All-cause mortality benefit of coronary revascularization vs. medical therapy in patients without known coronary artery disease undergoing coronary computed tomographic angiography: results from CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter Registry)

Aims To date, the therapeutic benefit of revascularization vs. medical therapy for stable individuals undergoing invasive coronary angiography (ICA) based upon coronary computed tomographic angiography (CCTA) findings has not been examined. Methods and results We examined 15 223 patients without known coronary artery disease (CAD) undergoing CCTA from eight sites and six countries who were followed for median 2.1 years (interquartile range 1.4-3.3 years) for an endpoint of all-cause mortality. Obstructive CAD by CCTA was defined as a ≥50% luminal diameter stenosis in a major coronary artery. Patients were categorized as having high-risk CAD vs. non-high-risk CAD, with the former including patients with at least obstructive two-vessel CAD with proximal left anterior descending artery involvement, three-vessel CAD, and left main CAD. Death occurred in 185 (1.2%) patients. Patients were categorized into two treatment groups: revascularization (n = 1103; 2.2% mortality) and medical therapy (n = 14 120, 1.1% mortality). To account for non-randomized referral to revascularization, we created a propensity score developed by logistic regression to identify variables that influenced the decision to refer to revascularization. Within this model (C index 0.92, χ2 = 1248, P < 0.0001), obstructive CAD was the most influential factor for referral, followed by an interaction of obstructive CAD with pre-test likelihood of CAD (P = 0.0344). Within CCTA CAD groups, rates of revascularization increased from 3.8% for non-high-risk CAD to 51.2% high-risk CAD. In multivariable models, when compared with medical therapy, revascularization was associated with a survival advantage for patients with high-risk CAD [hazards ratio (HR) 0.38, 95% confidence interval 0.18-0.83], with no difference in survival for patients with non-high-risk CAD (HR 3.24, 95% CI 0.76-13.89) (P-value for interaction = 0.03). Conclusion In an intermediate-term follow-up, coronary revascularization is associated with a survival benefit in patients with high-risk CAD by CCTA, with no apparent benefit of revascularization in patients with lesser forms of CA

Clinical pre-test probability for obstructive coronary artery disease: insights from the European DISCHARGE pilot study.

To test the accuracy of clinical pre-test probability (PTP) for prediction of obstructive coronary artery disease (CAD) in a pan-European setting. Patients with suspected CAD and stable chest pain who were clinically referred for invasive coronary angiography (ICA) or computed tomography (CT) were included by clinical sites participating in the pilot study of the European multi-centre DISCHARGE trial. PTP of CAD was determined using the Diamond-Forrester (D+F) prediction model initially introduced in 1979 and the updated D+F model from 2011. Obstructive coronary artery disease (CAD) was defined by one at least 50% diameter coronary stenosis by both CT and ICA. In total, 1440 patients (654 female, 786 male) were included at 25 clinical sites from May 2014 until July 2017. Of these patients, 725 underwent CT, while 715 underwent ICA. Both prediction models overestimated the prevalence of obstructive CAD (31.7%, 456 of 1440 patients, PTP: initial D+F 58.9% (28.1-90.6%), updated D+F 47.3% (34.2-59.9%), both p < 0.001), but overestimation of disease prevalence was higher for the initial D+F (p < 0.001). The discriminative ability was higher for the updated D+F 2011 (AUC of 0.73 95% confidence interval [CI] 0.70-0.76 versus AUC of 0.70 CI 0.67-0.73 for the initial D+F; p < 0.001; odds ratio (or) 1.55 CI 1.29-1.86, net reclassification index 0.11 CI 0.05-0.16, p < 0.001). Clinical PTP calculation using the initial and updated D+F prediction models relevantly overestimates the actual prevalence of obstructive CAD in patients with stable chest pain clinically referred for ICA and CT suggesting that further refinements to improve clinical decision-making are needed. https://www.clinicaltrials.gov/ct2/show/NCT02400229 KEY POINTS: • Clinical pre-test probability calculation using the initial and updated D+F model overestimates the prevalence of obstructive CAD identified by ICA and CT. • Overestimation of disease prevalence is higher for the initial D+F compared with the updated D+F. • Diagnostic accuracy of PTP assessment varies strongly between different clinical sites throughout Europe

Prediction model to estimate presence of coronary artery disease: retrospective pooled analysis of existing cohorts

