Kristian A. Øvrehus

Coronary plaque quantification and fractional flow reserve by coronary computed tomography angiography identify ischaemia-causing lesions

Abstract Aims Coronary plaque characteristics are associated with ischaemia. Differences in plaque volumes and composition may explain the discordance between coronary stenosis severity and ischaemia. We evaluated the association between coronary stenosis severity, plaque characteristics, coronary computed tomography angiography (CTA)-derived fractional flow reserve (FFRCT), and lesion-specific ischaemia identified by FFR in a substudy of the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps). Methods and results Coronary CTA stenosis, plaque volumes, FFRCT, and FFR were assessed in 484 vessels from 254 patients. Stenosis >50% was considered obstructive. Plaque volumes (non-calcified plaque [NCP], low-density NCP [LD-NCP], and calcified plaque [CP]) were quantified using semi-automated software. Optimal thresholds of quantitative plaque variables were defined by area under the receiver-operating characteristics curve (AUC) analysis. Ischaemia was defined by FFR or FFRCT ≤0.80. Plaque volumes were inversely related to FFR irrespective of stenosis severity. Relative risk (95% confidence interval) for prediction of ischaemia for stenosis >50%, NCP ≥185 mm3, LD-NCP ≥30 mm3, CP ≥9 mm3, and FFRCT ≤0.80 were 5.0 (3.0–8.3), 3.7 (2.4–5.6), 4.6 (2.9–7.4), 1.4 (1.0–2.0), and 13.6 (8.4–21.9), respectively. Low-density NCP predicted ischaemia independent of other plaque characteristics. Low-density NCP and FFRCT yielded diagnostic improvement over stenosis assessment with AUCs increasing from 0.71 by stenosis >50% to 0.79 and 0.90 when adding LD-NCP ≥30 mm3 and LD-NCP ≥30 mm3 + FFRCT ≤0.80, respectively. Conclusion Stenosis severity, plaque characteristics, and FFRCT predict lesion-specific ischaemia. Plaque assessment and FFRCT provide improved discrimination of ischaemia compared with stenosis assessment alone.

Coronary computed tomographic angiography in patients suspected of coronary artery disease: Impact of observer experience on diagnostic performance and interobserver reproducibility

BACKGROUND A high diagnostic performance of coronary computed tomographic angiography (CTA) in identifying coronary artery disease (CAD) has been shown in experienced high-volume centers. Whether this may be accomplished in centers with less CTA experience remains unknown. OBJECTIVES We determined the diagnostic performance and interobserver reproducibility of CTA in detecting significant CAD in a center with limited experience. METHODS In 209 patients, CTA was performed with 64-slice or dual-source CT technology, and analyses were performed independently by 2 inexperienced observers. Significant CAD by CTA was defined as >/=1 stenoses >/=50% or >/=1 nonevaluable segment, whereas significant CAD by invasive quantitative coronary angiography was defined as >/=1 stenoses >/=50%. We evaluated the influence of CAD pretest probability, Agatston score (AS), heart rate (HR), and observer experience on the diagnostic sensitivity, specificity, positive (PPV) and negative predictive values (NPV), interobserver reproducibility, and duration of CTA analysis. RESULTS Per-patient (CAD prevalence, 35%) sensitivity was 88%-99%, specificity was 78%-82%, PPV was 68%-74%, and NPV was 92%-99%. Overall interobserver reproducibility was good (kappa = 0.65). A significant temporal improvement was observed in diagnostic specificity (observer A: 68%-89%, P = 0.007; observer B: 71%-89%, P = 0.02), and interobserver reproducibility (kappa = 0.35-0.89, P = 0.01) during the study period. Duration of analysis decreased during the study period and was positively associated with CAD pretest probability and AS. CONCLUSIONS Suboptimal diagnostic performance and interobserver reproducibility must be anticipated during CTA implementation. A high diagnostic sensitivity, specificity, and interobserver reproducibility were achieved after a large number of studies performed with the state-of-the-art scanner technology.

