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Background Coronary artery calcium (CAC) has prognostic value for major adverse cardiovascular events (MACE) in asymptomatic individuals, whereas its role in symptomatic patients is less clear. Purpose To assess the prognostic value of CAC scoring for MACE in participants with stable chest pain initially referred for invasive coronary angiography (ICA). Materials and Methods This prespecified subgroup analysis from the Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial, conducted between October 2015 and April 2019 across 26 centers in 16 countries, focused on adult patients with stable chest pain referred for ICA. Participants were randomly assigned to undergo either ICA or coronary CT. CAC scores from noncontrast CT scans were categorized into low, intermediate, and high groups based on scores of 0, 1-399, and 400 or higher, respectively. The end point of the study was the occurrence of MACE (myocardial infarction, stroke, and cardiovascular death) over a median 3.5-year follow-up, analyzed using Cox proportional hazard regression tests. Results The study involved 1749 participants (mean age, 60 years ± 10 [SD]; 992 female). The prevalence of obstructive coronary artery disease (CAD) at CT angiography rose from 4.1% (95% CI: 2.8, 5.8) in the CAC score 0 group to 76.1% (95% CI: 70.3, 81.2) in the CAC score 400 or higher group. Revascularization rates increased from 1.7% to 46.2% across the same groups ( P < .001). The CAC score 0 group had a lower MACE risk (0.5%; HR, 0.08 [95% CI: 0.02, 0.30]; P < .001), as did the 1-399 CAC score group (1.9%; HR, 0.27 [95% CI: 0.13, 0.59]; P = .001), compared with the 400 or higher CAC score group (6.8%). No significant difference in MACE between sexes was observed ( P = .68). Conclusion In participants with stable chest pain initially referred for ICA, a CAC score of 0 showed very low risk of MACE, and higher CAC scores showed increasing risk of obstructive CAD, revascularization, and MACE at follow-up. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Hanneman and Gulsin in this issue.

Aims: Prominent left ventricular trabeculations is a phenotypic trait observed in cardiovascular diseases. In the general population, the extent of left ventricular trabeculations is highly variable, yet it is unknown whether increased trabeculation is associated with adverse outcome., Methods and Results: Left ventricular trabeculated mass (g/m2) was measured with contrast-enhanced cardiac computed tomography in 10 097 individuals from the Copenhagen General Population Study. The primary endpoint was a composite of major adverse cardiovascular events and defined as death, heart failure, myocardial infarction, or stroke. The secondary endpoints were the individual components of the primary endpoint. Cox regression models were adjusted for clinical parameters, medical history, electrocardiographic parameters, and cardiac chamber sizes. The mean trabeculated mass was 19.1 g/m2 (standard deviation 4.9 g/m2). During a median follow-up of 4.0 years (interquartile range 1.5-6.7), 710 major adverse cardiovascular events occurred in 619 individuals. Individuals with a left ventricular trabeculated mass in the highest quartile had a hazard ratio for major adverse cardiovascular events of 1.64 [95% confidence interval (CI) 1.30-2.08; P < 0.001] compared to those in the lowest quartile. Corresponding hazard ratios were 2.08 (95% CI 1.38-3.14; P < 0.001) for death, 2.63 (95% CI 1.61-4.31; P < 0.001) for heart failure, 1.08 (95% CI 0.56-2.08; P = 0.82) for myocardial infarction, and 1.07 (95% CI 0.72-1.57; P = 0.74) for stroke., Conclusion: Increased left ventricular trabeculation is independently associated with an increased rate of major adverse cardiovascular events in the general population., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: Left ventricular (LV) myocardial crypts are considered a subtle marker of hypertrophic cardiomyopathy. However, crypts have also been observed in seemingly healthy individuals and it is unknown whether myocardial crypts are associated with adverse outcome., Methods and Results: Myocardial crypts were defined as invaginations traversing >50% of the myocardial wall and assessed using contrast-enhanced cardiac computed tomography in 10 097 individuals from the Copenhagen General Population Study. Number of crypts, location, shape, penetrance, and volume were assessed. The endpoint was a composite of major adverse cardiovascular events and defined as death, myocardial infarction, heart failure, or stroke. Cox regression models were adjusted for clinical variables, medical history, electrocardiographic parameters, and cardiac chamber sizes. A total of 1199 LV myocardial crypts were identified in 915 (9.1%) individuals. Seven hundred (6.9%) had one crypt and 215 (2.1%) had multiple crypts. During a median follow-up of 4.0 years (interquartile range 1.5-6.7), major adverse cardiovascular events occurred in 619 individuals. Individuals with one or multiple crypts had a hazard ratio for major adverse cardiovascular events