Search

Background: Zalunfiban (RUC-4) is a novel, subcutaneously administered glycoprotein IIb/IIIa inhibitor (GPI) designed for prehospital treatment to initiate reperfusion in the infarct-related artery (IRA) before primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction (STEMI). Since GPIs have been reported to rapidly reperfuse IRAs, we assessed whether there was a dose-dependent relationship between zalunfiban treatment and angiographic reperfusion indices and thrombus grade of the IRA at initial angiogram in patients with STEMI., Methods: This was a post hoc analysis from the open-label Phase IIa study that investigated the pharmacodynamics, pharmacokinetics, and tolerability of three doses of zalunfiban - 0.075, 0.090 and 0.110 mg/kg - in STEMI patients. This analysis explored dose-dependent associations between zalunfiban and three angiographic indices of the IRA, namely coronary and myocardial blood flow and thrombus burden. Zalunfiban was administered in the cardiac catheterization laboratory prior to vascular access, ∼10 to 15 minutes before the initial angiogram. All angiographic data were analyzed by a blinded, independent, core laboratory., Results: Twentyfour out of 27 STEMI patients were evaluable for angiographic analysis (0.075 mg/kg [n=7], 0.090 mg/kg [n=9], and 0.110 mg/kg [n=8]). TIMI flow grade 2 or 3 was seen in 1/7 patients receiving zalunfiban at 0.075 mg/kg, in 6/9 patients receiving 0.090 mg/kg, and in 7/8 patients receiving 0.110 mg/kg (p trend  = 0.004). A similar trend was observed based on TIMI flow grade 3. Myocardial perfusion was also related to zalunfiban dose (p trend  = 0.005) as reflected by more frequent TIMI myocardial perfusion grade 3. Consistent with the dose-dependent trends in greater coronary and myocardial perfusion, TIMI thrombus ≥4 grade was inversely related to zalunfiban dose (p trend  = 0.02)., Conclusion: This post hoc analysis found that higher doses of zalunfiban administered in the cardiac catheterization lab prior to vascular access were associated with greater coronary and myocardial perfusion, and lower thrombus burden at initial angiogram in patients with STEMI undergoing primary percutaneous coronary intervention., Competing Interests: Conflict of Interest Sem A.O.F. Rikken has nothing to declare. Willem L. Bor has nothing to declare. Abi Selvarajah has nothing to declare. Kai L. Zheng has nothing to declare. Amy Hack has nothing to declare. C. Michael Gibson serves as a scientific advisory to CeleCor Therapeutics, Inc. Christopher B. Granger serves as a scientific advisory to CeleCor Therapeutics, Inc. Barry S. Coller is a founder of CeleCor Therapeutics, Inc., which is developing zalunfiban for human use, and is an equity owner in CeleCor and serves as a paid scientific advisor to CeleCor. Ohad Bentur has nothing to declare. Arnoud W.J. van ’t Hof serves as a scientific advisor to CeleCor Therapeutics, Inc. Jurriën M. ten Berg serves as a scientific advisor to CeleCor Therapeutics, Inc., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Neonatal rodents and piglets naturally regenerate the injured heart after myocardial infarction. We hypothesized that neonatal rabbits also exhibit natural heart regeneration after myocardial infarction., Methods: New Zealand white rabbit kits underwent sham surgery or left coronary ligation on postnatal day 1 (n = 94), postnatal day 4 (n = 11), or postnatal day 7 (n = 52). Hearts were explanted 1 day postsurgery to confirm ischemic injury, at 1 week postsurgery to assess cardiomyocyte proliferation, and at 3 weeks postsurgery to assess left ventricular ejection fraction and scar size. Data are presented as mean ± standard deviation., Results: Size of ischemic injury as a percentage of left ventricular area was similar after myocardial infarction on postnatal day 1 versus on postnatal day 7 (42.3% ± 5.4% vs 42.3% ± 4.7%, P = .9984). Echocardiography confirmed severely reduced ejection fraction at 1 day after postnatal day 1 myocardial infarction (33.7% ± 5.3% vs 65.2% ± 5.5% for postnatal day 1 sham, P = .0001), but no difference at 3 weeks after postnatal day 1 myocardial infarction (56.0% ± 4.0% vs 58.0% ± 3.3% for postnatal day 1 sham, P = .2198). Ejection fraction failed to recover after postnatal day 4 myocardial infarction (49.2% ± 1.8% vs 58.5% ± 5.8% for postnatal day 4 sham, P = .0109) and postnatal day 7 myocardial infarction (39.0% ± 7.8% vs 60.2% ± 5.0% for postnatal day 7 sham, P < .0001). At 3 weeks after infarction, fibrotic scar represented 5.3% ± 1.9%, 14.3% ± 4.9%, and 25.4% ± 13.3% of the left ventricle area in the postnatal day 1, postnatal day 4, and postnatal day 7 groups, respectively. An increased proportion of peri-infarct cardiomyocytes expressed Ki67 (15.9% ± 1.8% vs 10.2% ± 0.8%, P = .0039) and aurora B kinase (4.0% ± 0.9% vs 1.5% ± 0.6%, P = .0088) after postnatal day 1 myocardial infarction compared with sham, but no increase was observed after postnatal day 7 myocardial infarction., Conclusions: A neonatal leporine myocardial infarction model reveals that newborn rabbits are capable of age-dependent natural heart regeneration., (Copyright © 2021. Published by Elsevier Inc.)

Background: Patients who survive a myocardial infarction have progressive cardiac dysfunction and ventricular remodeling. Mitral regurgitation is often diagnosed in these patients, and is a risk factor that portends poor prognosis. Whether such postinfarction mitral regurgitation magnifies adverse left ventricular remodeling is unclear, which was studied in an animal model., Methods: Forty-one adult rats were induced with myocardial infarction using left coronary artery ligation and assigned to 3 groups: group 1, myocardial infarction only; group 2, myocardial infarction with severe mitral regurgitation introduced after 4 weeks; and group 3, myocardial infarction with severe mitral regurgitation introduced after 10 weeks. Valve regurgitation was introduced by advancing a transapical ultrasound-guided needle into the mitral valve anterior leaflet. Animals were survived to 20 weeks from the index procedure, with biweekly cardiac ultrasound, and invasive hemodynamics and histology at termination., Results: At 20 weeks, end diastolic volume was largest in the groups with mitral regurgitation, compared with the group without the valve lesion (group 1, 760.9 ± 124.6 μL; group 2, 958.0 ± 115.1 μL; group 3, 968.3 ± 214.9 μL). Similarly, end systolic volume was larger in groups with regurgitation (group 1, 431.2 ± 152.6 μL; group 2, 533.2 ± 130.8 μL; group 3, 533.1 ± 177.5 μL). In the infarction-only group, left ventricular remodeling was maximal until 6 weeks and plateaued thereafter. In groups with mitral regurgitation, left ventricular remodeling was significantly elevated at the onset of regurgitation and persisted., Conclusions: Mitral regurgitation is a potent driver of adverse cardiac remodeling after a myocardial infarction, irrespective of the timing of its onset., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Study Objective: To test whether the differences across sex and race in the treatment of and outcomes for ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) have changed over a recent decade., Methods: We conducted a retrospective analysis of patients with a diagnosis of STEMI or NSTEMI in California from 2005 to 2015 using the Office of State Health Planning and Development dataset. Using multivariable linear regression with county-fixed effects, we measured the baseline and change over time in the proportions of patients with STEMI or NSTEMI who underwent appropriately-timed coronary angiography (day of admission and within 3 days of admission, respectively) and survived at 1 year according to sex and race (Asian, Black, Hispanic, and White) and adjusting for comorbidities, payor, and hospital characteristics., Results: We analyzed 159,068 STEMI and 294,068 NSTEMI presentations. In 2005, 50.0% of 12,329 men and 35.7% of 6,939 women with STEMI and 45.0% of 14,379 men and 33.1% of 10,674 women with NSTEMI underwent timely angiography. In 2015, 76.7% of 6,257 men and 66.8% of 2,808 women with STEMI underwent timely angiography and 56.3% of 13,889 men and 45.9% of 9,334 women with NSTEMI underwent timely angiography. In 2005, 1-year survival was 82.3% for men and 69.6% for women after STEMI; in 2013, 1-year survival was 88.1% for men and 79.1% for women. In the multivariable model, the baseline difference was 1.1 percentage points (95% confidence interval [CI] 0.2 to 1.9), and survival increased for women compared with men by 0.3 percentage points per year (95% CI 0.2 to 0.5). In 2005, 46.0% (5,878) of 12,789 White patients and 31.2% (330) of 1,057 Black patients with STEMI underwent timely angiography; in 2015 75.2% of 3,928 White patients and 69.2% of 522 Black patients underwent timely angiography for STEMI. In the multivariable model, this difference was 6.4 percentage points at baseline (95% CI 4.5 to 8.3), and the probability of undergoing timely angiography for Black patients increased by 0.3 percentage points per year (95% CI -0.1 to 0.6)., Conclusion: Despite overall improvements in the treatment of and outcomes for STEMI and NSTEMI, disparities persist in the treatment of and outcomes for both the conditions, particularly for women., (Copyright © 2022 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Study Objective: Ventricular paced rhythm is thought to obscure the electrocardiographic diagnosis of acute coronary occlusion myocardial infarction. Our primary aim was to compare the sensitivity of the modified Sgarbossa criteria (MSC) to that of the original Sgarbossa criteria for the diagnosis of occlusion myocardial infarction in patients with ventricular paced rhythm., Methods: In this retrospective case-control investigation, we studied adult patients with ventricular paced rhythm and symptoms of acute coronary syndrome who presented in an emergency manner to 16 international cardiac referral centers between January 2008 and January 2018. The occlusion myocardial infarction group was defined angiographically as thrombolysis in myocardial infarction grade 0 to 1 flow or angiographic evidence of