Progression of non-obstructive coronary plaque: a practical CCTA-based risk score from the PARADIGM registry.

OBJECTIVES: No clear recommendations are endorsed by the different scientific societies on the clinical use of repeat coronary computed tomography angiography (CCTA) in patients with non-obstructive coronary artery disease (CAD). This study aimed to develop and validate a practical CCTA risk score to predict medium-term disease progression in patients at a low-to-intermediate probability of CAD. METHODS: Patients were part of the Progression of AtheRosclerotic PlAque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry. Specifically, 370 (derivation cohort) and 219 (validation cohort) patients with two repeat, clinically indicated CCTA scans, non-obstructive CAD, and absence of high-risk plaque (≥ 2 high-risk features) at baseline CCTA were included. Disease progression was defined as the new occurrence of ≥ 50% stenosis and/or high-risk plaque at follow-up CCTA. RESULTS: In the derivation cohort, 104 (28%) patients experienced disease progression. The median time interval between the two CCTAs was 3.3 years (2.7-4.8). Odds ratios for disease progression derived from multivariable logistic regression were as follows: 4.59 (95% confidence interval: 1.69-12.48) for the number of plaques with spotty calcification, 3.73 (1.46-9.52) for the number of plaques with low attenuation component, 2.71 (1.62-4.50) for 25-49% stenosis severity, 1.47 (1.17-1.84) for the number of bifurcation plaques, and 1.21 (1.02-1.42) for the time between the two CCTAs. The C-statistics of the model were 0.732 (0.676-0.788) and 0.668 (0.583-0.752) in the derivation and validation cohorts, respectively. CONCLUSIONS: The new CCTA-based risk score is a simple and practical tool that can predict mid-term CAD progression in patients with known non-obstructive CAD. CLINICAL RELEVANCE STATEMENT: The clinical implementation of this new CCTA-based risk score can help promote the management of patients with non-obstructive coronary disease in terms of timing of imaging follow-up and therapeutic strategies. KEY POINTS: • No recommendations are available on the use of repeat CCTA in patients with non-obstructive CAD. • This new CCTA score predicts mid-term CAD progression in patients with non-obstructive stenosis at baseline. • This new CCTA score can help guide the clinical management of patients with non-obstructive CAD.

Prognostic Significance of Nonobstructive Left Main Coronary Artery Disease in Patients With and Without Diabetes: Long-Term Outcomes From the CONFIRM Registry.

BACKGROUND: Prognostic significance of non-obstructive left main (LM) disease was recently reported. However, the influence of diabetes mellitus (DM) on event rates in patients with and without non-obstructive LM disease is not well-known. METHODS: We evaluated 27,252 patients undergoing coronary computed tomographic angiography from the COroNary CT Angiography Evaluation For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) Registry. Cumulative long-term incidence of all-cause mortality (ACM) was assessed between DM and non-DM patients by normal or non-obstructive LM disease (1-49% stenosis). RESULTS: The mean age of the study population was 57.6±12.6 years. Of the 27,252 patients, 4,434 (16%) patients had DM. A total of 899 (3%) deaths occurred during the follow-up of 3.6±1.9. years. Compared to patients with normal LM, those with non-obstructive LM had more pronounced overall coronary atherosclerosis and more cardiovascular risk factors. After clinical risk factors, segment involvement score, and stenosis severity adjustment, compared to patients without DM and normal LM, patients with DM were associated with increased ACM regardless of normal (HR 1.48, 95% CI 1.22-1.78, p<0.001) or non-obstructive LM (HR 1.46, 95% CI 1.04-2.04, p=0.029), while nonobstructive LM disease was not associated with increased ACM in patients without DM (HR 0.85, 95% CI 0.67-1.07, p=0.165) and there was no significant interaction between DM and LM status (HR 1.03, 95% CI 0.69-1.54, p=0.879). CONCLUSION: From the CONFIRM registry, we demonstrated that DM was associated with increased ACM. However, the presence of non-obstructive LM was not an independent risk marker of ACM, and there was no significant interaction between DM and non-obstructive LM disease for ACM.

Glycemic control is independently associated with rapid progression of coronary atherosclerosis in the absence of a baseline coronary plaque burden: a retrospective case-control study from the PARADIGM registry.

