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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]

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]

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]

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]

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]

Alterations in xanthine oxidase activity are known to be pathologically influential on coronary artery disease (CAD), but the association between purine-related blood metabolites and CAD has only been partially elucidated. We performed global metabolomics profiling and network analysis on blood samples from the Wonju and Pyeongchang (WP) cohort study (n = 2055) to elucidate the importance of purine related metabolites associated with potential CAD risk. Then, 5 selected serum metabolites were quantified from the WP cohort, Shinchon cohort (n = 259), and Shinchon case control (n = 424) groups to develop machine learning models for 10-year risk prediction, relapse within 10 years and diagnosis of the disease via 100 repeated 5-fold cross-validations of logistic models. The combination of purine metabolite levels or only xanthine levels in blood could be applied for machine learning model development for major adverse cardiac and cerebrovascular event (MACCE, cerebrovascular death, nonfatal myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft, and stroke) risk prediction, relapse of MACCEs among patients with myocardial infarction history and diagnosis of stable CAD. In particular, our research provided initial evidence that blood xanthine and uric acid levels play different roles in the development of machine learning models for primary/secondary prevention or diagnosis of CAD. In this research, we determined that purine-related metabolites in blood are applicable to machine learning model development for CAD risk prediction and diagnosis. Also, our work advances current CAD biomarker discovery strategies mainly relying on clinical features; emphasizes the differential biomarkers in first/secondary prevention or diagnosis studies. • Purine-related metabolites in blood are applicable to machine learning model for CAD risk prediction and diagnosis. • Xanthine and uric acid levels play different roles in the development of machine learning models for prevention or diagnosis of CAD. • There are possible changes in the role of metabolic features in machine learning model developments for prevention or diagnosis of diseases. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) have imposed a massive health and financial burden worldwide with high mortality and morbidity. However, the diagnostic value of current biomarkers might be impaired by a wide variety of noncardiac causes. Moreover, cardiovascular outcomes, survival, and prognosis of patients with CVDs remain poor despite advances in treatment. Therefore, novel diagnostic and therapeutic strategies are urgently required for timely identification of possible heart diseases in the early stage, which might effectively contribute to reducing the CVDs-caused morbidity and mortality. Circular RNA (circRNA) was initially identified as aberrant byproducts or abnormally spliced transcripts. However, with advances in bioinformatics and high-throughput sequencing technology, circRNAs has become an essential topic on a wide range of biological functions and emerged as novel players in diagnostic and therapeutic strategies for CVDs. In this article, we briefly introduce the biogenesis and functions of circRNAs. Moreover, we describe the roles of circRNAs in multiple CVDs, including atherosclerosis, coronary artery disease, myocardial infarction, as well as cardiomyopathy. In addition, we provide an overview on the current challenges and directions for further application. • Introduce the biogenesis and function of circRNAs. • Discuss the roles of circRNAs in atherosclerosis, coronary artery disease, myocardial infarction and cardiomyopathy. • Provide an overview on the potential diagnostic and therapeutic application of circRNAs in CVDs. [ABSTRACT FROM AUTHOR]