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Background: Prompt myocardial revascularization with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). However, as much as 50% of the loss of viable myocardium may be attributed to the reperfusion injury and the associated inflammatory response.Objectives: This study sought to evaluate the effect of the interleukin-6 receptor inhibitor tocilizumab on myocardial salvage in acute STEMI.Methods: The ASSAIL-MI trial was a randomized, double-blind, placebo-controlled trial conducted at 3 high-volume PCI centers in Norway. Patients admitted with STEMI within 6 h of symptom onset were eligible. Consenting patients were randomized in a 1:1 fashion to promptly receive a single infusion of 280 mg tocilizumab or placebo. The primary endpoint was the myocardial salvage index as measured by magnetic resonance imaging after 3 to 7 days.Results: We randomized 101 patients to tocilizumab and 98 patients to placebo. The myocardial salvage index was larger in the tocilizumab group than in the placebo group (adjusted between-group difference 5.6 [95% confidence interval: 0.2 to 11.3] percentage points, p = 0.04). Microvascular obstruction was less extensive in the tocilizumab arm, but there was no significant difference in the final infarct size between the tocilizumab arm and the placebo arm (7.2% vs. 9.1% of myocardial volume, p = 0.08). Adverse events were evenly distributed across the treatment groups.Conclusions: Tocilizumab increased myocardial salvage in patients with acute STEMI. (ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction [ASSAIL-MI]; NCT03004703). [ABSTRACT FROM AUTHOR]

Background: Evidence from prospective studies has suggested that long working hours are associated with incident coronary heart disease (CHD) events. However, no previous study has examined whether long working hours are associated with an increased risk of recurrent CHD events among patients returning to work after a first myocardial infarction (MI).Objectives: The purpose of this study was to examine the effect of long working hours on the risk of recurrent CHD events.Methods: This is a prospective cohort study of 967 men and women age 35 to 59 years who returned to work after a first MI. Patients were recruited from 30 hospitals across the province of Quebec, Canada. The mean follow-up duration was 5.9 years. Long working hours were assessed on average 6 weeks after their return to work. Incident CHD events (fatal or nonfatal MI and unstable angina) occurring during follow-up were determined using patients' medical files. Hazard ratios were estimated using Cox proportional hazard regression models. Splines and fractional polynomial regressions were used for flexible exposure and time modeling.Results: Recurrent CHD events occurred among 205 patients. Participants working long hours (≥55 h/week) had a higher risk of recurrent CHD events after controlling for sociodemographics, lifestyle-related risk factors, clinical risk factors, work environment factors, and personality factors (hazard ratio vs. 35 to 40 h/week: 1.67; 95% confidence interval: 1.10 to 2.53). These results showed a linear risk increase after 40 h/week and a stronger effect after the first 4 years of follow-up and when long working hours are combined with job strain.Conclusions: Among patients returning to work after a first MI, longer working hours per week is associated with an increased risk of recurrent CHD events. Secondary prevention interventions aiming to reduce the number of working hours among these patients may lower the risk of CHD recurrence. [ABSTRACT FROM AUTHOR]

Background: Phosphodiesterase 5 inhibitor (PDE5i) treatment is associated with reduced mortality compared with no treatment for erectile dysfunction after myocardial infarction (MI).Objectives: This study sought to investigate the association between treatment with PDE5i or alprostadil and outcomes in men with stable coronary artery disease.Methods: All Swedish men with a prior MI or revascularization who received PDE5i or alprostadil during 2006 through 2013 at >6 months after the event were included, using the Swedish Patient Register and the Swedish Prescribed Drug Register. Cox regression was used to estimate adjusted hazard ratios with 95% confidence intervals for all-cause mortality, MI, heart failure, cardiovascular mortality, noncardiovascular mortality, cardiac revascularization, peripheral arterial disease, and stroke in men treated with PDE5i versus alprostadil.Results: This study included 16,548 men treated with PDE5i and 1,994 treated with alprostadil. The mean follow-up was 5.8 years, with 2,261 deaths (14%) in the PDE5i group and 521 (26%) in the alprostadil group. PDE5i compared with alprostadil treatment was associated with lower mortality (hazard ratio: 0.88; 95% confidence interval: 0.79 to 0.98) and with similar associations for MI, heart failure, cardiovascular mortality, and revascularization. When quintiles (q) of filled PDE5i prescriptions were compared using q1 as reference, patients in q3, q4, and q5 had lower all-cause mortality. Among alprostadil users, those in q5 had a lower all-cause mortality compared to q1.Conclusions: In men with stable coronary artery disease, treatment with PDE5i is associated with lower risks of death, MI, heart failure, and revascularization compared with alprostadil treatment. Although the decrease in all-cause mortality was PDE5i dose dependent, the data do not permit the inference of causality or any clinical benefits of PDE5i because of the observational study design. [ABSTRACT FROM AUTHOR]

Background: Patients with obstructive coronary artery disease (CAD) are at high risk for cardiovascular disease (CVD) events. However, it remains unclear whether the high risk is due to high atherosclerotic disease burden or if presence of stenosis has independent predictive value.Objectives: The purpose of this study was to evaluate if obstructive CAD provides predictive value beyond its association with total calcified atherosclerotic plaque burden as assessed by coronary artery calcium (CAC).Methods: Among 23,759 symptomatic patients from the Western Denmark Heart Registry who underwent diagnostic computed tomography angiography (CTA), we assessed the risk of major CVD (myocardial infarction, stroke, and all-cause death) stratified by CAC burden and number of vessels with obstructive disease.Results: During a median follow-up of 4.3 years, 1,054 patients experienced a first major CVD event. The event rate increased stepwise with both higher CAC scores and number of vessels with obstructive disease (by CAC scores: 6.2 per 1,000 person-years (PY) for CAC = 0 to 42.3 per 1,000 PY for CAC >1,000; by number of vessels with obstructive disease: 6.1 per 1,000 PY for no CAD to 34.7 per 1,000 PY for 3-vessel disease). When stratified by 5 groups of CAC scores (0, 1 to 99, 100 to 399, 400 to 1,000, and >1,000), the presence of obstructive CAD was not associated with higher risk than presence of nonobstructive CAD.Conclusions: Plaque burden, not stenosis per se, is the main predictor of risk for CVD events and death. Thus, patients with a comparable calcified atherosclerosis burden generally carry a similar risk for CVD events regardless of whether they have nonobstructive or obstructive CAD. [ABSTRACT FROM AUTHOR]

Background: Sudden cardiac arrest is a serious complication of acute myocardial infarction (MI). Although in-hospital mortality from MI has decreased, the mortality of MI patients complicated with out-of-hospital cardiac arrest (OHCA) remains high. However, the features of acute MI patients with OHCA have not been well known.Objectives: We sought to characterize the clinical and angiographic features of acute MI patients with OHCA comparing with those without OHCA.Methods: We retrospectively analyzed 480 consecutive patients with acute MI undergoing percutaneous coronary intervention. Patients complicated with OHCA were compared with patients without OHCA.Results: Of the patients, 141 (29%) were complicated with OHCA. Multivariate analysis revealed that age (odds ratio [OR]: 0.8; 95% confidence interval [CI]: 0.7 to 0.9 per 5 years; p < 0.001), estimated glomerular filtration rate (OR: 0.8; 95% CI: 0.7 to 0.8 per 10 ml/min/1.73 m2; p < 0.001), peak creatine kinase-myocardial band (OR: 1.3; 95% CI: 1.2 to 1.4 per 102 U/l; p < 0.001), calcium-channel antagonists use (OR: 0.4; 95% CI: 0.2 to 0.7; p = 0.002), the culprit lesion at the left main coronary artery (OR: 5.3; 95% CI: 1.9 to 15.1; p = 0.002), and the presence of chronic total occlusion (OR: 2.9; 95% CI: 1.5 to 5.7; p = 0.001) were significantly associated with OHCA.Conclusions: Younger age, no use of calcium-channel antagonists, worse renal function, larger infarct size, culprit lesion in the left main coronary artery, and having chronic total occlusion were associated with OHCA. [ABSTRACT FROM AUTHOR]

