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BACKGROUND: Coronary accessibility following redo--transcatheter aortic valve replacement (redo-TAVR) is increasingly important, particularly in younger low-risk patients. This study aimed to predict coronary accessibility after simulated Sapien-3 balloon-expandable valve implantation within an Evolut supra-annular, self-expanding valve using pre-TAVR computed tomography (CT) imaging. METHODS: A total of 219 pre-TAVR CT scans from the Evolut Low-Risk CT substudy were analyzed. Virtual Evolut and Sapien-3 valves were sized using CT-based diameters. Two initial Evolut implant depths were analyzed, 3 and 5 mm. Coronary accessibility was evaluated for 2 Sapien-3 in Evolut implant positions: Sapien-3 outflow at Evolut node 4 and Evolut node 5. RESULTS: With a 3-mm initial Evolut implant depth, suitable coronary access was predicted in 84% of patients with the Sapien-3 outflow at Evolut node 4, and in 31% of cases with the Sapien-3 outflow at Evolut node 5 (P<0.001). Coronary accessibility improved with a 5-mm Evolut implant depth: 97% at node 4 and 65% at node 5 (P<0.001). When comparing 3- to 5-mm Evolut implant depth, sinus sequestration was the lowest with Sapien-3 outflow at Evolut node 4 (13% versus 2%; P<0.001), and the highest at Evolut node 5 (61% versus 32%; P<0.001). CONCLUSIONS: Coronary accessibility after Sapien-3 in Evolut redo-TAVR relates to the initial Evolut implant depth, the Sapien-3 outflow position within the Evolut, and the native annular anatomy. This CT-based quantitative analysis may provide useful information to inform and refine individualized preprocedural CT planning of the initial TAVR and guide lifetime management for future coronary access after redo-TAVR. [ABSTRACT FROM AUTHOR]

BACKGROUND: The use of predilation during transcatheter aortic valve replacement (TAVR) is variable, and its association with outcomes remains unknown. We evaluated the impact of predilation versus no predilation (direct TAVR) in the low-risk population enrolled in the PARTNER 3 trial (Placement of Aortic Transcatheter Valves). METHODS: In the PARTNER 3 trial, 495 patients with severe symptomatic aortic stenosis underwent TAVR with the SAPIEN 3 valve. The use of predilation was left to operator discretion. The primary end point was a composite of all-cause death, stroke, or rehospitalization. Secondary end points included valve hemodynamic performance and the need for postdilation. Propensity score matching was performed. RESULTS: Predilation and direct TAVR were performed in 286 (57.8%) and 209 (42.2%) patients, respectively. Before matching, the primary end point occurrence at 30 days (3.8% versus 4.8%, P=0.604) and 1 year (8.7% versus 8.1%, P=0.831) was similar in the predilation versus direct TAVR groups. Similar results were observed after matching (202 patients in each groups). Incidence of ≥ mild paravalvular regurgitation was similar in both groups. Incidence of severe prosthesis-patient mismatch was low but higher in the predilation group versus the direct TAVR group (8.2% versus 2.6%, P=0.023). Compared with direct TAVR, the use of predilation was associated with longer procedure duration (63.2 versus 51.4 minutes, P=0.001), while the rate of postdilation did not differ between the 2 groups (24.8% versus 18.8%, P=0.150). CONCLUSIONS: Predilation and direct TAVR are safe in patients with low surgical risk and favorable aortic valve anatomy. Direct TAVR decreased the procedure duration and did not predispose to more postdilation. [ABSTRACT FROM AUTHOR]