BACKGROUND: The baseline coronary plaque burden is the most important factor for rapid plaque progression (RPP) in the coronary artery. However, data on the independent predictors of RPP in the absence of a baseline coronary plaque burden are limited. Thus, this study aimed to investigate the predictors for RPP in patients without coronary plaques on baseline coronary computed tomography angiography (CCTA) images. METHODS: A total of 402 patients (mean age: 57.6 ± 10.0 years, 49.3% men) without coronary plaques at baseline who underwent serial coronary CCTA were identified from the Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry and included in this retrospective study. RPP was defined as an annual change of ≥ 1.0%/year in the percentage atheroma volume (PAV). RESULTS: During a median inter-scan period of 3.6 years (interquartile range: 2.7-5.0 years), newly developed coronary plaques and RPP were observed in 35.6% and 4.2% of the patients, respectively. The baseline traditional risk factors, i.e., advanced age (≥ 60 years), male sex, hypertension, diabetes mellitus, hyperlipidemia, obesity, and current smoking status, were not significantly associated with the risk of RPP. Multivariate linear regression analysis showed that the serum hemoglobin A1c level (per 1% increase) measured at follow-up CCTA was independently associated with the annual change in the PAV (ß: 0.098, 95% confidence interval [CI]: 0.048-0.149; P < 0.001). The multiple logistic regression models showed that the serum hemoglobin A1c level had an independent and positive association with the risk of RPP. The optimal predictive cut-off value of the hemoglobin A1c level for RPP was 7.05% (sensitivity: 80.0%, specificity: 86.7%; area under curve: 0.816 [95% CI: 0.574-0.999]; P = 0.017). CONCLUSION: In this retrospective case-control study, the glycemic control status was strongly associated with the risk of RPP in patients without a baseline coronary plaque burden. This suggests that regular monitoring of the glycemic control status might be helpful for preventing the rapid progression of coronary atherosclerosis irrespective of the baseline risk factors. Further randomized investigations are necessary to confirm the results of our study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02803411.

Association between Aortic Valve Calcification Progression and Coronary Atherosclerotic Plaque Volume Progression in the PARADIGM Registry.

Background Aortic valve calcification (AVC) is a key feature of aortic stenosis, and patients with aortic stenosis often have coronary -artery disease. Therefore, proving the association between the progression of AVC and coronary atherosclerosis could improve follow-up and treatment strategies. Purpose To explore the association between the progression of AVC and the progression of total and plaque volume composition from a large multicenter registry of serial coronary CT angiographic examinations. Materials and Methods A prospective multinational registry (PARADIGM) of consecutive participants who underwent serial coronary CT angiography at intervals of every 2 years or more was performed (January 2003-December 2015). AVC and the total and plaque volume composition at baseline and follow-up angiography were quantitatively analyzed. Plaque volumes were normalized by using the mean total analyzed vessel length of the study population. Multivariable linear mixed-effects models were constructed. Results Overall, 594 participants (mean age ± standard deviation, 62 years ± 10; 330 men) were included (mean interval between baseline and follow-up angiography, 3.9 years ± 1.5). At baseline, the AVC score was 31 Agatston units ± 117, and the normalized total plaque volume at baseline was 122 mm3 ± 219. After adjustment for age, sex, clinical risk factors, and medication use, AVC was independently associated with total plaque volume (standardized ß = 0.24; 95% CI: 0.16, 0.32; P < .001) and both calcified (ß = 0.26; 95% CI: 0.18, 0.34; P < .001) and noncalcified (ß = 0.17; 95% CI: 0.08, 0.25; P < .001) plaque volumes at baseline. The progression of AVC was associated with the progression of total plaque volume (ß = 0.13; 95% CI: 0.03, 0.22; P = .01), driven solely by calcified plaque volume (ß = 0.24; 95% CI: 0.14, 0.34; P < .001) but not noncalcified plaque volumes (ß = -0.06; 95% CI: -0.14, 0.03; P = .17). Conclusion The overall burden of coronary atherosclerosis was associated with aortic valve calcification at baseline. However, the progression of aortic valve calcification was associated with only the progression of calcified plaque volume but not with the -progression of noncalcified plaque volume. Clinical trial registration no. NCT02803411 © RSNA, 2021 See also the editorial by Sinitsyn in this issue.

18F-Sodium Fluoride Positron Emission Tomography/Computed Tomography in Ex Vivo Human Coronary Arteries With Histological Correlation.