Background: Varying definitions of procedural myocardial infarction (PMI) are in widespread use.Objectives: This study sought to determine the rates and clinical relevance of PMI using different definitions in patients with left main coronary artery disease randomized to percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) surgery in the EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial.Methods: The pre-specified protocol definition of PMI (PMIProt) required a large elevation of creatine kinase-MB (CK-MB), with identical threshold for both procedures. The Third Universal Definition of MI (types 4a and 5) (PMIUD) required lesser biomarker elevations but with supporting evidence of myocardial ischemia, different after PCI and CABG. For the PMIUD, troponins were used preferentially (available in 49.5% of patients), CK-MB otherwise. The multivariable relationship between each PMI type and 5-year mortality was determined.Results: PMIProt occurred in 34 of 935 (3.6%) patients after PCI and 56 of 923 (6.1%) patients after CABG (difference -2.4%; 95% confidence interval [CI]: -4.4% to -0.5%; p = 0.015). The corresponding rates of PMIUD were 37 (4.0%) and 20 (2.2%), respectively (difference 1.8%; 95% CI: 0.2% to 3.4%; p = 0.025). Both PMIProt and PMIUD were associated with 5-year cardiovascular mortality (adjusted hazard ratio [HR]: 2.18 [95% CI: 1.13 to 4.23] and 2.87 [95% CI: 1.44 to 5.73], respectively). PMIProt was associated with a consistent hazard of cardiovascular mortality after both PCI and CABG (pinteraction = 0.86). Conversely, PMIUD was strongly associated with cardiovascular mortality after CABG (adjusted HR: 11.94; 95% CI: 4.84 to 29.47) but not after PCI (adjusted HR: 1.14; 95% CI: 0.35 to 3.67) (pinteraction = 0.004). Results were similar for all-cause mortality and with varying PMIUD biomarker definitions. Only large biomarker elevations (CK-MB ≥10× upper reference limit and troponin ≥70× upper reference limit) were associated with mortality.Conclusions: The rates of PMI after PCI and CABG vary greatly with different definitions. In the EXCEL trial, the pre-specified PMIProt was associated with similar hazard after PCI and CABG, whereas PMIUD was strongly associated with mortality after CABG but not after PCI. (EXCEL Clinical Trial [EXCEL]; NCT01205776). [ABSTRACT FROM AUTHOR]

Background: Stress cardiac magnetic resonance (CMR) provides accurate assessment of both myocardial infarction (MI) and ischemia.Objectives: This study aimed to evaluate the incremental prognostic value of unrecognized myocardial infarction (UMI), detected during assessment of coronary artery disease (CAD) by stress CMR, beyond cardiac function and ischemia.Methods: In the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study, 2,349 consecutive patients (63 ± 11 years of age, 53% were male) with suspected CAD were assessed by stress CMR and followed over a median of 5.4 years. UMI was defined as the presence of late gadolinium enhancement consistent with MI in the absence of medical history of MI. This study investigated the association of UMI with all-cause mortality and nonfatal MI (death and/or MI), and major adverse cardiac events (MACE).Results: UMI was detected in 347 patients (14.8%) and clinically recognized myocardial infarction (RMI) in 358 patients (15.2%). Compared with patients with RMI, patients with UMI had a similar burden of cardiovascular risk factors, but significantly lower left ventricular ejection fraction (p < 0.001) and lower rates of guideline-directed medical therapies, including aspirin (p < 0.001), statin (p < 0.001), and beta-blockers (p = 0.002). During follow-up, 328 deaths and/or MIs and 528 MACE occurred. In univariate analysis, UMI and RMI were strongly associated with death and/or MI (UMI: hazard ratio [HR]: 2.15; 95% confidence interval [CI]: 1.63 to 2.83; p < 0.001; RMI: HR: 2.45; 95% CI: 1.89 to 3.18) and MACE. Compared with patients with RMI, patients with UMI presented an increased risk for heart failure hospitalization (UMI vs. RMI: HR: 2.60; 95% CI: 1.48 to 4.58; p < 0.001). In a multivariate model including ischemia and left ventricular ejection fraction, UMI and RMI maintained robust prognostic association with death and/or MI (UMI: HR: 1.82; 95% CI: 1.37 to 2.42; p < 0.001; RMI: HR: 1.54; 95% CI: 1.14 to 2.09) and MACE.Conclusions: In a multicenter cohort of patients with suspected CAD, presence of UMI or RMI portended an equally significant risk for death and/or MI, independently of the presence of ischemia. Compared with RMI patients, those with UMI were less likely to receive guideline-directed medical therapies and presented an increased risk for heart failure hospitalization that warrants further study. (Stress CMR Perfusion Imaging in the United States [SPINS]; NCT03192891). [ABSTRACT FROM AUTHOR]

Background: Autopsy studies suggest that implanting stents in lipid-rich plaque (LRP) may be associated with adverse outcomes.Objectives: The purpose of this study was to evaluate the association between LRP detected by near-infrared spectroscopy (NIRS) and clinical outcomes in patients with coronary artery disease treated with contemporary drug-eluting stents.Methods: In this prospective, multicenter registry, NIRS was performed in patients undergoing coronary angiography and possible percutaneous coronary intervention (PCI). Lipid core burden index (LCBI) was calculated as the fraction of pixels with the probability of LRP >0.6 within a region of interest. MaxLCBI4mm was defined as the maximum LCBI within any 4-mm-long segment. Major adverse cardiac events (MACE) included cardiac death, myocardial infarction, definite or probable stent thrombosis, or unplanned revascularization or rehospitalization for progressive angina or unstable angina. Events were subcategorized as culprit (treated) lesion-related, nonculprit (untreated) lesion-related, or indeterminate.Results: Among 1,999 patients who were enrolled in the COLOR (Chemometric Observations of Lipid Core Plaques of Interest in Native Coronary Arteries Registry), PCI was performed in 1,621 patients and MACE occurred in 18.0% of patients, of which 8.3% were culprit lesion-related, 10.7% were nonculprit lesion-related, and 3.1% were indeterminate during 2-year follow-up. Complications from NIRS imaging occurred in 9 patients (0.45%), which resulted in 1 peri-procedural myocardial infarction and 1 emergent coronary bypass. Pre-PCI NIRS imaging was obtained in 1,189 patients, and the 2-year rate of culprit lesion-related MACE was not significantly associated with maxLCBI4mm (hazard ratio of maxLCBI4mm per 100: 1.06; 95% confidence interval: 0.96 to 1.17; p = 0.28) after adjusting clinical and procedural factors.Conclusions: Following PCI with contemporary drug-eluting stents, stent implantation in NIRS-defined LRPs was not associated with increased periprocedural or late adverse outcomes compared with those without significant lipid. [ABSTRACT FROM AUTHOR]

Background: Recurrent myocardial infarction (MI) is common in patients with coronary artery disease and is associated with high mortality. Long-term reprogramming of myeloid progenitors occurs in response to inflammatory stimuli and alters the organism's response to secondary inflammatory challenges.Objectives: This study examined the effect of recurrent MI on bone marrow response and cardiac inflammation.Methods: The investigators developed a surgical mouse model in which 2 subsequent MIs affected different left ventricular regions in the same mouse. Recurrent MI was induced by ligating the left circumflex artery followed by the left anterior descending coronary artery branch. The study characterized the resulting ischemia by whole-heart fluorescent coronary angiography after optical organ clearing and by cardiac magnetic resonance imaging.Results: A first MI-induced bone marrow "memory" via a circulating signal, reducing hematopoietic maintenance factor expression in bone marrow macrophages. This dampened the organism's reaction to subsequent events. Despite a similar extent of injury according to troponin levels, recurrent MI caused reduced emergency hematopoiesis and less leukocytosis than a first MI. Consequently, fewer leukocytes migrated to the ischemic myocardium. The hematopoietic response to lipopolysaccharide was also mitigated after a previous MI. The increase of white blood count in 28 patients was lower after recurrent MI compared with their first MI.Conclusions: The data suggested that hematopoietic and innate immune responses are shaped by a preceding MI. [ABSTRACT FROM AUTHOR]

Background: Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C).Objectives: A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE).Methods: One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina.Results: Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081).Conclusions: Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402). [ABSTRACT FROM AUTHOR]

Background: Limited data are available on the relative performances between different types of drug-eluting stents (DES) for obstructive left main coronary artery disease (LMCAD).Objectives: This study sought to compare effectiveness and safety profiles of various second-generation DES for LMCAD in real-world clinical practice.Methods: Among 4,470 patients in 3, multicenter, prospective registries (IRIS-DES [Interventional Cardiology Research Incorporation Society-Drug-Eluting Stents] registry, the IRIS-MAIN [Interventional Cardiology Research Incorporation Society-Left MAIN Revascularization] registry, and the PRECOMBAT [PREmier of Randomized COMparison of Bypass Surgery versus AngioplasTy Using Drug-Eluting Stent in Patients with Left Main Coronary Artery Disease] study) treated between July 2007 and July 2015, the authors identified 2,692 patients with significant LMCAD who received second-generation DES; 1,254 with cobalt-chromium everolimus-eluting stents (CoCr-EES), 232 with biodegradable polymer biolimus-eluting stents (BP-BES), 616 with platinum-chromium EES (PtCr-EES), and 590 with Resolute zotarolimus-eluting stent (Re-ZES). The primary outcome was target-vessel failure.Results: The observed 3-year rates of target-vessel failure were not significantly different for the different types of DES (16.7% for the CoCr-EES, 13.2% for the BP-BES, 18.7% for the PtCr-EES, and 14.7% for the Re-ZES; p = 0.15). In multiple treatment propensity score analysis, the adjusted hazard ratios (HRs) for target-vessel failure were similar in between-group comparisons of the different DES, except for the PtCr-EES versus the BP-BES (reference; HR: 1.60; 95% confidence interval: 1.01 to 2.54; p = 0.046). There were no significant differences in risk of composite of all-cause death, any myocardial infarction, or any revascularization and its individual components according to the different types of DES. Although the 3-year incidence of stent thrombosis was considerably low (≤1.0%) for all types of DES, between-group differences were observed, generally favoring the EES platforms.Conclusions: In this pooled analysis of 3 prospective registries involving unrestricted use of various second-generation DES for LMCAD, we found no significant between-group differences in 3-year risk of target-vessel failure, except for a higher risk of primary outcome with PtCr-EES compared to BP-BES. (Evaluation of the First, Second, and New Drug-Eluting Stents in Routine Clinical Practice [IRIS-DES]; NCT01186133). [ABSTRACT FROM AUTHOR]