Coronary 18F-fluoride positron emission tomography identifies ruptured and high-risk atherosclerotic plaque. The optimal method to identify, to quantify, and to categorize increased coronary 18F-fluoride uptake and determine its reproducibility has yet to be established. This study aimed to optimize the identification, quantification, categorization, and scan-rescan reproducibility of increased 18F-fluoride activity in coronary atherosclerotic plaque. METHODS: In a prospective observational study, patients with multivessel coronary artery disease underwent serial 18F-fluoride positron emission tomography. Coronary 18F-fluoride activity was visually assessed, quantified, and categorized with reference to maximal tissue to background ratios. Levels of agreement for both visual and quantitative methods were determined between scans and observers. RESULTS: Thirty patients (90% male, 20 patients with stable coronary artery disease, and 10 with recent type 1 myocardial infarction) underwent paired serial positron emission tomography-coronary computed tomography angiography imaging within an interval of 12±5 days. A mean of 3.7±1.8 18F-fluoride positive plaques per patient was identified after recent acute coronary syndrome, compared with 2.4±2.3 positive plaques per patient in stable coronary artery disease. The bias in agreement in maximum tissue to background ratio measurements in visually positive plaques was low between observers (mean difference, −0.01; 95% limits of agreement, −0.32 to 0.30) or between scans (mean difference, 0.06; 95% limits of agreement, −0.49 to 0.61). Good agreement in the categorization of focal 18F-fluoride uptake was achieved using visual assessment alone (κ=0.66) and further improved at higher maximum tissue to background ratio values. CONCLUSIONS: Coronary 18F-fluoride activity is a precise and reproducible metric in the coronary vasculature. The analytical performance of 18F-fluoride is sufficient to assess the prognostic utility of this radiotracer as a noninvasive imaging biomarker of plaque vulnerability [ABSTRACT FROM AUTHOR]

The aims of the current statement are to refine the definition of quality in cardiovascular imaging and to propose novel methodological approaches to inform the demonstration of quality in imaging in future clinical trials and registries. We propose defining quality in cardiovascular imaging using an analytical framework put forth by the Institute of Medicine whereby quality was defined as testing being safe, effective, patient-centered, timely, equitable, and efficient. The implications of each of these components of quality health care are as essential for cardiovascular imaging as they are for other areas within health care. Our proposed statement may serve as the foundation for integrating these quality indicators into establishing designations of quality laboratory practices and developing standards for value-based payment reform for imaging services. We also include recommendations for future clinical research to fulfill quality aims within cardiovascular imaging, including clinical hypotheses of improving patient outcomes, the importance of health status as an end point, and deferred testing options. Future research should evolve to define novel methods optimized for the role of cardiovascular imaging for detecting disease and guiding treatment and to demonstrate the role of cardiovascular imaging in facilitating healthcare quality. [ABSTRACT FROM AUTHOR]

Background--Patients with obstructive (≥50% stenosis) left main (LM) coronary artery disease (CAD) are at high risk for adverse events; prior studies have also documented worse outcomes among women than men with severe multivessel/LM CAD. However, the prognostic significance of nonobstructive (1%-49% stenosis) LM CAD, including sex-specific differences, has not been previously examined. Methods and Results--In the long-term CONFIRM (Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter) registry, patients underwent elective coronary computed tomographic angiography for suspected CAD and were followed for 5 years. After excluding those with obstructive LM CAD, 5166 patients were categorized as having normal LM or nonobstructive LM (18% of cohort). Cumulative 5-year incidence of death, myocardial infarction, or revascularization was higher among patients with nonobstructive LM than normal LM in both women and men: women (34.3% versus 15.4%; P<0.0001); men (24.6% versus 18.2%; P<0.0001). A significant interaction existed between sex and LM status for the composite outcome (P=0.001). In multivariable Cox regression, the presence of nonobstructive LM plaque increased the risk for the composite outcome in women (adjusted hazard ratio, 1.48; P=0.005) but not in men (adjusted hazard ratio, 0.98, P=0.806). In subgroup analysis, women with nonobstructive LM CAD had a nearly 80% higher risk for events than men with nonobstructive LM CAD (adjusted hazard ratio, 1.78; P=0.017); sex-specific interactions were not observed across other patterns (eg, location or extent) of nonobstructive plaque. Conclusion--Nonobstructive LM CAD was frequently detected on coronary computed tomographic angiography and strongly associated with adverse events among women. Recognizing the sex-specific prognostic significance of nonobstructive LM plaque may augment risk stratification efforts. [ABSTRACT FROM AUTHOR]

