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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 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]

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]

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]

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 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]