Comparison of Usefulness of Exercise Testing Versus Coronary Computed Tomographic Angiography for Evaluation of Patients Suspected of Having Coronary Artery Disease

In patients suspected of having coronary artery disease (CAD), we compared the diagnostic sensitivity and specificity of exercise testing using ST-segment changes alone and ST-segment changes, angina pectoris, and hemodynamic variables compared to coronary computed tomographic angiography (CTA). Quantitative invasive coronary angiography was the reference method (>50% coronary lumen reduction). A positive exercise test was defined as the development of significant ST-segment changes (> or =1 mV measured 80 ms from the J-point), and the occurrence of one or more of the following criteria: ST-segment changes > or =1 mV measured 80 ms from the J-point, angina pectoris, ventricular arrhythmia (the occurrence of > or =3 premature ventricular beats), and > or =20 mm Hg decrease in systolic blood pressure during the test. Positive results on CTA were defined as a coronary lumen reduction of > or =50%. In 100 patients (61 +/- 9 years old, 50% men, and 29% prevalence of significant CAD), the diagnostic sensitivity and specificity of exercise testing using ST-segment changes was 45% (95% confidence interval 53% to 87%) and 63% (95% confidence interval 61% to 84%), respectively. However, the inclusion of all test variables yielded a sensitivity of 72% (95% confidence interval 53% to 87%) and a specificity of 37% (95% confidence interval 26% to 49%). The diagnostic sensitivity of 97% (95% confidence interval 82% to 100%) and specificity of 80% (95% confidence interval 69% to 89%) for CTA, however, were superior to any of the exercise test analysis strategies. In conclusion, in patients suspected of having CAD, the diagnostic sensitivity of exercise testing significantly improves if all test variables are included compared to using ST-segment changes exclusively. Furthermore, the superior diagnostic performance of CTA for the detection and exclusion of significant CAD might favor CTA as the first-line diagnostic test in patients suspected of having CAD.

Influence of coronary computed tomographic angiography on patient treatment and prognosis in patients with suspected stable angina pectoris.

We evaluated the influence of coronary computed tomographic angiography (CTA) as a first-line diagnostic test on patient treatment and prognosis. A total of 1,055 consecutive patients with suspected stable angina pectoris (mean age 55 ± 10 years, 56% women) and a low to intermediate pretest likelihood of coronary artery disease (CAD) were included in the present study. The patients were followed for a median of 18 months. The use of downstream diagnostic testing and medical therapy after CTA were recorded. The CTA result was normal in 49%, and nonobstructive and obstructive CAD (≥50% stenosis) was demonstrated in 31% and 15% of the patients, respectively. Coronary CTA was inconclusive in 5% of the patients. The use of antiplatelet therapy decreased with normal findings from CTA, and the use of antiplatelet and lipid-lowering agents increased in patients with CAD. Additional testing was performed in 2% of patients with normal CTA findings and in 7% and 82% of patients with nonobstructive or obstructive CAD, respectively. No patients without CAD, 0.9% of patients with nonobstructive CAD, and 1.9% of patients with obstructive CAD met the primary end point (cardiovascular death and myocardial infarction, p = 0.008). No patients without CAD, 1.5% of patients with nonobstructive CAD, and 30% patients with obstructive CAD met the secondary end point (cardiovascular death, myocardial infarction, and coronary revascularization, p <0.0001). In conclusion, in patients suspected of having angina, the findings from CTA influence patient treatment without resulting in excessive additional testing. Coronary CTA provides important prognostic information, with excellent intermediate-term outcomes in patients with normal CTA findings.

The coronary calcium score is a more accurate predictor of significant coronary stenosis than conventional risk factors in symptomatic patients: Euro-CCAD study ☆

AIMS In this retrospective study we assessed the predictive value of the coronary calcium score for significant (>50%) stenosis relative to conventional risk factors. METHODS AND RESULTS We investigated 5515 symptomatic patients from Denmark, France, Germany, Italy, Spain and the USA. All had risk factor assessment, computed tomographic coronary angiogram (CTCA) or conventional angiography and a CT scan for coronary artery calcium (CAC) scoring. 1539 (27.9%) patients had significant stenosis, 5.5% of whom had zero CAC. In 5074 patients, multiple binary regression showed the most important predictor of significant stenosis to be male gender (B=1.07) followed by diabetes mellitus (B=0.70) smoking, hypercholesterolaemia, hypertension, family history of CAD and age but not obesity. When the log transformed CAC score was included, it became the most powerful predictor (B=1.25), followed by male gender (B=0.48), diabetes, smoking, family history and age but hypercholesterolaemia and hypertension lost significance. The CAC score is a more accurate predictor of >50% stenosis than risk factors regardless of the means of assessment of stenosis. The sensitivity of risk factors, CAC score and the combination for prediction of >50% stenosis when measured by conventional angiogram was considerably higher than when assessed by CTCA but the specificity was considerably higher when assessed by CTCA. The accuracy of CTCA for predicting >50% stenosis using the CAC score alone was higher (AUC=0.85) than using a combination of the CAC score and risk factors with conventional angiography (AUC=0.81). CONCLUSION In symptomatic patients, the CAC score is a more accurate predictor of significant coronary stenosis than conventional risk factors.