Hypertension is an atherosclerosis factor and is associated with cardiovascular risk. We investigated the relationship between hypertension and the presence, extent, and severity of coronary atherosclerosis in coronary computed tomographic angiography and cardiac events risk. Of 17 181 patients enrolled in the CONFIRM registry (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) who underwent ≥64-detector row coronary computed tomographic angiography, we identified 14 803 patients without known coronary artery disease. Of these, 1434 hypertensive patients were matched to 1434 patients without hypertension. Major adverse cardiac events risk of hypertension and non-hypertensive patients was evaluated with Cox proportional hazards models. The prognostic associations between hypertension and no-hypertension with increasing degree of coronary stenosis severity (nonobstructive or obstructive ≥50%) and extent of coronary artery disease (segment involvement score of 1-5, >5) was also assessed. Hypertension patients less commonly had no coronary atherosclerosis and more commonly had nonobstructive and 1-, 2-, and 3-vessel disease than the no-hypertension group. During a mean follow-up of 5.2±1.2 years, 180 patients experienced cardiac events, with 104 (2.0%) occurring in the hypertension group and 76 (1.5%) occurring in the no-hypertension group (hazard ratios, 1.4; 95% confidence intervals, 1.0-1.9). Compared with no-hypertension patients without coronary atherosclerosis, hypertension patients with no coronary atherosclerosis and obstructive coronary disease tended to have higher risk of cardiac events. Similar trends were observed with respect to extent of coronary artery disease. Compared with no-hypertension patients, hypertensive patients have increased presence, extent, and severity of coronary atherosclerosis and tend to have an increase in major adverse cardiac events. [ABSTRACT FROM AUTHOR]

Transcatheter interventions to treat mitral and tricuspid valve disease are becoming increasingly available because of the growing number of elderly patients with significant comorbidities or high operative risk. Thorough clinical and imaging evaluation in these patients is essential. The latter involves both characterization of the mechanism and severity of valvular disease as well as determining the hemodynamic consequences and extent of ventricular remodeling, which is an important predictor of future outcomes. Moreover, an assessment of the suitability and risk of complications associated with device-specific therapies is also an important component of the preprocedural evaluation in this cohort. Although echocardiography including 2-dimensional and 3-dimensional methods has an important role in the initial assessment and procedural guidance, cross-sectional imaging, including both computed tomographic imagning and cardiac magnetic resonance imaging, is increasingly being integrated into the evaluation of mitral and tricuspid valve disease. In this review, we discuss the role of cross-sectional imaging in mitral and tricuspid valve disease, primarily valvular regurgitation assessment, with an emphasis on the preprocedural evaluation and implications for transcatheter interventions. [ABSTRACT FROM AUTHOR]

Background--Previously, through the use of computed tomography (CT), it has been proposed that D-shaped versus saddleshaped mitral annulus (MA) segmentation is more biomechanically appropriate to determine transcatheter mitral valve implantation size and eligibility. Methods and Results--Forty-one patients with severe mitral regurgitation being considered for transcatheter mitral valve implantation who had undergone cardiac CT and 3-dimensional transesophageal echocardiography (3D-TEE) were retrospectively evaluated. A standardized segmentation protocol for the D-shaped MA was developed using Philips Q-Laboratory mitral valve quantification software. MA dimensions were compared using Spearman's rank correlation and Bland-Altman analysis. Inter- and intraobserver agreement was quantified by intraclass correlation coefficient and Bland-Altman analysis. Mean age was 77±14 years; 71% male (n=29); mitral regurgitation pathogenesis was functional in 54% (n=22) and myxomatous in 46% (n=19). