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Background Lipoprotein(a) [Lp(a)] is a genetic risk factor for cardiovascular disease (CVD), and proinflammatory interleukin-1 (IL-1) genotypes may influence Lp(a)-mediated CVD events. The genotype IL-1(+) is associated with higher rates of inflammation than IL-1(−) genotype. Targeting IL-1β was recently shown to decrease CVD events independent of low-density lipoprotein-cholesterol levels. Objective The objective of the study is to assess the modulatory effect of IL-1 genotypes on risk mediated by Lp(a) Methods We assessed whether IL-1 genotypes modulate the effect of Lp(a) on major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke/transient ischemic attack) and angiographically determined coronary artery disease (CAD). IL-1 genotypes and Lp(a) were measured in 603 patients without diabetes mellitus undergoing angiography. Major adverse cardiovascular events and CAD were assessed over a median of 45 months. Results In multivariable-adjusted analysis, Lp(a) was associated with major adverse cardiovascular events (hazard ratio [HR] [95% confidence interval {CI}]: 2.95 [1.16–7.54], P = .023) and CAD (odds ratio [OR] [95% CI]: 1.84 [1.12–3.03], P = .016) comparing quartile 4 vs quartile 1. In Cox regression analysis, IL-1(+) patients with Lp(a) above the median (>9.2 mg/dL) had a worse event-free cumulative survival (HR [95% CI]: 3.59 [1.07–12.03], P = .039) compared to IL-1(−) patients with Lp(a) below the median. In IL-1(+) patients aged ≤60 years, Lp(a) was also associated with angiographically determined CAD (OR [95% CI]: 2.90 [1.07–7.86], P = .036) comparing quartile 4 vs quartile 1 but not IL-1(−) patients. Conclusion Proinflammatory IL-1(+) genotypes modulate the risk of Lp(a) long-term CVD events and CAD. These data suggest that the dual genetic contributions of elevated Lp(a) levels and IL-1(+) genotypes may identify younger subjects at particularly high risk for CVD events. [ABSTRACT FROM AUTHOR]

Background We aimed to clarify the impact of metabolic syndrome (MetS) as assessed by different definitions on the cardiovascular mortality in patients with coronary heart disease (CHD). Methods A total of 1692 patients, 6–24 months after myocardial infarction and/or coronary revascularization at baseline, were followed in a prospective cohort study. MetS was identified using four different definitions: standard National Cholesterol Education Program definition (NCEP-ATPIII) based on the presence of ≥ 3 of the following factors: increased waist circumference, raised blood pressure, hypetriglyceridemia, low high-density lipoprotein cholesterol, and increased fasting glycemia; modified NCEP-ATPIII definition (similar, but omitting antihypertensive treatment as an alternative criterion); presence of “atherogenic dyslipidemia”; or “hypertriglyceridemic waist”. The primary outcome was a fatal cardiovascular event at 5 years. Results During 5-year follow-up, 117 patients (6.9%) died from a cardiovascular cause. Patients with MetS by modified NCEP-ATPIII ( n = 1066, 63.0% of the whole sample) had significantly higher 5-year cardiovascular mortality [adjusted hazard risk ratio (HRR) 2.01 [95%CI:1.26–3.22]; p = 0.003] than subjects without MetS. However, when testing single MetS component factors, the majority of attributable mortality risk was driven by increased fasting glycemia (≥ 5.6 mmol/L) [HRR 2.69 (95%CI:1.29–5.62), p = 0.009] and the significance of MetS disappeared. None of the other MetS definitions, i.e., standard NCEP-ATPIII ( n = 1210; 71.5%), “hypertriglyceridemic waist” ( n = 455; 26.9%) or “atherogenic dyslipidemia” ( n = 223; 13.2%) were associated with any significant mortality risk. Conclusions The co-incidence of MetS has a limited mortality impact in CHD patients, while an increase in fasting glycemia seems to be more a specific marker of mortality risk. [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]

Background: The choice of either anatomical or functional noninvasive testing to evaluate suspected coronary artery disease might affect subsequent clinical management and outcomes.Objectives: This study analyzed the association of initial noninvasive cardiac testing in outpatients with stable symptoms, with subsequent use of medications, invasive procedures, and clinical outcomes.Methods: We studied patients enrolled in a Danish nationwide register who underwent initial noninvasive cardiac testing with either coronary computed tomography angiography (CTA) or functional testing (exercise electrocardiography or nuclear stress testing) from 2009 to 2015. Further use of noninvasive testing, invasive procedures, medications, and medical costs within 120 days were evaluated. Risks of long-term mortality and myocardial infarction (MI) were analyzed using adjusted Cox proportional hazard models.Results: A total of 86,705 patients underwent either functional testing (n = 53,744, mean age 57.4 years, 49% males) or coronary CTA (n = 32,961, mean age 57.4 years, 45% males), and were followed for a median of 3.6 years. Compared with functional testing, there was significantly higher use of statins (15.9% vs. 9.1%), aspirin (12.7% vs. 8.5%), invasive coronary angiography (14.7% vs. 10.1%), and percutaneous coronary intervention (3.8% vs. 2.1%); all p < 0.001 after coronary CTA. The mean costs of subsequent testing, invasive procedures, and medications were higher after coronary CTA ($995 vs. $718; p < 0.001). Unadjusted rates of mortality (2.1% vs. 4.0%) and MI hospitalization (0.8% vs. 1.5%) were lower after coronary CTA than functional testing (both p < 0.001). After adjustment, coronary CTA was associated with a comparable all-cause mortality (hazard ratio: 0.96; 95% confidence interval: 0.88 to 1.05), and a lower risk of MI (hazard ratio: 0.71; 95% confidence interval: 0.61 to 0.82).Conclusions: In stable patients undergoing initial evaluation for suspected coronary artery disease, coronary CTA was associated with greater use of statins, aspirin, and invasive procedures, and higher costs than functional testing. Coronary CTA was associated with a lower risk of MI, but a similar risk of all-cause mortality. [ABSTRACT FROM AUTHOR]

Background: To determine the rate of all cause and cardiac death, new myocardial infarction (MI) or coronary revascularisation at over three years from index visit in emergency department chest pain patients without known coronary artery disease (CAD) at index presentation who had a negative electrocardiogram (ECG) and biomarker workup for acute coronary syndrome (ACS).Methods: An unplanned sub-study of a prospective observational study of consecutive adult patients presenting to the ED with atraumatic chest pain (or equivalents). The primary outcome of interest was the predictive performance of a negative ECG and biomarker work-up for ACS for all cause and cardiac mortality over more than three years' follow-up in patients not known to have pre-existing CAD presenting to the ED with chest pain. Secondary outcomes were rate of new MI or revascularisation not related to the index visit.Results: 237 patients were studied. Median age was 52 years (IQR 42 - 62) and 55.3% were male. Median follow-up was 48 months. There were seven deaths (3%, 95% CI 1.4 - 6%), one of which was potentially cardiac in origin with cause of death given as pulmonary hypertension and cardiac failure (0.4%, 95% CI 0.02 - 2.3%). There was one confirmed MI (0.6%, 95% CI 0.03 - 3.8%). The rate of revascularisation not related to the index visit was 3.1% (95% CI 1.1 - 7.4%).Conclusion: Patients who present to ED with potentially cardiac chest pain but who do not have known CAD, and have non-ischaemic ECGs and troponin assays below the 99th percentile are at low risk of cardiac death or MI in long-term follow-up. This challenges the recommendation for routine functional or anatomic testing. [ABSTRACT FROM AUTHOR]

Background and Aim: It was hypothesized that the pattern of coronary occlusion (thrombus composition) might contribute to the onset of ventricular arrhythmia and sudden cardiac death (SCD) in myocardial infarction (MI).Methods: The TIDE (Thrombus and Inflammation in sudden DEath) study included patients with angiographically-proven acute coronary occlusion as the cause of a ST elevation MI (STEMI) complicated by Sudden Cardiac Death (SCD group) or not (STEMI group). Thrombi were obtained by thrombo-aspiration before primary percutaneous coronary stenting and analyzed with a quantitative method using scanning electron microscopy. We compared the composition of the thrombi responsible for the coronary occlusion between the two groups and evaluated factors influencing its composition.Results: We included 121 patients and found that thrombus composition was not different between the SCD group (n=23) and the STEMI group (n=98) regarding content of fibrin fibers (60.3±18.4% vs. 62.4±18.4% respectively, p=0.68), platelets (16.3±19.2% vs. 15.616.7±%, p=0.76), erythrocytes (14.6±12.5% vs. 13±12.1%, p=0.73) and leukocytes (0.6±0.9% vs. 0.8±1.5%, p=0.93). Thrombus composition did not differ between patients receiving upstream-use of glycoprotein IIb/IIIa platelet receptor inhibitors (GPI) and patients free of GPI. The only factor found to influence thrombus composition was the ischemic time from symptom onset to primary PCI, with a decreased content in fibrin fibers (57.8±18.5% vs. 71.9±10.1%, p=0.0008) and a higher platelet content (19.2±19.1% vs. 7.9±5.7% p=0.014) in early presenters (<3h of ischemic time) vs. late presenters (>6h of ischemic time).Conclusion: Composition of intracoronary thrombi in STEMI patients does not differ between those presenting with and without SCD. Time from symptom onset to coronary reperfusion seems to be the strongest factor influencing thrombus composition in MI. [ABSTRACT FROM AUTHOR]

Background: Noninvasive models to predict the presence of coronary artery disease (CAD) may help reduce the societal burden of CAD.Objectives: From a prospective registry of patients referred for coronary angiography, the goal of this study was to develop a clinical and biomarker score to predict the presence of significant CAD.Methods: In a training cohort of 649 subjects, predictors of ≥70% stenosis in at least 1 major coronary vessel were identified from >200 candidate variables, including 109 biomarkers. The final model was then validated in a separate cohort (n = 278).Results: The scoring system consisted of clinical variables (male sex and previous percutaneous coronary intervention) and 4 biomarkers (midkine, adiponectin, apolipoprotein C-I, and kidney injury molecule-1). In the training cohort, elevated scores were predictive of ≥70% stenosis in all subjects (odds ratio [OR]: 9.74; p < 0.001), men (OR: 7.88; p <0.001), women (OR: 24.8; p < 0.001), and those with no previous CAD (OR: 8.67; p < 0.001). In the validation cohort, the score had an area under the receiver-operating characteristic curve of 0.87 (p < 0.001) for coronary stenosis ≥70%. Higher scores were associated with greater severity of angiographic stenosis. At optimal cutoff, the score had 77% sensitivity, 84% specificity, and a positive predictive value of 90% for ≥70% stenosis. Partitioning the score into 5 levels allowed for identifying or excluding CAD with >90% predictive value in 42% of subjects. An elevated score predicted incident acute myocardial infarction during 3.6 years of follow up (hazard ratio: 2.39; p < 0.001).Conclusions: We described a clinical and biomarker score with high accuracy for predicting the presence of anatomically significant CAD. (The CASABLANCA Study: Catheter Sampled Blood Archive in Cardiovascular Diseases; NCT00842868). [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus causes microcirculatory rarefaction and may impair the responsiveness of ischemic myocardium to proangiogenic factors.Objectives: This study sought to determine whether microvascular destabilization affects organ function and therapeutic neovascularization in diabetes mellitus.Methods: The authors obtained myocardial samples from patients with end-stage heart failure at time of transplant, with or without diabetes mellitus. Diabetic (db) and wild-type (wt) pigs were used to analyze myocardial vascularization and function. Chronic ischemia was induced percutaneously (day 0) in the circumflex artery. At day 28, recombinant adeno-associated virus (rAAV) (5 × 1012 viral particles encoding vascular endothelial growth factor-A [VEGF-A] or thymosin beta 4 [Tβ4]) was applied regionally. CD31+ capillaries per high power field (c/hpf) and NG2+ pericyte coverage were analyzed. Global myocardial function (ejection fraction [EF] and left ventricular end-diastolic pressure) was assessed at days 28 and 56.Results: Diabetic human myocardial explants revealed capillary rarefaction and pericyte loss compared to nondiabetic explants. Hyperglycemia in db pigs, even without ischemia, induced capillary rarefaction in the myocardium (163 ± 14 c/hpf in db vs. 234 ± 8 c/hpf in wt hearts; p < 0.005), concomitant with a distinct loss of EF (44.9% vs. 53.4% in nondiabetic controls; p < 0.05). Capillary density further decreased in chronic ischemic hearts, as did EF (both p < 0.05). Treatment with rAAV.Tβ4 enhanced capillary density and maturation in db hearts less efficiently than in wt hearts, similar to collateral growth. rAAV.VEGF-A, though stimulating angiogenesis, induced neither pericyte recruitment nor collateral growth. As a result, rAAV.Tβ4 but not rAAV.VEGF-A improved EF in db hearts (34.5 ± 1.4%), but less so than in wt hearts (44.8 ± 1.5%).Conclusions: Diabetes mellitus destabilized microvascular vessels of the heart, affecting the amplitude of therapeutic neovascularization via rAAV.Tβ4 in a translational large animal model of hibernating myocardium. [ABSTRACT FROM AUTHOR]

The effect of invasive percutaneous coronary procedures on complement activation has not been elucidated. We enrolled stable angina patients with elective percutaneous coronary intervention (SA-PCI, n = 24), diagnostic coronary angiography (CA, n = 52) and 23 patients with ST segment elevation myocardial infarction and primary PCI (STEMI-PCI). Complement activation products (C1rC1sC1inh, C3bBbP and SC5b-9) were measured on admission, 6 and 24 h after coronary procedures. The alternative pathway product, C3bBbP significantly and reversibly increased 6 h after elective PCI (baseline: 7.81 AU/ml, 6 h: 16.09 AU/ml, 24 h: 4.27 AU/ml, p < 0.01, n = 23) and diagnostic angiography (baseline: 6.13 AU/ml, 6 h: 12.08 AU/ml, 24 h: 5.4 AU/ml, p < 0.01, n = 52). Six hour C3bBbP values correlated with post-procedural CK, creatinine level and the applied contrast material volume (r = 0.41, r = 0.4, r = 0.3, p < 0.05, respectively). In STEMI-PCI, baseline C3bBbP level was higher, compared to SA-PCI or CA patients (11.33 AU/ml vs. 7.81 AU/ml or 6.13 AU/ml, p < 0.001). Similarly, the terminal complex (SC5b-9) level was already elevated at baseline compared to SA-PCI group (3.49 AU/ml vs. 1.87 AU/ml, p = 0.011). Complement pathway products did not increase further after primary PCI. Elective coronary procedures induced transient alternative complement pathway activation, influenced by the applied contrast volume. In STEMI, the alternative complement pathway is promptly activated during the atherothrombotic event and PCI itself had no further detectable effect. [ABSTRACT FROM AUTHOR]