Objectives To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations

Early and Late Postnatal Myocardial and Vascular Changes in a Protein Restriction Rat Model of Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) is a risk factor for cardiovascular disease in later life. Early structural and functional changes in the cardiovascular system after IUGR may contribute to its pathogenesis. We tested the hypothesis that IUGR leads to primary myocardial and vascular alterations before the onset of hypertension. A rat IUGR model of maternal protein restriction during gestation was used. Dams were fed low protein (LP; casein 8.4%) or isocaloric normal protein diet (NP; casein 17.2%). The offspring was reduced to six males per litter. Immunohistochemical and real-time PCR analyses were performed in myocardial and vascular tissue of neonates and animals at day 70 of life. In the aortas of newborn IUGR rats expression of connective tissue growth factor (CTGF) was induced 3.2-fold. At day 70 of life, the expression of collagen I was increased 5.6-fold in aortas of IUGR rats. In the hearts of neonate IUGR rats, cell proliferation was more prominent compared to controls. At day 70 the expression of osteopontin was induced 7.2-fold. A 3- to 7-fold increase in the expression of the profibrotic cytokines TGF-β and CTGF as well as of microfibrillar matrix molecules was observed. The myocardial expression and deposition of collagens was more prominent in IUGR animals compared to controls at day 70. In the low-protein diet model, IUGR leads to changes in the expression patterns of profibrotic genes and discrete structural abnormalities of vessels and hearts in adolescence, but, with the exception of CTGF, not as early as at the time of birth. Invasive and non-invasive blood pressure measurements confirmed that IUGR rats were normotensive at the time point investigated and that the changes observed occurred independently of an increased blood pressure. Hence, altered matrix composition of the vascular wall and the myocardium may predispose IUGR animals to cardiovascular disease later in life

Health-related qualify of life, angina type and coronary artery disease in patients with stable chest pain.

Health-related quality of life (HRQoL) is impaired in patients with stable angina but patients often present with other forms of chest pain. The aim of this study was to compare the pre-diagnostic HRQoL in patients with suspected coronary artery disease (CAD) according to angina type, gender, and presence of obstructive CAD. From the pilot study for the European DISCHARGE trial, we analysed data from 24 sites including 1263 patients (45.9% women, 61.1 ± 11.3 years) who were clinically referred for invasive coronary angiography (ICA; 617 patients) or coronary computed tomography angiography (CTA; 646 patients). Prior to the procedures, patients completed HRQoL questionnaires: the Short Form (SF)-12v2, the EuroQoL (EQ-5D-3 L) and the Hospital Anxiety and Depression Scale. Fifty-five percent of ICA and 35% of CTA patients had typical angina, 23 and 33% had atypical angina, 18 and 28% had non-anginal chest discomfort and 5 and 5% had other chest discomfort, respectively. Patients with typical angina had the poorest physical functioning compared to the other angina groups (SF-12 physical component score; 41.2 ± 8.8, 43.3 ± 9.1, 46.2 ± 9.0, 46.4 ± 11.4, respectively, all age and gender-adjusted p < 0.01), and highest anxiety levels (8.3 ± 4.1, 7.5 ± 4.1, 6.5 ± 4.0, 4.7 ± 4.5, respectively, all adjusted p < 0.01). On all other measures, patients with typical or atypical angina had lower HRQoL compared to the two other groups (all adjusted p < 0.05). HRQoL did not differ between patients with and without obstructive CAD while women had worse HRQoL compared with men, irrespective of age and angina type. Prior to a diagnostic procedure for stable chest pain, HRQoL is associated with chest pain characteristics, but not with obstructive CAD, and is significantly lower in women. Clinicaltrials.gov, NCT02400229

Comparative effectiveness of initial computed tomography and invasive coronary angiography in women and men with stable chest pain and suspected coronary artery disease: multicentre randomised trial

To assess the comparative effectiveness of computed tomography and invasive coronary angiography in women and men with stable chest pain suspected to be caused by coronary artery disease

Does coronary CT angiography improve risk stratification over coronary calcium scoring in symptomatic patients with suspected coronary artery disease? Results from the prospective multicenter international CONFIRM registry

