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Aims Dynamic myocardial computed tomography (CT) perfusion (DM-CTP) can, in combination with coronary CT angiography (CCTA), provide anatomical and functional evaluation of coronary artery disease (CAD). However, normal values of myocardial blood flow (MBF) are needed to identify impaired myocardial blood supply in patients with suspected CAD. We aimed to establish normal values for MBF measured using DM-CTP, to assess the effects of age and sex, and to assess regional distribution of MBF. Methods and results A total of 82 healthy individuals (46 women) aged 45–78 years with normal coronary arteries by CCTA underwent either rest and adenosine stress DM-CTP (n = 30) or adenosine-induced stress DM-CTP only (n = 52). Global and segmental MBF were assessed. Global MBF at rest and during stress were 0.93 ± 0.42 and 3.58 ± 1.14 mL/min/g, respectively. MBF was not different between the sexes (P = 0.88 at rest and P = 0.61 during stress), and no correlation was observed between MBF and age (P = 0.08 at rest and P = 0.82 during stress). Among the 16 myocardial segments, significant intersegmental differences were found (P < 0.01), which was not related to age, sex, or coronary dominance. Conclusion MBF assessed by DM-CTP in healthy individuals with normal coronary arteries displays significant intersegmental heterogeneity which does not seem to be affected by age, sex, or coronary dominance. Normal values of MBF may be helpful in the clinical evaluation of suspected myocardial ischaemia using DM-CTP. [ABSTRACT FROM AUTHOR]

We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT). 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue. Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p <0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm3; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm3; patients with ACS: 370 [332-412] vs. 159 [139-182] mm3. After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm3, p <0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm3, p <0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm3) compared to both asymptomatic individuals (15 [13-18] mm3, p <0.0001) and acute chest pain patients without ACS (21 [18-24] mm3, p <0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm3, p >0.3 respectively. Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not. [ABSTRACT FROM AUTHOR]

Background Studies on the pulmonary consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are impeded by limited access to pre–SARS-CoV-2 examinations. Methods We invited Copenhagen General Population Study participants with a confirmed SARS-CoV-2 polymerase chain reaction (PCR) test during the first and second coronavirus disease 2019 waves in Denmark for a repeat chest computed tomography (CT) scan. Paired CT scans were independently assessed for interstitial and noninterstitial abnormalities by 2 trained radiologists. A semiquantitative CT score (ranging from 0 to 20) was used to quantify the extent of interstitial abnormalities. Results Of 111 SARS-CoV-2–infected individuals, 102 (91.2%) experienced symptoms and 12 (11.2%) were hospitalized. Follow-up examination was performed at median of 5.4 (interquartile range, 4.1–7.8) months after a positive SARS-CoV-2 PCR test. Of 67 individuals with paired CT scans, ground glass opacities and reticulation were present in 31 (46.3%) individuals post–SARS-CoV-2 compared to 23 (34.1%) pre–SARS-CoV-2 (mean CT score, 3.0 vs 1.3; P =.011). Results were similar for nonhospitalized individuals. We did not detect development of bronchiectasis, emphysema, or nodules. Conclusions SARS-CoV-2 infection in predominantly nonhospitalized individuals with mild disease was associated with a small increase in only interstitial lung abnormalities. [ABSTRACT FROM AUTHOR]

Background Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and represents a wide spectrum ranging from mild steatosis to non-alcoholic steatohepatitis with or without fibrosis to overt cirrhosis. Patients with NAFLD have a high risk of developing cardiovascular disease and chronic kidney disease (CKD). So far there has been scarce evidence of the prevalence of NAFLD among patients with CKD. We investigated the prevalence of moderate–severe hepatic steatosis graded according to the definition of NAFLD in a cohort of patients with CKD. Methods Hepatic liver fat content was evaluated by computed tomography (CT) scan in 291 patients from the Copenhagen CKD Cohort Study and in 866 age- and sex-matched individuals with normal kidney function from the Copenhagen General Population Study. Liver attenuation density <48 HU was used as a cut-off value for moderate–severe hepatic steatosis. Results The prevalence of moderate–severe hepatic steatosis was 7.9 and 10.7% (P = 0.177) among patients with CKD and controls, respectively. No association between liver fat content and CKD stage was found. In the pooled dataset from both cohorts, adjusted odds ratios for moderate–severe hepatic steatosis among persons with diabetes, overweight and obesity were 3.1 [95% confidence interval (CI) 1.6–5.9], 14.8 (95% CI 4.6–47.9) and 42.0 (95% CI 12.9–136.6), respectively. Conclusions In a cohort of 291 patients with CKD, kidney function was not associated with the prevalence of moderate–severe hepatic steatosis as assessed by CT scan. [ABSTRACT FROM AUTHOR]

Aims The role of atherosclerosis in the pathogenesis of aortic enlargement is uncertain. We aimed to evaluate the relationship between the diameters of the ascending, descending and abdominal aorta, and coronary artery calcification. Methods and results Individuals in the Copenhagen General Population Study underwent thoracic and abdominal computed tomography. Maximal aortic diameters were measured in each aortic segment and coronary artery calcium scores (CACS) were calculated. Participants were stratified into five predefined groups according to CACSs and compared to aortic dimensions. The relation between aortic diameter and CACS was adjusted for risk factors for aortic dilatation in a multivariable model. A total of 2678 eligible individuals were included. In all segments of the aorta, aortic diameter was associated to CACSs, with mean increases in aortic diameters ranging from 0.7 to 3.5 mm in individuals with calcified coronary arteries compared to non-calcified subjects (P -value < 0.001). After correction for risk factors, individuals with CACS above 400 had larger ascending, descending and abdominal aortic diameter than the non-calcified reference group (P -value < 0.01). Conclusion Enlarged thoracic and abdominal aortic vascular segments are associated with co-existing coronary artery calcification in the general population. [ABSTRACT FROM AUTHOR]

A correction to the article "Computed Tomography Versus Invasive Coronary Angiography in Patients With Diabetes and Suspected Coronary Artery Disease" in the Diabetes Care (date) issue is presented which includes the addition of the clinical trial number.