coronary thrombosis and peak cardiac troponin I ≥10.0 ng/mL or troponin T ≥1.0 ng/mL. There were 2 control groups: the "non-occlusion myocardial infarction-angio" group consisted of patients who underwent coronary angiography for presumed type I myocardial infarction but did not meet the definition of occlusion myocardial infarction; the "no occlusion myocardial infarction" control group consisted of randomly selected emergency department patients without occlusion myocardial infarction., Results: There were 59 occlusion myocardial infarction, 90 non-occlusion myocardial infarction-angio, and 102 no occlusion myocardial infarction subjects (mean age, 72.0 years; 168 [66.9%] men). For the diagnosis of occlusion myocardial infarction, the MSC were more sensitive than the original Sgarbossa criteria (sensitivity 81% [95% confidence interval [CI] 69 to 90] versus 56% [95% CI 42 to 69]). Adding concordant ST-depression in V4 to V6 to the MSC yielded 86% (95% CI 75 to 94) sensitivity. For the no occlusion myocardial infarction control group of ED patients, additional test characteristics of MSC and original Sgarbossa criteria, respectively, were as follows: specificity 96% (95% CI 90 to 99) versus 97% (95% CI 92 to 99); negative likelihood ratio (LR) 0.19 (95% CI 0.11 to 0.33) versus 0.45 (95% CI 0.34 to 0.65); and positive LR 21 (95% CI 7.9 to 55) versus 19 (95% CI 6.1 to 59). For the non-occlusion myocardial infarction-angio control group, additional test characteristics of MSC and original Sgarbossa criteria, respectively, were as follows: specificity 84% (95% CI 76 to 91) versus 90% (95% CI 82 to 95); negative LR 0.22 (95% CI 0.13 to 0.38) versus 0.49 (95% CI 0.35 to 0.66); and positive LR 5.2 (95% CI 3.2 to 8.6) versus 5.6 (95% CI 2.9 to 11)., Conclusion: For the diagnosis of occlusion myocardial infarction in the presence of ventricular paced rhythm, the MSC were more sensitive than the original Sgarbossa criteria; specificity was high for both rules. The MSC may contribute to clinical decisionmaking for patients with ventricular paced rhythm., (Copyright © 2021 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Myocardial infarction with nonobstructive coronary arteries (MINOCA) occurs when a patient presents with positive cardiac enzymes in the absence of obstructive atherosclerosis on coronary angiography. Several hypotheses for the pathogenesis of MINOCA have been suggested and multiple potential underlying etiologies have been reported. This review will outline the reported causes of MINOCA and associated major imaging features. In doing so, it will increase awareness of this entity and equip cardiac imagers with the knowledge to appropriately tailor imaging to make a prompt and accurate diagnosis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Sodium glucose cotransporter 2 (SGLT2) inhibitors are established antidiabetic drugs with proven cardiovascular benefit. Although growing evidence suggests beneficial effects on myocardial remodeling, fluid balance and cardiac function, the impact of empagliflozin initiated early after acute myocardial infarction (AMI) has not been investigated yet. Therefore, the impact of EMpagliflozin on cardiac function and biomarkers of heart failure in patients with acute MYocardial infarction (EMMY) trial was designed to investigate the efficacy and safety of empagliflozin in diabetic and non-diabetic patients after severe AMI., Methods: Within a multicenter, randomized, double-blind, placebo-controlled, phase 3b trial we will enroll patients with AMI and characteristics suggestive of severe myocardial necrosis are randomized in a 1:1 ratio to empagliflozin (10 mg once daily) or matching placebo. The primary endpoint is the impact of empagliflozin on changes in NT-proBNP within 6 months after AMI. Secondary endpoints include changes in echocardiographic parameters, levels of ketone body concentrations, HbA1c levels and body weight, respectively. Hospitalization rate due to heart failure or other causes, the duration of hospital stay and all-cause mortality will be assessed as exploratory secondary endpoints., Discussion: The EMMY trial will test empagliflozin in patients with AMI regardless of their diabetic status. The EMMY trial may therefore underpin the concept of SGLT2 inhibition to improve cardiac remodeling, pre-and afterload reduction and cardiac metabolism regardless of its antidiabetic effects. Results will provide the rationale for the conduct of a cardiovascular outcome trial to test the effect of empagliflozin in patients with AMI., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Elevated troponin level findings among patients presenting with suspected acute coronary syndrome (ACS) or another intercurrent illness undeniably identifies patients at increased risk of mortality. Whilst enhancing our capacity to discriminate risk, the use of high-sensitivity troponin assays frequently identifies patients with myocardial injury (i.e. troponin rise without acute signs of myocardial ischemia) or type 2 myocardial infarction (T2MI; oxygen supply-demand imbalance). This leads to the clinically challenging task of distinguishing type 1 myocardial infarction (T1MI; coronary plaque rupture) from myocardial injury and T2MI in the context of concurrent acute illness. Diagnostic discernment in this context is crucial because MI classification has implications for further investigation and care. Early invasive management is of well-established benefit among patients with T1MI. However, the appropriateness of this investigation in the heterogeneous context of T2MI, where there is high competing mortality risk, remains unknown. Although coronary angiography in T2MI is advocated by some, there is insufficient evidence in existing literature to support this opinion as highlighted by current national guidelines., Objective: The objective is to evaluate the clinical and economic impact of early invasive management with coronary angiography in T2MI in terms of all-cause mortality and cost effectiveness., Design: This prospective, pragmatic, multicenter, randomized trial among patients with suspected supply demand ischemia leading to troponin elevation (n=1,800; T2MI [1,500], chronic myocardial injury [300]) compares the impact of invasive angiography (or computed tomography angiography as per local preference) within 5 days of randomization versus conservative management (with or without functional testing at clinician discretion) on all-cause mortality by 2 years. Randomized treatment allocation will be stratified by baseline estimated risk of mortality using the Acute Physiology, Age, and Chronic Health Evaluation (APACHE) III risk score. Cost-effectiveness will be evaluated by follow-up on clinical events, quality of life, and resource utilization over 24 months., Summary: Ascertaining the most appropriate first-line investigative strategy for these commonly encountered high-risk T2MI patients in a randomized comparative study will be pivotal in informing evidence-based guidelines that lead to better patient and health care outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Ischemic mitral regurgitation (IMR) results from ischemic left ventricular (LV) distortion and remodeling, which displaces the papillary muscles and tethers the mitral valve leaflets apically. The aim of this experimental study was to examine efficacy of an adjustable novel polymer filled mesh (poly-mesh) device to reverse LV remodeling and reduce IMR., Methods: Acute (N = 8) and chronic (8 weeks; N = 5) sheep models of IMR were studied. IMR was produced by ligation of circumflex branches to create myocardial infarction. An adjustable poly-mesh device was attached to infarcted myocardium in acute and chronic IMR models and compared with untreated sham sheep. Two- and 3-dimensional echocardiography and hemodynamic measurements were performed at baseline, post IMR, and post poly-mesh (humanely killed)., Results: In acute models, moderate IMR developed in all sheep and decreased to trace/mild (vena contracta: 0.50 ± 0.09 cm to 0.26 ± 0.12 cm; P < .01) after poly-mesh. In chronic models, IMR decreased in all sheep after poly-mesh, and this reduction persisted over 8 weeks (vena contracta: 0.42 ± 0.09 cm to 0.08 ± 0.12 cm; P < .01) with significant increase in the slope of end-systolic pressure-volume relationship (1.1 ± 0.5 mm Hg/mL to 2.9 ± 0.7 mm Hg/mL; P < .05). There was a significant reduction in LV volumes from chronic IMR to euthanasia stage with poly-mesh compared with sham group (%end-diastolic volume change -20 ± 11 vs 15% ± 16%, P < .01; %end-systolic volume change -14% ± 19% vs 22% ± 22%, P < .05; poly-mesh vs sham group) consistent with reverse remodeling., Conclusions: An adjustable polymer filled mesh device reduces IMR and prevents continued LV remodeling during chronic follow-up., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Coronary artery disease (CAD) remains a significant cause of morbidity and mortality around the world. Patients with stable CAD can have an unpredictable clinical trajectory; thus, additional tools to prognosticate risk in this cohort are warranted. In recent years, a wide range of biomarkers has been recognized for their diagnostic capabilities in patients with stable CAD, identifying those with obstructive disease who may require more intensive preventive therapies or even consideration of percutaneous coronary intervention in some circumstances. In addition, a multiple-biomarker approach may identify stable CAD patients at highest risk for future major adverse cardiac events. Thus, randomized controlled trials to assess biomarker-guided preventive therapy in this cohort appear warranted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Although several preclinical studies have shown that bone marrow cell (BMC) transplantation promotes cardiac recovery after myocardial infarction, clinical trials with unfractionated bone marrow have shown variable improvements in cardiac function., Methods: To determine whether in a population of post-myocardial infarction patients, functional recovery after BM transplant is associated with specific BMC subpopulation, we examined the association between BMCs with left ventricular (LV) function in the LateTIME-CCTRN trial., Results: In this population, we found that older individuals had higher numbers of BM CD133(+) and CD3(+) cells. Bone marrow from individuals with high body mass index had lower CD45(dim)/CD11b(dim) levels, whereas those with hypertension and higher C-reactive protein levels had higher numbers of CD133(+) cells. Smoking was associated with higher levels of CD133(+)/CD34(+)/VEGFR2(+) cells and lower levels of CD3(+) cells. Adjusted multivariate analysis indicated that CD11b(dim) cells were negatively associated with changes in LV ejection fraction and wall motion in both the infarct and border zones. Change in LV ejection fraction was positively associated with CD133(+), CD34(+), and CD45(+)/CXCR4(dim) cells as well as faster BMC growth rates in endothelial colony forming assays., Conclusions: In the LateTIME population, BM composition varied with patient characteristics and treatment. Irrespective of cell therapy, recovery of LV function was greater in patients with greater BM abundance of CD133(+) and CD34(+) cells and worse in those with higher levels of CD11b(dim) cells. Bone marrow phenotype might predict clinical response before BMC therapy and administration of selected BM constituents could potentially improve outcomes of other future clinical trials., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Adherence to guideline-based therapy improves patient outcomes after acute myocardial infarction (AMI) and hospital AMI volume is associated with reperfusion care, but the extent hospital AMI volume is associated with overall guideline adherence is unclear., Methods and Results: We studied 486 hospitals treating 249,877 AMI patients in ACTION Registry-GWTG from January 1, 2007, to March 31, 2011. Hospital adherence to each American College of Cardiology/American Heart Association performance measure was compared between tertiles defined by hospital AMI volume: low (≤108 cases/y), middle (≥109 and ≤227 cases/y), and high (≥228 cases/y). Multivariable logistic regression, adjusting for patient and hospital characteristics, was used to examine the association between annual AMI volume and adherence to each measure. Similar modeling was used to evaluate the relationship between AMI volume and in-hospital mortality. Compared with high-volume hospitals, lower-volume hospitals were less likely to be academically affiliated, or to have cardiac surgery capabilities, electronic health records, or dedicated tobacco treatment services. Higher-volume hospitals had greater adherence to each performance measure, except aspirin use at arrival and reperfusion therapy. The greatest difference was in the rates of referral to cardiac rehabilitation (59%, 76%, and 83% in low-, middle-, and high-volume hospitals, respectively). After multivariable adjustment, higher AMI volume (up to 400 AMI patients/y) remained associated with higher-performance measure adherence. There was no association between AMI volume and in-hospital mortality after adjusting for patient and hospital characteristics., Conclusions: Higher hospital AMI volume was correlated with better adherence to process of care measures, but not in-hospital mortality., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Management of patients with acute chest pain remains challenging. Cardiac biomarker testing reduces the likelihood of erroneously discharging patients with acute myocardial infarction (AMI). Despite normal contemporary troponins, physicians have still been reluctant to discharge patients without additional testing. Nowadays, the extremely high negative predictive value of current high-sensitivity cardiac troponin (hs-cTn) assays challenges this need. However, the decreased specificity of hs-cTn assays to diagnose AMI poses a new problem as noncoronary diseases (eg, pulmonary embolism, myocarditis, cardiomyopathies, hypertension, renal failure, etc) may also cause elevated hs-cTn levels. Subjecting patients with noncoronary diseases to unnecessary pharmacological therapy or invasive procedures must be prevented. Attempts to improve the positive predictive value to diagnose AMI by defining higher initial cutoff values or dynamic changes over time inherently lower the sensitivity of troponin assays. In this review, we anticipate a potential changing role of noninvasive imaging from ruling out myocardial disease when troponin values are normal toward characterizing myocardial disease when hs-cTn values are (mildly) abnormal., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Objective: Three large, multicenter, randomized, clinical trials have shown that coronary computed tomography (CT) angiography allows efficient evaluation and safe discharge of patients with low- to intermediate-risk chest pain who present to the emergency department (ED). We report 1-year event rates and resource use from the American College of Radiology Imaging Network-Pennsylvania 4005 multicenter trial., Methods: Patients with low- to intermediate-risk chest pain and presenting to the ED were randomized in a 2:1 ratio to a coronary CT angiography care pathway or traditional care. Subjects were contacted by telephone at least 1 year after ED presentation. Medical record review was performed for all cardiac hospitalizations, procedures and diagnostic tests, and adverse cardiac events. Our main outcome was the composite of cardiac death and myocardial infarction within 1 year. The secondary outcome was resource use., Results: One thousand three hundred sixty-eight patients enrolled and 1,285 (94%) had direct participant or proxy contact at 1 year. All others had record review or death index search. From index presentation through 1 year, there was no difference between patients in the coronary CT angiography arm versus traditional care with respect to major adverse cardiac event (1.4% versus 1.1%; difference 0.3%; 95% CI -5.5% to 6.0%). From hospital discharge through 1 year, there was also no difference in ED revisits (36% versus 38%; difference -2.1%; 95% CI -7.9% to 3.7%), hospital admissions (16% versus 17%; difference -0.9%; 95% CI -6.7% to 4.9%), or subsequent cardiac testing (13% versus 13%; difference -0.4%; 95% CI -6.2% to 5.5%). One of 640 subjects with a negative coronary CT angiography result had a major adverse cardiac event within 1 year of presentation (0.16%; 95% CI 0.004% to 0.87%)., Conclusion: A coronary CT angiography-based strategy for evaluation of patients with low- to intermediate-risk chest pain who present to the ED does not result in increased resource use during 1 year. A negative coronary CT angiography result is associated with a less than 1% major adverse cardiac event rate during the first year after testing., (Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Among patients presenting with ST-segment elevation myocardial infarction (STEMI) for primary percutaneous coronary intervention (PCI), the associations between clinical outcomes and both baseline renal function and the development of acute kidney injury (AKI) have not been reported in a trial population with unselected baseline renal function., Methods: Patients enrolled in the APEX-AMI trial who underwent primary PCI for the treatment of STEMI were categorized according to (a) baseline renal function and (b) the development of AKI. Patient characteristics, clinical outcomes, and treatment patterns were analyzed according to baseline renal function and the development of AKI. A prediction model for AKI after primary PCI for STEMI was also developed., Results: A total of 5,244 patients were included in this analysis and stratified according to baseline estimated glomerular filtration rate (eGFR) (milliliters per minute per 1.73 m(2)) of >90, 60 to 90, 30 to 59, or <30 or as dialysis dependent. Patients with lower eGFR were older, more often female, and less often treated with evidence-based medicines and had worse angiographic outcomes and higher mortality. The rates of AKI for patients with a baseline eGFR of >90, 60 to 90, 30 to 59, and <30 were 2.5%, 4.1%, 8.1%, and 1.6%, respectively (P < .0001). The strongest predictors of AKI were age and presenting in Killip class III or IV., Conclusions: Among patients undergoing primary PCI for STEMI, impaired renal function at presentation and development of post-PCI AKI were highly associated with worse clinical and angiographic outcomes, including death. The risk of developing AKI was low and only modestly associated with baseline renal function., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Adequate hydration is recommended for acute ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) to prevent contrast-induced nephropathy (CIN). However, the optimal hydration regimen has not been well established in these high-risk patients. The objective of this study is to evaluate the efficacy of a preprocedural loading dose plus postprocedural aggressive hydration with normal saline guided by the left ventricular end-diastolic pressure (LVEDP) compared with general hydration for CIN prevention. The ATTEMPT study is a multicenter, open-label, investigator-driven, randomized controlled trial in China. Approximately 560 patients with STEMI undergoing primary PCI will be randomized (1:1) to receive either periprocedural general hydration (control group) or aggressive hydration (treatment group). Patients in the control group receive periprocedural general hydration with ≤500 mL normal saline (within 6 hours) at a normal rate (0.5 or 1 mL/kg · h). Patients in the treatment group receive a preprocedural loading dose (125/250 mL) of normal saline within 30 minutes and intravenous hydration at a normal rate until LVEDP is available, followed by postprocedural aggressive hydration guided by LVEDP for 4 hours and then continuous intravascular hydration at the normal rate until 24 hours after PCI. The primary end point is CIN, defined as a >25% or 0.5-mg/dL increase in serum creatinine from baseline during the first 48 to 72 hours after procedure. The ATTEMPT study has the potential to identify optimal hydration regimens for STEMI patients undergoing PCI., (Copyright © 2015. Published by Elsevier Inc.)