OBJECTIVE: 18F-sodium fluoride (NaF) position emission tomography (PET) activity correlates with high-risk plaque. We examined the correlation between 18F-NaF PET activity and extent of calcification (microcalcification and macrocalcification) in coronary arteries. Approach and Results: Eighteen ex vivo human coronary arteries were imaged with 18F-NaF PET/CT, and target to background ratios were analyzed from 101 plaques. Histopathologic analysis evaluated for microcalcification and macrocalcification, plaque morphology, and inflammation. Plaques with microcalcification demonstrated higher 18F-NaF PET activity (n=84; mean target to background ratio±SD, 9.0±9.7,) than plaques without microcalcification (n=17, 2.9±3.8; P<0.0001). Higher 18F-NaF PET activity was associated with advanced plaques characterized by fibroatheroma (n=54, 10.7±10.3) compared with plaques with intimal thickening (n=22, 3.5±3.9) or pathological intimal thickening (n=25, 6.1±8.4; P=0.004). No significant association was found between 18F-NaF PET activity and inflammation (P=0.08). CONCLUSIONS: In ex vivo human coronary arteries, higher 18F-NaF PET activity was associated with microcalcification and advanced plaque morphology. Since microcalcification and fibroatheromas are high-risk plaque features, 18F-NaF PET/CT may improve risk-stratification.

Machine learning of clinical variables and coronary artery calcium scoring for the prediction of obstructive coronary artery disease on coronary computed tomography angiography: analysis from the CONFIRM registry.

AIMS: Symptom-based pretest probability scores that estimate the likelihood of obstructive coronary artery disease (CAD) in stable chest pain have moderate accuracy. We sought to develop a machine learning (ML) model, utilizing clinical factors and the coronary artery calcium score (CACS), to predict the presence of obstructive CAD on coronary computed tomography angiography (CCTA). METHODS AND RESULTS: The study screened 35 281 participants enrolled in the CONFIRM registry, who underwent ≥64 detector row CCTA evaluation because of either suspected or previously established CAD. A boosted ensemble algorithm (XGBoost) was used, with data split into a training set (80%) on which 10-fold cross-validation was done and a test set (20%). Performance was assessed of the (1) ML model (using 25 clinical and demographic features), (2) ML + CACS, (3) CAD consortium clinical score, (4) CAD consortium clinical score + CACS, and (5) updated Diamond-Forrester (UDF) score. The study population comprised of 13 054 patients, of whom 2380 (18.2%) had obstructive CAD (≥50% stenosis). Machine learning with CACS produced the best performance [area under the curve (AUC) of 0.881] compared with ML alone (AUC of 0.773), CAD consortium clinical score (AUC of 0.734), and with CACS (AUC of 0.866) and UDF (AUC of 0.682), P < 0.05 for all comparisons. CACS, age, and gender were the highest ranking features. CONCLUSION: A ML model incorporating clinical features in addition to CACS can accurately estimate the pretest likelihood of obstructive CAD on CCTA. In clinical practice, the utilization of such an approach could improve risk stratification and help guide downstream management.

Quantitative assessment of coronary plaque volume change related to triglyceride glucose index: The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry.

BACKGROUND: The association between triglyceride glucose (TyG) index and coronary atherosclerotic change remains unclear. We aimed to evaluate the association between TyG index and coronary plaque progression (PP) using serial coronary computed tomography angiography (CCTA). METHODS: A total of 1143 subjects (aged 60.7 ± 9.3 years, 54.6% male) who underwent serial CCTA with available data on TyG index and diabetic status were analyzed from The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. PP was defined as plaque volume (PV) (mm3) at follow-up minus PV at index > 0. Annual change of PV (mm3/year) was defined as PV change divided by inter-scan period. Rapid PP was defined as the progression of percent atheroma volume (PV divided by vessel volume multiplied by 100) ≥ 1.0%/year. RESULTS: The median inter-scan period was 3.2 (range 2.6-4.4) years. All participants were stratified into three groups based on TyG index tertiles. The overall incidence of PP was 77.3%. Baseline total PV (group I [lowest]: 30.8 (0.0-117.7), group II: 47.2 (6.2-160.4), and group III [highest]: 57.5 (8.4-154.3); P < 0.001) and the annual change of total PV (group I: 5.7 (0.0-20.2), group II: 7.6 (0.5-23.5), and group III: 9.4 (1.4-27.7); P = 0.010) were different among all groups. The risk of PP (odds ratio [OR] 1.648; 95% confidence interval [CI] 1.167-2.327; P = 0.005) and rapid PP (OR 1.777; 95% CI 1.288-2.451; P < 0.001) was increased in group III compared to that in group I. TyG index had a positive and significant association with an increased risk of PP and rapid PP after adjusting for confounding factors. CONCLUSION: TyG index is an independent predictive marker for the progression of coronary atherosclerosis. Clinical registration ClinicalTrials.gov NCT02803411.

Prognostic value of coronary computed tomographic angiography findings in asymptomatic individuals: a 6-year follow-up from the prospective multicentre international CONFIRM study.