Background: Pulmonary artery enlargement is a marker of pulmonary hypertension. We aimed to determine the proportion with pulmonary artery enlargement among well-treated persons with human immunodeficiency virus HIV (PWH) and uninfected controls.Methods: PWH with a chest computed tomography were included from the ongoing Copenhagen Comorbidity in HIV Infection (COCOMO) study. Age and sex-matched uninfected controls were recruited from the Copenhagen General Population Study. Pulmonary artery enlargement was defined as a ratio of >1 between the diameter of the main pulmonary artery (at the level of its bifurcation) and the diameter of the ascending aorta.Results: In total, 900 PWH were included, and 44 (5%) had a pulmonary artery-aorta ratio (PA:A) >1. After adjustment for age, sex, and body mass index, obesity (adjusted odds ratio, 4.33; 95% confidence interval, 1.76-10.65; P = .001) and injection drug use (IDU) (4.90; 1.00-18.46; P = .03) were associated with higher odds of having a PA:A >1, and pulmonary indices and smoking status were not. HIV seropositivity was borderline associated with a PA:A >1 (adjusted odds ratio, 1.89; 95% confidence interval, .92-3.85; P = .08).Conclusions: A PA:A >1 was common in PWH. Obesity and IDU were independently associated with this finding and HIV serostatus was borderline associated with it, but HIV-related factors were not. Increased awareness may be appropriate in obese PWH and those with IDU. [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]

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. [ABSTRACT FROM AUTHOR]

Background Increased pericardial adipose tissue is associated with higher risk of cardiovascular disease. We aimed to determine whether human immunodeficiency virus (HIV) status was independently associated with larger pericardial adipose tissue volume and to explore possible HIV-specific risk factors. Methods Persons with HIV (PWH) were recruited from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study and matched 1:1 on age and sex to uninfected controls. Pericardial adipose tissue volume was measured using cardiac computed tomography. Results A total of 587 PWH and 587 controls were included. Median age was 52 years, and 88% were male. Human immunodeficiency virus status was independently associated with 17 mL (95% confidence interval [CI], 10–23; P < .001) larger pericardial adipose tissue volume. Larger pericardial adipose tissue volume was associated with low CD4+ nadir and prior use of stavudine, didanosine, and indinavir. Among PWH without thymidine analogue or didanosine exposure, time since initiating combination antiretroviral treatment (per 5-year use) was associated with l6 mL (95% CI, −6 to −25; P  = .002) lower pericardial adipose tissue volume. Conclusions Human immunodeficiency virus status was independently associated with larger pericardial adipose tissue volume. Severe immunodeficiency, stavudine, didanosine, and indinavir were associated with larger pericardial adipose tissue volume. Persons with HIV with prior exposure to these drugs may constitute a distinct cardiovascular risk population. [ABSTRACT FROM AUTHOR]

Purpose: Quantitative computed tomography (QCT) provides important prognostic information of coronary atherosclerosis. We investigated intraobserver and interobserver QCT reproducibility in asymptomatic individuals, patients with acute chest pain without acute coronary syndrome (ACS), and patients with acute chest pain and ACS. Methods: Fifty patients from each cohort, scanned between 01/02/2010-14/11/2013 and matched according to age and gender, were retrospectively assessed for inclusion. Patients with no coronary artery disease, previous coronary artery bypass graft surgery, and poor image quality were excluded. Coronary atherosclerosis was measured semi-automatically by 2 readers. Reproducibility of minimal lumen area (MLA), minimal lumen diameter (MLD), area stenosis, diameter stenosis, vessel remodeling, plaque eccentricity, plaque burden, and plaque volumes was assessed using concordance correlation coefficient (CCC), Bland-Altman, coefficient of variation, and Cohen’s kappa. Results: A total of 84 patients (63 matched) were included. Intraobserver and interobserver reproducibility estimates were acceptable for MLA (CCC = 0.94 and CCC = 0.91, respectively), MLD (CCC = 0.92 and CCC = 0.86, respectively), plaque burden (CCC = 0.86 and CCC = 0.80, respectively), and plaque volume (CCC = 0.97 and CCC = 0.95, respectively). QCT detected area and diameter stenosis ≥50%, positive remodeling, and eccentric plaque with moderate-good intraobserver and interobserver reproducibility (kappa: 0.64–0.66, 0.69–0.76, 0.46–0.48, and 0.41–0.62, respectively). Reproducibility of plaque composition decreased with decreasing plaque density (intraobserver and interobserver CCC for dense calcium (>0.99; 0.98), fibrotic (0.96; 0.93), fibro-fatty (0.95; 0.91), and necrotic core tissue (0.89; 0.84). Reproducibility generally decreased with worsening clinical risk profile. Conclusions: Semi-automated QCT of coronary plaque morphology is reproducible, albeit with some decline in reproducibility with worsening patient risk profile. [ABSTRACT FROM AUTHOR]