Background: Acute kidney injury (AKI) is a well-recognized predictor of morbidity and mortality after percutaneous coronary intervention. However, the impact of AKI on the outcome of patients with acute coronary syndromes (ACS) in relation to coronary artery bypass grafting (CABG) has not been established., Methods: Of the 17,421 patients who presented with non-ST-segment elevation ACS or ST-segment elevation myocardial infarction enrolled in the ACUITY and HORIZONS-AMI trials, 1,406 (8.0%) underwent CABG as principal treatment after coronary angiography. End points were measured at 1 month and 1 year and included death, myocardial infarction, and ischemia-driven target vessel revascularization. Acute kidney injury was defined as a rise in creatinine of ≥ 0.5 mg/dL, or > 25%, from baseline at initial angiography., Results: Acute kidney injury occurred during hospital admission in 449 (31.9%) of the 1,406 patients treated with CABG. One-month and 1-year mortality was 6.7% vs 2.2% (P < .0001) and 10.4% vs 4.3% (P < .0001) for patients with vs without AKI, respectively. Analogously, the 1-month and 1-year incidence of composite major adverse cardiac events (MACEs; death, MI, or target vessel revascularization) was 17.6% vs 12.4% (P = .003) and 22.0% vs 15.3% (P = .002) for patients with vs without AKI, respectively. After adjustment for age, sex, race, diabetes, hypertension, and baseline creatinine clearance, AKI was an independent predictor of mortality (overall and cardiac-related) and MACE at both 1 month and 1 year in patients treated with CABG., Conclusions: Acute kidney injury occurred in approximately 1 of every 3 patients with ACS treated with CABG and is a powerful independent predictor of death and MACE. These data highlight the need for AKI prevention strategies in patients undergoing CABG., (Copyright © 2015. Published by Elsevier Inc.)

Background: In the SAFE-PCI for Women trial, patient preference for radial access for future procedures was greater than for femoral access. We sought to assess whether radial or femoral access impacts formal measures of quality-of-life (QOL) among women undergoing cardiac catheterization., Methods: We assessed QOL using European quality of life-5 dimensions (EQ-5D) and EQ visual analog scale (EQ-VAS) scores among 304 women randomized to radial or femoral arteriotomy in the SAFE-PCI for Women trial at sites with QOL substudy approval. Patient surveys were administered at baseline, hospital discharge, and 30 days (for percutaneous coronary intervention patients)., Results: Women randomized to both treatments had similar EQ-5D index and EQ-VAS scores at baseline, hospital discharge, and 30-day follow-up. After adjustment for baseline scores, there was no effect of assigned treatment on EQ-5D (discharge 0.004; 95% CI -0.03 to 0.04; 30 days -0.03; 95% CI -0.09 to 0.02) or EQ-VAS (discharge -1.31; 95% CI -4.74 to 2.12; 30 days -2.10; 95% CI -8.92 to 4.71) scores. At discharge, 60.5% versus 63.5% (P = .60) of patients in radial and femoral groups were free from access site pain; at 30 days, rates were 85.7% versus 77.6% (P = .30), respectively. Patient preference for the same access strategy for repeat procedures was greater in the radial versus femoral group (77.2% vs 26.8%; P < .0001)., Conclusions: Using established QOL instruments, we did not measure any difference in QOL or functional status according to access site strategy in women undergoing cardiac catheterization, yet patient preference for the radial approach was significantly greater. Other factors influencing patient choice for radial access should be investigated., (Published by Elsevier Inc.)

Background: Elderly patients with ST-segment elevation myocardial infarction (STEMI) have worse outcomes and a greater risk of intracranial bleeding than nonelderly patients. Baseline characteristics, clinical outcomes, and the relationship of the tenecteplase (TNK) dose reduction to the efficacy, safety, and electrocardiographic indicators of reperfusion efficacy were evaluated in STEMI patients ≥75 years., Methods: The STREAM trial evaluated early presenting STEMI patients who could not undergo primary percutaneous coronary intervention within 1 hour of first medical contact. Because of excess intracranial hemorrhage (ICH) in patients ≥75 years, the dose of TNK was reduced by 50%., Results: Before dose amendment, there were 3 (7.1%) of 42 elderly patients with ICH; 2 of these were fatal, whereas no ICH occurred in the 93 elderly patients who received half-dose TNK postamendment. The median extent of ST-segment elevation resolution (≥50%) and proportion of patients with ≥2 mm in the electrocardiogram lead with greatest ST-segment elevation was comparable in elderly patients preamendment and postamendment (63.2% vs 56.0% and 43.6% vs 40.0%, respectively). Patients requiring rescue coronary intervention after TNK was also similar (42.9% vs 44.1%). The primary composite end point (30-day all-cause death, cardiogenic shock, congestive heart failure, and reinfarction) was 31.0% before versus 24.7% postamendment., Conclusions: Our data, from a modest-sized population of elderly STEMI patients, indicate that half-dose TNK reduces the likelihood of ICH without compromising reperfusion efficacy. These observations are hypothesis generating and warrant further confirmation in randomized clinical trials in the elderly., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The incremental prognostic value of admission measurements of biomarkers beyond clinical characteristics and extent of coronary artery disease (CAD) in patients treated with primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) is unclear., Methods: Centrally analyzed plasma for biomarker measurements was available in 5,385 of the STEMI patients treated with PPCI in the PLATO trial. Extent of CAD was graded by operators in association with PPCI. We evaluated the prognostic value of high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and growth differentiation factor 15 (GDF-15) beyond clinical characteristics and extent of CAD using Cox proportional hazards analyses, C-index, and net reclassification improvement (NRI). Outcomes were cardiovascular death (CVD) and spontaneous myocardial infarction (MI)., Results: Angiographic data on extent of CAD improved the prediction of CVD compared to clinical risk factors alone, increasing the C-index from 0.760 to 0.778, total NRI of 0.31. Biomarker information provided additional prognostic value for CVD beyond clinical risk factors and extent of CAD, C-indices ranging from 0.792 to 0.795 for all biomarkers, but with a higher NRI for NT-proBNP. Extent of CAD and high-sensitivity cardiac troponin T were not associated with spontaneous MI. The prediction of spontaneous MI beyond clinical characteristics and extent of CAD (C-index 0.647) was improved by both NT-proBNP (C-index 0.663, NRI 0.22) and GDF-15 (C-index 0.652, NRI 0.05)., Conclusions: Biomarker measurement on admission is feasible and provides incremental risk stratification in patients with STEMI treated with PPCI, with NT-proBNP and GDF-15 being most valuable due to the association with both CVD and spontaneous MI., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Sensitive troponin (Tn) assays have been developed for the evaluation of patients with suspected acute coronary syndrome (ACS). We sought to compare the performance of a commercially available sensitive Tn I (sTnI) and precommercial highly sTnI (hsTnI) method to conventional Tn (cTn) assays., Methods: Among patients with acute chest pain but normal cTn in the emergency department of 6 centers, sTnI and hsTnI were measured at baseline, 2 and 4 hours after presentation. Diagnostic accuracy of sTnI and hsTnI relative to cTn for diagnosis during index hospitalization as well as their associations with coronary artery disease in patients randomized to coronary computed tomographic angiography (CTA) was assessed., Results: Overall, 322 patients were enrolled, of whom 161 had a CTA; 28 had ACS (8.7%), including 21 with unstable angina pectoris (UAP). Both sTnI and hsTnI values at baseline and second draw had significantly higher sensitivity for ACS and UAP than cTn and had significantly greater area under the receiver operator characteristic curve than cTn at first and second draws. Compared with cTn, 29% of ACS cases previously categorized as UAP were reclassified to acute myocardial infarction with sTnI or hsTnI. An hsTnI below limit of detection had 100% negative predictive value for ACS or significant coronary artery stenosis in those randomized to CTA., Conclusions: In patients with acute chest discomfort, use of sTnI and hsTnI methods led to significant improvement in the early diagnostic accuracy for ACS, reclassifying one-third of UAP to myocardial infarction. Very low values for hsTnI excluded underlying coronary artery disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: In patients with acute non-ST-elevation myocardial infarction (NSTEMI), coronary arteriography is usually recommended; but visual interpretation of the angiogram is subjective. We hypothesized that functional assessment of coronary stenosis severity with a pressure-sensitive guide wire (fractional flow reserve [FFR]) would have additive diagnostic, clinical, and health economic utility as compared with angiography-guided standard care., Methods and Design: A prospective multicenter parallel-group 1:1 randomized controlled superiority trial in 350 NSTEMI patients with ≥1 coronary stenosis ≥30% severity (threshold for FFR measurement) will be conducted. Patients will be randomized immediately after coronary angiography to the FFR-guided group or angiography-guided group. All patients will then undergo FFR measurement in all vessels with a coronary stenosis ≥30% severity including culprit and nonculprit lesions. Fractional flow reserve will be disclosed to guide treatment in the FFR-guided group but not disclosed in the "angiography-guided" group. In the FFR-guided group, an FFR ≤0.80 will be an indication for revascularization by percutaneous coronary intervention or coronary artery bypass surgery, as appropriate. The primary outcome is the between-group difference in the proportion of patients allocated to medical management only compared with revascularization. Secondary outcomes include the occurrence of cardiac death or hospitalization for myocardial infarction or heart failure, quality of life, and health care costs. The minimum and average follow-up periods for the primary analysis are 6 and 18 months, respectively., Conclusions: Our developmental clinical trial will address the feasibility of FFR measurement in NSTEMI and the influence of FFR disclosure on treatment decisions and health and economic outcomes., (© 2013.)

