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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: 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: 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: 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: 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]

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]

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]