Background: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes.Methods: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure.Results: A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1-4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78-1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events) >140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67-1.01; P value for interaction=0.023).Conclusions: A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes.Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891. [ABSTRACT FROM AUTHOR]

Aims To compare the diagnostic performance of a reduced-order computed tomography-derived fractional flow reserve (CT-FFR) technique derived from luminal deformation and static CT stress myocardial perfusion (CTP). Methods and results Forty-six patients (84 vessels) with suspected coronary artery disease from a single institution planned for elective coronary angiography prospectively underwent research indicated invasive fractional flow reserve (FFR) and 320-detector CT coronary angiography (CTA) and static CTP. Analyses were performed in separate blinded core laboratories for CT-FFR and CTP. CT-FFR was derived using a reduced-order model with dedicated software on a standard desktop computer. CTP was assessed visually and quantitatively by transmural perfusion ratio (TPR). Invasive FFR was significant in 33% (28/84) of vessels. Overall per-vessel sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for CT-FFR were 81%, 84%, 71%, 90%, and 83%, respectively, those of visual CTP were 54%, 92%, 79%, 77%, and 78%, respectively, and TPR were 64%, 48%, 42%, 70%, and 54%, respectively. Per-vessel receiver operator curve analysis demonstrated a significantly larger area under the curve (AUC) for CT-FFR (0.89) with that for visual CTP (0.72; P  = 0.016), TPR (0.55; P  < 0.0001), and CTA (0.76; P  = 0.04). The addition of CT-FFR to CTA provided superior improvement in performance (AUC 0.93; P  < 0.0001) compared with CTA alone, a combination of CTA with visual CTP (AUC 0.82; P  = 0.007) and CTA with TPR (AUC 0.78; P  = 0.0006). Conclusion Based on this selected cohort of patients, a reduced-order CT-FFR technique is superior to visual and quantitatively assessed static CTP in detecting haemodynamically significant coronary stenosis as assessed by invasive FFR. [ABSTRACT FROM AUTHOR]

Objectives: Diagnostic accuracy of conventional coronary CT angiography (CCTAconv) may be compromised by blooming artifacts from calcifications or stents. Blooming artifacts may be reduced by subtraction coronary CT angiography (CCTAsub) in which non-contrast and contrast CT data sets are subtracted digitally. We tested whether CCTAsub in patients with severe coronary calcification or stents reduces the number of false-positive stenosis evaluations compared with CCTAconv.Methods: In this study, 180 symptomatic patients scheduled for invasive coronary angiography (ICA) were prospectively enrolled and CT scanned (2013-2016) at three international centers. CCTAconv, and CCTAsub data sets were reconstructed. Target segments were defined as motion-free coronary segments with a suspected stenosis (> 50% of lumen) potentially due to blooming of either calcium or stents. Target segments were evaluated with respect to misregistration artifacts from the CCTAsub reconstruction process, in which case evaluation was omitted. CCTAsub and CCTAconv were compared with ICA. Primary outcome measure was the frequency of false positives by CCTAconv versus CCTAsub to identify > 50% coronary stenosis by ICA on a per-segment level.Results: After exclusion of 76 patients, 104 (14% females) with mean age 67 years and median Agatston score 852 were included. There were 136 target segments with misregistration and 121 target segments without. Accuracy calculations in target segments without misregistration showed a reduction of the false positives from 72% [95% confidence interval (CI): 63-80%] in CCTAconv to 33% (CI:25-42%) in CCTAsub, at the expense of 7% (CI:3-14%) false negatives in CCTAsub.Conclusions: In severely calcified coronary arteries or stents, CCTAsub reduces the false-positive rate in well-aligned, calcified or stent segments suspected of significant stenosis on CCTAconv. Nevertheless, misregistration artifacts are frequent in CCTAsub.Key Points: • A high calcium-score reduces the diagnostic accuracy in patients scanned with cardiac CT. • These patients would normally need an invasive angiogram for diagnosis. • In this prospective, multicenter study, subtraction CT, when evaluable, reduces false-positive stenosis evaluations. • Subtraction coronary CT angiography may, when evaluable, reduce excessive downstream testing. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to assess the commissural alignment between bioprosthetic and native aortic valve leaflets following surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) and to investigate its impact on valvular function and coronary filling. Background Expansion and geometry have been shown to affect leaflets of implanted transcatheter aortic bioprosthesis, but commissural alignment has not been studied. Methods Pre- and post-procedural multidetector computed tomography (MDCT) of 28 SAVR patients and 212 TAVR patients were analyzed. Commissural alignment between the bioprosthetic (post) and native (pre) aortic valves was categorized as aligned (0° to 15° angle deviation) or as mild (15° to 30°), moderate (30° to 45°), or severe (45° to 60°) commissural misalignment (CMA). Results With SAVR, 27 of 28 cases (96%) were aligned and 1 had mild CMA. For all types of transcatheter heart valves (THVs), there was random valve implantation with regard to commissural alignment: 22% of THVs were aligned, 25% had mild CMA, 22% had moderate CMA, and 31% had severe CMA. The degree of commissural alignment was not associated with a difference in transvalvular gradient, paravalvular aortic regurgitation, or simulated coronary filling. However, there was a significantly higher rate of mild central aortic regurgitation in those THVs with moderate or greater CMA compared with those THV with mild or less CMA (7.8% vs. 1.1%; p = 0.03). Conclusions Commissural alignment is excellent in case of SAVR but random in case of TAVR. There is no association between CMA and transvalvular gradient or coronary filling; however, there is a significantly higher rate of mild central aortic regurgitation in case of moderate or greater CMA. [ABSTRACT FROM AUTHOR]

Aims: The third isotype of beta adrenergic receptors (β3 ARs) has distinctly different effects on cardiomyocytes compared with β1 and β2 ARs. Stimulation of β3 ARs may reduce cardiomyocyte Na+ overload and reduce oxidative stress in heart failure (HF). We examined if treatment with the β3 AR agonist mirabegron increases LVEF in patients with HF.Methods and Results: In a double-blind trial we randomly assigned 70 patients with NYHA class II-III HF and LVEF <40% at screening-echocardiography to receive mirabegron or placebo for 6 months as add-on to optimized standard therapy. The primary endpoint was an increase in LVEF after 6 months as measured by computed tomography (CT). Changes in LVEF after 6 months between treatment groups were not significantly different (0.4%, -3.5 to 3.8%, P = 0.82). In an exploratory analysis, based on an expectation that the pathophysiological substrate targeted with treatment is dependent on the baseline LVEF, patients with LVEF <40% by CT given mirabegron had a significant increase in LVEF while no increase was seen in patients given placebo. The changes were significantly different between groups (5.5%, 0.6-10.4%, P < 0.03). Additionally, there was interaction between baseline LVEF and change in LVEF in the entire group of patients treated with mirabegron (R2  = 0.40, β  = -0.63, P < 0.001), but not in the placebo group (R2  = 0.00, β  = -0.01, P = 0.95). Treatment was generally well tolerated. Three patients in each group had fatal or life-threatening events.Conclusions: The primary endpoint was not reached. Exploratory analysis indicated that β3 AR stimulation by mirabegron increased LVEF in patients with severe HF. Treatment appeared safe. Additional studies in severe HF are needed.Trial Registration: NCT01876433. [ABSTRACT FROM AUTHOR]

Objectives: To test if cardiac computed tomography angiography (CCTA) can be used in the triage of patients at high risk of coronary artery disease.Design: The diagnostic value of 64-detector CCTA was evaluated in 400 patients presenting with non-ST segment elevation myocardial infarction using invasive coronary angiography (ICA) as the reference method. The relation between the severity of disease by CCTA and a combined endpoint of death, re-hospitalization due to new myocardial infarction, or symptom-driven coronary revascularization was assessed.Results: CCTA detects significant (>50%) coronary artery diameter stenosis with a sensitivity, specificity, and positive and negative predictive value of 99%, 81%, 96% and 95%, respectively. CCTA was used to triage patients into guideline defined treatment groups of "no or medical treatment", "referral to percutaneous coronary intervention" or to "coronary artery bypass graft surgery" and was compared to the index ICA. CCTA correctly triaged patients in 86% of cases. During a median follow-up of 50 months, the presence of an occluded artery by CCTA was associated with adverse outcome.Conclusion: CCTA has high diagnostic and prognostic value in patients with high likelihood of coronary artery disease and could, in theory, be used to triage high risk patients. As many obstacles remain, including logistical and safety issues, our study does not support the use of CCTA as an additional diagnostic test before ICA in an all-comer NSTEMI population. [ABSTRACT FROM AUTHOR]

Background—Coronary computed tomographic angiography (CTA) and myocardial perfusion imaging (CTP) is a validated approach for detection and exclusion of flow-limiting coronary artery disease (CAD), but little data are available on gender-specific performance of these modalities. In this study, we aimed to evaluate the diagnostic accuracy of combined coronary CTA and CTP in detecting flow-limiting CAD in women compared with men.Methods and Results—Three hundred and eighty-one patients who underwent both CTA-CTP and single-photon emission computed tomography myocardial perfusion imaging preceding invasive coronary angiography as part of the CORE320 multicenter study (Coronary Artery Evaluation Using 320-row Multidetector Computed Tomography Angiography and Myocardial Perfusion) were included in this ancillary study. All 4 image modalities were analyzed in blinded, independent core laboratories. Prevalence of flow-limiting CAD defined by invasive coronary angiography equal to 50% or greater with an associated single-photon emission computed tomography myocardial perfusion imaging defect was 45% (114/252) and 23% (30/129) in males and females, respectively. Patient-based diagnostic accuracy defined by the area under the receiver operating curve for detecting flow-limiting CAD by CTA alone in females was 0.83 (0.75–0.89) and for CTA-CTP was 0.92 (0.86–0.97; P=0.003) compared with men where the area under the receiver operating curve for detecting flow-limiting CAD by CTA alone was 0.82 (0.77–0.87) and for CTA-CTP was 0.84 (0.80–0.89; P=0.29).Conclusions—The combination of CTA-CTP was performed similarly in men and women for identifying flow-limiting coronary stenosis; however, in women, CTP had incremental value over CTA alone, which was not the case in men. [ABSTRACT FROM AUTHOR]