Background: In patients with ST-elevation myocardial infarction (STEMI) and multivessel disease, guidelines recommend infarct-related artery (IRA) only intervention during primary percutaneous coronary intervention (PCI) except in patients with hemodynamic instability. To assess the available evidence, we performed a systematic review and meta-analysis comparing outcomes of non-IRA PCI as an adjunct to primary PCI (same sitting PCI [SS-PCI]) with IRA only PCI (IRA-PCI) in the setting of STEMI., Methods and Results: A comprehensive search identified 14 studies [11 cohort, 3 randomized controlled trials] comprising of 35,239 patients. For cohort studies, patients undergoing SS-PCI had higher rate of anterior infarction (48% vs. 45%, P = .04) and cardiogenic shock (11% vs. 9%, P = .0001) at baseline compared with IRA-PCI. The primary composite end point of death, myocardial infarction and revascularization was higher in the SS-PCI group in the short term (OR, 1.63; CI, 1.12-2.37) and long term (OR, 1.60; CI, 1.18-2.16). However, after excluding patients with shock, there was no difference in primary endpoint for the short (OR, 1.33; CI, 0.67-2.63) and long term (OR, 1.39; CI, 0.80-2.42) follow-up. In analyses limited to randomized controlled trials, primary end point was similar during short term (OR, 0.79; CI, 0.19-3.28) and significantly lower for SS-PCI group in the long term (OR, 0.55; CI, 0.34-0.91)., Conclusions: There is paucity of randomized data to guide management of STEMI patients with multivessel disease. SS-PCI group in cohort studies has higher baseline risk compared to IRA-PCI. The primary end point is higher for SS-PCI in observational cohort studies but this difference did not persist after exclusion of shock patients and for analysis limited to randomized controlled trials. These findings underscore the need of a large randomized controlled trial to guide therapy for a commonly encountered clinical situation., (© 2013.)

Background: In patients with acute ST-elevation myocardial infarction (STEMI) needing early coronary artery bypass graft (CABG) surgery, it is unknown whether primary percutaneous balloon angioplasty (PTCA)-without stent implantation-allows safe transition to subsequent CABG., Methods: We examined acute STEMI patients enrolled in the Stent-PAMI and CADILLAC trials to study the differences in the early clinical events between those treated with primary PTCA (n = 1494) or primary stenting (n = 1488)., Results: Baseline clinical and pre- and post-procedural angiographic features including post-intervention TIMI 3 flow rates were similar in the 2 groups with the exception of higher median infarct-artery residual stenosis in the PTCA group (26% [IQR 19%-34%] vs. 18% [IQR 11-25%], P < .001]. Provisional stenting was required in 16% of patients in PTCA group, while stents could not be implanted in 2% of the stent group. Sixty-percent of PTCA patients had stent-like balloon result. The rate of 30-day ischemia-driven target vessel revascularization was higher in the PTCA group (4.3% vs. 2.0%, P < .001 [4.6% vs 2.3%, P < .001 among patients with multivessel disease and 3.4% vs. 2.0%, P = .044 in patients with stent-like balloon results]) while 30-day major adverse cardiac events (6.2% vs 4.9%), death (1.8% versus 2.8%), and reinfarction (0.9% vs. 0.7%) were similar in the 2 groups., Conclusions: Compared with primary stenting, primary PTCA of infarct artery in STEMI patients was associated with significant increase in ischemia-driven target vessel revascularization (ITVR) rate, yet with no increased risk of major adverse cardiac events, reinfarction or death. Thus, provided close surveillance is maintained and prompt treatment initiated for early ischemic events, PTCA (particularly in those with stent-like balloon result) may be a reasonable and safe option in STEMI patients needing early CABG., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Stent deployment may be associated with distal embolization and slow flow in coronary thrombotic lesions. There are no data on the risk of distal thrombus embolization according to the stent design. The aim was to evaluate coronary flow after percutaneous coronary interventions (PCI) in acute myocardial infarction according to the employed stent (closed versus open cell design)., Methods: From March 2010 to December 2011, 223 consecutive patients with acute ST-elevation myocardial infarction were randomized to primary PCI either with an open cell (112 patients, 88 men) or with a closed cell stent design (111 patients, 92 men). The primary endpoint was the corrected TIMI frame count (cTFC) after the procedure., Results: There were no significant differences in procedural success nor in-stent deployment in the 2 groups. At baseline, there were no significant differences in cTFC between the 2 groups (70 ± 37 and 67 ± 39, P = .65, respectively). After the procedure, the open cell group showed significantly higher cTFC compared to the closed cell group (18 ± 11 and 15 ± 5, P = .003 respectively). This difference was associated with a significant lower rate of TIMI 3 flow (87% and 95%, P = .037) and myocardial blush grade 3 (65% and 87%, P = .001) in the open compared to the closed cell group. There were 2 cases of death in the open cell and 1 case in the closed cell group., Conclusions: The use of a closed cell stent design rather than an open cell during PCI for acute ST-elevation myocardial infarction is associated with better coronary angiographic flow after PCI., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: The biomechanical response to a myocardial infarction consists of ventricular remodeling that leads to dilatation, loss of contractile function, abnormal stress patterns, and ultimately heart failure. We hypothesized that intramyocardial injection of our previously designed pro-angiogenic chemokine, an engineered stromal cell-derived factor-1α analog (ESA), improves mechanical properties of the heart after infarction., Methods: Male rats (n = 54) underwent either sham surgery (n = 17) with no coronary artery ligation or ligation of the left anterior descending artery (n = 37). The rats in the myocardial infarction group were then randomized to receive either saline (0.1 mL, n = 18) or ESA (6 μg/kg, n = 19) injected into the myocardium at 4 predetermined spots around the border zone. Echocardiograms were performed preoperatively and before the terminal surgery. After 4 weeks, the hearts were explanted and longitudinally sectioned. Uniaxial tensile testing was completed using an Instron 5543 Microtester. Optical strain was evaluated using custom image acquisition software, Digi-Velpo, and analyzed in MATLAB., Results: Compared with the saline control group at 4 weeks, the ESA-injected hearts had a greater ejection fraction (71.8% ± 9.0% vs 55.3% ± 12.6%, P = .0004), smaller end-diastolic left ventricular internal dimension (0.686 ± 0.110 cm vs 0.763 ± 0.160 cm, P = .04), greater cardiac output (36 ± 11.6 mL/min vs 26.9 ± 7.3 mL/min, P = .05), and a lower tensile modulus (251 ± 56 kPa vs 301 ± 81 kPa, P = .04). The tensile modulus for the sham group was 195 ± 56 kPa, indicating ESA injection results in a less stiff ventricle., Conclusions: Direct injection of ESA alters the biomechanical response to myocardial infarction, improving the mechanical properties in the postinfarct heart., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: After an acute myocardial infarction (AMI), early coronary revascularization alleviates the synthesis of cardiac collagen and ventricular remodeling. However, the impact of late coronary revascularization on the synthesis of myocardial collagen or on serum collagen biomarkers is unknown. This study aimed to investigate the effects of late coronary revascularization on serum collagen biomarkers after AMI., Methods: Forty-five patients were divided into early (n = 20) and late (n = 25) coronary revascularization groups. The early coronary revascularization group received either successful percutaneous coronary intervention (PCI) or thrombolytic therapy within 6 hours of their myocardial infarction (MI), whereas the late PCI group received PCI between 12 and 14 days after their MI. Serum type I procollagen (PICP) and type III procollagen (PIIINP) were measured by radioimmunoassay., Results: In the early coronary revascularization group, the amount of serum PICP on days 60 and 180 was similar to that of week 1 (P > .05). The PICP on days 90 and 180 in the late coronary revascularization group was higher than in the early coronary revascularization group at the same time point (P < .05). No significant difference was evident in mean serum PIIINP between the two groups on day 60 or 180 after the MI (P < .05)., Conclusion: Late coronary revascularization in patients with acute ST-elevation MI was associated with an elevation in serum PICP. Early coronary revascularization should be performed in patients with ST-elevation, to alleviate myocardial remodeling., (Crown Copyright © 2012. Published by Mosby, Inc. All rights reserved.)

Background: Compared to troponin alone, a dual-marker strategy with natriuretic peptides may improve acute coronary syndrome (ACS) diagnosis with a single blood draw and provide physiologic information regarding underlying heart disease. We evaluate the value of adding natriuretic peptides (myocyte stress markers) to troponins (myocardial injury markers) for diagnosing ACS in emergency department patients with chest pain., Methods: In 328 patients (53 ± 12 years, 63% men) with an initially negative conventional troponin and nonischemic electrocardiogram who underwent 64-slice cardiac computed tomography (CT), we measured conventional troponin-T (cTnT), high-sensitivity troponin-T (hsTnT), N-terminal pro-B type natriuretic peptide, and mid-regional pro-atrial natriuretic peptide. ACS was defined as myocardial infarction or unstable angina. CT was evaluated for coronary plaque, stenosis, and regional wall motion abnormality., Results: Patients with ACS (n = 29, 9%) had higher concentrations of each biomarker compared to those without (all P < .01). Adding natriuretic peptides, especially N-terminal pro-B type natriuretic peptide, to both cTnT or hsTnT improved the C-statistics and net reclassification index for ACS, largely driven by correctly reclassifying events. Dual-negative marker results improved sensitivity (cTnT 38% to 83%-86%, hsTnT 59% to 86%-90%; all P < .01) and negative predictive value (cTnT 94% to 97%-98%, hsTnT 96% to 97%-98%) for ACS. Patients with dual-negative markers had the lowest percentage of CT coronary plaque, stenosis, and regional wall motion abnormality (all P-trend <.001)., Conclusion: Among emergency department patients with low-intermediate likelihood of ACS, combining natriuretic peptides with either conventional or highly-sensitive troponin improved discriminatory capacity and allowed for better reclassification of ACS, findings supported by structural and functional CT results., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: Information on practice patterns and outcomes in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary interventions (PCIs) in Canada vs United States is limited., Methods: We evaluated differences in clinical and angiographic features, practice patterns, and outcomes between Canada and United States in 2,086 patients with ST-elevation myocardial infarction undergoing primary PCI in the APEX AMI trial., Results: Of 2,086 patients, 335 (19%) were enrolled in Canada. Compared with US patients, Canadians were older with lower body mass index and creatinine clearance and less likely to have history of hypertension, smoking, or prior revascularization. Baseline infarct artery patency was higher, and the use of intra-aortic balloon pump and drug-eluting stents was lower in Canadian patients. Median door-to-PCI time was significantly shorter among Canadian patients (0.9 hours [interquartile range 0.6-1.3] vs 1.2 hours [interquartile range 0.8-1.7]). Clinical outcomes at 90 days were lower among Canadian patients, including shock (2.7% vs 4.2%), heart failure (3.6% vs 5.6%), bleeding (3.6% vs 9.6%), and atrial (3.6% vs 7.4%) and ventricular (3.0% vs 6.4%) arrhythmias. However, 90-day mortality (2.7% vs 4.8%, adjusted hazard ratio 0.62, 95% CI 0.47-1.28) and composite of death, shock, or heart failure (6.8% vs 11.5%, adjusted hazard ratio 0.77, 95% CI 0.47-1.27) were similar in the 2 cohorts., Conclusions: Compared with US patients, Canadian patients had shorter door-to-PCI time but similar 90-day outcomes. These data suggest an opportunity for US sites to examine and learn from the Canadian systems of processes of care and implement changes so as to improve the timeliness of primary PCI., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: Acute myocardial infarction (AMI) may contribute to health status declines including "independence loss" and "physical function decline." Despite the importance of these outcomes for prognosis and quality of life, their incidence and predictors have not been well described., Methods: We studied 2,002 patients with AMI enrolled across 24 sites in the TRIUMPH registry who completed assessments of independence and physical function at the time of AMI and 1 year later. Independence was evaluated by the EuroQol-5D (mobility, self-care, and usual activities), and physical function was assessed with the Short Form-12 physical component score. Declines in ≥1 level on EuroQol-5D and >5 points in PCS were considered clinically significant changes. Hierarchical, multivariable, modified Poisson regression models accounting for within-site variability were used to identify predictors of independence loss and physical function decline., Results: One-year post AMI, 43.0% of patients experienced health status declines: 12.8% independence loss alone, 15.2% physical function decline alone, and 15.0% both. After adjustment, variables that predicted independence loss included female sex, nonwhite race, unmarried status, uninsured status, end-stage renal disease, and depression. Variables that predicted physical function decline were uninsured status, lack of cardiac rehabilitation referral, and absence of pre-AMI angina. Age was not predictive of either outcome after adjustment., Conclusions: >40% of patients experience independence loss or physical function decline 1 year after AMI. These changes are distinct but can occur simultaneously. Although some risk factors are not modifiable, others suggest potential targets for strategies to preserve patients' health status., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objectives: The aim of this study was to assess the feasibility, safety, and preliminary efficacy of a novel percutaneous left ventricular partitioning device (VPD) in patients with chronic heart failure (HF) and a prior anterior myocardial infarction., Background: Anterior myocardial infarction is frequently followed by left ventricular remodeling, HF, and increased long-term morbidity and mortality., Methods: Thirty-nine patients were enrolled in a multinational, nonrandomized, longitudinal investigation. The primary end point was an assessment of safety, defined as the successful delivery and deployment of the VPD and absence of device-related major adverse cardiac events over 6 months. Secondary (exploratory) efficacy end points included changes in hemodynamics and functional status and were assessed serially throughout the study., Results: Ventricular partitioning device placement was not attempted in 5 (13%) of 39 subjects. The device was safely and successfully implanted in 31 (91%) of the remaining 34 patients or 79% of all enrolled patients. The 6-month rate of device-related major adverse cardiac event occurred in 5 (13%) of 39 enrolled subjects and 5 (15%) of 34 treated subjects, with 1 additional event occurring between 6 and 12 months. For patients discharged with the device to 12 months (n = 28), New York Heart Association class (2.5 ± 0.6 to 1.3 ± 0.6, P < .001) and quality-of-life scores (38.6 ± 6.1 to 28.4 ± 4.4, P < .002) improved significantly; however, the 6-minute hall walk distance (358.5 ± 20.4 m to 374.7 ± 25.6 m, P nonsignificant) only trended toward improvement., Conclusions: The left VPD appears to be relatively safe and potentially effective in the treatment for patients with HF and a prior anterior myocardial infarction. However, these limited results suggest the need for further evaluation in a larger randomized controlled trial., (Copyright © 2012 Mosby, Inc. All rights reserved.)

A 23-year-old man with no history of heart disease was admitted to Beijing Anzhen Hospital Affiliated to Capital Medical University for an abnormal electrocardiogram of ST-T changes mimicking myocardial infarction. Catheterization revealed normal coronary and peripheral arteries. The echocardiogram and delayed enhancement cardiovascular magnetic resonance imaging indicated a markedly reduced left ventricular function and enlarged left ventricular cavity with evidence of fibrous tissue. Given the patient's history of multiple blunt trauma 7 years previously and acute myocardial infarction diagnosis at that time, he was diagnosed with traumatic myocardial infarction (TMI). We describe the natural course of such a patient with TMI. There is a possibility of spontaneous healing of coronary artery dissection induced by trauma. Although early revascularization may be helpful for preventing cardiac remodeling after TMI in some cases, more data are needed to compare the long-term outcome among different interventions in large sample cases., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The assumption that atherosclerosis accumulates in the proximal coronary arteries and that distal segments are spared has yet to be systematically shown in vivo., Methods: We used intravascular ultrasound to analyze complete proximal, mid, and distal segments from 75 diseased left anterior descending arteries (LADs) and 61 diseased right coronary arteries (RCAs) (including either the posterolateral [PLA; n = 38] or posterior descending artery [PDA; n = 23]) to document that distal coronary arteries are more often free of disease vs proximal vessels. External elastic membrane, lumen, and plaque and media areas were measured every 0.4 mm (median), and plaque burden (plaque and media/external elastic membrane) and percentage of normal (plaque and media thickness <0.3 mm) cross sections/segment were determined., Results: Left anterior descending artery plaque was heaviest in proximal and mid segments, diminishing significantly in distal segments; plaque burden was 46% ± 9% in proximal, 39% ± 8% in mid, and 31% ± 9% in distal LAD (P < .0001), with 93% (median) of distal LAD cross sections being normal compared with 21% of mid and 0% of proximal cross sections (P < .0001). Right coronary artery plaque gradient was less pronounced vs the LAD; plaque burden was 37% ± 13% in proximal, 40% ± 10% in mid, and 36% ± 10% in distal RCA, followed by 31% ± 11% in PDA and 33% ± 10% in PLA. This was supported by the median percentage of normal cross sections/segment: 0% proximal, 0% mid, and 23% distal RCA sections plus 100% PDA and 48% PLA sections., Conclusions: Intravascular ultrasound data indicated a proximal-to-distal LAD plaque gradient; significant disease was uncommon in the distal LAD. Conversely, the proximal-to-distal RCA plaque gradient was less distinct than the LAD, although disease in the PDA was still reduced compared with proximal segments., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Transporting patients with an ST segment elevation myocardial infarction (STEMI) is a fairly common practice for most critical care transport teams. When a STEMI is complicated by ventricular septal rupture, the care can become more challenging, especially if the rupture is not yet diagnosed. This article describes such a transport and reviews the pathophysiology of the process along with treatment options., (Copyright © 2012 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.)