The AngelMed Guardian System is an implantable device similar to a single chamber pacemaker that continuously monitors the intracardiac electrogram for evidence of ST segment shift indicating acute coronary artery occlusion. The system aims to reduce time to presentation by alerting patients to present to a medical facility whether symptoms are present or not. In March 2016, the US Food and Drug Administration (FDA) assembled a meeting of the Circulatory System Devices Panel to review the results of the AngelMed for Early Recognition and Treatment of STEMI (ALERTS) pivotal trial and the accompanying premarket approval (PMA) application for regulatory approval of the AngelMed Guardian System in the US. In this review, we examine the ALERTS trial methodology and results, and describe the FDA panel's deliberations and recommendations. [ABSTRACT FROM AUTHOR]

Ischemic heart disease is a complex disease process caused by the development of coronary atherosclerosis, with downstream effects on the left ventricular myocardium. It is characterized by a long preclinical phase, abrupt development of myocardial infarction, and more chronic disease states such as stable angina and ischemic cardiomyopathy. Recent advances in computed tomography (CT) and cardiac magnetic resonance (CMR) now allow detailed imaging of each of these different phases of the disease, potentially allowing ischemic heart disease to be tracked during a patient's lifetime. In particular, CT has emerged as the noninvasive modality of choice for imaging the coronary arteries, whereas CMR offers detailed assessments of myocardial perfusion, viability, and function. The clinical utility of these techniques is increasingly being supported by robust randomized controlled trial data, although the widespread adoption of cardiac CT and CMR will require further evidence of clinical efficacy and cost effectiveness. [ABSTRACT FROM AUTHOR]

Background Cardiac troponin T and I are important diagnostic and prognostic markers in patients with acute coronary syndrome (ACS). Troponin elevations in various non-ACS scenarios have been documented, but few studies have been conducted on the general hospitalized population, none compared the diagnostic performance of troponin I and T. Methods and results Patients aged > 18 years (n = 1097), consecutively admitted to a district hospital, were included in the study. Blood samples were collected at admission and analysed with three different troponin assays. Serum was available in 92.2%, giving a study population of 1012 patients (mean age 61.6 years, 510 (50.4%) female). ACS was diagnosed among 125 (12.4%) of the patients. Remaining patients were admitted with a broad spectrum of medical and surgical conditions. Of the total population, sc-cTnI was above the 99th percentile in 93 (9.2%), hs-cTnI was above the 99th percentile in 80 (7.9%) and hs-cTnT was above the 99th percentile in 400 (39.5%) of the patients (p < 0.001 for all differences). Hs-cTnT was stronger correlated with estimated glomerular filtration rate (r [2] = 0.13 vs r [2] = 0.06) and haemoglobin (r [2] = 0.1 vs r2 = 0.02) than with hs-cTnI, none were correlated with C-reactive protein (r [2] = 0.04 vs r [2] = 0.02). The correlation between ln(hs-cTnT) and ln(hs-cTnI) was better in ACS patients than in non-ACS patients (r [2] = 0.79 vs r [2] = 0.47, p < 0.001). Conclusion Hs-cTnT was elevated above the 99th percentile in more than one third of the non-ACS patients, while hs-cTnI and sc-cTnI were elevated in approximately one tenth. The correlation between hs-cTnT and hs-cTnI concentrations was significantly stronger in ACS patients than in non-ACS patients. [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: T-wave morphology in the setting of left bundle branch block (LBBB) has been proposed as an indicator of myocardial ischemia.Objectives: We sought to identify T-wave morphology findings in patients with LBBB that predict non-ST-segment elevation myocardial infarction (NSTEMI). We hypothesized that two or more contiguous leads with concordant T waves would be predictive of NSTEMI.Methods: This was a retrospective cohort study performed by chart review in a tertiary care center emergency department. We identified a consecutive cohort who presented with LBBB and symptoms consistent with acute coronary syndrome. Exclusion criteria were diastolic blood pressure > 120 mm Hg, heart rate > 130 beats/min, positive pressure ventilation, potassium > 5.5 mEq/L, and cardiac arrest without prearrest electrocardiogram (ECG) available. We collected ECGs and classified T waves into five categories based on morphology, blinded to clinical outcome. Clinical outcome data were collected blinded to ECG findings. Those with ECG diagnostic of STEMI by modified Sgarbossa criteria were excluded from the primary analysis, which was sensitivity and specificity of two or more contiguous leads with concordant T waves for NSTEMI.Results: There were 246 patients included. Mean age was 73 years; 160 (65%) were female, and 32 had myocardial infarction. Thirty percent had two or more contiguous precordial leads with partially or completely concordant T waves. For NSTEMI, the sensitivity and specificity of this finding were 19% (95% confidence interval [CI] 8-37) and 68% (95% CI 61-74).Conclusions: We found no clinically useful relationship between T-wave concordance and myocardial infarction in our patient population. Future investigation of LBBB T-wave morphology should focus on alternative populations and findings. [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]

Stent thrombosis (ST) remains a catastrophic problem in patients undergoing percutaneous coronary intervention (PCI). However, a paucity of data exist regarding the incidence, implications, and predictors of ST in patients with acute myocardial infarction (AMI). We consecutively enrolled patients with AMI in the CardiOvascular Risk and idEntificAtion of potential high-risk population in AMI registry who underwent PCI from January 2004 to December 2009 and analyzed definite or probable ST according to Academic Research Consortium definitions. The median follow-up duration was 41.9 months. Definite or probable ST occurred in 136 patients (3.7%), including 44 with early ST (1.0%), 38 with late ST (0.9%), and 54 with very late ST (2.0%). The annual incidence of very late ST ranged from 0.5% to 0.6%. The all-cause mortality rate after ST was 29%, which was higher than that for patients without ST (17%; p <0.001). The independent predictors of ST were no-reflow phenomenon (hazard ratio [HR] 1.96, 95% confidence interval [CI] 1.28 to 3.03), decreased left ventricular ejection fraction (HR 1.70, 95% CI 1.21 to 2.40), anemia (HR 1.54, 95% CI 1.09 to 2.18), and a mean stent diameter <3.0 mm (HR 1.53, 95% CI 1.04 to 2.27). ST is not uncommon in patients with AMI and continues to occur beyond 1 year after PCI, irrespective of the stent type or clinical presentation. Patients with ST are associated with higher mortality than patients without ST. No reflow, decreased left ventricular ejection fraction, anemia, and a mean stent diameter <3.0 mm are independent predictors of ST. [ABSTRACT FROM AUTHOR]

Coronary artery calcium score (CACS) is a strong predictor of adverse cardiovascular events in the general population. Recent data confirm the prognostic utility of single-photon emission computed tomographic (SPECT) imaging in end-stage renal disease, but whether performing CACS as part of hybrid imaging improves risk prediction in this population is unclear. Consecutive patients (n = 284) were identified after referral to a university hospital for cardiovascular risk stratification in assessment for renal transplantation. Participants underwent technetium-99m SPECT imaging after exercise or standard adenosine stress in those unable to achieve 85% maximal heart rate; multislice CACS was also performed (Siemens Symbia T16, Siemens, Erlangen, Germany). Subjects with known coronary artery disease (n = 88) and those who underwent early revascularization (n = 2) were excluded. The primary outcome was a composite of death or first myocardial infarction. An abnormal SPECT perfusion result was seen in 22% (43 of 194) of subjects, whereas 45% (87 of 194) had at least moderate CACS (>100 U). The frequency of abnormal perfusion (summed stress score ≥4) increased with increasing CACS severity (p = 0.049). There were a total of 15 events (8 deaths, and 7 myocardial infarctions) after a median duration of 18 months (maximum follow-up 3.4 years). Univariate analysis showed diabetes mellitus (Hazard ratio [HR] 3.30, 95% CI 1.14 to 9.54; p = 0.028), abnormal perfusion on SPECT (HR 5.32, 95% CI 1.84 to 15.35; p = 0.002), and moderate-to-severe CACS (HR 3.55, 95% CI 1.11 to 11.35; p = 0.032) were all associated with the primary outcome. In a multivariate model, abnormal perfusion on SPECT (HR 4.18, 95% CI 1.43 to 12.27; p = 0.009), but not moderate-to-severe CACS (HR 2.50, 95% CI 0.76 to 8.20; p = 0.130), independently predicted all-cause death or myocardial infarction. The prognostic value of CACS was not incremental to clinical and SPECT perfusion data (global chi-square change = 2.52, p = 0.112). In conclusion, a perfusion defect on SPECT is an independent predictor of adverse outcome in potential renal transplant candidates regardless of the CACS. The use of CACS as an adjunct to SPECT perfusion data does not provide incremental prognostic utility for the prediction of mortality and nonfatal myocardial infarction in end-stage renal disease. [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]

SCOT-HEART (Scottish COmputed Tomography of the HEART) and PROMISE (PROspective Multicenter Imaging Study for Evaluation of chest pain) represent the 2 largest and most comprehensive cardiovascular imaging outcome trials in patients with stable chest pain and provide significant insights into patient diagnosis, management, and outcomes. These trials are particularly timely, given the well-recognized knowledge gaps and widespread use of noninvasive imaging. The overall goal of this review is to distill the data generated from these 2 pivotal trials to better inform the practicing clinician in the selection of noninvasive testing for stable chest pain. Similarities and differences between SCOT-HEART and PROMISE are highlighted, and clinical and practical implications are discussed. Both trials show that coronary computed tomography angiography should have a greater role in the diagnostic pathway of patients with stable chest pain. [ABSTRACT FROM AUTHOR]

Background Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) significantly improves outcomes compared with angio-guided PCI in patients with multivessel coronary artery disease. However, there is a theoretical concern that in patients with reduced left ventricular ejection fraction (EF) FFR may be less accurate and FFR-guided PCI less beneficial. Methods From the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) trial database, we compared FFR values between patients with reduced EF (both ≤ 40%, n = 90 and ≤ 50%, n = 252) and preserved EF (> 40%, n = 825 and > 50%, n = 663) according to the angiographic stenosis severity. We also compared differences in 1 year outcomes between FFR- vs. angio-guided PCI in patients with reduced and preserved EF. Results Both groups had similar FFR values in lesions with 50–70% stenosis (p = 0.49) and with 71–90% stenosis (p = 0.89). The reduced EF group had a higher mean FFR compared to the preserved EF group across lesions with 91–99% stenosis (0.55 vs. 0.50, p = 0.02), although the vast majority of FFR values remained ≤ 0.80. There was a similar reduction in the composite end point of death, nonfatal myocardial infarction, and repeat revascularization with FFR-guided compared to angio-guided PCI for both the reduced (14.5% vs. 19.0%, relative risk = 0.76, p = 0.34) and the preserved EF group (13.8 vs. 17.0%, relative risk = 0.81, p = 0.25). The results were similar with an EF cutoff of 40%. Conclusion Reduced EF has no influence on the FFR value unless the stenosis is very tight, in which case a theoretically explainable, but clinically irrelevant overestimation might occur. As a result, FFR-guided PCI remains beneficial regardless of EF. [ABSTRACT FROM AUTHOR]

Background/purpose: Patients with acute coronary syndrome due to left main and/or three-vessel disease (LM/3VD) are at the highest risk of short- and long-term adverse cardiovascular events. Neutrophil-to-lymphocyte ratio (NLR) has been shown to predict the severity of coronary artery disease in various clinical settings, but its independent predictive value for LM/3VD has not been investigated in patients with non-ST-segment elevation myocardial infarction (NSTEMI). We aimed to evaluate the independent predictive value of NLR for LM/3VD in NSTEMI patients.Methods/materials: We performed a retrospective analysis of consecutive NSTEMI patients who underwent coronary angiography. NLR was calculated as the ratio of neutrophil to lymphocyte based on the laboratory data on admission. The primary outcome was the presence of LM/3VD.Results: In all, 396 patients were included in the final analysis. Median NLR in the entire study population was 3.43 (interquartile range, 2.12-5.51). By receiver operating characteristics curve analysis, the optimal cutoff value of NLR in predicting LM/3VD was 2.80 (area under the curve 0.60, sensitivity 73%, specificity 43%). Of the 396 patients, 244 patients (62%) had NLR ≥2.8. Patients with NLR ≥2.8 were older and had a higher prevalence of LM/3VD (30 % vs. 18%, p=0.005). According to multivariate logistic regression analysis, NLR ≥2.8 was an independent predictor of LM/3VD after adjusting for other clinical variables including ST depression and ST elevation in lead aVR (odds ratio 1.83, 95% confidence interval 1.07-3.21, p=0.03).Conclusion: Our study demonstrates that NLR ≥2.8 is an independent predictor of LM/3VD in patients with NSTEMI. [ABSTRACT FROM AUTHOR]

Purpose We evaluated whether a quantitative circumferential strain (CS) analysis using adenosine triphosphate (ATP)-stress/rest 3-T tagged magnetic resonance (MR) imaging can depict myocardial ischemia as contractile dysfunction during stress in patients with suspected coronary artery disease (CAD). We evaluated whether it can differentiate between non-ischemia, myocardial ischemia, and infarction. We assessed its diagnostic performance in comparison with ATP-stress myocardial perfusion MR and late gadolinium enhancement (LGE)-MR imaging. Methods In 38 patients suspected of having CAD, myocardial segments were categorized as non-ischemic ( n = 485), ischemic ( n = 74), or infarcted ( n = 49) from the results of perfusion MR and LGE-MR. The peak negative CS value, peak circumferential systolic strain rate (CSR), and time-to-peak CS were measured in 16 segments. Results A cutoff value of −12.0% for CS at rest allowed differentiation between infarcted and other segments with a sensitivity of 79%, specificity of 76%, accuracy of 76%, and an area under the curve (AUC) of 0.81. Additionally, a cutoff value of 477.3 ms for time-to-peak CS at rest allowed differentiation between infarcted and other segments with a sensitivity of 61%, specificity of 91%, accuracy of 88%, and an AUC of 0.75. The differences in CS values between ATP-stress and rest conditions (ΔCS) in non-ischemic segments (median [first quartile, third quartile] −1.7 [−3.2, −0.1] %) were smaller than in segments with ischemia (+1.1 [+0.3, +2.3] %, p < 0.001). A cutoff value of +0.3% for the ΔCS value could differentiate segments with ischemia from non-ischemic segments with a sensitivity of 75%, a specificity of 82%, an accuracy of 82%, and an AUC of 0.86. Conclusions Circumferential strain analysis using tagged MR can quantitatively assess contractile dysfunction in ischemic and infarcted myocardium. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are tiny non-coding RNA molecules that regulate gene expression predominantly at the post-transcriptional level. Far from being simple intracellular regulators, miRNAs have recently been involved in intercellular communication and have been shown to circulate in the bloodstream in stable forms. In the past years specific miRNA expression patterns have been linked to the development of atherosclerosis and coronary artery disease, two closely related conditions. The study of miRNAs has promoted our understanding of the processes involved in the pathogenesis of atherosclerosis and innovative diagnostic and therapeutic approaches have emerged. In this review, we present the role of miRNAs in the development of atherosclerosis, on coronary artery disease progression and we assess their role as diagnostic biomarkers. Finally we evaluate the therapeutic and preventive opportunities that arise from the study of miRNAs in coronary artery disease and especially in myocardial infarction. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to investigate the prognostic value of myocardial focal fibrosis quantified by late gadolinium enhanced (LGE) magnetic resonance imaging (MRI) in patients with heart failure with preserved ejection fraction (HFpEF). Methods One-hundred eleven HFpEF patients (mean age: 70 ± 14 years, 55 (50%) female) were enrolled. We excluded patients with previous history of coronary artery disease and/or ischemic pattern of hyper enhancement on LGE MRI. Myocardial enhancement was defined using signal intensity > 2SD above the mean signal intensity of a remote myocardium. Major adverse cardiovascular events were defined as cardiovascular death and heart failure requiring hospitalization. Results During a mean follow up period of 851 ± 609 days, 10 events (2 cardiovascular death, 8 hospitalization for heart failure decompensation) were observed. Area under the receiver operating characteristics curve of LGE% for the detection of future events was 0.721 (95% CI: 0.628-0.802). Multivariate Cox proportional hazard analysis showed that LGE% is an independent predictor of future events after the adjustment with prognostic 5 factors - age, diabetes mellitus, New York Heart Association classification, history of heart failure hospitalization and left ventricular ejection fraction - which were identified in the I-PRESERVE study (Irbesartan in Heart Failure with Preserved Ejection Fraction Study) (hazard ratio = 7.913, 95% CI: 1.603-39.05, P = 0.012). Conclusions Larger size of LGE was significantly associated with high rate of future cardiovascular death and heart failure hospitalization, suggesting that the quantification of myocardial focal fibrosis by LGE MRI could be useful for the risk stratification in HFpEF patients. [ABSTRACT FROM AUTHOR]