Aims Normal values of left ventricular mass (LVM) and cardiac chamber sizes are prerequisites for the diagnosis of individuals with heart disease. LVM and cardiac chamber sizes may be recorded during cardiac computed tomography angiography (CCTA), and thus modality specific normal values are needed. Methods and results We studied 569 healthy subjects undergoing 320-detector CCTA as a part of the Copenhagen General Population Study. LVM as well as ventricular and atrial volumes was assessed with semi-automated software stratified by gender and age decades and indexed by body surface area (BSA). Mean age was 55 (range: 40-84) years, and 188 (33%) were men. BSA-indexed 97.5th percentile cut-off values: LVM = 80 and 65 gr/m², left ventricular volume = 97 and 83 mL/m², right ventricular volume = 120 and 102 mL/m², left atrial volume = 60 and 57 mL/m², and right atrial volume = 85 and 73 mL/m² for men and women, respectively. Men had greater absolute and indexed LVM and chamber volumes than women. For both genders, indexed ventricular volumes declined, whereas indexed atrial volumes increased in advancing age groups. For men, indexed LVM declined in advancing age groups. In multivariate analyses, gender, BSA, systolic blood pressure, and hard physical activity accounted for 63% of variance in LVM. Conclusion In this cross-sectional general population study, men have greater indexed LVM and chamber volumes than women, and cardiac indexed volumes vary between age groups in both genders. These findings demonstrate the need for age- and gender-specific normal values for clinical diagnostic purposes. [ABSTRACT FROM AUTHOR]

Objective: There is a lack of disease-modifying treatments in hypertrophic cardiomyopathy (HCM). The aim of this randomised, placebo-controlled study was to assess if losartan could improve or ameliorate deterioration of cardiac function and exercise capacity.Methods: Echocardiography, exercise test and MRI or CT were performed at baseline and after 12 months in 133 patients (52±13 years, 35% female) randomly allocated to losartan (100 mg/day) or placebo.Results: Losartan had no effect on systolic function compared with placebo (mean difference for left ventricular ejection fraction (LVEF) 0% (95% CI -3% to 4%), p=0.84 or global longitudinal strain 0.7% (95% CI -0.2% to 1.6%), p=0.13). Neither Doppler measures of diastolic function, left atrial volume (mean difference 2 mL/m(2) (95% CI -4 to 8 mL/m(2)) p=0.53) nor exercise capacity (mean difference -0.3 metabolic equivalents (METS) (95% CI -1.0 to 0.3 METS), p=0.28) differed between the treatment groups. At follow-up, there was further progression of disease, with the most prominent impairment being an increase in left atrial volume of 6 mL/m(2) (95% CI 3 to 9 mL/m(2), p<0.0001) in both groups combined. LVEF decreased (mean change -2%, (95% CI -3% to -1%), p=0.037) and 4% of patients had end-stage HCM with a LVEF of less than 50% at the end of the study.Conclusion: Treatment with losartan had no effect on cardiac function or exercise capacity compared with placebo. Losartan fail to improve myocardial performance and failed to alter the progression of the disease. These findings do not support the use of angiotensin II receptor blockers as disease modifiers in adult patients with overt HCM.Trial Registration Number: NCT01447654-results. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Background: Image noise and multiple sources of artifact may affect the accurate interpretation of myocardial CT perfusion (CTP) studies. Although artifact within the image is often time dependent, tissue characteristics remain unchanged irrespective of cardiac phase. Objective: We assessed a new technique of 4-dimensional, spatiotemporal analysis, using redundant time domain information within additional phase acquisitions to reduce CTP image noise. Methods: Four-dimensional analysis was assessed in a static phantom and in 10 CTP studies with invasive fractional flow reserve (FFR) correlation. For each voxel within the CTP study the distribution of local Hounsfield values was measured in both time and space with the use of a customized program within MATLAB software. These values were filtered to eliminate those likely to represent noise or rapidly changing beam hardening artifact. All CTP images were acquired within a single heartbeat with 320 detector-row CT. Image noise was quantified as the SD of voxel values within myocardial segments. Contrast was measured between normal and abnormal vascular territories as assessed by FFR. Results: The mean image noise within the unprocessed CTP images was 30 HU (range, 23–42 HU). After 4-dimensional filtering the mean image noise was 22 HU (range, 15–29 HU). The mean reduction in image noise was 28% (P < 0.001). The mean contrast between normally perfused and ischemic segments was not significantly changed. The mean increase in contrast-to-noise ratio between ischemic territories and the myocardial average was 52% (P < 0.001). Conclusion: Four-dimensional analysis of CTP significantly reduces image noise and may assist in the assessment of myocardial perfusion studies. [Copyright &y& Elsevier]

Abstract: Multidetector coronary computed tomography angiography (CTA) is a promising modality for widespread clinical application because of its noninvasive nature and high diagnostic accuracy as found in previous studies using 64 to 320 simultaneous detector rows. It is, however, limited in its ability to detect myocardial ischemia. In this article, we describe the design of the CORE320 study (“Combined coronary atherosclerosis and myocardial perfusion evaluation using 320 detector row computed tomography”). This prospective, multicenter, multinational study is unique in that it is designed to assess the diagnostic performance of combined 320-row CTA and myocardial CT perfusion imaging (CTP) in comparison with the combination of invasive coronary angiography and single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). The trial is being performed at 16 medical centers located in 8 countries worldwide. CT has the potential to assess both anatomy and physiology in a single imaging session. The co-primary aim of the CORE320 study is to define the per-patient diagnostic accuracy of the combination of coronary CTA and myocardial CTP to detect physiologically significant coronary artery disease compared with (1) the combination of conventional coronary angiography and SPECT-MPI and (2) conventional coronary angiography alone. If successful, the technology could revolutionize the management of patients with symptomatic CAD. [Copyright &y& Elsevier]