Background: Subjects undergoing coronary stenting with complex lesion anatomy may experience different risks and benefits with prolonged dual antiplatelet therapy.Objectives: The authors assessed the effect of 30 months versus 12 months of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) based on the presence or absence of anatomically-complex target lesions.Methods: In the DAPT Study, combined myocardial infarction (MI) or stent thrombosis and moderate/severe bleeding were assessed in enrolled (n = 25,416) and randomized (n = 11,554) subjects. Complex lesions had any of the following characteristics: unprotected left main, >2 lesions/vessel, length ≥30 mm, bifurcation with side branch ≥2.5 mm, vein bypass graft, or thrombus-containing lesion. Events were evaluated according to increasing number of complexity characteristics and compared according to DAPT score.Results: Enrolled subjects with more complex target lesions had higher rates of MI or stent thrombosis in the first 12 months after PCI (3.9% vs. 2.4%; p < 0.001). Among those who were event-free at 12 months, rates of MI or stent thrombosis between 12 and 30 months were similar between those with versus without complex anatomy (3.5% vs. 2.9%; p = 0.07). Reduction of MI or stent thrombosis with continued thienopyridine beyond 12 months versus placebo was similar for subjects with (2.5% vs. 4.5%; hazard ratio: 0.55; 95% confidence interval: 0.38 to 0.79; p = 0.001) and without (2.0% vs. 3.8%; hazard ratio: 0.52; 95% confidence interval: 0.39 to 0.69; p < 0.001) anatomic complexity (pinteraction = 0.81), as was increase in moderate/severe bleeding (pinteraction = 0.44). Among subjects with anatomic complexity, those with DAPT scores ≥2 randomized to continued thienopyridine had greater reductions in MI or stent thrombosis (3.0% vs. 6.1%; p < 0.001) compared with subjects with scores <2 (1.7% vs. 2.3%; p = 0.42; p value comparing risk differences = 0.03).Conclusions: Complex target-lesion anatomy is associated with increased ischemic events, particularly within the first year after PCI. Among those without events in the first 12 months, the benefits of extending DAPT were similar in subjects with and without complex lesions. A high DAPT score identified those experiencing the most benefit from extended treatment among patients with and without complex anatomy. (The Dual Antiplatelet Therapy Study [DAPT Study]; NCT00977938). [ABSTRACT FROM AUTHOR]

Background: Uncertainties regarding the most appropriate definition and treatment of type 2 myocardial infarction (T2MI) due to supply-demand mismatch have contributed to inconsistent adoption in clinical practice.Objectives: This study sought a better understanding of the effect of the definition of T2MI on its incidence, treatment, and event-related mortality, thereby addressing an important unmet clinical need.Methods: The final diagnosis was adjudicated in patients presenting with symptoms suggestive of myocardial infarction by 2 independent cardiologists by 2 methods: 1 method required the presence of coronary artery disease, a common interpretation of the 2007 universal definition (T2MI2007); and 1 method did not require coronary artery disease, the 2012 universal definition (T2MI2012).Results: Overall, 4,015 consecutive patients were adjudicated. The incidence of T2MI based on the T2MI2007 definition was 2.8% (n = 112). The application of the more liberal T2MI2012 definition resulted in an increase of T2MI incidence of 6% (n = 240), a relative increase of 114% (128 reclassified patients, defined as T2MI2012reclassified). Among T2MI2007, 6.3% of patients received coronary revascularization, 22% dual-antiplatelet therapy, and 71% high-dose statin therapy versus 0.8%, 1.6%, and 31% among T2MI2012reclassified patients, respectively (all p < 0.01). Cardiovascular mortality at 90 days was 0% among T2MI2012reclassified, which was similar to patients with noncardiac causes of chest discomfort (0.2%), and lower than T2MI2007 (3.6%) and type 1 myocardial infarction (T1MI) (4.8%) (T2MI2012reclassified vs. T2MI2007 and T1MI: p = 0.03 and 0.01, respectively).Conclusions: T2MI2012reclassified has a substantially lower event-related mortality rate compared with T2MI2007 and T1MI. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study; NCT00470587). [ABSTRACT FROM AUTHOR]

Objectives: To determine the cost-effectiveness of complete revascularization at index admission compared with infarct-related artery (IRA) treatment only, in patients with multivessel disease undergoing primary percutaneous coronary intervention (P-PCI) for ST-segment elevation myocardial infarction.Methods: An economic evaluation of a multicenter randomized trial was conducted, comparing complete revascularization at index admission to IRA-only P-PCI in patients with multivessel disease (12-month follow-up). Overall hospital costs (costs for P-PCI procedure(s), hospital length of stay, and any subsequent re-admissions) were estimated. Outcomes were major adverse cardiac events (MACEs, a composite of all-cause death, recurrent myocardial infarction, heart failure, and ischemia-driven revascularization) and quality-adjusted life-years (QALYs) derived from the three-level EuroQol five-dimensional questionnaire. Multiple imputation was undertaken. The mean incremental cost and effect, with associated 95% confidence intervals, the incremental cost-effectiveness ratio, and the cost-effectiveness acceptability curve were estimated.Results: On the basis of 296 patients, the mean incremental overall hospital cost for complete revascularization was estimated to be -£215.96 (-£1390.20 to £958.29), compared with IRA-only, with a per-patient mean reduction in MACEs of 0.170 (0.044 to 0.296) and a QALY gain of 0.011 (-0.019 to 0.041). According to the cost-effectiveness acceptability curve, the probability of complete revascularization being cost-effective was estimated to be 72.0% at a willingness-to-pay threshold value of £20,000 per QALY.Conclusions: Complete revascularization at index admission was estimated to be more effective (in terms of MACEs and QALYs) and cost-effective (overall costs were estimated to be lower and complete revascularization thereby dominated IRA-only). There was, however, some uncertainty associated with this decision. [ABSTRACT FROM AUTHOR]

Background: First-generation drug-eluting coronary stents (DES) were introduced in 2003 to 2004, and their use resulted in a considerable reduction in the development of in-stent restenosis at the cost of an increased risk of late stent thromboses.Objectives: This study followed clinical outcomes of patients included in a large randomized trial for 10 years to enable detection of late changes in annual event rates that could necessitate medical attention.Methods: A total of 2,098 unselected all-comer patients (50% with acute coronary syndrome) were randomly assigned to have a first-generation DES implanted. This study recorded the occurrence of a major adverse cardiac event (MACE) assessed as the composite of cardiac death, myocardial infarction, and target vessel revascularization. Stent thromboses were also assessed.Results: Of the 2,098 unselected patients, 73.1% were still alive after 10 years. During the follow-up period, MACE occurred in 346 (32.5%) in the group receiving a sirolimus-eluting stent and in 342 (33.1%) in the group receiving a paclitaxel-eluting stent (hazard ratio: 0.96; 95% confidence interval: 0.83 to 1.11; p = 0.60), with a steady annual rate of 2.6% after the first year. Definite, probable, and possible stent thrombosis appeared in 279 patients (13.3%), with no difference between stent types and with a steady annual rate of 1.3% after the first year.Conclusions: Among the surviving patients, the long-term annual MACE rate and the stent thrombosis rate appeared constant for both stent types, with no apparent late changes. Although there is no need for extraordinary medical attention for these patients, the absence of declines in annual event rates calls for continuous surveillance. (Danish Organization on Randomized Trials With Clinical Outcome II [SORT OUT II]; NCT00388934). [ABSTRACT FROM AUTHOR]