Aims: The prognostic value of coronary artery calcium (CAC) scoring is well established and has been suggested for use to exclude significant coronary artery disease (CAD) for symptomatic individuals with CAD. Contrast-enhanced coronary computed tomographic angiography (CCTA) is an alternative modality that enables direct visualization of coronary stenosis severity, extent, and distribution. Whether CCTA findings of CAD add an incremental prognostic value over CAC in symptomatic individuals has not been extensively studied. Methods and results: We prospectively identified symptomatic patients with suspected but without known CAD who underwent both CAC and CCTA. Symptoms were defined by the presence of chest pain or dyspnoea, and pre-test likelihood of obstructive CAD was assessed by the method of Diamond and Forrester (D–F). CAC was measured by the method of Agatston. CCTAs were graded for obstructive CAD (>70% stenosis); and CAD plaque burden, distribution, and location. Plaque burden was determined by a segment stenosis score (SSS), which reflects the number of coronary segments with plaque, weighted for stenosis severity. Plaque distribution was established by a segment-involvement score (SIS), which reflects the number of segments with plaque irrespective of stenosis severity. Finally, a modified Duke prognostic index—accounting for stenosis severity, plaque distribution, and plaque location—was calculated. Nested Cox proportional hazard models for a composite endpoint of all-cause mortality and non-fatal myocardial infarction (D/MI) were employed to assess the incremental prognostic value of CCTA over CAC. A total of 8627 symptomatic patients (50% men, age 56 ± 12 years) followed for 25 months (interquartile range 17–40 months) comprised the study cohort. By CAC, 4860 (56%) and 713 (8.3%) patients had no evident calcium or a score of >400, respectively. By CCTA, 4294 (49.8%) and 749 (8.7%) had normal coronary arteries or obstructive CAD, respectively. At follow-up, 150 patients experienced D/MI. CAC improved discrimination beyond D–F and clinical variables (area under the receiver-operator characteristic curve 0.781 vs. 0.788, P = 0.004). When added sequentially to D–F, clinical variables, and CAC, all CCTA measures of CAD improved discrimination of patients at risk for D/MI: obstructive CAD (0.82, P < 0.001), SSS (0.81, P < 0.001), SIS (0.81, P = 0.003), and Duke CAD prognostic index (0.82, P < 0.0001). Conclusion: In symptomatic patients with suspected CAD, CCTA adds incremental discriminatory power over CAC for discrimination of individuals at risk of death or MI

Health-related qualify of life, angina type and coronary artery disease in patients with stable chest pain

Background Health-related quality of life (HRQoL) is impaired in patients with stable angina but patients often present with other forms of chest pain. The aim of this study was to compare the pre-diagnostic HRQoL in patients with suspected coronary artery disease (CAD) according to angina type, gender, and presence of obstructive CAD. Methods From the pilot study for the European DISCHARGE trial, we analysed data from 24 sites including 1263 patients (45.9% women, 61.1 +/- 11.3 years) who were clinically referred for invasive coronary angiography (ICA; 617 patients) or coronary computed tomography angiography (CTA; 646 patients). Prior to the procedures, patients completed HRQoL questionnaires: the Short Form (SF)-12v2, the EuroQoL (EQ-5D-3 L) and the Hospital Anxiety and Depression Scale. Results Fifty-five percent of ICA and 35% of CTA patients had typical angina, 23 and 33% had atypical angina, 18 and 28% had non-anginal chest discomfort and 5 and 5% had other chest discomfort, respectively. Patients with typical angina had the poorest physical functioning compared to the other angina groups (SF-12 physical component score; 41.2 +/- 8.8, 43.3 +/- 9.1, 46.2 +/- 9.0, 46.4 +/- 11.4, respectively, all age and gender-adjusted p < 0.01), and highest anxiety levels (8.3 +/- 4.1, 7.5 +/- 4.1, 6.5 +/- 4.0, 4.7 +/- 4.5, respectively, all adjusted p < 0.01). On all other measures, patients with typical or atypical angina had lower HRQoL compared to the two other groups (all adjusted p < 0.05). HRQoL did not differ between patients with and without obstructive CAD while women had worse HRQoL compared with men, irrespective of age and angina type. Conclusions Prior to a diagnostic procedure for stable chest pain, HRQoL is associated with chest pain characteristics, but not with obstructive CAD, and is significantly lower in women

Cardiac Computed Tomography: State of the Art and Future Horizons

Cardiac computed tomography (CT) has evolved over the past 20 years from an alternative, promising noninvasive imaging modality to a Class I indication for the non-invasive evaluation of patients with low-to-intermediate, pre-test probability of coronary artery disease (CAD), as per the European Society of Cardiology (ESC) guidelines published in 2019 [...