Objectives: We sought to test the hypothesis that measures of left atrial (LA) function are independent predictors of mortality in patients with acute myocardial infarction. Background: Left atrial maximal volume (LAmax) is known to predict mortality in patients with acute myocardial infarction. In a previous pilot study, however, we found that LA function in terms of fractional change and left atrial ejection fraction (LAEF) assessed by multidetector computed tomography (MDCT) is more closely related to clinical heart failure than LAmax. Methods: We prospectively included 384 patients presenting with non–ST-segment elevation myocardial infarction (NSTEMI) who underwent retrospectively gated, 64-slice MDCT coronary angiography and subsequent measurements of LA size and function. All patients were treated according to the current guidelines based on invasive coronary angiography. Patients were followed for a minimum of 2 years. The study endpoint was all-cause mortality. Results: The median follow-up time was 36 months (range 10 to 1,551 days). During follow-up, 35 (9%) patients died. Overall, 1- and 2-year survival in the study cohort was 97% and 94%. LA size and mechanical function was obtained in all patients: mean LAmax was 55 ± 11 ml/m2, LA minimal volume 31 ± 11 ml/m2, fractional change 45 ± 9%, and LAEF 32 ± 9%. Using a Cox proportional hazards model with adjustments for age, number of diseased coronary vessels, left ventricular ejection fraction (LVEF), and Killip class, both fractional change (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.45 to 0.94) and LAEF (HR: 0.63; 95% CI: 0.44 to 0.91) remained independent predictors of mortality. In contrast to this, LAmax was not significantly associated with an increased risk of mortality in this population. Conclusions: In a low-risk group of patients with NSTEMI, reduced LA function is an independent predictor of mortality and provides prognostic value incremental to that of LAmax. [Copyright &y& Elsevier]

Objectives: We sought to determine whether the amount of noncalcified plaque (NCP) in nonobstructive coronary lesions as detected by multidetector computed tomography (MDCT) was a predictor of future coronary events. Background: Patients presenting with non–ST-segment elevation myocardial infarction (NSTEMI) frequently have multiple coronary plaques, which may be detected with MDCT. Methods: We included 312 consecutive patients presenting with NSTEMI, who underwent 64-slice MDCT coronary angiography and coronary artery calcium scoring before invasive coronary angiography. All patients were treated according to current guidelines based on an invasive treatment approach. Quantitative measurements of plaque composition and volume were performed by MDCT in all nonobstructive coronary lesions. The endpoint was cardiac death, acute coronary syndrome, or symptom-driven revascularization. Results: After a median follow-up of 16 months, 23 patients had suffered a cardiac event. Age, male sex, and diabetes mellitus were all associated with an increasing amount of NCP. In a multivariate regression analysis for events, the total amount of NCP in nonobstructive lesions was independently associated with an increased hazard ratio (1.18/100-mm3 plaque volume increase, p = 0.01). Contrary to this, neither Agatston score nor the amount of calcium in nonobstructive lesions was associated with an increased risk. Conclusions: Multidetector computed tomography plaque imaging identified patients at increased risk of recurrent coronary events after NSTEMI by measuring the total amount of NCP in nonobstructive lesions. The amount of calcified plaque was not associated with an increased risk. [ABSTRACT FROM AUTHOR]

Although the descending aortic diameter is larger in smokers, data about thoracic aortic growth is missing. Our aim is to present the distribution of thoracic aortic growth in smokers and to compare it with literature of the general population. Current and ex-smokers aged 50–70 years from the longitudinal Danish Lung Cancer Screening Trial, were included. Mean and 95th percentile of annual aortic growth of the ascending aortic (AA) and descending aortic (DA) diameters were calculated with the first and last non-contrast computed tomography scans during follow-up. Determinants of change in aortic diameter over time were investigated with linear mixed models. A total of 1987 participants (56% male, mean age 57.4 ± 4.8 years) were included. During a median follow-up of 48 months, mean AA and DA growth rates were comparable between males (AA 0.12 ± 0.31 mm/year and DA 0.10 ± 0.30 mm/year) and females (AA 0.11 ± 0.29 mm/year and DA 0.13 ± 0.27 mm/year). The 95th percentile ranged from 0.42 to 0.47 mm/year, depending on sex and location. Aortic growth was comparable between current and ex-smokers and aortic growth was not associated with pack-years. Our findings are consistent with aortic growth rates of 0.08 to 0.17 mm/years in the general population. Larger aortic growth was associated with lower age, increased height, absence of medication for hypertension or hypercholesterolemia and lower Agatston scores. This longitudinal study of smokers in the age range of 50–70 years shows that ascending and descending aortic growth is approximately 0.1 mm/year and is consistent with growth in the general population. • In current and ex-smokers, the ascending and descending aorta grows on average 0.1 mm/year • Aortic growth was comparable between current and ex-smokers and was not associated with pack-years • Thoracic aortic growth in smokers is consistent with cross-sectional data from the general population • Annual growth did not statistically significantly differ between males and females • Based on 95th percentiles, aortic growth of 0.5 mm/year can be considered the upper limit of normal [ABSTRACT FROM AUTHOR]