Aim: The long-term prognostic benefit of coronary computed tomographic angiography (CCTA) findings of coronary artery disease (CAD) in asymptomatic populations is unknown. Methods and results: From the prospective multicentre international CONFIRM long-term study, we evaluated asymptomatic subjects without known CAD who underwent both coronary artery calcium scoring (CACS) and CCTA (n = 1226). Coronary computed tomographic angiography findings included the severity of coronary artery stenosis, plaque composition, and coronary segment location. Using the C-statistic and likelihood ratio tests, we evaluated the incremental prognostic utility of CCTA findings over a base model that included a panel of traditional risk factors (RFs) as well as CACS to predict long-term all-cause mortality. During a mean follow-up of 5.9 ± 1.2 years, 78 deaths occurred. Compared with the traditional RF alone (C-statistic 0.64), CCTA findings including coronary stenosis severity, plaque composition, and coronary segment location demonstrated improved incremental prognostic utility beyond traditional RF alone (C-statistics range 0.71-0.73, all P < 0.05; incremental χ2 range 20.7-25.5, all P < 0.001). However, no added prognostic benefit was offered by CCTA findings when added to a base model containing both traditional RF and CACS (C-statistics P > 0.05, for all). Conclusions: Coronary computed tomographic angiography improved prognostication of 6-year all-cause mortality beyond a set of conventional RF alone, although, no further incremental value was offered by CCTA when CCTA findings were added to a model incorporating RF and CACS.

Imaging to Assess Ischemic Heart Disease in Women.

PURPOSE OF REVIEW: Ischemic heart disease is a leading cause of morbidity and mortality for women and men around the world. However, traditional cardiovascular risk factors do not fully capture cardiac risk in women. This review summarizes sex-based differences in the clinical presentation, pathophysiology, and risk assessment of ischemic heart disease. We also examine the use of anatomic and functional imaging modalities in the diagnosis of ischemic heart disease in women. RECENT FINDINGS: Recent studies with women subjects have bolstered the predictive value of the coronary artery calcium (CAC) score in predicting atherosclerotic cardiovascular disease risk and major adverse cardiac events in a graded fashion. In addition, combined CAC scoring and coronary computed tomography (CCTA) has shown promise in excluding coronary artery disease (CAD). Using CCTA, data have suggested that increasing cardiovascular risk factors are associated with an increase in noncalcified coronary plaque in women compared with an increase in both calcified and noncalcified plaque in men with cardiac risk factors. Some data have suggested that women obtain greater prognostic benefit from CCTA than from other noninvasive tests. Fractional flow reserve obtained from a CCTA (FFRCT) is a new mathematical assessment of coronary blood flow that determines the presence of lesion-specific myocardial ischemia. Prevention and identification of ischemic heart disease remains a foundation of cardiology and public health. In women, atypical symptoms and limitations in traditional risk factor assessment lead to challenges in the identification of ischemic heart disease. With improvements in technologies such as CAC scoring, CCTA, instantaneous flow reserve (iFR), optical coherence tomography (OCT), and FFRCT, there is great promise for identification of ischemic heart disease, and the future of prevention in women. Future studies with strong female representation should investigate the role of novel imaging techniques in women.

Incremental role of resting myocardial computed tomography perfusion for predicting physiologically significant coronary artery disease: A machine learning approach.

BACKGROUND: Evaluation of resting myocardial computed tomography perfusion (CTP) by coronary CT angiography (CCTA) might serve as a useful addition for determining coronary artery disease. We aimed to evaluate the incremental benefit of resting CTP over coronary stenosis for predicting ischemia using a computational algorithm trained by machine learning methods. METHODS: 252 patients underwent CCTA and invasive fractional flow reserve (FFR). CT stenosis was classified as 0%, 1-30%, 31-49%, 50-70%, and >70% maximal stenosis. Significant ischemia was defined as invasive FFR < 0.80. Resting CTP analysis was performed using a gradient boosting classifier for supervised machine learning. RESULTS: On a per-patient basis, accuracy, sensitivity, specificity, positive predictive, and negative predictive values according to resting CTP when added to CT stenosis (>70%) for predicting ischemia were 68.3%, 52.7%, 84.6%, 78.2%, and 63.0%, respectively. Compared with CT stenosis [area under the receiver operating characteristic curve (AUC): 0.68, 95% confidence interval (CI) 0.62-0.74], the addition of resting CTP appeared to improve discrimination (AUC: 0.75, 95% CI 0.69-0.81, P value .001) and reclassification (net reclassification improvement: 0.52, P value < .001) of ischemia. CONCLUSIONS: The addition of resting CTP analysis acquired from machine learning techniques may improve the predictive utility of significant ischemia over coronary stenosis.

Diagnostic Performance of a Novel Coronary CT Angiography Algorithm: Prospective Multicenter Validation of an Intracycle CT Motion Correction Algorithm for Diagnostic Accuracy.

OBJECTIVE: Motion artifact can reduce the diagnostic accuracy of coronary CT angiography (CCTA) for coronary artery disease (CAD). The purpose of this study was to compare the diagnostic performance of an algorithm dedicated to correcting coronary motion artifact with the performance of standard reconstruction methods in a prospective international multicenter study. SUBJECTS AND METHODS: Patients referred for clinically indicated invasive coronary angiography (ICA) for suspected CAD prospectively underwent an investigational CCTA examination free from heart rate-lowering medications before they underwent ICA. Blinded core laboratory interpretations of motion-corrected and standard reconstructions for obstructive CAD (≥ 50% stenosis) were compared with ICA findings. Segments unevaluable owing to artifact were considered obstructive. The primary endpoint was per-subject diagnostic accuracy of the intracycle motion correction algorithm for obstructive CAD found at ICA. RESULTS: Among 230 patients who underwent CCTA with the motion correction algorithm and standard reconstruction, 92 (40.0%) had obstructive CAD on the basis of ICA findings. At a mean heart rate of 68.0 ± 11.7 beats/min, the motion correction algorithm reduced the number of nondiagnostic scans compared with standard reconstruction (20.4% vs 34.8%; p < 0.001). Diagnostic accuracy for obstructive CAD with the motion correction algorithm (62%; 95% CI, 56-68%) was not significantly different from that of standard reconstruction on a per-subject basis (59%; 95% CI, 53-66%; p = 0.28) but was superior on a per-vessel basis: 77% (95% CI, 74-80%) versus 72% (95% CI, 69-75%) (p = 0.02). The motion correction algorithm was superior in subgroups of patients with severely obstructive (≥ 70%) stenosis, heart rate ≥ 70 beats/min, and vessels in the atrioventricular groove. CONCLUSION: The motion correction algorithm studied reduces artifacts and improves diagnostic performance for obstructive CAD on a per-vessel basis and in selected subgroups on a per-subject basis.

Machine learning for prediction of all-cause mortality in patients with suspected coronary artery disease: a 5-year multicentre prospective registry analysis.

AIMS: Traditional prognostic risk assessment in patients undergoing non-invasive imaging is based upon a limited selection of clinical and imaging findings. Machine learning (ML) can consider a greater number and complexity of variables. Therefore, we investigated the feasibility and accuracy of ML to predict 5-year all-cause mortality (ACM) in patients undergoing coronary computed tomographic angiography (CCTA), and compared the performance to existing clinical or CCTA metrics. METHODS AND RESULTS: The analysis included 10 030 patients with suspected coronary artery disease and 5-year follow-up from the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry. All patients underwent CCTA as their standard of care. Twenty-five clinical and 44 CCTA parameters were evaluated, including segment stenosis score (SSS), segment involvement score (SIS), modified Duke index (DI), number of segments with non-calcified, mixed or calcified plaques, age, sex, gender, standard cardiovascular risk factors, and Framingham risk score (FRS). Machine learning involved automated feature selection by information gain ranking, model building with a boosted ensemble algorithm, and 10-fold stratified cross-validation. Seven hundred and forty-five patients died during 5-year follow-up. Machine learning exhibited a higher area-under-curve compared with the FRS or CCTA severity scores alone (SSS, SIS, DI) for predicting all-cause mortality (ML: 0.79 vs. FRS: 0.61, SSS: 0.64, SIS: 0.64, DI: 0.62; P< 0.001). CONCLUSIONS: Machine learning combining clinical and CCTA data was found to predict 5-year ACM significantly better than existing clinical or CCTA metrics alone.

Rationale and design of the Coronary Computed Tomographic Angiography for Selective Cardiac Catheterization: Relation to Cardiovascular Outcomes, Cost Effectiveness and Quality of Life (CONSERVE) trial.

