and extent of disease. Women had higher rates of the primary composite [HR 1.48, p=0.0002], death [HR 1.50, p=0.001] and heart failure [HR 2.53, p<0.0001] but not reinfarction [HR 1.12, p=0.57]. Female sex was not independently associated with the primary endpoint or death on multivariate analysis. There was a trend toward independent association of female sex with heart failure [HR 1.66, p=0.02].
Women in OAT had a higher primary endpoint event rate than men, mainly driven by heart failure. Female sex was not independently associated with death or MI in this well-defined cohort with comparable extent of coronary artery disease, similar medical therapy and equivalent LVEF by sex.
PMCID: PMC3308117  PMID: 22424018
23.  Long Term Effects of Percutaneous Coronary Intervention of the Totally Occluded Infarct-Related Artery in the Subacute Phase after Myocardial Infarction 
Circulation  2011;124(21):2320-2328.
Despite observations suggesting a benefit for late opening of occluded infarct-related arteries (IRA) post-myocardial infarction (MI), the Occluded Artery Trial (OAT) demonstrated no reduction in the composite of death, reinfarction and class IV heart failure (HF) over 2.9-yearmean follow-up. Follow-up was extended to determine whether late trends would favor either treatment group.
Methods and Results
OAT randomized 2201 stable patients with IRA occlusion >24hours (calendar days3-28) after MI. Severe inducible ischemia, rest angina, class III-IV HF and 3-vessel/left main disease were excluded. We conducted extended followed up of enrolled patients for an additional 3 years for the primary endpoint and angina (6-year median survivor follow up, longest 9 years, 12,234 patient-years).Rates of the primary endpoint (HR 1.06, 95% CI 0.88-1.28), fatal and nonfatal MI (HR 1.25, 95% CI 0.89-1.75), death and class IV HF were similar for PCI vs. MED groups. No interaction between baseline characteristics and treatment group on outcomes were observed. The vast majority of patients at each follow-up visit did not report angina. There was less angina in the PCI group through early in follow-up; by 3 years the between group difference was consistently <4 patients per 100 treated and not significantly different though there was a trend toward less angina in the PCI group at 3 and 5 years. The 7-year rate of PCI of the IRA during follow up was 11.1% for the PCI group compared to 14.7% for the MED group (HR 0.79, 95% CI 0.61-1.01. p=0.06).
Extended follow up of the OAT cohort provides robust evidence for no reduction of long-term rates of clinical events after routine PCI in stable patients with an occluded IRA and without severe inducible ischemia in the subacute phase post-MI.
PMCID: PMC3235739  PMID: 22025606
myocardial infarction; stents; trials
24.  Rapid Complete Reversal of Systemic Hypoperfusion following Intra-Aortic Balloon Pump Counterpulsation and Survival in Cardiogenic Shock Complicating an Acute Myocardial Infarction 
American heart journal  2011;162(2):268-275.
In patients with cardiogenic shock (CS) complicating an acute myocardial infarction, a strategy of emergency revascularization vs. initial medical stabilization improves survival. Intra-aortic balloon counterpulsation (IABC) provides hemodynamic support and facilitates coronary angiography and revascularization in CS patients.
Methods and Results
We evaluated 499 patients with record of systemic hypoperfusion status, as an early response to IABC from the SHOCK Trial (n=185) and Registry (n=314) to determine the association between rapid complete reversal of systemic hypoperfusion following 30 minutes of IABC(CRH)and 30-day and 1-year mortality. CRH was highly associated with lower 30-day mortality (45% vs. 78%, p<0.001) in all patients. In the SHOCK Trial, among patients assigned to ERV vs. IMS, 30-day mortality was 26% vs. 29% with CRH, and 61% vs. 81% respectively without CRH, after commencing IABC. The corresponding 1-year mortality rates were 35% vs. 52% for ERV and 69% vs. 87% for IMS (interaction p ≥ 0.25 at both time points). After adjusting for important correlates of outcome (LV ejection fraction, age, and randomization to ERV) a significant association remained between CRH and 30-day mortality (odds ratio 0.18; 95% CI 0.08–0.42, p<0.001) and 1-year mortality (odds ratio 0.28; 95% CI 0.12–0.67, p<0.001).
In CS patients, CRH after commencing IABC was independently associated with improved 30-day and 1-year survival regardless of emergency revascularization. In CS patients, CRH with IABC is an important early prognostic feature.
PMCID: PMC3155687  PMID: 21835287
cardiogenic shock; intra-aortic balloon counterpulsation; systemic hypoperfusion; survival
25.  The Occluded Artery Trial (OAT) Viability Ancillary Study (OAT-NUC): Influence of Infarct Zone Viability on Left Ventricular Remodeling After Percutaneous Coronary Intervention vs. Optimal Medical Therapy Alone 
American heart journal  2011;161(3):611-621.
The Occluded Artery Trial (OAT) showed no difference in outcomes between percutaneous coronary intervention (PCI) vs. optimal medical therapy (MED) in patients with persistent total occlusion of the infarct related artery (IRA) 3–28 days post-MI. Whether PCI may benefit a subset of patients with preservation of infarct zone (IZ) viability is unknown.
Methods and Results
The OAT nuclear ancillary study hypothesized that; 1) IZ viability influences left ventricular (LV) remodeling, and that 2) PCI as compared to MED attenuates adverse remodeling in post-MI patients with preserved viability. Enrolled were 124 OAT patients, who underwent resting nitroglycerin-enhanced 99mTc sestamibi SPECT prior to OAT randomization, with repeat imaging at 1 year. All images were quantitatively analyzed for infarct size, IZ viability, LV volumes and function in a core lab. At baseline, mean infarct size was 26%±18 of the LV, mean IZ viability was 43%±8 of peak uptake, and the majority (70%) of patients had at least moderately retained IZ viability. There were no significant differences in 1-year EDV or ESV change between those with severely reduced vs. moderately retained IZ viability, or when compared by treatment assignment PCI vs. MED. In multivariable models, increasing baseline viability independently predicted improvement in EF (p=0.005). There was no interaction between IZ viability and treatment assignment for any measure of LV remodeling.
In the contemporary era of optimal medical therapy, PCI of the IRA compared to medical therapy alone does not impact LV remodeling irrespective of IZ viability.
PMCID: PMC3073850  PMID: 21392619
Acute Coronary Syndrome; Total Occlusions; Percutaneous Coronary Intervention; Coronary Flow; Viability; Remodeling

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