Background: Subclinical leaflet thickening and reduced leaflet motion of bioprosthetic aortic valves have been documented by four-dimensional computed tomography (CT). Whether anticoagulation can reduce these phenomena after transcatheter aortic-valve replacement (TAVR) is not known.Methods: In a substudy of a large randomized trial, we randomly assigned patients who had undergone successful TAVR and who did not have an indication for long-term anticoagulation to a rivaroxaban-based antithrombotic strategy (rivaroxaban [10 mg] plus aspirin [75 to 100 mg] once daily) or an antiplatelet-based strategy (clopidogrel [75 mg] plus aspirin [75 to 100 mg] once daily). Patients underwent evaluation by four-dimensional CT at a mean (±SD) of 90±15 days after randomization. The primary end point was the percentage of patients with at least one prosthetic valve leaflet with grade 3 or higher motion reduction (i.e., involving >50% of the leaflet). Leaflet thickening was also assessed.Results: A total of 231 patients were enrolled. At least one prosthetic valve leaflet with grade 3 or higher motion reduction was found in 2 of 97 patients (2.1%) who had scans that could be evaluated in the rivaroxaban group, as compared with 11 of 101 (10.9%) in the antiplatelet group (difference, -8.8 percentage points; 95% confidence interval [CI], -16.5 to -1.9; P = 0.01). Thickening of at least one leaflet was observed in 12 of 97 patients (12.4%) in the rivaroxaban group and in 33 of 102 (32.4%) in the antiplatelet group (difference, -20.0 percentage points; 95% CI, -30.9 to -8.5). In the main trial, the risk of death or thromboembolic events and the risk of life-threatening, disabling, or major bleeding were higher with rivaroxaban (hazard ratios of 1.35 and 1.50, respectively).Conclusions: In a substudy of a trial involving patients without an indication for long-term anticoagulation who had undergone successful TAVR, a rivaroxaban-based antithrombotic strategy was more effective than an antiplatelet-based strategy in preventing subclinical leaflet-motion abnormalities. However, in the main trial, the rivaroxaban-based strategy was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than the antiplatelet-based strategy. (Funded by Bayer; GALILEO-4D ClinicalTrials.gov number, NCT02833948.). [ABSTRACT FROM AUTHOR]

Aims: Type 1 diabetes is associated with increased cardiovascular (CV) morbidity and mortality, and cardiovascular autonomic neuropathy (CAN) is an important CV risk factor. The study aimed to explore associations between CAN and altered cardiac chamber sizes in persons with type 1 diabetes.Methods: This was a cross-sectional study of 71 asymptomatic, normoalbuminuric participants with long-term type 1 diabetes (39 with CAN, determined by >1 abnormal autonomic function test) examined with cardiac multi detector computed tomography scans, which allowed measurements of left ventricular mass and all four cardiac chamber volumes. Cardiac chambers were indexed according to body surface area (ml/m2 or g/m2).Results: Persons with and without CAN had mean ± SD age of 57 ± 7 and 50 ± 8 years (p < 0.001) and diabetes duration of 36 ± 11 and 32 ± 9 years (p < 0.05), respectively. Increasing autonomic dysfunction, evaluated by decrease in heart rate variability during deep breathing (in beats per minute), was associated with larger right (-0.5, 95% CI -1.0 to -0.0, p < 0.05) and trend towards larger left (-0.4, 95% CI -0.8-0.0, p < 0.1) ventricular volumes in multivariable linear regression.Conclusions: Our results suggest that impaired autonomic function may be associated with modest enlargement of ventricular volumes; this might be an early sign of progression towards heart failure. [ABSTRACT FROM AUTHOR]