of 1.00 [95% confidence interval (CI): 0.72-1.40; P = 0.98] and 0.90 (95% CI: 0.47-1.75; P = 0.76), respectively, compared with those with no crypts. No specific pattern of crypt location, shape, penetrance, or volume was associated to an increased hazard ratio for major adverse cardiovascular events., Conclusion: LV myocardial crypts are frequent in the general population and are not associated with intermediate-term major adverse cardiovascular events., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: Myocardial infarction (MI) and gallstone disease (GSD) are intrinsically linked via cholesterol metabolism. We tested the hypothesis that genetic variants in the gene encoding cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver, are associated with risk of MI and GSD in the general population., Methods and Results: We performed tests of association between lipid levels and eight rare non-synonymous mutations and two common variants, rs2081687 and rs3808607, in CYP7A1 in 100 149 individuals from the general population. We further tested whether weighted allele scores for rs2081687 and rs3808607, which were associated with increased plasma levels of low-density lipoprotein (LDL) cholesterol, were associated with an increased risk of both MI and symptomatic GSD. During a mean follow-up of 7 years (0-23 years), MI developed in 2326 individuals and GSD in 2007. For rare mutations, CYP7A1 allele count was associated with an increase in LDL cholesterol of 12% (0.4 mmol/L) for individuals with the highest vs. the lowest allele count (P for trend = 3 × 10-4). For common variants, CYP7A1 weighted allele scores in individuals with a score >0.04 vs. ≤0 were associated with stepwise increases in LDL cholesterol of up to 2.4% (0.08 mmol/L), and with corresponding multifactorially adjusted hazard ratios of 1.25 [95% confidence interval (CI) 1.10-1.41] for MI and 1.39 (95% CI 1.22-1.59) for GSD (P for trend = 5 × 10-4 and 2 × 10-7, respectively). Results were similar in meta-analyses including publicly available data from large consortia., Conclusion: Genetic variants in CYP7A1 which are associated with increased levels of LDL cholesterol, are associated with an increased risk of both MI and GSD.

Background: Despite successful treatment of the culprit artery lesion by primary percutaneous coronary intervention (PCI) with stent implantation, thrombotic embolisation occurs in some cases, which impairs the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). We aimed to assess the clinical outcomes of deferred stent implantation versus standard PCI in patients with STEMI., Methods: We did this open-label, randomised controlled trial at four primary PCI centres in Denmark. Eligible patients (aged >18 years) had acute onset symptoms lasting 12 h or less, and ST-segment elevation of 0·1 mV or more in at least two or more contiguous electrocardiographic leads or newly developed left bundle branch block. Patients were randomly assigned (1:1), via an electronic web-based system with permuted block sizes of two to six, to receive either standard primary PCI with immediate stent implantation or deferred stent implantation 48 h after the index procedure if a stabilised flow could be obtained in the infarct-related artery. The primary endpoint was a composite of all-cause mortality, hospital admission for heart failure, recurrent infarction, and any unplanned revascularisation of the target vessel within 2 years' follow-up. Patients, investigators, and treating clinicians were not masked to treatment allocation. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01435408., Findings: Between March 1, 2011, and Feb 28, 2014, we randomly assigned 1215 patients to receive either standard PCI (n=612) or deferred stent implantation (n=603). Median follow-up time was 42 months (IQR 33-49). Events comprising the primary endpoint occurred in 109 (18%) patients who had standard PCI and in 105 (17%) patients who had deferred stent implantation (hazard ratio 0·99, 95% CI 0·76-1·29; p=0·92). Procedure-related myocardial infarction, bleeding requiring transfusion or surgery, contrast-induced nephopathy, or stroke occurred in 28 (5%) patients in the conventional PCI group versus 27 (4%) patients in the deferred stent implantation group, with no significant differences between groups., Interpretation: In patients with STEMI, routine deferred stent implantation did not reduce the occurrence of death, heart failure, myocardial infarction, or repeat revascularisation compared with conventional PCI. Results from ongoing randomised trials might shed further light on the concept of deferred stenting in this patient population., Funding: Danish Agency for Science, Technology and Innovation, and Danish Council for Strategic Research., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: The objective of this study was to test the hypothesis that the extent and severity of left ventricular myocardial hypoperfusion at rest, in addition to signs of left ventricular myocardial scar, are related to adverse long-term outcome in patients with non-ST-segment elevation