Aims: The mechanisms responsible for the increased risk of heart failure (HF) post-myocardial infarction (MI) may differ between patients with versus without diabetes. We hypothesized that after high-risk MI, patients with diabetes would demonstrate patterns of remodeling that are suggestive of reduced ventricular compliance and that are associated with an increased risk of death or HF., Methods and Results: We performed quantitative echocardiographic analysis in 153 patients with diabetes and 451 patients without diabetes enrolled in the VALIANT Echo study. Diabetes was associated with a higher risk of death or HF in age-adjusted models (hazard ratio 1.44, 95% CI 1.04-2.00, P = .028). Diabetic patients were similar to nondiabetic patients with respect to left ventricular (LV) volume and ejection fraction but had higher LV mass index (104.1 ± 27.5 vs 97.1 ± 28.6 g/m(2), P = .009), relative wall thickness (0.41 ± 0.08 vs 0.38 ± 0.07, P < .0001), and left atrial volume index (LAVi) (26.2 ± 8.1 vs 24.0 ± 8.2 mL/m(2), P = .008)-all parameters that were significantly related to the risk of death or HF hospitalization. Changes in LV volume and ejection fraction from baseline to 20 months were not different, although diabetic patients demonstrated greater increase in LAVi (4.4 ± 7.7 vs 2.2 ± 6.7 mL/m(2), P = .01)., Conclusions: After high-risk MI, diabetic patients were at higher risk of death or HF and demonstrated greater baseline LV mass index, relative wall thickness, and LAVi as well as greater left atrial enlargement at 20-month follow-up. These findings suggest greater baseline concentric remodeling and long-term elevation in LV diastolic pressure post-MI among diabetic patients, which may partially mediate this risk., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Insufficient platelet inhibition is a major determinant of stent thrombosis (STh), although the etiology is multifactorial. On-clopidogrel platelet reactivity was investigated in patients with previous angiographically confirmed STh, myocardial infarction (MI), and controls., Methods: Using the Swedish Coronary Angiography and Angioplasty Registry, we identified patients with angiographically confirmed STh (n = 48) or MI (n = 30) while on dual antiplatelet therapy within 6 months of percutaneous coronary intervention (PCI) and matched control patients (n = 78). On-clopidogrel platelet reactivity was measured with VerifyNow P2Y12 and vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay., Results: The mean P2Y12 reaction units (PRU) was higher (246.8 ± 75.9 vs 200.0 ± 82.7, P = .001) in STh patients compared with controls. The optimal cutoff for STh was 222 PRU or higher (area under the curve 0.69, P < .0001) in a receiver operating characteristics (ROC) analysis. The cutoff level resulted in 70.2% sensitivity and 67.3% specificity. There was no significant difference in mean PRU but a higher device-reported percent inhibition (45.1 ± 23.8 vs 32.1 ± 23.2, P = .04) in patients with MI compared with controls. Results with the VASP phosphorylation assay were not related to the occurrence of STh or MI., Conclusions: STh was associated with high on-clopidogrel platelet reactivity measured with VerifyNow (cutoff level of PRU ≥222) but spontaneous MI in stented patients on clopidogrel treatment was not. There was, however, a substantial overlap in on-clopidogrel platelet reactivity between patients with and without on-treatment STh questioning the clinical use of platelet function testing to identify patients at high risk for STh., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Echocardiographic measurements of left ventricular (LV) function, predominantly LV ejection fraction (LVEF), have been used to define risk in patients after myocardial infarction. However, the extent to which measures of LV structure and function provide incremental prognostic value over clinical variables in survivors of high-risk myocardial infarction has not been well defined., Methods: Predictors of death and development of heart failure were assessed in 603 patients from the Valsartan in Acute Myocardial Infarction (VALIANT) echocardiographic substudy. We used multivariable proportional hazards models to assess the individual predictive value of echocardiographic measures including left ventricular mass index, LVEF, LV volumes, left atrial volume index, right ventricular fractional area change, mitral regurgitation, and deceleration time. We adjusted for the 11 clinical variables found previously to be most associated with all-cause mortality in this cohort. Receiver operating characteristic curves obtained via binary response regression were used to assess the incremental predictive value of echocardiographic measures in predicting outcomes of death and hospital stay for heart failure., Results: Each echocardiographic measure was independently associated with outcome of death or development of heart failure (all P < .002). Left ventricular ejection fraction alone added minimal prognostic value to the clinical assessment, yet adding additional echocardiographic assessments to a multivariable model improved in predicting 17-month survival free of heart failure significantly, increasing the c-statistic from 0.74 to 0.84 (P < .001)., Conclusion: Echocardiographic measures of cardiac structure and function beyond LVEF provide important prognostic information beyond the clinical assessment., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: The aim of this study was to determine the impact of myocardial perfusion imaging (MPI) on the outcomes of death, myocardial infarction (MI), and late coronary revascularization procedures., Methods: In patients undergoing exercise-stress MPI (January 1, 2003-March 31, 2007), we determined the impact of summed stress score (SSS) and percent left ventricular (LV) ischemia on (a) death or MI and (b) composite of death, MI, or late coronary revascularization occurring more than 90 days post-MPI., Results: During 35,007 person-years of follow-up among 9,605 patients (mean ± SD age 54.4 ± 13.2 years, 60.3% men), there were 290 deaths, 175 MIs, and 525 coronary revascularization procedures. Of those who attained ≥10 metabolic equivalents (METS) workload, major stress perfusion defects (SSS ≥7) were present in 4.2% overall and in 3.7% without ST-segment shifts, whereas large ischemic defects (≥10% LV ischemia) were present in 1% overall and 0.7% without ST-segment shifts. For those with 1% to 4%, 5% to 9%, and ≥10% LV ischemia, adjusted hazard ratios were 1.40 (95% CI 1.13-1.73, P = .002), 2.07 (95% CI 1.56-2.74, P < .001), and 3.03 (95% CI 2.21-4.16, P < .001) for the outcome of late revascularization, MI, or death versus no ischemia. Summed stress scores ≥7 were associated with increased risk of death or MI, with an adjusted hazard ratio of 1.57 (95% CI 1.16-2.13, P = .004) compared with those with no stress perfusion defects., Conclusion: Although workload ≥10 METS conferred lower frequency of major ischemia (≥10%), %LV ischemia predicted the occurrence of cardiovascular events and death (eg, MI, late coronary revascularization, or death). Presence of a large stress perfusion defect (SSS ≥7) predicted increased risk of MI or death., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Although therapy with aspirin or aspirin plus a thienopyridine reduces the incidence of long-term adverse cardiovascular events among patients with acute coronary syndrome (ACS), there remains a significant residual risk of cardiovascular death, recurrent myocardial infarction (MI), and stroke. In a phase 2 trial (ClinicalTrials.gov NCT00402597) in which the addition of the factor Xa inhibitor rivaroxaban was compared with placebo, among ACS patients receiving either aspirin alone or dual-antiplatelet therapy with aspirin and a thienopyridine, the end point of death, MI, or stroke compared with placebo was reduced (87/2331 [3.9%] vs 62/1160 [5.5%]; hazard ratio 0.69, [95% CI 0.50-0.96], P = .027). Two candidate doses of rivaroxaban were selected for further evaluation in a pivotal phase 3., Design: The second ATLAS-ACS 2 TIMI 51 Trial is an international, randomized, double-blind, event-driven (n = 983) phase 3 trial involving more than 15,570 patients hospitalized with ACS (ClinicalTrials.gov NCT00809965). All patients are treated with a background of standard therapy including low-dose aspirin, and patients are stratified by the administration of a thienopyridine (clopidogrel or ticlopidine; stratum 2) or not (stratum 1). Within each stratum, patients are randomly assigned in a 1:1:1 ratio to receive rivaroxaban 2.5 mg twice daily, or rivaroxaban 5 mg twice daily, or placebo twice daily. The primary efficacy end point is the composite of cardiovascular death, MI, or stroke. The primary safety end point is thrombolysis in MI major bleeding not associated with coronary artery bypass graft surgery., Summary: The ATLAS-ACS 2 TIMI 51 is testing the hypothesis that anticoagulation with the oral factor Xa inhibitor rivaroxaban reduces cardiovascular death, MI, and stroke among patients with ACS treated with guideline-based therapies for ACS., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: In the treatment of chronic total occlusions (CTOs), some uncertainty exists regarding the effect of drug-eluting stents (DESs) compared with the effects of bare mental stents (BMSs). We reviewed outcomes of DES vs. BMS implantation for CTO lesions, to evaluate the risk-benefit ratio of DES implantation., Methods: Relevant studies of long-term clinical outcomes or angiographic outcomes of both BMS and DES implantation were examined. The primary endpoint comprised major adverse cardiovascular events (MACEs), including all-cause deaths, myocardial infarctions (MIs), and target lesion revascularizations (TLRs). A fixed-effect model and random-effect model were used to analyze the pooling results., Results: Ten studies were included according to the selection criteria. Eight were nonrandomized controlled trials, and two consisted of a randomized controlled comparison between DES and BMS implantation. No significant difference was evident for in-hospital MACE rates between the two groups (odds ratio [OR], 1.07; 95% confidence interval [CI], .53 to 2.13), but the long-term MACE rates in the DES group were significantly lower than in the BMS group (OR, .22; 95% CI, .13 to .38; P < .00001). The rates of stent restenosis and reocclusions were also significantly lower in the DES group (OR, .14; 95% CI, .09 to .20; and OR, .23; 95% CI, .12 to .41, respectively)., Conclusion: Implantation of the DES improves long-term angiographic and clinical outcomes compared with BMS in the treatment of CTO lesions., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: The study aims to evaluate sex differences in extent and severity of coronary artery disease (CAD) and myocardial findings at autopsy among young people with fatal ischemic heart disease (IHD)., Background: Women with acute coronary syndrome are less likely than men to display obstructive CAD at angiography. This suggests unique mechanisms of acute coronary syndrome exist in women or may reflect prehospital death of women with the most severe CAD., Methods: Reports of autopsies by the Office of the Chief Medical Examiner of New York City on people aged 21 to 54 years who died between January 1, 2006, and December 31, 2008, were reviewed. A total of 639 cases of death due to atherosclerotic or arteriosclerotic cardiovascular disease according to the medical examiner were analyzed. Significant CAD was defined as ≥75% cross-sectional area stenosis in an epicardial vessel or ≥50% left main., Results: Women were less likely to have obstructive CAD (63% vs 77% of men, P = .002). There was pathologic evidence of myocardial infarction (MI) in 43% of cases, 17% of which had nonobstructive CAD. Frequency of MI did not vary by sex overall (38% of women vs 45% of men, P = .18) or among those without significant CAD (23% vs 29%, P = .45)., Conclusions: Among young people determined at autopsy to have died of IHD, fewer women had obstructive CAD, consistent with angiographic data in other IHD syndromes. Pathologic evidence of MI may exist in the absence of obstructive CAD., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Although culprit lesions in ST-segment elevation myocardial infarction (STEMI) cluster in the proximal coronary arteries, their relationship to bifurcations and curvatures, where blood flow is disturbed, is unknown. We hypothesized that (a) culprit lesions localize to disturbed flow distal to bifurcations and curvatures and (b) the distribution of culprit lesions in the left (LCA) and right coronary arteries (RCA) and resulting infarct size are related to the location of bifurcations and curvatures., Methods: Emory University's contribution to the National Cardiovascular Data Registry was queried for STEMIs. Using quantitative coronary angiography, the distances from the vessel ostium, major bifurcations, and major curvatures to the culprit lesion were measured in 385 patients., Results: Culprit lesions were located within 20 mm of a bifurcation in 79% of patients and closer to the bifurcation in the LCA compared with the RCA (7.4 ± 7.3 vs 17.7 ± 14.8 mm, P < .0001). Of RCA culprit lesions, 45% were located within 20 mm of a major curvature. Compared with those in the RCA, culprit lesions in the LCA were located more proximally (24.4 ± 16.5 vs 44.7 ± 28.8 mm, P = .0003) and were associated with larger myocardial infarctions as assessed by peak creatine kinase-MB (208 ± 222 vs 140 ± 153 ng/dL, P = .001) and troponin I (59 ± 62 vs 40 ± 35 ng/dL, P = .0006) and with higher in-hospital mortality (5.2% vs 1.1%, P = .04)., Conclusions: In patients with STEMI, culprit lesions are frequently located immediately distal to bifurcations and in proximity to major curvatures where disturbed flow is known to occur. This supports the role of wall shear stress in the pathogenesis of STEMI., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: the OAT found that routine late (3-28 days post-myocardial infarction) percutaneous coronary intervention (PCI) of an occluded infarct-related artery did not reduce death, reinfarction, or heart failure relative to medical treatment (MED). Angina rates were lower in PCI early, but the advantage over MED was lost by 3 years., Methods: angina and revascularization status were collected at 4 months, then annually. We assessed whether non-protocol revascularization procedures in MED accounted for loss of the early symptomatic advantage of PCI., Results: seven per 100 more PCI patients were angina-free at 4 months (P < .001) and 5 per 100 at 12 months (P = .005) with the difference narrowing to 1 per 100 at 3 years (P = .34). Non-protocol revascularization was more frequent in MED (5-year rate 22% vs 19% PCI, P = .05). Indications for revascularization included acute coronary syndromes (39% PCI vs 38% MED), stable angina/inducible ischemia (39% in each group), and physician preference (17% PCI vs 15% MED). Revascularization rates among patients with angina at any time during follow-up (35% of cohort) did not differ by treatment group (5-year rates 26% PCI vs 28% MED). Most symptomatic patients were treated without revascularization during follow-up (77%)., Conclusions: in a large randomized clinical trial of stable post-myocardial infarction patients, the modest benefit on angina from PCI of an occluded infarct-related artery was lost by 3 years. Revascularization was slightly more common in MED during follow-up but was not driven by acute ischemia, and almost 1 in 5 procedures were attributed to physician preference alone.

Objective: Although stem cells hold a great therapeutic potential for injured tissues, limited survival of transplanted stem cells has hindered the clinical application of this technology. We hypothesized that an omentum-based stem cell-supporting patch could provide adequate nutrients and microenvironment to prolong cell survival. We examined this hypothesis in rats with experimental myocardial infarction., Methods: The omentum-based supporting patch was constructed by stitching polylactic acid-co-glycolic acid polymer seeded with mesenchymal stem cells from male Sprague-Dawley rats. Eight weeks after the experimental myocardial infarction, which was created by ligating the left coronary artery of female Sprague-Dawley rats, mesenchymal stem cells were transplanted with (n = 16) or without (n = 14) the supporting patch. After 4 weeks, transplanted mesenchymal stem cell survival, ventricular remodeling, and cardiac performance were examined., Results: Significantly more cells survived after 4 weeks in rats transplanted with mesenchymal stem cells on the supporting patch assessed by means of polymerase chain reaction detection of the Sry gene than seen in those without the supporting patch (2.61 ± 0.40 vs 1.19 ± 0.12, P < .05). Rats with myocardial infarction that received mesenchymal stem cells with the patch also had significantly improved ventricular remodeling and cardiac function than those without the patch. Wrapping infarcted myocardium with omentum alone did not change the myocardial function., Conclusions: The omentum-based cell-supporting patch provided a favorable microenvironment for transplanted mesenchymal stem cell survival, which resulted in favorable ventricular remodeling and restoration of cardiac function in rats with experimental myocardial infarction. Further validation of the technique in human subjects could make mesenchymal stem cell transplantation a viable therapeutic option for patients with cardiac disease., (Copyright © 2010. Published by Mosby, Inc.)

Assessment of myocardial "blush" by either Myocardial Blush Grade or TIMI Myocardial Perfusion Grade, is the angiographic method currently preferred to confirm myocardial tissue-level perfusion after primary percutaneous intervention. This review focuses on the utility of angiographic "blush" as a simple, widely available, and virtually costless technique for the immediate diagnosis of microvascular impairment at the time of acute catheterization. We comprehensively outline the available evidence behind the "blush," its use in clinical practice, and draw comparisons with other new technologies for assessment of microvascular integrity., (Copyright © 2010 Mosby, Inc. All rights reserved.)