Background: Subclinical leaflet thrombosis of bioprosthetic aortic valves after transcatheter valve replacement (TAVR) and surgical aortic valve replacement (SAVR) has been found with CT imaging. The objective of this study was to report the prevalence of subclinical leaflet thrombosis in surgical and transcatheter aortic valves and the effect of novel oral anticoagulants (NOACs) on the subclinical leaflet thrombosis and subsequent valve haemodynamics and clinical outcomes on the basis of two registries of patients who had CT imaging done after TAVR or SAVR.Methods: Patients enrolled between Dec 22, 2014, and Jan 18, 2017, in the RESOLVE registry, and between June 2, 2014, and Sept 28, 2016, in the SAVORY registry, had CT imaging done with a dedicated four-dimensional volume-rendered imaging protocol at varying intervals after TAVR and SAVR. We defined subclinical leaflet thrombosis as the presence of reduced leaflet motion, along with corresponding hypoattenuating lesions shown with CT. We collected data for baseline demographics, antithrombotic therapy, and clinical outcomes. We analysed all CT scans, echocardiograms, and neurological events in a masked fashion.Findings: Of the 931 patients who had CT imaging done (657 [71%] in the RESOLVE registry and 274 [29%] in the SAVORY registry), 890 [96%] had interpretable CT scans (626 [70%] in the RESOLVE registry and 264 [30%] in the SAVORY registry). 106 (12%) of 890 patients had subclinical leaflet thrombosis, including five (4%) of 138 with thrombosis of surgical valves versus 101 (13%) of 752 with thrombosis of transcatheter valves (p=0·001). The median time from aortic valve replacement to CT for the entire cohort was 83 days (IQR 33-281). Subclinical leaflet thrombosis was less frequent among patients receiving anticoagulants (eight [4%] of 224) than among those receiving dual antiplatelet therapy (31 [15%] of 208; p<0·0001); NOACs were equally as effective as warfarin (three [3%] of 107 vs five [4%] of 117; p=0·72). Subclinical leaflet thrombosis resolved in 36 (100%) of 36 patients (warfarin 24 [67%]; NOACs 12 [33%]) receiving anticoagulants, whereas it persisted in 20 (91%) of 22 patients not receiving anticoagulants (p<0·0001). A greater proportion of patients with subclinical leaflet thrombosis had aortic valve gradients of more than 20 mm Hg and increases in aortic valve gradients of more than 10 mm Hg (12 [14%] of 88) than did those with normal leaflet motion (seven [1%] of 632; p<0·0001). Although stroke rates were not different between those with (4·12 strokes per 100 person-years) or without (1·92 strokes per 100 person-years) reduced leaflet motion (p=0·10), subclinical leaflet thrombosis was associated with increased rates of transient ischaemic attacks (TIAs; 4·18 TIAs per 100 person-years vs 0·60 TIAs per 100 person-years; p=0·0005) and all strokes or TIAs (7·85 vs 2·36 per 100 person-years; p=0·001).Interpretation: Subclinical leaflet thrombosis occurred frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. Anticoagulation (both NOACs and warfarin), but not dual antiplatelet therapy, was effective in prevention or treatment of subclinical leaflet thrombosis. Subclinical leaflet thrombosis was associated with increased rates of TIAs and strokes or TIAs. Despite excellent outcomes after TAVR with the new-generation valves, prevention and treatment of subclinical leaflet thrombosis might offer a potential opportunity for further improvement in valve haemodynamics and clinical outcomes.Funding: RESOLVE (Cedars-Sinai Heart Institute) and SAVORY (Rigshospitalet). [ABSTRACT FROM AUTHOR]

Objective: Population studies have shown coronary calcium score to improve risk stratification in subjects suspected for cardiovascular disease. The aim of this work was to assess the validity of multidetector computed tomography (MDCT) for measurement of calibrated mass scores (MS) in a phantom study, and to investigate inter-scanner variability for MS and Agaston score (AS) recorded in a population study on two different high-end MDCT scanners.Materials and Methods: A calcium phantom was scanned by a first (A) and second (B) generation 320-MDCT. MS was measured for each calcium deposit from repeated measurements in each scanner and compared to known physical phantom mass. Random samples of human subjects from the Copenhagen General Population Study were scanned with scanner A (N=254) and scanner B (N=253) where MS and AS distributions of these two groups were compared.Results: The mean total MS of the phantom was 32.9±0.8mg and 33.1±0.9mg (p=0.43) assessed by scanner A and B respectively - the physical calcium mass was 34.0mg. Correlation between measured MS and physical calcium mass was R2=0.99 in both scanners. In the population study the median total MS was 16.8mg (interquartile range (IQR): 3.5-81.1) and 15.8mg (IQR: 3.8-63.4) in scanner A and B (p=0.88). The corresponding median total AS were 92 (IQR: 23-471) and 89 (IQR: 40-384) (p=0.64).Conclusion: Calibrated calcium mass score may be assessed with very high accuracy in a calcium phantom by different generations of 320-MDCT scanners. In population studies, it appears acceptable to pool calcium scores acquired on different 320-MDCT scanners. [ABSTRACT FROM AUTHOR]

Background Myocardial CT perfusion (CTP) has been validated as an incremental diagnostic predictor over coronary computed tomography angiography (CTA) in assessing hemodynamically significant stenosis. Objectives To assess the diagnostic performance of CTA and CTP alone versus combined CTA–CTP stratified by Morise's pre-test probability and coronary artery calcium (CAC, Agatston) score. Methods 381 individuals (153 low/intermediate-risk for CAD, 83 high-risk, 145 known CAD) were further stratified based on CAC score cut-offs of 1–399 and ≥ 400. Area under the curve for receiver operating characteristics (AUC) was calculated to assess the diagnostic performance. Reference standards were QCA ≥ 50% stenosis + corresponding SPECT summed stress score ≥ 1. Results In both pre-test risk groups with an Agatston score of 1–399, AUCs of CTA–CTP were not significantly different than that from CTA alone. In the low/intermediate-risk group with CAC score 1–399, AUC for CTA–CTP (89) was higher than that for CTP (76, p = 0.003) alone. In the same group with CAC score ≥ 400, AUCs were higher for CTA–CTP (97) than that for CTA (88, p = 0.030) and CTP (83, p = 0.033). In high risk/known CAD patients with CAC 1–399, diagnostic performance for CTA–CTP (77) was superior to CTP (71, p = 0.037) alone. In the high risk/known CAD group with CAC score ≥ 400, AUCs for combined imaging were higher (86) than that for CTA (75, p < 0.001) as well as CTP (78, p = 0.020). Conclusions The incremental diagnostic accuracy of CTP over CTA persists in patients across severity spectra of pre-test probability of CAD and coronary artery calcification. In patients with severe coronary calcification (CAC score ≥ 400), combined CTA–CTP has better diagnostic accuracy than CTA and CTP alone. [ABSTRACT FROM AUTHOR]