Prognostic assessment of stable coronary artery disease as determined by coronary computed tomography angiography: a Danish multicentre cohort study

Aims To examine the 3.5 year prognosis of stable coronary artery disease (CAD) as assessed by coronary computed tomography angiography (CCTA) in real-world clinical practice, overall and within subgroups of patients according to age, sex, and comorbidity. Methods and results This cohort study included 16,949 patients (median age 57 years; 57% women) with new-onset symptoms suggestive of CAD, who underwent CCTA between January 2008 and December 2012. The endpoint was a composite of late coronary revascularization procedure >90 days after CCTA, myocardial infarction, and all-cause death. The Kaplan–Meier estimator was used to compute 91 day to 3.5 year risk according to the CAD severity. Comparisons between patients with and without CAD were based on Cox-regression adjusted for age, sex, comorbidity, cardiovascular risk factors, concomitant cardiac medications, and post-CCTA treatment within 90 days. The composite endpoint occurred in 486 patients. Risk of the composite endpoint was 1.5% for patients without CAD, 6.8% for obstructive CAD, and 15% for three-vessel/left main disease. Compared with patients without CAD, higher relative risk of the composite endpoint was observed for non-obstructive CAD [hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.01–1.63], obstructive one-vessel CAD (HR: 1.83; 95% CI: 1.37–2.44), two-vessel CAD (HR: 2.97; 95% CI: 2.09–4.22), and three-vessel/left main CAD (HR: 4.41; 95% CI :2.90–6.69). The results were consistent in strata of age, sex, and comorbidity. Conclusion Coronary artery disease determined by CCTA in real-world practice predicts the 3.5 year composite risk of late revascularization, myocardial infarction, and all-cause death across different groups of age, sex, or comorbidity burden.

Coronary calcification among 3477 asymptomatic and symptomatic individuals

Background Coronary artery calcification (CAC) can be detected by cardiac computed tomography (CT), is associated to cardiovascular risk, and common in asymptomatic individuals and patients referred for cardiac CT. Design CAC was evaluated in asymptomatic individuals and symptomatic patients referred for cardiac CT, to assess whether differences in CAC may be explained by symptoms or traditional cardiovascular risk factors. Methods The presence and extent of CAC, gender, family history of coronary artery disease, hypertension, hyperlipidaemia, diabetes and tobacco were compared in 1220 asymptomatic individuals aged 49–61 years and 2257 age-matched symptomatic patients referred for cardiac CT with suspected coronary artery disease. Results Symptomatic individuals had a higher frequency of a family history of coronary artery disease (46% vs. 23%, p < 0.001), hypertension (38% vs. 21%, p < 0.001), hyperlipidaemia (42% vs. 12%, p < 0.001), a trend for more diabetes (6% vs. 5%, p = 0.05), but no significant difference was observed for the presence of CAC (Agatston > 0; 45% vs. 45%, p = 0.94) or severe calcifications (Agatston > 400; 6% vs. 5%, p = 0.36). In multivariate analyses age (odds ratio (OR) 1.09–1.18), male gender (OR 3.5–6.43), hypertension (OR 1.42–1.79), hyperlipidaemia (OR 1.86–2.09) and tobacco use (OR 1.83–2.01) were predictors for the presence and extent of CAC, whereas symptoms were not predictive for the presence of (Agatston > 0, OR 0.70 (0.59–0.83)), mild (Agatston ≥ 10; OR 0.85 (0.71–1.02)), moderate (Agatston ≥ 100; OR 0.99 (0.79–1.24)) or severe calcifications (Agatston ≥ 400; OR 0.93 (0.65–1.33)). Conclusion No difference in the presence or severity of coronary calcifications was observed between asymptomatic and symptomatic middle-aged individuals. After adjusting for cardiovascular risk factors, symptoms were not predictive for the presence or extent of CAC.

Paradigm of pretest risk stratification before coronary computed tomography

BACKGROUND The optimal method of determining the pretest risk of coronary artery disease as a patient selection tool before coronary multidetector computed tomography (MDCT) is unknown. OBJECTIVE We investigated the ability of 3 different clinical risk scores to predict the outcome of coronary MDCT. METHODS This was a retrospective study of 551 patients consecutively referred for coronary MDCT on a suspicion of coronary artery disease. Diamond-Forrester, Duke, and Morise risk models were used to predict coronary artery stenosis (>50%) as assessed by coronary MDCT. The models were compared by receiver operating characteristic analysis. The distribution of low-, intermediate-, and high-risk persons, respectively, was established and compared for each of the 3 risk models. RESULTS Overall, all risk prediction models performed equally well. However, the Duke risk model classified the low-risk patients more correctly than did the other models (P < 0.01). In patients without coronary artery calcification (CAC), the predictive value of the Duke risk model was superior to the other risk models (P < 0.05). Currently available risk prediction models seem to perform better in patients without CAC. Between the risk prediction models, there was a significant discrepancy in the distribution of patients at low, intermediate, or high risk (P < 0.01). CONCLUSIONS The 3 risk prediction models perform equally well, although the Duke risk score may have advantages in subsets of patients. The choice of risk prediction model affects the referral pattern to MDCT.