Background: A 1-year follow-up, polymer-free metallic stent coated with biolimus-A9 followed by 1-month dual antiplatelet therapy is safer and more effective than a bare-metal stent (BMS) for patients with high risk of bleeding.Objectives: This study analyzed 2-year outcomes to determine whether these benefits are maintained.Methods: In a prospective, multicenter, double-blind trial, we randomized 2,466 high bleeding risk patients to receive a drug-coated stent (DCS) or a BMS followed by 1-month dual antiplatelet therapy. The primary safety endpoint was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy endpoint was clinically driven target lesion revascularization.Results: At 2 years, the primary safety endpoint had occurred in 147 DCS and 180 BMS patients (15.3%) (hazard ratio: 0.80; 95% confidence interval: 0.64 to 0.99; p = 0.039). Clinically driven target lesion revascularization occurred for 77 DCS and 136 BMS patients (12.0%) (hazard ratio: 0.54; 95% confidence interval: 0.41 to 0.72; p < 0.0001). Major bleeding occurred in 8.9% of DCS and 9.2% of BMS patients (p = 0.95), and a coronary thrombotic event (myocardial infarction and/or stent thrombosis) occurred in 8.2% of DCS and 10.6% of BMS patients (p = 0.045). One-year mortality was 27.1% for a major bleed and 26.3% for a thrombotic event. At 2 years, multivariate correlates of major bleeding were age >75 years, anemia, raised plasma creatinine, and planned long-term anticoagulation. Correlates of the primary safety endpoint were age, anemia, congestive heart failure, multivessel disease, number of stents implanted, and use of a BMS rather than a DCS.Conclusions: Safety and efficacy benefits of DCS over BMS were maintained for 2 years in high bleeding risk patients. Rates of major bleeding and coronary thrombotic events were no different and were associated with a substantial and comparable mortality risk. (A Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug Coated Stent Versus the Gazelle Bare Metal Stent in Patients With High Risk of Bleeding [LEADERS FREE]; NCT01623180). [ABSTRACT FROM AUTHOR]

Background: Pathogenesis and diagnostic biomarkers for diseases can be discovered by metabolomic profiling of human fluids. If the various types of coronary artery disease (CAD) can be accurately characterized by metabolomics, effective treatment may be targeted without using unnecessary therapies and resources.Objectives: The authors studied disturbed metabolic pathways to assess the diagnostic value of metabolomics-based biomarkers in different types of CAD.Methods: A cohort of 2,324 patients from 4 independent centers was studied. Patients underwent coronary angiography for suspected CAD. Groups were divided as follows: normal coronary artery (NCA), nonobstructive coronary atherosclerosis (NOCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI). Plasma metabolomic profiles were determined by liquid chromatography-quadrupole time-of-flight mass spectrometry and were analyzed by multivariate statistics.Results: We made 12 cross-comparisons to and within CAD to characterize metabolic disturbances. We focused on comparisons of NOCA versus NCA, SA versus NOCA, UA versus SA, and AMI versus UA. Other comparisons were made, including SA versus NCA, UA versus NCA, AMI versus NCA, UA versus NOCA, AMI versus NOCA, AMI versus SA, significant CAD (SA/UA/AMI) versus nonsignificant CAD (NCA/NOCA), and acute coronary syndrome (UA/AMI) versus SA. A total of 89 differential metabolites were identified. The altered metabolic pathways included reduced phospholipid catabolism, increased amino acid metabolism, increased short-chain acylcarnitines, decrease in tricarboxylic acid cycle, and less biosynthesis of primary bile acid. For differential diagnosis, 12 panels of specific metabolomics-based biomarkers provided areas under the curve of 0.938 to 0.996 in the discovery phase (n = 1,086), predictive values of 89.2% to 96.0% in the test phase (n = 933), and 85.3% to 96.4% in the 3-center external sets (n = 305).Conclusions: Plasma metabolomics are powerful for characterizing metabolic disturbances. Differences in small-molecule metabolites may reflect underlying CAD and serve as biomarkers for CAD progression. [ABSTRACT FROM AUTHOR]

Background: The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines recommend primary prevention with statins for individuals with ≥7.5% 10-year risk for atherosclerotic cardiovascular disease (ASCVD). Everyone living long enough will become eligible for risk-based statin therapy due to age alone.Objectives: This study sought to personalize ACC/AHA risk-based statin eligibility using noninvasive assessment of subclinical atherosclerosis.Methods: In 5,805 BioImage participants without known ASCVD at baseline, those with ≥7.5% 10-year ASCVD risk were down-classified from statin eligible to ineligible if imaging revealed no coronary artery calcium (CAC) or carotid plaque burden (cPB). Intermediate-risk individuals were up-classified from optional to clear statin eligibility if CAC was ≥100 (or equivalent cPB).Results: At a median follow-up of 2.7 years, 91 patients had coronary heart disease and 138 had experienced a cardiovascular disease event. Mean age of the participants was 69 years, and 86% qualified for ACC/AHA risk-based statin therapy, with high sensitivity (96%) but low specificity (15%). CAC or cPB scores of 0 were common (32% and 23%, respectively) and were associated with low event rates. With CAC-guided reclassification, specificity for coronary heart disease events improved 22% (p < 0.0001) without any significant loss in sensitivity, yielding a binary net reclassification index (NRI) of 0.20 (p < 0.0001). With cPB-guided reclassification, specificity improved 16% (p < 0.0001) with a minor loss in sensitivity (7%), yielding an NRI of 0.09 (p = 0.001). For cardiovascular disease events, the NRI was 0.14 (CAC-guided) and 0.06 (cPB-guided). The positive NRIs were driven primarily by down-classifying the large subpopulation with CAC = 0 or cPB = 0.Conclusions: Withholding statins in individuals without CAC or carotid plaque could spare a significant proportion of elderly people from taking a pill that would benefit only a few. This individualized disease-guided approach is simple and easy to implement in routine clinical practice. [ABSTRACT FROM AUTHOR]

Background: Patients with diabetes appear to be at elevated risk of atherothrombotic events.Objectives: The purpose of this study was to determine the effect of antiplatelet therapy with ticagrelor on recurrent ischemic events in patients with diabetes and prior myocardial infarction (MI).Methods: We examined the subgroups of patients with diabetes (n = 6,806) and without diabetes (n = 14,355) from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54), in which 21,162 patients with a history of MI 1 to 3 years prior and with additional risk factors were randomized to ticagrelor (90 or 60 mg twice daily) or placebo. Patients were followed for a median of 33 months. The primary efficacy endpoint was major adverse cardiovascular events (MACE) (cardiovascular death, MI, stroke) and the primary safety endpoint was TIMI (Thrombolysis In Myocardial Infarction) major bleeding.Results: The relative risk reduction in MACE with ticagrelor was consistent for the pooled doses versus placebo in patients with diabetes (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.72 to 0.99; p = 0.035) and without diabetes (HR: 0.84; 95% CI: 0.74 to 0.96; p = 0.013; p interaction = 0.99). As patients with diabetes were at higher risk of MACE, the absolute risk reduction tended to be greater in patients with versus without diabetes (1.5% vs. 1.1%, with corresponding 3-year number needed to treat of 67 vs. 91). In patients with diabetes requiring pharmacological therapy (n = 5,960), the absolute risk reduction was 1.9% with a 3-year number needed to treat of 53. Additionally, in patients with diabetes, ticagrelor reduced cardiovascular death by 22% and coronary heart disease death by 34%. Similar to patients without diabetes, there was increased TIMI major bleeding in patients with diabetes (HR: 2.56; 95% CI: 1.52 to 4.33; p = 0.0004).Conclusions: In patients with diabetes with prior MI, adding ticagrelor to aspirin significantly reduces the risk of recurrent ischemic events, including cardiovascular and coronary heart disease death. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562). [ABSTRACT FROM AUTHOR]

Background: Although risk stratification is an important goal of cardiac noninvasive tests (NITs), few contemporary data exist on the prognostic value of different NITs according to patient sex.Objectives: The goal of this study was to compare the results and prognostic information derived from anatomic versus stress testing in stable men and women with suspected coronary artery disease.Methods: In 8,966 patients tested at randomization (4,500 to computed tomography angiography [CTA], 52% female; 4,466 to stress testing, 53% female), we assessed the relationship between sex and NIT results and between sex and a composite of death, myocardial infarction, or unstable angina hospitalization.Results: In women, a positive CTA (≥70% stenosis) was less likely than a positive stress test result (8% vs. 12%; adjusted odds ratio: 0.67). Compared with negative test results, a positive CTA was more strongly associated with subsequent clinical events than a positive stress test result (CTA-adjusted hazard ratio of 5.86 vs. stress-adjusted hazard ratio of 2.27; adjusted p = 0.028). Men were more likely to have a positive CTA than a positive stress test result (16% vs. 14%; adjusted odds ratio: 1.23). Compared with negative test results, a positive CTA was less strongly associated with subsequent clinical events than a positive stress test result in men, although this difference was not statistically significant (adjusted p = 0.168). Negative CTA and stress test results were equally likely to predict an event in both sexes. A significant interaction between sex, NIT type, and test result (p = 0.01) suggests that sex and NIT type jointly influence the relationship between test result and clinical events.Conclusions: The prognostic value of an NIT result varies according to test type and patient sex. Women seem to derive more prognostic information from a CTA, whereas men tend to derive similar prognostic value from both test types. [ABSTRACT FROM AUTHOR]