Many see the broadened eligibility of cardiac rehabilitation (CR) to include heart failure with reduced ejection fraction (HFrEF) as a likely catalyst to high CR enrollment and improved care. However, such expectation contrasts with the reality that CR enrollment of eligible coronary heart disease patients has remained low for decades. In this review, entrenched obstacles impeding utilization of CR are considered, particularly in relation to potential HFrEF management. The strengths and limitations of the HF-ACTION (Heart Failure–A Controlled Trial Investigating Outcomes of Exercise Training) trial to advance precepts of CR are considered, as well as gaps that this trial failed to address, such as the utility of CR for patients with heart failure with preserved ejection fraction and the conundrum of poor patient adherence. [ABSTRACT FROM AUTHOR]

Introduction Fibrin structure and cellular composition of thrombi profoundly affect the clinical outcomes in ischemic coronary and peripheral artery disease. Our study addressed the interrelations of structural features of thrombi and routinely measured laboratory parameters. Materials and methods Thrombi removed by thromboaspiration following acute myocardial infarction (n = 101) or thrombendarterectomy of peripheral arteries (n = 50) were processed by scanning electron microscopy and immunostaining for fibrin and platelet antigen GPIIb/IIIa to determine fibrin fibre diameter and relative occupancy by fibrin and cells. Correlations between the structural characteristics and selected clinical parameters (age, sex, vascular localization, blood cell counts, ECG findings, antiplatelet medication, accompanying diseases, smoking) were assessed. Results We observed significant differences in mean fibre diameter (122 vs. 135 nm), fibrin content (70.5% vs. 83.9%), fluorescent fibrin/platelet coverage ratio (0.18 vs. 1.06) between coronary and peripheral thrombi. Coronary thrombi from smokers contained more fibrin than non-smokers (78.1% vs. 62.2% mean occupancy). In the initial 24 h, fibrin content of coronary thrombi decreased with time, whereas in peripheral thrombi platelet content increased in the first 7 days. In coronaries, higher platelet content and smaller vessel diameter were associated with thinner fibrin fibres, whereas hematocrit higher than 0.35 correlated with larger intrathrombotic platelet occupancy. Smoking and dyslipidaemia strengthened the dependence of clot platelet content on systemic platelet count (the adjusted determination coefficient increased from 0.33 to 0.43 and 0.65, respectively). Conclusion Easily accessible clinical parameters could be identified as significant determinants of ultrastructure and composition of coronary and peripheral thrombi. Highlights • Fibrin in coronary thrombi is composed of thinner fibers than in peripheral thrombi • Platelet occupancy of coronary thrombi is higher than in peripheral thrombi • Higher haematocrit increases the platelet content of coronary thrombi • Smoking reinforces systemic platelet count as a determinant of thrombus structure. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have been extensively used to study common complex diseases such as coronary artery disease (CAD), revealing 153 suggestive CAD loci, of which at least 46 have been validated as having genome-wide significance. However, these loci collectively explain <10% of the genetic variance in CAD. Thus, we must address the key question of what factors constitute the remaining 90% of CAD heritability. We review possible limitations of GWAS, and contextually consider some candidate CAD loci identified by this method. Looking ahead, we propose systems genetics as a complementary approach to unlocking the CAD heritability and etiology. Systems genetics builds network models of relevant molecular processes by combining genetic and genomic datasets to ultimately identify key “drivers” of disease. By leveraging systems-based genetic approaches, we can help reveal the full genetic basis of common complex disorders, enabling novel diagnostic and therapeutic opportunities. [ABSTRACT FROM AUTHOR]

We report on a 9-year-old healthy boy with a left main coronary artery arising from the right sinus of Valsalva coursing between the aorta and pulmonary artery who experienced a myocardial infarction after a syncopal episode during exercise. The high risk of sudden death associated with this anomaly during or immediately after vigorous activity makes immediate diagnosis and surgical intervention paramount. Diagnosis was made by transthoracic echocardiogram and confirmed by autopsy. [ABSTRACT FROM AUTHOR]

Purpose The biomarker Osteoprotegerin (OPG) is associated with coronary artery disease (CAD). The main purpose of this study was to evaluate the diagnostic value of OPG in healthy subjects and in patients with suspected angina pectoris (AP). Methods A total of 1805 persons were enrolled: 1152 healthy subjects and 493 patients with suspected AP. For comparison 160 patients with acute myocardial infarction (MI) were included. To uncover subclinical coronary atherosclerosis, a non-contrast cardiac-CT scan was performed in healthy subjects; while in patients with suspected AP a contrast coronary angiography was used to detect significant stenosis. OPG concentrations were analyzed and compared between groups. ROC-analyses were performed to estimate OPG cut-off values. Results OPG concentrations increased according to disease severity with the highest levels found in patients with acute MI. No significant difference ( p = 0.97) in OPG concentrations was observed between subgroups of healthy subjects according to severity of coronary calcifications. A significant difference ( p < 0.0001) in OPG concentrations was found between subgroups of patients with suspected stable AP according to severity of CAD. ROC-analysis showed an AUC of 0.62 (95% CI: 0.57–0.67). The optimal cut-off value of OPG (<2.29 ng/mL) had a sensitivity of 56.2% (95% CI: 49.2–63.0%) and a specificity of 62.9% (95% CI: 57.3–68.2%). Conclusion OPG cannot be used to differentiate between healthy subjects with low versus high levels of coronary calcifications. In patients with suspected AP a single OPG measurement is of limited use in the diagnosis of CAD. [ABSTRACT FROM AUTHOR]

Fibromuscular dysplasia (FMD) involving the coronary arteries is an uncommon but important condition that can present as acute coronary syndrome, left ventricular dysfunction, or potentially sudden cardiac death. Although the classic angiographic “string of beads” that may be observed in renal artery FMD does not occur in coronary arteries, potential manifestations include spontaneous coronary artery dissection, distal tapering or long, smooth narrowing that may represent dissection, intramural hematoma, spasm, or tortuosity. Importantly, FMD must be identified in at least one other noncoronary arterial territory to attribute any coronary findings to FMD. Although there is limited evidence to guide treatment, many lesions heal spontaneously; thus, a conservative approach is generally preferred. The etiology is poorly understood, but there are ongoing efforts to better characterize FMD and define its genetic and molecular basis. This report reviews the clinical course of FMD involving the coronary arteries and provides guidance for diagnosis and treatment strategies. [ABSTRACT FROM AUTHOR]