Although coronary computed tomography angiography (CCTA) has shown promise as a "gatekeeper" to invasive coronary angiography (ICA) in longitudinal cohort studies, it remains unknown whether the strategy of selective ICA by initial performance of CCTA is either safe or effective when compared with a direct ICA strategy in patients with an American Heart Association (AHA)/American College of Cardiology (ACC) guideline-directed indication for ICA. OBJECTIVES: The CONSERVE trial is a prospective randomized multicenter trial to determine the clinical effectiveness of "selective catheterization" vs "direct catheterization" strategies for stable patients with suspected but without known coronary artery disease, who meet AHA/ACC guideline indication for ICA. METHODS: Patients being referred for clinically indicated nonemergent ICA with an AHA/ACC class II guideline indication for ICA will be randomized to either direct catheterization or selective catheterization strategy. Patients in the direct catheterization arm will proceed directly to ICA as planned, whereas patients in the select catheterization arm will undergo initial CCTA, followed by ICA at the discretion of the site physician. All CCTAs and ICAs will be interpreted on site. Follow-up testing and/or therapy after CCTA or ICA will be at the discretion of the site physician. RESULTS: This trial will report a primary clinical end point of noninferiority rates of major adverse cardiac events, as defined by the composite of death, nonfatal myocardial infarction, unstable angina, stroke, urgent or emergent coronary revascularization, or cardiac hospitalization. CONCLUSION: The CONSERVE trial will determine whether selective catheterization strategy, based on initial CCTA in patients being referred to ICA, is safe and effective.

Prognostic Importance of Diastolic Dysfunction in Relation to Post Procedural Aortic Insufficiency in Patients Undergoing Transcatheter Aortic Valve Replacement.

OBJECTIVES: We sought to examine whether baseline diastolic dysfunction (DD) is associated with increased mortality in patients who develop aortic insufficiency (AI) after transcatheter aortic valve replacement (TAVR). BACKGROUND: Significant post-TAVR AI is associated with increased mortality, likely secondary to adverse hemodynamics secondary to volume overload and decreased LV compliance from chronic pressure overload. However, the effect of baseline DD on outcomes of patients with post-TAVR AI has not been studied. METHODS: A total of 195 patients undergoing TAVR were included in the study. Patients with moderate-to-severe mitral stenosis, prior mitral valve replacement or atrial fibrillation were excluded. DD was classified at baseline by a 2-step approach as recommended by the American Society of Echocardiography while AI was evaluated 30 days post-TAVR. Follow up data up to 2 years post-TAVR was used in survival analysis. RESULTS: Patients with severe baseline DD who developed ≥mild post-TAVR AI had increased mortality compared to all other patients (HR = 3.89, CI: 1.76-8.6, P = 0.001), which remained significant after adjusting for post-TAVR AI, pre-TAVR AI, baseline mitral regurgitation, ejection fraction, pulmonary artery pressure, creatinine clearance and history of stroke. CONCLUSIONS: Even mild post-TAVR AI may have a negative impact on outcomes of patients with underlying severe DD. © 2016 Wiley Periodicals, Inc.

Prognostic and therapeutic implications of statin and aspirin therapy in individuals with nonobstructive coronary artery disease: results from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry) registry.

OBJECTIVE: We sought to examine the risk of mortality associated with nonobstructive coronary artery disease (CAD) and to determine the impact of baseline statin and aspirin use on mortality. APPROACH AND RESULTS: Coronary computed tomographic angiography permits direct visualization of nonobstructive CAD. To date, the prognostic implications of nonobstructive CAD and the potential benefit of directing therapy based on nonobstructive CAD have not been carefully examined. A total of 27 125 consecutive patients who underwent computed tomographic angiography (12 enrolling centers and 6 countries) were prospectively entered into the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry. Patients, without history of previous CAD or obstructive CAD, for whom baseline statin and aspirin use was available were analyzed. Each coronary segment was classified as normal or nonobstructive CAD (1%-49% stenosis). Patients were followed up for a median of 27.2 months for all-cause mortality. The study comprised 10 418 patients (5712 normal and 4706 with nonobstructive CAD). In multivariable analyses, patients with nonobstructive CAD had a 6% (95% confidence interval, 1%-12%) higher risk of mortality for each additional segment with nonobstructive plaque (P=0.021). Baseline statin use was associated with a reduced risk of mortality (hazard ratio, 0.44; 95% confidence interval, 0.28-0.68; P=0.0003), a benefit that was present for individuals with nonobstructive CAD (hazard ratio, 0.32; 95% confidence interval, 0.19-0.55; P<0.001) but not for those without plaque (hazard ratio, 0.66; 95% confidence interval, 0.30-1.43; P=0.287). When stratified by National Cholesterol Education Program/Adult Treatment Program III, no mortality benefit was observed in individuals without plaque. Aspirin use was not associated with mortality benefit, irrespective of the status of plaque. CONCLUSIONS: The presence and extent of nonobstructive CAD predicted mortality. Baseline statin therapy was associated with a significant reduction in mortality for individuals with nonobstructive CAD but not for individuals without CAD. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov/. Unique identifier NCT01443637.

Prevalence and Distribution of Coronary Artery Calcification in Asymptomatic United States and Korean Adults　- Cross-Sectional Propensity-Matched Analysis.

BACKGROUND: The incidence of coronary artery disease (CAD) varies depending on ethnicity, but the precise differences remain to be firmly established. This study therefore evaluated the disparity in coronary artery calcification (CAC), as a marker of CAD, in asymptomatic US and Korean adults.Methods and Results:CAC score was compared between asymptomatic Korean (n=15,128) and US (n=7,533) adults. Propensity score matching was performed according to age, gender, hypertension, diabetes, dyslipidemia, and current smoking, which generated 2 cohorts of 5,427 matched pairs. Both cohorts were categorized according to age group: 45-54, 55-64, and 65-74 years. Overall, the prevalence of CAC score >0, >100, and >400 in Korean adults was lower than in US adults (P<0.001, all). According to increasing age groups, the likelihood of CAC was most often lower in Korean adults, especially in Korean women. The odds of having CAC >400 in Korean adults aged 65-74 years was 0.66 (95% CI: 0.48-0.91) overall, 0.78 (95% CI: 0.52-1.19) in men, and 0.50 (95% CI: 0.29-0.86) in women, compared with US counterparts. CONCLUSIONS: Korean adults have a lower prevalence and severity of atherosclerotic burden as assessed on CAC, compared with US adults, but the disparity in CAC according to ethnicity may decline with older age. (Circ J 2016; 80: 2349-2355).

Rationale and Design of the CREDENCE Trial: computed TomogRaphic evaluation of atherosclerotic DEtermiNants of myocardial IsChEmia.

BACKGROUND: Coronary computed tomography angiography (CCTA) allows for non-invasive assessment of obstructive coronary artery disease (CAD) beyond measures of stenosis severity alone. This assessment includes atherosclerotic plaque characteristics (APCs) and calculation of fractional flow reserve (FFR) from CCTA (FFRCT). Similarly, stress imaging by myocardial perfusion scintigraphy (MPS) provides vital information. To date, the diagnostic performance of integrated CCTA assessment versus integrated MPS assessment for diagnosis of vessel-specific ischemia remains underexplored. METHODS: CREDENCE will enroll adult individuals with symptoms suspicious of CAD referred for non-emergent invasive coronary angiography (ICA), but without known CAD. All participants will undergo CCTA, MPS, ICA and FFR. FFR will be performed for lesions identified at the time of ICA to be ≥40 and <90 % stenosis, or those clinically indicated for evaluation. Study analyses will focus on diagnostic performance of CCTA versus MPS against invasive FFR reference standard. An integrated stenosis-APC-FFRCT metric by CCTA for vessel-specific ischemia will be developed from derivation cohort and tested against a validation cohort. Similarly, integrated metric by MPS for vessel-specific ischemia will be developed, validated and compared. An FFR value of ≤0.80 will be considered as ischemia causing. The primary endpoint will be the diagnostic accuracy of vessel territory-specific ischemia of integrated stenosis-APC-FFRCT measure by CCTA, compared with perfusion or perfusion-myocardial blood flow stress imaging testing, against invasive FFR. DISCUSSION: CREDENCE will determine the performance of integrated CCTA metric compared to integrated MPS measure for diagnosis of vessel-specific ischemia. If proven successful, this study may reduce the number of missed diagnoses and help to optimally predict ischemia-causing lesions. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02173275 . Registered on June 23, 2014.

Impact of Paravalvular Aortic Insufficiency on Left Ventricular Remodeling and Mortality after Transcatheter Aortic Valve Replacement.

BACKGROUND: Paravalvular aortic regurgitation (PAR) remains a common complication following transcatheter aortic valve replacement (TAVR), and has been associated with increased mortality. Adverse left ventricular (LV) remodelling has been reported in patients with post-TAVR PAR, but the association between adverse LV remodeling and increased mortality remains unclear. The aim of the present study was to examine the association between PAR, LV remodeling and mortality following TAVR in a non-PARTNER (Placement of Aortic Transcatheter Valves) trial population. METHODS: A total of 195 patients that underwent TAVR was included in the study. The LV ejection fraction (LVEF), LV mass index (LVMI), LV internal dimension at systole (LVIDs) and diastole (LVIDd) were compared between patients with different degrees of PAR at baseline, and at one month and one year after TAVR. Survival analysis was performed for different degrees of PAR and LV remodeling. RESULTS: PAR ≥moderate was associated with increased mortality (HR 4.58 [1.80-11.63], p = 0.001), but PAR >mild was not. The LVIDd and LVIDs were persistently increased at one year after TAVR in patients with PAR >mild compared to those with PAR ≤mild (5.9 ± 0.8 cm versus 5.4 ± 0.7 cm, p = 0.02 and 4.4 ± 0.8 cm versus 3.9 ± 0.8, p = 0.03, respectively). The LVEF was improved similarly between the two groups at one year after TAVR (p = 0.1). Patients with PAR ≥moderate had significantly more adverse LV remodeling at one month after TAVR in terms of LVIDd, LVIDs, and LVMI. The degree of remodeling as expressed in terms of LVIDd, LVIDs, LVMI and LVEF changes from baseline did not have a direct impact on mortality. CONCLUSIONS: A worse PAR was associated with more adverse LV remodeling and a higher mortality after TAVR in a non-PARTNER patient population.