Background: Pre-clinical trials have demonstrated that, during intravenous microbubble infusion, high mechanical index (HMI) impulses from a diagnostic ultrasound (DUS) transducer might restore epicardial and microvascular flow in acute ST-segment elevation myocardial infarction (STEMI).Objectives: The purpose of this study was to test the safety and efficacy of this adjunctive approach in humans.Methods: From May 2014 through September 2015, patients arriving with their first STEMI were randomized to either DUS intermittent HMI impulses (n = 20) just prior to emergent percutaneous coronary intervention (PCI) and for an additional 30 min post-PCI (HMI + PCI), or low mechanical index (LMI) imaging only (n = 10) for perfusion assessments before and after PCI (LMI + PCI). All studies were conducted during an intravenous perflutren lipid microsphere infusion. A control reference group (n = 70) arrived outside of the time window of ultrasound availability and received emergent PCI alone (PCI only). Initial epicardial recanalization rates prior to emergent PCI and improvements in microvascular flow were compared between ultrasound-treated groups.Results: Median door-to-dilation times were 82 ± 26 min in the LMI + PCI group, 72 ± 15 min in the HMI + PCI group, and 103 ± 42 min in the PCI-only group (p = NS). Angiographic recanalization prior to PCI was seen in 12 of 20 HMI + PCI patients (60%) compared with 10% of LMI + PCI and 23% of PCI-only patients (p = 0.002). There were no differences in microvascular obstructed segments prior to treatment, but there were significantly smaller proportions of obstructed segments in the HMI + PCI group at 1 month (p = 0.001) and significant improvements in left ventricular ejection fraction (p < 0.005).Conclusions: HMI impulses from a diagnostic transducer, combined with a commercial microbubble infusion, can prevent microvascular obstruction and improve functional outcome when added to the contemporary PCI management of acute STEMI. (Therapeutic Use of Ultrasound in Acute Coronary Artery Disease; NCT02410330). [ABSTRACT FROM AUTHOR]

Background: Takotsubo stress cardiomyopathy (TSC) is a syndrome characterized by transient myocardial dysfunction with unknown etiology. Although recent studies have suggested that the syndrome is associated with comorbidity and has a dismal prognosis, there is a lack of comprehensive data describing the epidemiology and prognosis of TSC.Objectives: This study compared risk markers and mortality in patients with TSC with that of individuals with or without coronary artery disease (CAD).Methods: Patients with TSC and control subjects were identified from the Swedish Coronary Angiography and Angioplasty Register between 2009 and 2013 and linked with the Swedish national patient registry, cause of death registry, prescription drug registry, and education and income registries.Results: Patients with TSC were characterized by a low cardiovascular risk factor profile but with increased chronic obstructive pulmonary disease, migraine, and affective disorders. The use of beta-blockers was less common but use of β2-adrenergic agonist agents was more common in patients with TSC compared with either of the control groups. Being a patient with TSC was associated with a hazard ratio of 2.1 for death compared with the control subjects without CAD (95% confidence interval: 1.4 to 3.2). This was similar to the excess mortality risk seen among the CAD control subjects compared with control subjects without CAD (hazard ratio: 2.5; 95% confidence interval: 1.8 to 3.3). These associations remained significant after adjusting for CAD risk factors and risk markers for TSC.Conclusions: The findings of increased risk associated with β2-adrenergic agonist agents together with stress related to affective disorders emphasize the pathogenic role of sympathetic stimulation. The prognosis regarding mortality is worse than in control subjects without CAD and similar to patients with CAD emphasizing the urgent need for studies on optimal treatment of TSC. [ABSTRACT FROM AUTHOR]

Background: In a prospective, multicenter, randomized controlled trial, 4,146 patients were randomized to receive standard care or standard care plus coronary computed tomography angiography (CCTA).Objectives: The purpose of this study was to explore the consequences of CCTA-assisted diagnosis on invasive coronary angiography, preventive treatments, and clinical outcomes.Methods: In post hoc analyses, we assessed changes in invasive coronary angiography, preventive treatments, and clinical outcomes using national electronic health records.Results: Despite similar overall rates (409 vs. 401; p = 0.451), invasive angiography was less likely to demonstrate normal coronary arteries (20 vs. 56; hazard ratios [HRs]: 0.39 [95% confidence interval (CI): 0.23 to 0.68]; p < 0.001) but more likely to show obstructive coronary artery disease (283 vs. 230; HR: 1.29 [95% CI: 1.08 to 1.55]; p = 0.005) in those allocated to CCTA. More preventive therapies (283 vs. 74; HR: 4.03 [95% CI: 3.12 to 5.20]; p < 0.001) were initiated after CCTA, with each drug commencing at a median of 48 to 52 days after clinic attendance. From the median time for preventive therapy initiation (50 days), fatal and nonfatal myocardial infarction was halved in patients allocated to CCTA compared with those assigned to standard care (17 vs. 34; HR: 0.50 [95% CI: 0.28 to 0.88]; p = 0.020). Cumulative 6-month costs were slightly higher with CCTA: difference $462 (95% CI: $303 to $621).Conclusions: In patients with suspected angina due to coronary heart disease, CCTA leads to more appropriate use of invasive angiography and alterations in preventive therapies that were associated with a halving of fatal and non-fatal myocardial infarction. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590). [ABSTRACT FROM AUTHOR]

Background: The residual SYNTAX score (RSS) and SYNTAX revascularization index (SRI) quantitatively assess angiographic completeness of revascularization for patients with multivessel coronary artery disease. Whether residual angiographic disease remains of prognostic importance after "functionally" complete revascularization with fractional flow reserve (FFR) guidance is unknown.Objectives: This study sought to investigate the prognostic value of the RSS and SRI after FFR-guided functionally complete revascularization.Methods: From the FFR-guided percutaneous coronary intervention (PCI) cohort of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) trial, the RSS and SRI were calculated in 427 patients after functionally complete revascularization. The RSS was defined as the SYNTAX score (SS) recalculated after PCI. The SRI was calculated as: 100 × (1 - RSS/baseline SS) (%). We compared differences in 1- and 2-year outcomes among patients with RSS of 0, >0 to 4, >4 to 8, and >8, and with SRI of 100%, 50% to <100%, and 0 to <50%.Results: The mean baseline SS, RSS, and SRI were 14.4 ± 7.2, 6.5 ± 5.8, and 55.1 ± 32.5%, respectively. Major adverse cardiac events (MACE) at 1 year occurred in 53 patients (12.4%). Patients with MACE had higher SS than those without (18.0 [interquartile range (IQR): 11.0 to 21.0] vs. 12.0 [IQR: 9.0 to 18.0], p = 0.001), but had similar RSS and SRI after PCI (RSS: 6.0 [IQR: 3.0 to 10.0] vs. 5.0 [IQR: 2.0 to 9.5], p = 0.51 and SRI: 60.0% [IQR: 40.9% to 78.9%] vs. 58.8% [IQR: 26.7% to 81.8%], p = 0.24, respectively). Kaplan-Meier analysis showed similar 1-year incidence of MACE with RSS/SRI stratifications (log-rank p = 0.55 and p = 0.54, respectively). Results were similar with 2-year outcome data analysis.Conclusions: After functionally complete revascularization with FFR guidance, residual angiographic lesions that are not functionally significant do not reflect residual ischemia or predict a worse outcome, supporting functionally complete, rather than angiographically complete, revascularization. (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation [FAME]; NCT00267774). [ABSTRACT FROM AUTHOR]

Background: In patients undergoing percutaneous coronary intervention (PCI), drug-eluting stents (DES) reduce repeat revascularizations compared with bare-metal stents (BMS), but their effects on death and myocardial infarction (MI) are mixed. Few studies have focused on patients with end-stage renal disease.Objectives: This study compared mortality and cardiovascular morbidity during percutaneous coronary intervention with DES and with BMS in dialysis patients.Methods: We identified 36,117 dialysis patients from the USRDS (United States Renal Data System) who had coronary stenting in the United States between April 23, 2003, and December 31, 2010, and examined the association of DES versus BMS with 1-year outcomes: death; death or MI; and death, MI, or repeat revascularization. We also conducted a temporal analysis by dividing the study period into 3 DES eras: Transitional (April 23, 2003, to June 30, 2004); Liberal (July 1, 2004, to December 31, 2006); and Selective (January 1, 2007, to December 31, 2010).Results: One-year event rates were high, with 38 deaths; 55 death or MI events; and 71 death, MI, or repeat revascularization events per 100 person-years. DES, compared with BMS, were associated with a significant 18% lower risk of death; 16% lower risk of death or MI; and 13% lower risk of death, MI, or repeat revascularization. DES use varied, from 56% in the Transitional era to 85% in the Liberal era and 62% in the Selective era. DES outcomes in the Liberal era were significantly better than in the Transitional Era, but not significantly better than in the Selective Era.Conclusions: DES for percutaneous coronary intervention appears to be safe for use in U.S. dialysis patients and is associated with lower rates of death, MI, and repeat revascularization. [ABSTRACT FROM AUTHOR]