Background The effectiveness of beta-blockers for preventing cardiac events has been questioned for patients who have coronary heart disease (CHD) without a prior myocardial infarction (MI). Objectives The purpose of this study was to assess the association of beta-blockers with outcomes among patients with new-onset CHD. Methods We studied consecutive patients discharged after the first CHD event (acute coronary syndrome or coronary revascularization) between 2000 and 2008 in an integrated healthcare delivery system who did not use beta-blockers in the year before entry. We used time-varying Cox regression models to determine the hazard ratio (HR) associated with beta-blocker treatment and used treatment-by-covariate interaction tests (pint) to determine whether the association differed for patients with or without a recent MI. Results A total of 26,793 patients were included, 19,843 of whom initiated beta-blocker treatment within 7 days of discharge from their initial CHD event. Over an average of 3.7 years of follow-up, 6,968 patients had an MI or died. Use of beta-blockers was associated with an adjusted HR for mortality of 0.90 (95% confidence limits [CL]: 0.84 to 0.96), and an adjusted HR for death or MI of 0.92 (CL: 0.87 to 0.97). The association between beta-blockers and outcomes differed significantly between patients with and without a recent MI (HR for death: 0.85 vs. 1.02, pint = 0.007; and HR for death or MI: 0.87 vs. 1.03, pint = 0.005). Conclusions Use of beta-blockers among patients with new-onset CHD was associated with a lower risk of cardiac events only among patients with a recent MI. [ABSTRACT FROM AUTHOR]

Abstract: Background: Although combined supine and prone acquisitions improve the detection of inferolateral obstructive coronary artery disease (CAD), the predictors of inaccurate detection of inferolateral ischemia have not been reported by using cadmium zinc telluride (CZT) myocardial perfusion imaging (MPI). Methods and results: Vasodilator stress 99mTc tetrofosmin MPI using CZT camera and coronary angiography was performed in 322 patients within an interval of 2months. Prone MPI was performed immediately after supine MPI. Narrowing of the luminal diameter ≥75% was considered significant. The presence of an abnormality on both supine and prone images was considered significant. Combined supine and prone imaging, compared with supine-only quantification, was more specific (93% vs. 72%, respectively, p<0.0001) and accurate (88% vs. 74%, p<0.0001) without compromising sensitivity (82% vs. 68%, p=0.10). The area under the curve for detecting inferolateral ischemia was 0.769 (95% CI 0.705–0.833) for supine imaging and 0.802 (95% CI 0.730–0.875) for combined supine and prone imaging (p<0.05). Multivariable analysis revealed that previous inferolateral myocardial infarction was an independent predictor of a false diagnosis (odds ratio=3.45, 95% confidence interval [CI] 1.62–7.37, p<0.001). Conclusions: Combined supine and prone quantitative CZT MPI enhances the detection of inferolateral CAD without adversely affecting its sensitivity. However, we recommend inferolateral ischemia be monitored in patients with a history of previous inferolateral MI because previous inferolateral MI is a predictor of inaccurate diagnosis. [Copyright &y& Elsevier]

Objectives: This study sought to determine the frequency and impact of coronary calcification among patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS). Background: Small studies in patients with stable coronary artery disease have suggested a worse prognosis after PCI of calcified compared with noncalcified lesions. Little is known about the impact of coronary calcification on outcomes after PCI for patients presenting with non–ST-segment elevation and ST-segment elevation ACS. Methods: Data from 6,855 patients presenting with ACS in whom PCI was performed were pooled from 2 large-scale randomized, controlled trials, ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) and HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction). One-year outcomes were analyzed according to the severity of PCI target lesion calcification (none/mild, moderate, or severe) as assessed by an independent angiographic core laboratory. Results: Target lesion calcification was severe in 402 patients (5.9%), moderate in 1,788 (26.1%), and none/mild in 4,665 (68.1%). Moderate/severe target lesion calcification was more frequent in older patients, men, hypertensive patients, and those presenting with ST-segment elevation myocardial infarction (STEMI). The unadjusted 1-year rates of death, cardiac death, definite stent thrombosis, and ischemic target lesion revascularization (TLR) and target vessel revascularization were significantly increased in patients with moderate/severe target lesion calcification. By multivariable analysis, the presence of moderate/severe target lesion calcification was an independent predictor of 1-year definite stent thrombosis (hazard ratio [HR]: 1.62; 95% confidence interval [CI]: 1.14 to 2.30; p = 0.007) and ischemic TLR (HR: 1.44; 95% CI: 1.17 to 1.78; p = 0.0007). Conclusions: Moderate/severe lesion calcification was relatively frequent in patients with non–ST-segment elevation ACS and STEMI and was strongly predictive of stent thrombosis and ischemic TLR at 1 year. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158; Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966) [ABSTRACT FROM AUTHOR]

The goal of this study was to review the prognostic value of cardiac magnetic resonance (CMR) imaging findings for future cardiovascular events in patients with a recent myocardial infarction (MI) and patients with suspected or known coronary artery disease (CAD). Although the diagnostic value of CMR findings is established, the independent prognostic association with future cardiovascular events remains largely unclear. Studies published by February 2013, identified by systematic MEDLINE and EMBASE searches, were reviewed for associations between CMR findings (left ventricular ejection fraction [LVEF], wall motion abnormalities [WMA], abnormal myocardial perfusion, microvascular obstruction, late gadolinium enhancement, edema, and intramyocardial hemorrhage) and hard events (all-cause mortality, cardiac death, cardiac transplantation, and MI) or major adverse cardiovascular events (MACE) (hard events and other cardiovascular events defined by the authors of the evaluated papers). Fifty-six studies (n = 25,497) were evaluated. For patients with recent MI, too few patients were evaluated to establish associations between CMR findings and hard events. LVEF (range of adjusted hazard ratios [HRs]: 1.03 to 1.05 per % decrease) was independently associated with MACE. In patients with suspected or known CAD, WMA (adjusted HRs: 1.87 to 2.99), inducible perfusion defects (adjusted HRs: 3.02 to 7.77), LVEF (adjusted HRs: 0.72 to 0.82 per 10% increase), and infarction (adjusted HRs: 2.82 to 9.43) were independently associated with hard events, and the presence of inducible perfusion defects was associated with MACE (adjusted HRs: 1.76 to 3.21). The independent predictor of future cardiovascular events for patients with a recent MI was LVEF, and the predictors for patients with suspected or known CAD were WMA, inducible perfusion defects, LVEF, and presence of infarction. [Copyright &y& Elsevier]