myocardial infarction (NSTEMI)., Background: Multidetector computed tomography (MDCT) is a noninvasive test with a spatial resolution that allows for the assessment of transmural myocardial perfusion. In patients with suspected NSTEMI, the assessment of myocardial hypoperfusion could be clinically useful., Methods: MDCT was performed at rest before invasive treatment in 396 patients with NSTEMI. The transmural involvement of left ventricular hypoperfusion, the presence of intramyocardial fat or calcification, a summed defect score adding the extent of left ventricular myocardial hypoperfusion (0 to 64 point scale), and the transmural attenuation ratio between the subendocardial and the subepicardial myocardium were assessed. The study endpoint was a combination of death and hospitalization due to heart failure., Results: The median follow-up time of the study was 50 months, and the study endpoint was reached in 56 (15%) of the patients. In a Cox proportional hazards survival model with adjustments for known risk factors, both the summed defect score and transmural attenuation ratio were independently associated with adverse outcome (hazard ratio [HR]: 1.07; 95% confidence interval [CI]: 1.02 to 1.11; p = 0.004 and HR: 0.61; 95% CI: 0.44 to 0.85; p = 0.003, respectively). The presence of intramyocardial fat or calcification was also associated with adverse outcome (HR: 3.5; 95% CI: 1.2 to 10.7; p = 0.03) when compared with patients without any perfusion defect., Conclusions: The extent and severity of left ventricular myocardial hypoperfusion at rest and signs of left ventricular myocardial scar assessed with MDCT before invasive treatment is strongly linked to adverse long-term outcome in patients with NSTEMI., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Severity and extent of coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) guide treatment and may predict clinical outcome in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS).Objectives: This study tested the hypothesis that coronary computed tomography angiography (CTA) is equivalent to ICA for risk assessment in patients with NSTEACS.Methods: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial evaluated timing of treatment in relation to outcome in patients with NSTEACS and included a clinically blinded coronary CTA conducted prior to ICA. Severity of CAD was defined as obstructive (coronary stenosis ≥50%) or nonobstructive. Extent of CAD was defined as high risk (obstructive left main or proximal left anterior descending artery stenosis and/or multivessel disease) or non-high risk. The primary endpoint was a composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or heart failure.Results: Coronary CTA and ICA were conducted in 978 patients. During a median follow-up time of 4.2 years (interquartile range: 2.7 to 5.5 years), the primary endpoint occurred in 208 patients (21.3%). The rate of the primary endpoint was up to 1.7-fold higher in patients with obstructive CAD compared with in patients with nonobstructive CAD as defined by coronary CTA (hazard ratio [HR]: 1.74; 95% confidence interval [CI]: 1.22 to 2.49; p = 0.002) or ICA (HR: 1.54; 95% CI: 1.13 to 2.11; p = 0.007). In patients with high-risk CAD, the rate of the primary endpoint was 1.5-fold higher compared with the rate in those with non-high-risk CAD as defined by coronary CTA (HR: 1.56; 95% CI: 1.18 to 2.07; p = 0.002). A similar trend was noted for ICA (HR: 1.28; 95% CI: 0.98 to 1.69; p = 0.07).Conclusions: Coronary CTA is equivalent to ICA for the assessment of long-term risk in patients with NSTEACS. (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes [VERDICT]; NCT02061891). [ABSTRACT FROM AUTHOR]

Aims  Prominent left ventricular trabeculations is a phenotypic trait observed in cardiovascular diseases. In the general population, the extent of left ventricular trabeculations is highly variable, yet it is unknown whether increased trabeculation is associated with adverse outcome. Methods and results  Left ventricular trabeculated mass (g/m2) was measured with contrast-enhanced cardiac computed tomography in 10 097 individuals from the Copenhagen General Population Study. The primary endpoint was a composite of major adverse cardiovascular events and defined as death, heart failure, myocardial infarction, or stroke. The secondary endpoints were the individual components of the primary endpoint. Cox regression models were adjusted for clinical parameters, medical history, electrocardiographic parameters, and cardiac chamber sizes. The mean trabeculated mass was 19.1 g/m2 (standard deviation 4.9 g/m2). During a median follow-up of 4.0 years (interquartile range 1.5–6.7), 710 major adverse cardiovascular events occurred in 619 individuals. Individuals with a left ventricular trabeculated mass in the highest quartile had a hazard ratio for major adverse cardiovascular events of 1.64 [95% confidence interval (CI) 1.30–2.08; P  < 0.001] compared to those in the lowest quartile. Corresponding hazard ratios were 2.08 (95% CI 1.38–3.14; P  < 0.001) for death, 2.63 (95% CI 1.61–4.31; P  < 0.001) for heart failure, 1.08 (95% CI 0.56–2.08; P  = 0.82) for myocardial infarction, and 1.07 (95% CI 0.72–1.57; P  = 0.74) for stroke. Conclusion  Increased left ventricular trabeculation is independently associated with an increased rate of major adverse cardiovascular events in the general population. [ABSTRACT FROM AUTHOR]