Background: There are no data available on specific causes of death from randomized trials that have compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI).Objectives: The purpose of this study was to investigate specific causes of death, and its predictors, after revascularization for complex coronary disease in patients.Methods: An independent Clinical Events Committee consisting of expert physicians who were blinded to the study treatment subclassified causes of death as cardiovascular (cardiac and vascular), noncardiovascular, or undetermined according to the trial protocol. Cardiac deaths were classified as sudden cardiac, related to myocardial infarction (MI), and other cardiac deaths.Results: In the randomized cohort, there were 97 deaths after CABG and 123 deaths after PCI during a 5-year follow-up. After CABG, 49.4% of deaths were cardiovascular, with the greatest cause being heart failure, arrhythmia, or other causes (24.6%), whereas after PCI, the majority of deaths were cardiovascular (67.5%) and as a result of MI (29.3%). The cumulative incidence rates of all-cause death were not significantly different between CABG and PCI (11.4% vs. 13.9%, respectively; p = 0.10), whereas there were significant differences in terms of cardiovascular (5.8% vs. 9.6%, respectively; p = 0.008) and cardiac death (5.3% vs. 9.0%, respectively; p = 0.003), which were caused primarily by a reduction in MI-related death with CABG compared with PCI (0.4% vs. 4.1%, respectively; p <0.0001). Treatment with PCI versus CABG was an independent predictor of cardiac death (hazard ratio: 1.55; 95% confidence interval: 1.09 to 2.33; p = 0.045). The difference in MI-related death was seen largely in patients with diabetes, 3-vessel disease, or high SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries) trial scores.Conclusions: During a 5-year follow-up, CABG in comparison with PCI was associated with a significantly reduced rate of MI-related death, which was the leading cause of death after PCI. Treatments following PCI should target reducing post-revascularization spontaneous MI. Furthermore, secondary preventive medication remains essential in reducing events post-revascularization. (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972). [ABSTRACT FROM AUTHOR]

Background: Catheter ablation reduces ventricular tachycardia (VT) recurrence and implantable cardioverter defibrillator shocks in patients with VT and ischemic cardiomyopathy. The most effective catheter ablation technique is unknown.Objectives: This study determined rates of VT recurrence in patients undergoing ablation limited to clinical VT along with mappable VTs ("clinical ablation") versus substrate-based ablation.Methods: Subjects with ischemic cardiomyopathy and hemodynamically tolerated VT were randomized to clinical ablation (n = 60) versus substrate-based ablation that targeted all "abnormal" electrograms in the scar (n = 58). Primary endpoint was recurrence of VT. Secondary endpoints included periprocedural complications, 12-month mortality, and rehospitalizations.Results: At 12-month follow-up, 9 (15.5%) and 29 (48.3%) patients had VT recurrence in substrate-based and clinical VT ablation groups, respectively (log-rank p < 0.001). More patients undergoing clinical VT ablation (58%) were on antiarrhythmic drugs after ablation versus substrate-based ablation (12%; p < 0.001). Seven (12%) patients with substrate ablation and 19 (32%) with clinical ablation required rehospitalization (p = 0.014). Overall 12-month mortality was 11.9%; 8.6% in substrate ablation and 15.0% in clinical ablation groups, respectively (log-rank p = 0.21). Combined incidence of rehospitalization and mortality was significantly lower with substrate ablation (p = 0.003). Periprocedural complications were similar in both groups (p = 0.61).Conclusions: An extensive substrate-based ablation approach is superior to ablation targeting only clinical and stable VTs in patients with ischemic cardiomyopathy presenting with tolerated VT. (Ablation of Clinical Ventricular Tachycardia Versus Addition of Substrate Ablation on the Long Term Success Rate of VT Ablation (VISTA); NCT01045668). [ABSTRACT FROM AUTHOR]

Background: Up to 65% of patients with ST-segment elevation myocardial infarction (STEMI) have multivessel coronary artery disease (MVCAD). Long-term health status of STEMI patients after multivessel revascularization is unknown.Objectives: This study investigated the relationship between multivessel revascularization and health status outcomes (symptoms and quality of life [QoL]) in STEMI patients with MVCAD.Methods: Using a U.S. myocardial infarction registry and the Seattle Angina Questionnaire (SAQ), we determined the health status of patients with STEMI and MVCAD at the time of STEMI and 1 year later. We assessed the association of multivessel revascularization during index hospitalization with 1-year health status using multivariable linear regression analysis, and also examined demographic, clinical, and angiographic factors associated with multivessel revascularization.Results: Among 664 STEMI patients with MVCAD, 251 (38%) underwent multivessel revascularization. Most revascularizations were staged during the index hospitalization (64.1%), and 8.0% were staged after discharge, with 27.9% performed during primary percutaneous coronary intervention. Multivessel revascularization was associated with age and more diseased vessels. At 1 year, multivessel revascularization was independently associated with improved symptoms (4.5 points higher SAQ angina frequency score; 95% confidence interval [CI]: 1.0 to 7.9) and QoL (6.6 points higher SAQ QoL score; 95% CI: 2.7 to 10.6). One-year mortality was not different between those who did and did not undergo multivessel revascularization (3.6% vs. 3.4%; log-rank test p = 0.88).Conclusions: Multivessel revascularization improved angina and QoL in STEMI patients with MVCAD. Patient-centered outcomes should be considered in future trials of multivessel revascularization. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction (MI) documented by late gadolinium enhancement (LGE) has clinical and prognostic importance, but its detection is sometimes compromised by poor contrast between blood and MI. MultiContrast Delayed Enhancement (MCODE) is a technique that helps discriminate subendocardial MI from blood pool by simultaneously providing a T2-weighted image with a PSIR (phase sensitive inversion recovery) LGE image. In this clinical validation study, our goal was to prospectively compare standard LGE imaging to MCODE in the detection of MI. Methods: Imaging was performed on a 1.5 T scanner on patients referred for CMR including a LGE study. Prospective comparisons between MCODE and standard PSIR LGE imaging were done by targeted, repeat imaging of slice locations. Clinical data were used to determine MI status. Images at each of multiple time points were read on separate days and categorized as to whether or not MI was present and whether an infarction was transmural or subendocardial. The extent of infarction was scored on a sector-by-sector basis. Results: Seventy-three patients were imaged with the specified protocol. The majority were referred for vasodilator perfusion exams and viability assessment (37 ischemia assessment, 12 acute MI, 10 chronic MI, 12 other diagnoses). Forty-six patients had a final diagnosis of MI (30 subendocardial and 16 transmural). MCODE had similar specificity compared to LGE at all time points but demonstrated better sensitivity compared to LGE performed early and immediately before and after the MCODE (p = 0.008 and 0.02 respectively). Conventional LGE only missed cases of subendocardial MI. Both LGE and MCODE identified all transmural MI. Based on clinical determination of MI, MCODE had three false positive MI's; LGE had two false positive MI's including two of the three MCODE false positives. On a per sector basis, MCODE identified more infarcted sectors compared to LGE performed immediately prior to MCODE (p < 0.001). Conclusion: While both PSIR LGE and MCODE were good in identifying MI, MCODE demonstrated more subendocardial MI's than LGE and identified a larger number of infarcted sectors. The simultaneous acquisition ofT1 and T2-weighted images improved differentiation of blood pool from enhanced subendocardial MI. [ABSTRACT FROM AUTHOR]

Background: The study of myofiber reorganization in the remote zone after myocardial infarction has been performed in 2D. Microstructural reorganization in remodeled hearts, however, can only be fully appreciated by considering myofibers as continuous 3D entities. The aim of this study was therefore to develop a technique for quantitative 3D diffusion CMR tractography of the heart, and to apply this method to quantify fiber architecture in the remote zone of remodeled hearts. Methods: Diffusion Tensor CMR of normal human, sheep, and rat hearts, as well as infarcted sheep hearts was performed ex vivo. Fiber tracts were generated with a fourth-order Runge-Kutta integration technique and classified statistically by the median, mean, maximum, or minimum helix angle (HA) along the tract. An index of tract coherence was derived from the relationship between these HA statistics. Histological validation was performed using phase-contrast microscopy. Results: In normal hearts, the subendocardial and subepicardial myofibers had a positive and negative HA, respectively, forming a symmetric distribution around the midmyocardium. However, in the remote zone of the infarcted hearts, a significant positive shift in HA was observed. The ratio between negative and positive HA variance was reduced from 0.96 ± 0.16 in normal hearts to 0.22 ± 0.08 in the remote zone of the remodeled hearts (p<0.05). This was confirmed histologically by the reduction of HA in the subepicardium from -52.03° ± 2.94° in normal hearts to -37.48° ± 4.05° in the remote zone of the remodeled hearts (p < 0.05). Conclusions: A significant reorganization of the 3D fiber continuum is observed in the remote zone of remodeled hearts. The positive (rightward) shift in HA in the remote zone is greatest in the subepicardium, but involves all layers of the myocardium. Tractography-based quantification, performed here for the first time in remodeled hearts, may provide a framework for assessing regional changes in the left ventricle following infarction. [ABSTRACT FROM AUTHOR]

Certain nutrients have been shown to be effective in preventing coronary heart disease. We hypothesized that a daily intake of low amounts of a number of these nutrients would exert beneficial effects on risk factors and clinical variables in patients that suffered from myocardial infarction (MI) and were following a cardiac rehabilitation program. Forty male MI patients were randomly allocated into 2 groups. The supplemented group consumed 500 mL/d of a fortified dairy product containing eicosapentaenoic acid, docosahexaenoic acid, oleic acid, folic acid, and vitamins A, B-6, D, and E. The control group consumed 500 mL/d of semi-skimmed milk with added vitamins A and D. The patients received supervised exercise training, lifestyle and dietary recommendations, and they were instructed to consume the products in addition to their regular diet. Blood extractions and clinical examinations were performed after 0, 3, 6, 9, and 12 mo. Plasma concentrations of eicosapentaenoic acid, docosahexaenoic acid, oleic acid, folic acid, vitamin B-6, and vitamin E increased after supplementation (P<0.05). Plasma total and LDL-cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein concentrations decreased in the supplemented group (P<0.05), and plasma total homocysteine decreased in both groups. There were no changes in heart rate, blood pressure, or cardiac electrocardiographic parameters in either group. Therapeutic lifestyle changes, effected through a CR program comprising regular exercise and the intake of a combination of dietary nutrients, reduced a variety of risk factors in MI patients, which supports the rationale for nutritional programs in the secondary prevention of coronary heart disease. [ABSTRACT FROM AUTHOR]

The consumption of fruit and vegetables is associated with a reduced rate of coronary heart disease (CHD) in observational cohorts. The purpose of this study was to assess the strength of this association in a meta-analysis. Cohort studies were selected if they reported relative risks (RRs) and 95% CI for coronary heart disease or mortality and if they presented a quantitative assessment of fruit and vegetable intake. The pooled RRs were calculated for each additional portion of fruit and/or vegetables consumed per day, and the linearity of the associations were examined. Nine studies were eligible for inclusion in the meta-analysis that consisted of 91,379 men, 129,701 women, and 5,007 CHD events. The risk of CHD was decreased by 4% [RR (95% CI): 0.96 (0.93-0.99), P = 0.0027] for each additional portion per day of fruit and vegetable intake and by 7% [0.93 (0.89-0.96), P < 0.0001] for fruit intake. The association between vegetable intake and CHD risk was heterogeneous (P = 0.0043), more marked for cardiovascular mortality [0.74 (0.75-0.84), P < 0.0001] than for fatal and nonfatal myocardial infarction [0.95 (0.92-0.99), P = 0.0058]. Visual inspection of the funnel plot suggested a publication bias, although not statistically significant. Therefore, the reported RRs are probably overestimated. This meta-analysis of cohort studies shows that fruit and vegetable consumption is inversely associated with the risk of CHD. The causal mechanism of this association, however, remains to be demonstrated. [ABSTRACT FROM AUTHOR]

Palm oil and soybean oil are the 2 most widely used cooking oils in the world. Palm oil is consumed mainly in developing countries, where morbidity and mortality due to cardiovascular disease (CVD) are on the rise. Although claims about adverse or protective effects of these oils are commonly made, there are no epidemiologic studies assessing the association between these oils and cardiovascular disease endpoints. We examined whether consumption of palm oil relative to soybean oil and other unsaturated oils (predominantly sunflower) is associated with myocardial infarction (MI) in Costa Rica. The cases (n = 2111) were survivors of a first acute MI and were matched to randomly selected population controls (n = 2111). Dietary intake was assessed with a validated semiquantitative FFQ. Adipose tissue profiles of essential fatty acids were assessed to validate cooking oil intake and found to be consistent with self-reported major oils used for cooking. The data were analyzed using conditional logistic regression. Palm oil users were more likely to have an MI than users of soybean oil [odds ratio (OR) = 1.33; 95% CI: 1.08-1.63] or other cooking oils (OR = 1.23; CI: 0.99-1.52), but they did not differ from users of soybean oil with a high trans-fatty acid content (OR = 1.14; CI: 0.84-1.56). These data suggest that as currently used in Costa Rica, and most likely in many other developing countries, the replacement of palm oil with a polyunsaturated nonhydrogenated vegetable oil would reduce the risk of MI. [ABSTRACT FROM AUTHOR]

Vitamin K-dependent proteins, including matrix Gla-protein, have been shown to inhibit vascular calcification. Activation of these proteins via carboxylation depends on the availability of vitamin K. We examined whether dietary intake of phylloquinone (vitamin K-1) and menaquinone (vitamin K-2) were related to aortic calcification and coronary heart disease (CHD) in the population-based Rotterdam Study. The analysis included 4807 subjects with dietary data and no history of myocardial infarction at baseline (1990-1993) who were followed until January 1, 2000. The risk of incident CHD, all-cause mortality, and aortic atherosclerosis was studied in tertiles of energy-adjusted vitamin K intake after adjustment for age, gender, BMI, smoking, diabetes, education, and dietary factors. The relative risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any of the outcomes. These findings suggest that an adequate intake of menaquinone could be important for CHD prevention. [ABSTRACT FROM AUTHOR]

Heavy coffee consumption has been associated with increased coronary heart disease (CHD) risk although many studies have not observed any relation. We studied the effect of coffee consumption, assessed with a 4-d food record, on the incidence of nonfatal acute myocardial infarction or coronary death in a cohort of 1971 men who were 42 to 60 y old and free of symptomatic CHD at baseline in 1984-1989. During a mean follow-up of 14 y, 269 participants experienced an acute coronary event. After adjustment for age, smoking, exercise ischemia, diabetes, income, and serum insulin concentration, the rate ratios (95% CIs) in daily nondrinkers and light (375 mL or less), moderate (reference level), and heavy (814 mL or more) drinkers were 0.84 (0.41-1.72), 1.22 (0.90-1.64), 1.00, and 1.43 (1.06-1.94). To address time dependence of the effect, the analysis was repeated for 75 CHD events that occurred during the first 5 y; the respective rate ratios were 0.42 (0.06-3.10), 2.00 (1.16-3.44), 1.00, and 2.07 (1.17-3.65). Further adjustment for serum HDL and LDL cholesterol concentration, diastolic blood pressure, maximal oxygen uptake, and waist-hip ratio slightly increased the rate ratio for heavy coffee intake. Neither the brewing method (boiling vs. filtering) nor the serum LDL cholesterol concentration had any impact on the risk estimates for coffee intake. In conclusion, heavy coffee consumption increases the short-term risk of acute myocardial infarction or coronary death, independent of the brewing method or currently recognized risk factors for CHD. [ABSTRACT FROM AUTHOR]

In autopsy files from April 1999 to April 2001, five cases showed macroscopic subendocardial small infarct above 1 cm diameter in the superior ventricular septum (SVS) near the atrioventricular (AV) junction, and all five were finally considered to be sudden cardiac death after full investigation. All these small infarcts in these Japanese patients were located at the posterior site of the SVS, an area mainly nourished by branches which ramified from the AV node artery and which branched from the right coronary artery (RCA). Four of the five showed acute (A) or subacute (SA) foci in or around the healed (H) lesion and surviving myocytes were visible in infarcts, in all cases, which suggested a recurrent or chronic prolonged ischemia in the territory. Four of the five had a significant stenosis of the RCA and in the other one, there was an anomalous origin of the RCA. As all five had also small artery disease in the SVS, small infarct of the posterior SVS may have formed by hemodynamic impairment in the territory of the AV node artery caused by RCA disorders. We consider the evidence of macroscopic small infarct of the posterior SVS greatly aids in determining the cause of sudden death in forensic autopsy and may be notable lesion for discussing the pathogenesis of sudden cardiac death with RCA disorder. [Copyright &y& Elsevier]

The effect of coffee consumption on cardiovascular disease has been debated for many years. In this work, we evaluated the association between coffee consumption and the risk of developing acute coronary syndromes, based on a random sample of 848 patients with their first coronary heart disease event and 1078 frequency-matched controls with no cardiovascular disease in their medical history, from the entire country. The multivariate analysis raises a J-shaped association between the risk of developing acute coronary syndromes and the quantity of coffee consumed per day. In particular, the odds ratios for moderate (<300 mL/d), heavy (300-600 mL/d), and very heavy (>600 mL/d), consumption, relative to no consumption, were 0.69 (95% CI, 0.50-0.86), 1.56 (95% CI, 1.10-2.34) and 3.10 (95% CI, 1.82-5.26), respectively, after controlling for the presence of hypertension, hypercholesterolemia, diabetes mellitus, family history of premature coronary heart disease, physical activity status, smoking habits, BMI, alcohol consumption, triglycerides, consumption of several food items, depression scale score and education status. The suggested J-shaped association between coffee consumption and the risk of developing acute coronary syndromes may partially explain the conflicting results from other studies in the past. [ABSTRACT FROM AUTHOR]

: ObjectivesWe sought to study the effect of long-term statin use on psychometric measures in an adult population with underlying coronary artery disease (CAD).: BackgroundPrevious studies have suggested associations between cholesterol lowering and psychological well-being.: MethodsStudy subjects were recruited from an outpatient cardiology clinic. Psychological well-being was assessed at baseline and annually during follow-up. The exposure of interest was long-term statin use and the outcomes of interest were depression, anxiety, and hostility. We estimated the odds ratios (ORs) and 95% confidence intervals (CI) that represented the strength of association between statin use (vs. no use of any cholesterol-lowering drug) and the risk of having abnormal depression, anxiety, and hostility scores.: ResultsStudy subjects had an average follow-up of four years and maximum of seven years. Comparing the 140 patients who had continuous use of statins with the 231 patients who did not use any cholesterol-lowering drugs, statin use was associated with lower risk of abnormal depression scores (OR 0.63, 95% CI 0.43 to 0.93), anxiety (OR 0.69, 95% CI 0.47 to 0.99), and hostility (OR 0.77, 95% CI 0.58 to 0.93) after adjustment for the propensity for statin use and potential confounders. The beneficial psychological effects of the statins appeared to be independent of the drugs'' cholesterol-lowering effects.: ConclusionsLong-term use of statins among patients with CAD appeared to be associated with reduced risk of anxiety, depression, and hostility. [Copyright &y& Elsevier]

: ObjectivesThe purpose of this study was to define the role of cell–cell coupling as an independent determinant of infarct size following coronary occlusion.: BackgroundElectrical uncoupling induced by acute ischemia enhances arrhythmogenesis, but it may also protect the heart by limiting intercellular spread of chemical mediators of injury.: MethodsThe left anterior descending coronary artery was ligated in wild-type (Cx43+/+) mice and Cx43-deficient (Cx43+/−) mice that are heterozygous for a null allele in the gene encoding the major gap junction channel protein, connexin43 (Cx43). Ventricular remodeling and infarct size were compared in both groups.: ResultsEchocardiography at 1 and 10 weeks after infarction showed that left ventricular end-diastolic volume and mass increased and ejection fraction decreased in proportion to infarct size in both Cx43+/− and Cx43+/+ hearts. However, infarct size measured histologically in healing infarcts (eight days after infarction) was 29% smaller in Cx43+/− hearts (17 ± 14% of total left ventricular area, n = 30) than in Cx43+/+ hearts (24 ± 15%, n = 23; p = 0.037). Fully healed infarcts were smaller than healing infarcts, owing to resorption of necrotic tissue and maturation of scar, but infarct size at 10 weeks after coronary occlusion was still smaller (by 50%) in Cx43+/− hearts (6 ± 5%, n = 9) compared with Cx43+/+ hearts (12 ± 7%, n = 17; p = 0.037).: ConclusionsCx43-deficient mice develop smaller infarcts than wild-type mice following coronary ligation. New therapies designed to decrease the risk of arrhythmias by enhancing intercellular communication could lead to larger infarcts caused by persistent coronary occlusion. [Copyright &y& Elsevier]

: ObjectivesThe goal of this study was to assess soluble intercellular adhesion molecule-1 (sICAM-1) level as a predictor of future acute coronary events in patients with chronic coronary heart disease (CHD).: BackgroundIncreased sICAM-1 concentration has been shown to be associated with the incidence of CHD in healthy persons. Its significance in patients with CHD has been scarcely investigated.: MethodsWe designed a prospective, nested case-control study. Sera were collected from patients with CHD enrolled in a secondary prevention trial that evaluated the efficacy of bezafibrate in reducing coronary events. We measured baseline sICAM-1 concentration in the sera of patients who developed subsequent cardiovascular events (cases: n = 136) during follow-up (mean: 6.2 years) and in age- and gender-matched controls (without events: n = 136).: ResultsBaseline serum concentrations of sICAM-1 were significantly higher in cases versus controls (375 vs. 350 ng/ml; p < 0.05). Each 100 ng/ml increase in sICAM-1 concentration was associated with 1.27 (95% confidence interval [CI]: 1.00 to 1.63) higher relative odds of coronary events. Soluble ICAM-1 concentration in the highest quartile (>394 ng/ml) was associated with significantly higher odds of coronary events (compared with the lowest quartile), even after multivariate adjustment (2.31, 95% CI: 1.02 to 5.50). After adding fibrinogen and total white blood cell count to the multivariate model, the relative odds were 2.12 (95% CI: 0.88 to 5.35) and 2.70 (95% CI: 1.10 to 7.05), respectively.: ConclusionsElevated sICAM-1 concentration in CHD patients is associated with increased risk of future coronary events independent of other traditional risk factors. [Copyright &y& Elsevier]

: ObjectivesThe study was done to evaluate whether ethnic differences exist in the prevalence of coronary artery calcification (CAC), and to determine whether differences in calcification correlate with the degree of coronary obstruction.: BackgroundElectron beam tomography (EBT) can be used to quantitate the amount of CAC and assist in prognostication of future cardiac events. It is unclear whether ethnic differences in coronary mortality are related to differences in the prevalence of coronary obstruction and CAC.: MethodsA total of 782 symptomatic subjects underwent both EBT and angiography. A 50% luminal narrowing defined an angiographic obstruction.: ResultsWe observed substantial ethnic differences in prevalence of both CAC and angiographic stenosis. In whites (n = 453), prevalence of CAC (score >0) was 84%, and significant obstruction on angiogram was 71%. Compared with whites, blacks (n = 108) had a significantly lower prevalence of CAC (62%, p < 0.001) and angiographic disease (49%, p < 0.01). Hispanics (n = 177) also had a lower prevalence of CAC (71%, p < 0.001) and angiographic obstruction (58%, p < 0.01). Asians (n = 44) were not significantly different in regard to CAC (73%, p = 0.06) or angiographic stenosis (64%, p = 0.30). These ethnic differences remained after simultaneously controlling (by use of multiple logistic regression) for age, gender and cardiac risk factors.: ConclusionsAs compared with whites, blacks and Hispanics had significantly lower prevalence of CAC and obstructive coronary disease. Ethnic differences in risk-factor profiles do not explain these differences. This study demonstrated that whites have a higher atherosclerotic burden than blacks and Hispanics, independent of risk-factor differences among symptomatic patients referred for angiography. [Copyright &y& Elsevier]

: ObjectivesThe goal of this study was to establish the role of ventricular filling on the 1b phase of ischemia-induced arrhythmias.: BackgroundIschemia-induced ventricular arrhythmias occur in two phases. The mechanism of the initiation of delayed (1b) arrhythmias is unknown. The 1b arrhythmias (15 to 60 min of ischemia) are abundant in in situ hearts but scarce in isolated perfused hearts (with drained ventricles).: MethodsLeft ventricular (LV) epicardial mapping (11 × 11 matrix, 5 mm interelectrode distance) of the initiation of delayed arrhythmias was performed in open-chested pigs (group A, n = 7) and isolated pig hearts without (group B, n = 8) and with a filled intraventricular balloon (group C, n = 5).: ResultsThere were no differences in ischemic zone size between groups. The ischemia-induced rise in tissue impedance was similar in groups A and B. Arrhythmias were less frequent and less severe in group B than in groups A or C, with no differences between groups A and C. An epicardial focal origin was detected in 26% of all first beats, significantly more from the ischemic border than from elsewhere. During a pacing protocol with a long pause (a separate group of four isolated hearts with a balloon), more premature beats occurred in the first postpause interval than in any other interval.: ConclusionsIn isolated hearts 1b arrhythmias were less frequent and less severe than in working preparations. Focal activity was documented in 26% of arrhythmias and emerged from the ischemic border. Postpause contractile potentiation was associated with more arrhythmias. Our study suggests that the initiation of ischemia-induced 1b arrhythmias is related to LV wall stress. [Copyright &y& Elsevier]