Individual patient data meta-analysis for the clinical assessment of coronary computed tomography angiography: protocol of the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT)

BackgroundCoronary computed tomography angiography has become the foremost noninvasive imaging modality of the coronary arteries and is used as an alternative to the reference standard, conventional coronary angiography, for direct visualization and detection of coronary artery stenoses in patients with suspected coronary artery disease. Nevertheless, there is considerable debate regarding the optimal target population to maximize clinical performance and patient benefit. The most obvious indication for noninvasive coronary computed tomography angiography in patients with suspected coronary artery disease would be to reliably exclude significant stenosis and, thus, avoid unnecessary invasive conventional coronary angiography. To do this, a test should have, at clinically appropriate pretest likelihoods, minimal false-negative outcomes resulting in a high negative predictive value. However, little is known about the influence of patient characteristics on the clinical predictive values of coronary computed tomography angiography. Previous regular systematic reviews and meta-analyses had to rely on limited summary patient cohort data offered by primary studies. Performing an individual patient data meta-analysis will enable a much more detailed and powerful analysis and thus increase representativeness and generalizability of the results. The individual patient data meta-analysis is registered with the PROSPERO database (CoMe-CCT, CRD42012002780).Methods/DesignThe analysis will include individual patient data from published and unpublished prospective diagnostic accuracy studies comparing coronary computed tomography angiography with conventional coronary angiography. These studies will be identified performing a systematic search in several electronic databases. Corresponding authors will be contacted and asked to provide obligatory and additional data. Risk factors, previous test results and symptoms of individual patients will be used to estimate the pretest likelihood of coronary artery disease. A bivariate random-effects model will be used to calculate pooled mean negative and positive predictive values as well as sensitivity and specificity. The primary outcome of interest will be positive and negative predictive values of coronary computed tomography angiography for the presence of coronary artery disease as a function of pretest likelihood of coronary artery disease, analyzed by meta-regression. As a secondary endpoint, factors that may influence the diagnostic performance and clinical value of computed tomography, such as heart rate and body mass index of patients, number of detector rows, and administration of beta blockade and nitroglycerin, will be investigated by integrating them as further covariates into the bivariate random-effects model.DiscussionThis collaborative individual patient data meta-analysis should provide answers to the pivotal question of which patients benefit most from noninvasive coronary computed tomography angiography and thus help to adequately select the right patients for this test.

Computed tomography derived fractional flow reserve testing in stable patients with typical angina pectoris: influence on downstream rate of invasive coronary angiography

Abstract Aims To assess the use of downstream coronary angiography (ICA) and short-term safety of frontline coronary CT angiography (CTA) with selective CT-derived fractional flow reserve (FFRCT) testing in stable patients with typical angina pectoris. Methods and results Between 1 January 2016 and 30 June 2016 all patients (N = 774) referred to non-emergent ICA or coronary CTA at Aarhus University Hospital on a suspicion of CAD had frontline CTA performed. Downstream testing and treatment within 3 months and adverse events ≥90 days were registered. Patients were divided into two groups according to the presence of typical angina pectoris, which according to local practice would have resulted in referral to ICA, (low-intermediate-risk, n = 593 [76%]; high-risk, n = 181 [24%]) with mean pre-test probability of CAD of 31 ± 16% and 67 ± 16%, respectively. Coronary CTA was performed in 745 (96%) patients in whom FFRCT was prescribed in 212 (28%) patients. In the high- vs. low-intermediate-risk group, ICA was cancelled in 75% vs. 91%. Coronary revascularization was performed more frequently in high-risk than in low-intermediate-risk patients, 76% vs. 52% (P = 0.03). Mean follow-up time was 157 ± 50 days. Serious clinical events occurred in four patients, but not in any patients with cancelled ICA by coronary CTA with selective FFRCT testing. Conclusion Frontline coronary CTA with selective FFRCT testing in stable patients with typical angina pectoris in real-world practice is associated with a high rate of safe cancellation of planned ICAs.