Abstract: Background: Coronary artery disease (CAD) diagnosis by coronary computed tomographic angiography (CCTA) is useful for identification of symptomatic diabetic individuals at heightened risk for death. Whether CCTA-detected CAD enables improved risk assessment of asymptomatic diabetic individuals beyond clinical risk factors and coronary artery calcium scoring (CACS) remains unexplored. Methods: From a prospective 12-center international registry of 27,125 individuals undergoing CCTA, we identified 400 asymptomatic diabetic individuals without known CAD. Coronary stenosis by CCTA was graded as 0%, 1–49%, 50–69%, and ≥70%. CAD was judged on a per-patient, per-vessel and per-segment basis as maximal stenosis severity, number of vessels with ≥50% stenosis, and coronary segments weighted for stenosis severity (segment stenosis score), respectively. We assessed major adverse cardiovascular events (MACE) – inclusive of mortality, nonfatal myocardial infarction (MI), and late target vessel revascularization ≥90 days (REV) – and evaluated the incremental utility of CCTA for risk prediction, discrimination and reclassification. Results: Mean age was 60.4 ± 9.9 years; 65.0% were male. At a mean follow-up 2.4 ± 1.1 years, 33 MACE occurred (13 deaths, 8 MI, 12 REV) [8.25%; annualized rate 3.4%]. By univariate analysis, per-patient maximal stenosis [hazards ratio (HR) 2.24 per stenosis grade, 95% confidence interval (CI) 1.61–3.10, p < 0.001], increasing numbers of obstructive vessels (HR 2.30 per vessel, 95% CI 1.75–3.03, p < 0.001) and segment stenosis score (HR 1.14 per segment, 95% CI 1.09–1.19, p < 0.001) were associated with increased MACE. After adjustment for CAD risk factors and CACS, maximal stenosis (HR 1.80 per grade, 95% CI 1.18–2.75, p = 0.006), number of obstructive vessels (HR 1.85 per vessel, 95% CI 1.29–2.65, p < 0.001) and segment stenosis score (HR 1.11 per segment, 95% CI 1.05–1.18, p < 0.001) were associated with increased risk of MACE. Beyond age, gender and CACS (C-index 0.64), CCTA improved discrimination by maximal stenosis, number of obstructive vessels and segment stenosis score (C-index 0.77, 0.77 and 0.78, respectively). Similarly, CCTA findings improved risk reclassification by per-patient maximal stenosis [integrated discrimination improvement (IDI) index 0.03, p = 0.03] and number of obstructive vessels (IDI index 0.06, p = 0.002), and by trend for segment stenosis score (IDI 0.03, p = 0.06). Conclusion: For asymptomatic diabetic individuals, CCTA measures of CAD severity confer incremental risk prediction, discrimination and reclassification on a per-patient, per-vessel and per-segment basis. [Copyright &y& Elsevier]

Objectives: Knowing about a diagnostic probability requires general knowledge about the way in which the probability depends on the diagnostic indicators involved in the specification of the case at issue. Diagnostic probability functions (DPFs) are generally unavailable at present. Our objective was to illustrate how diagnostic experts' case-specific tacit knowledge about diagnostic probabilities could be garnered in the form of DPFs. Study Design and Setting: Focusing on diagnosis of acute coronary heart disease (ACHD), we presented doctors with extensive experience in hospitals' emergency departments a set of hypothetical cases specified in terms of an inclusive set of diagnostic indicators. We translated the medians of these experts' case-specific probabilities into a logistic DPF for ACHD. Results: The principal result was the experts' typical diagnostic probability for ACHD as a joint function of the set of diagnostic indicators. A related result of note was the finding that the experts' probabilities in any given case had a surprising degree of variability. Conclusion: Garnering diagnostic experts' case-specific tacit knowledge about diagnostic probabilities in the form of DPFs is feasible to accomplish. Thus, once the methodology of this type of work has been ''perfected,'' practice-guiding diagnostic expert systems can be developed. [ABSTRACT FROM AUTHOR]

Abstract: Background: We aimed to determine if timing of polysomnography (PSG) influences the diagnosis of obstructive sleep apnea (OSA) in acute myocardial infarction (AMI) or stable coronary artery disease (CAD). Methods: A total of 160 patients admitted with AMI or stable CAD were consecutively recruited for either in-hospital (n =80) or postdischarge (n =80) PSG. Results: The median time from admission to PSG for the in-hospital and postdischarge groups was 1day and 17days, respectively (P <.001). Overall, 59 patients (36.9%) were diagnosed with OSA (apnea–hypopnea index [AHI] ⩾15), and they were more likely to have diabetes mellitus (DM), hypertension, hyperlipidemia, chronic renal failure, and a greater body mass index (BMI) (P <.05 for all). The diagnosis of OSA was significantly higher (P =.037) in patients who had a PSG performed as an inpatient than those who had a PSG as an outpatient. There was a significant interaction between clinical presentation and the effect of PSG timing on the diagnosis of OSA (P =.003). For the patients presenting with AMI but not those with stable CAD, in-hospital PSG was an independent predictor of OSA (adjusted odds ratio, 3.84 [95% confidence interval, 1.42–10.41]; P =.008). Conclusion: The timing of PSG influenced the diagnosis of OSA in patients who presented with AMI but not in those who presented with stable CAD. [Copyright &y& Elsevier]

Abstract: Background: Angiographically-normal coronary arteries are reported in 10–20% of patients undergoing diagnostic coronary angiography despite screening with risk factors and functional tests. We sought to validate and determine the clinical value of radial artery pulse wave analysis (PWA), a simple, quick and non-invasive marker of central artery stiffness and define its ability to predict coronary artery disease in high-risk patients. Materials and methods: 531 consecutive patients referred for elective coronary angiography, irrespective of previous co-morbidity, were assessed in a prospective, multicenter observational study [the Alternative Risk Markers in Coronary Artery Disease (ARM-CAD) study]. Results: Mean age was 65±11years, 33% were women, 18% had impaired left-ventricular function and 22% a prior myocardial infarction. Angiography demonstrated normal coronary arteries in 20% of participants. The only independent associations with this outcome were younger age, female gender, absence of diabetes and PWA-derived central augmentation pressure <24mm Hg. The odds ratio for the latter after adjustment for medications and baseline risk factors (including blood pressure, high-sensitivity C-reactive protein and B-type natriuretic peptide) was 3.4 (95% CI 1.2 to 9.5; p=0.021). The specificity for the multivariate model that included PWA was 95.7% with a receiver operator curve area of 0.876. Validation studies suggested that systolic variables from PWA were robust regardless of waveform quality and similar to measured aortic pressures (mean difference 2.7mm Hg). Conclusions: Assessment of radial artery waveforms is a useful non-invasive clinical test that can stratify the likelihood of coronary disease and assist in identifying patients who require diagnostic angiography. [Copyright &y& Elsevier]

Purpose: The purpose of this study is to compare the clinical characteristics and outcomes of patients with and without coronary artery disease (CAD) confirmed by coronary angiography in critically ill patients clinically diagnosed with myocardial infarction. Materials and methods: This retrospective observational study involved 56 patients who were clinically diagnosed with myocardial infarction and subsequently underwent coronary angiography during their intensive care unit stay. Results: Only 18 patients (32%) were finally confirmed to have CAD by coronary angiography. There were no significant differences in laboratory findings and clinical outcomes between patients with and without CAD. However, patients who developed shock (P = .009) and needed vasopressor support (P = .021) were less likely to be diagnosed with CAD. In addition, regional wall motion abnormality on echocardiography was more frequently observed in patients with CAD (P = .072). In a multiple logistic regression analysis, male sex (adjusted odds ratio [OR], 5.093; 95% confidence interval [CI], 1.177- 22.037) and focal hypokinesia on echocardiography (adjusted OR, 5.134; 95% CI, 1.071-24.614) were independently associated with CAD. However, development of shock was inversely associated with CAD (adjusted OR, 0.107; 95% CI, 0.019-0.606). Conclusion: Coronary angiography in critically ill patients should only be performed in highly selected patients with predicting factors for CAD. [ABSTRACT FROM AUTHOR]

Abstract: Coronary atherosclerosis is the leading cause of sudden death in developed nations. Triggers for sudden death include physical and emotional stress. At autopsy coronary artery atheroma is a common finding and may or may not be related to the cause of death. The forensic pathologist must consider the relative significant of disease, trauma and toxicological findings when determining the cause of death. This requires a consideration of evidence beyond the autopsy including the history, scene and ancillary investigations. Certain drugs including cocaine and methamphetamine are known to be atherogenic and acute and chronic use may be a factor in sudden death with underlying coronary artery atherosclerosis. Sudden death may also be associated with criminal conduct, when the scenario of “homicide by heart attack” needs to be considered. This paper analyses forensic aspects of coronary artery disease. [Copyright &y& Elsevier]