Current but not past smoking increases the risk of cardiac events: insights from coronary computed tomographic angiography.

AIMS: We evaluated coronary artery disease (CAD) extent, severity, and major adverse cardiac events (MACEs) in never, past, and current smokers undergoing coronary CT angiography (CCTA). METHODS AND RESULTS: We evaluated 9456 patients (57.1 ± 12.3 years, 55.5% male) without known CAD (1588 current smokers; 2183 past smokers who quit ≥3 months before CCTA; and 5685 never smokers). By risk-adjusted Cox proportional-hazards models, we related smoking status to MACE (all-cause death or non-fatal myocardial infarction). We further performed 1:1:1 propensity matching for 1000 in each group evaluate event risk among individuals with similar age, gender, CAD risk factors, and symptom presentation. During a mean follow-up of 2.8 ± 1.9 years, 297 MACE occurred. Compared with never smokers, current and past smokers had greater atherosclerotic burden including extent of plaque defined as segments with any plaque (2.1 ± 2.8 vs. 2.6 ± 3.2 vs. 3.1 ± 3.3, P < 0.0001) and prevalence of obstructive CAD [1-vessel disease (VD): 10.6% vs. 14.9% vs. 15.2%, P < 0.001; 2-VD: 4.4% vs. 6.1% vs. 6.2%, P = 0.001; 3-VD: 3.1% vs. 5.2% vs. 4.3%, P < 0.001]. Compared with never smokers, current smokers experienced higher MACE risk [hazard ratio (HR) 1.9, 95% confidence interval (CI) 1.4-2.6, P < 0.001], while past smokers did not (HR 1.2, 95% CI 0.8-1.6, P = 0.35). Among matched individuals, current smokers had higher MACE risk (HR 2.6, 95% CI 1.6-4.2, P < 0.001), while past smokers did not (HR 1.3, 95% CI 0.7-2.4, P = 0.39). Similar findings were observed for risk of all-cause death. CONCLUSION: Among patients without known CAD undergoing CCTA, current and past smokers had increased burden of atherosclerosis compared with never smokers; however, risk of MACE was heightened only in current smokers.

Incremental prognostic utility of coronary CT angiography for asymptomatic patients based upon extent and severity of coronary artery calcium: results from the COronary CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter (CONFIRM) study.

AIM: Prior evidence observed no predictive utility of coronary CT angiography (CCTA) over the coronary artery calcium score (CACS) and the Framingham risk score (FRS), among asymptomatic individuals. Whether the prognostic value of CCTA differs for asymptomatic patients, when stratified by CACS severity, remains unknown. METHODS AND RESULTS: From a 12-centre, 6-country observational registry, 3217 asymptomatic individuals without known coronary artery disease (CAD) underwent CACS and CCTA. Individuals were categorized by CACS as: 0-10, 11-100, 101-400, 401-1000, >1000. For CCTA analysis, the number of obstructive vessels-as defined by the per-patient presence of a ≥50% luminal stenosis-was used to grade the extent and severity of CAD. The incremental prognostic value of CCTA over and above FRS was measured by the likelihood ratio (LR) χ(2), C-statistic, and continuous net reclassification improvement (NRI) for prediction, discrimination, and reclassification of all-cause mortality and non-fatal myocardial infarction. During a median follow-up of 24 months (25th-75th percentile, 17-30 months), there were 58 composite end-points. The incremental value of CCTA over FRS was demonstrated in individuals with CACS >100 (LRχ(2), 25.34; increment in C-statistic, 0.24; NRI, 0.62, all P < 0.001), but not among those with CACS ≤100 (all P > 0.05). For subgroups with CACS >100, the utility of CCTA for predicting the study end-point was evident among individuals whose CACS ranged from 101 to 400; the observed predictive benefit attenuated with increasing CACS. CONCLUSION: Coronary CT angiography provides incremental prognostic utility for prediction of mortality and non-fatal myocardial infarction for asymptomatic individuals with moderately high CACS, but not for lower or higher CACS.