Background Signs of pulmonary congestion obtained from cardiac computed tomography angiographic (coronary CTA) images have not previously been related to clinical congestion or outcome and the clinical value is, therefore, unknown. Our objective was to test the hypothesis that signs of pulmonary congestion predict clinical heart failure and adverse outcome in patients with myocardial infarction. Methods Coronary CTA was performed before invasive treatment in 400 prospectively included patients with non ST segment elevation myocardial infarction in an observational study. Using a previously described chest computed tomography evaluation algorithm, patients were classified as having “no congestion”, “mild to moderate congestion” or “severe congestion”. Results Using multivariate analyses, presence of pulmonary congestion on coronary CTA images was associated with age, female gender, left ventricular ejection fraction (LVEF) and left atrial size. The diagnostic accuracy for predicting clinical heart failure, defined as Killip class >1, was: sensitivity: 83%, specificity: 69%, positive predictive value: 25%, and negative predictive value: 97%. The median follow-up time was 50 months and the study end-point of death or hospitalization due to heart failure was reached in 68 (16%) patients. In a Cox proportional hazards model with adjustments for known risk factors and Killip class, the presence of “mild to moderate congestion” and “severe congestion” was independently associated with adverse outcome (Hazard ratio: 2.6 (95% CI:1.3–5.0) and 3.2 (1.3–7.5)). Conclusion Signs of pulmonary congestion on coronary CTA images are closely correlated to cardiac dysfunction, predict clinical heart failure, and provide prognostic value independent of LVEF and Killip class. [ABSTRACT FROM AUTHOR]

Background: We sought to assess predictability of excessive bleeding using thrombelastography (TEG), multiplate impedance aggregometry, and conventional coagulation tests including fibrinogen in patients undergoing coronary artery bypass graft (CABG) surgery.Methods: A total of 170 patients were enrolled in this prospective observational study. TEG, Multiplate aggregometry, and coagulation tests were sampled on the day before surgery. Excessive bleeding was defined as >1000 mL over 18 hours.Results: Multiplate-adenosine diphosphate (ADP) measurements were significantly lower in patients with excessive bleeding, 85.5AU ± 32.8 versus 108.5AU ± 30.0, p = 0.012. Bivariate analysis revealed body mass index, myocardial infarction, and multiplate-ADP as predictors of bleeding. In multivariable linear regression analysis, multiplate-ADP remained a significant predictor of bleeding (β: -6.2 [confidence interval: -12.0 to -0.3], p = 0.035). The lowest interval of multiplate-ADP (<50 AUC) was associated with significantly more bleeding and need for platelet concentrate transfusion. Fibrinogen levels <2.5 g/L were also found to be associated with excess bleeding (p = 0.020).Conclusions: Multiplate impedance aggregometry identified patients at risk for excessive bleeding after CABG. Low fibrinogen levels were associated with increased bleeding. Neither routine TEG parameters nor conventional coagulation tests were correlated with bleeding. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide and challenges the capacity of health care systems globally. Atherosclerosis is the underlying pathophysiological entity in two-thirds of patients with CVD. When considering that atherosclerosis develops over decades, there is potentially great opportunity for prevention of associated events such as myocardial infarction and stroke. Subclinical atherosclerosis has been identified in its early stages in young individuals; however, there is no consensus on how to prevent progression to symptomatic disease. Given the growing burden of CVD, a paradigm shift is required—moving from late management of atherosclerotic CVD to earlier detection during the subclinical phase with the goal of potential cure or prevention of events. Studies must focus on how precision medicine using imaging and circulating biomarkers may identify atherosclerosis earlier and determine whether such a paradigm shift would lead to overall cost savings for global health. [Display omitted] • Early-stage subclinical atherosclerosis can be identified in young individuals, but evidence-based strategies are needed to prevent progression of disease and clinical events. • Precision medicine using imaging and circulating biomarkers could facilitate early identification of atherosclerosis and the development of curative interventions. • A paradigm shift based on these principles could reduce the global burden of CVD with enormous implications for population health. [ABSTRACT FROM AUTHOR]