Abstract: Coronary artery calcification (CAC) is a well-known marker for coronary artery disease and has important prognostic implications. CAC is able to provide clinicians with a reliable source of information related to cardiovascular atherosclerosis, which carries incremental information beyond Framingham risk. However, non-contrast scans of the heart provide additional information beyond the Agatston score. These studies are also able to measure various sources of fat, including intrathoracic (eg, pericardial or epicardial) and hepatic, both of which are thought to be metabolically active and linked to increased incidence of subclinical atherosclerosis as well as increased prevalence of type 2  diabetes. Testing for CAC is also useful in identifying extracoronary sources of calcification. Specifically, aortic valve calcification, mitral annular calcification, and thoracic aortic calcium (TAC) provide additional risk stratification information for cardiovascular events. Finally, scanning for CAC is able to evaluate myocardial scaring due to myocardial infarcts, which may also add incremental prognostic information. To ensure the benefits outweigh the risks of a scanning for CAC for an appropriately selected asymptomatic patient, the full utility of the scan should be realized. This review describes the current state of the art interpretation of non-contrast cardiac CT, which clinically should go well beyond coronary artery Agatston scoring alone. [Copyright &y& Elsevier]

Background: In acute myocardial infarction (AMI), both tissue necrosis and edema are present and both might be implicated in the development of intraventricular dyssynchrony. However, their relative contribution to transient dyssynchrony is not known. Cardiovascular magnetic resonance (CMR) can detect necrosis and edema with high spatial resolution and it can quantify dyssynchrony by tagging techniques. Methods: Patients with a first AMI underwent percutaneous coronary interventions (PCI) of the infarct-related artery within 24 h of onset of chest pain. Within 5-7 days after the event and at 4 months, CMR was performed. The CMR protocol included the evaluation of intraventricular dyssynchrony by applying a novel 3D-tagging sequence to the left ventricle (LV) yielding the CURE index (circumferential uniformity ratio estimate; 1 = complete synchrony). On T2-weighted images, edema was measured as high-signal (>2 SD above remote tissue) along the LV mid-myocardial circumference on 3 short-axis images (% of circumference corresponding to the area-at-risk). In analogy, on late-gadolinium enhancement (LGE) images, necrosis was quantified manually as percentage of LV mid-myocardial circumference on 3 short-axis images. Necrosis was also quantified on LGE images covering the entire LV (expressed as %LV mass). Finally, salvaged myocardium was calculated as the area-at-risk minus necrosis (expressed as % of LV circumference). Results: After successful PCI (n = 22, 2 female, mean age: 57 ± 12y), peak troponin T was 20 ± 36ug/l and the LV ejection fraction on CMR was 41 ± 8%. Necrosis mass was 30 ± 10% and CURE was 0.91 ± 0.05. Edema was measured as 58 ± 14% of the LV circumference. In the acute phase, the extent of edema correlated with dyssynchrony (r2 = ?0.63, p<0.01), while extent of necrosis showed borderline correlation (r2 =-0.19, p = 0.05). PCI resulted in salvaged myocardium of 27 ± 14%. LV dyssynchrony (=CURE) decreased at 4 months from 0.91 ± 0.05 to 0.94 ± 0.03 (p<0.004, paired t-test). At 4 months, edema was absent and scar %LV slightly shrunk to 23.7 ± 10.0% (p<0.002 vs baseline). Regression of LV dyssynchrony during the 4 months follow-up period was predicted by both, the extent of edema and its necrosis component in the acute phase. Conclusions: In the acute phase of infarction, LV dyssynchrony is closely related to the extent of edema, while necrosis is a poor predictor of acute LV dyssynchrony. Conversely, regression of intraventricular LV dyssynchrony during infarct healing is predicted by the extent of necrosis in the acute phase. [ABSTRACT FROM AUTHOR]

The article presents a study on the costs of different methods for the detection of coronary artery stenoses in patients with possible coronary artery disease (CAD). It used a group of patients who underwent cardiovascular magnetic resonance (CMR). It performed methods such as cost analysis and randomized controlled trials (RCTs). Results show cost savings of 50%, 25% and 23% in the public sectors of the health care systems in Germany, Great Britain and Switzerland, respectively.

Objectives: The purpose of this study was to determine the prognostic value of strain-encoded magnetic resonance imaging (SENC) during high-dose dobutamine stress cardiac magnetic resonance imaging (DS-MRI) compared with conventional wall motion readings. Background: Detection of inducible ischemia by DS-MRI on the basis of assessing cine images is subjective and depends on the experience of the readers, which may influence not only the diagnostic classification but also the risk stratification of patients with ischemic heart disease. Methods: In all, 320 consecutive patients with suspected or known coronary artery disease underwent DS-MRI, using a standard protocol in a 1.5T MR scanner. Wall motion abnormalities (WMA) and myocardial strain were assessed at baseline and during stress, and outcome data including cardiac deaths, nonfatal myocardial infarctions (“hard events”), and revascularization procedures performed >90 days after the MR scans were collected. Results: Thirty-five hard events occurred during a 28 ± 9 month follow-up period, including 10 cardiac deaths and 25 nonfatal myocardial infarctions, and 32 patients underwent coronary revascularization. Using a series of Cox proportional-hazards models, both resting and inducible WMA offered incremental information for the assessment of hard cardiac events compared to clinical variables (chi-square = 13.0 for clinical vs. chi-square = 26.1 by adding resting WMA, p < 0.001, vs. chi-square = 39.3 by adding inducible WMA, p < 0.001). Adding visual SENC or quantitative strain rate reserve to this model further improved the prediction of outcome (chi-square = 50.7 vs. chi-square = 52.5, p < 0.001 for both). In a subset of patients (n = 175) who underwent coronary angiography, SENC yielded significantly higher sensitivity for coronary artery disease detection (96% vs. 84%, p < 0.02), whereas specificity and accuracy were not significantly different (88% vs. 94% and 93% vs. 88%, p = NS for both). Conclusions: Strain-encoded MRI aids the accurate identification of patients at high risk for future cardiac events and revascularization procedures, beyond the assessment of conventional atherogenic risk factors and resting or inducible WMA on cine images. (Strain-Encoded Cardiac Magnetic Resonance Imaging as an Adjunct for Dobutamine Stress Testing; NCT00758654) [Copyright &y& Elsevier]

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Abstract: Backgrounds: In a recent small study, patients with autoantibodies to cardiac troponin (cTnaAb) had higher cardiac troponin I (cTnI) release during an episode of acute coronary syndrome (ACS) than patients without cTnaAb and continued to have higher long-term levels of cTnI. However, the prognostic importance of the occurrence of cTnaAb is unknown. Methods: In 957 nonST-elevation ACS patients cTnaAb and cTnI were analyzed at randomization and after 6months. Outcomes were assessed through 5years. Results: Seven and 11% of the patients were cTnaAb positive at inclusion and 6months, respectively. The cardiac troponin I (cTnI) concentration at inclusion was independently associated with the development of cTnaAb (OR 1.53, 95% CI 1.25–1.88). The presence of cTnaAb was associated with an increased cTnI level at 6months (OR 2.39, 95% CI 1.50–3.81). cTnaAb was not independently associated with death and AMI during follow-up (HR 0.97, 95% CI 0.61–1.54). Conclusion: Development of cTnaAb after an episode of nonST-elevation ACS is associated with the acute myocardial damage, but occurs only in a minority of patients. Furthermore, the presence of cTnaAb is associated with chronically elevated cTnI concentrations. However, the occurrence of cTnaAb is not associated with an adverse long-term prognosis. [ABSTRACT FROM AUTHOR]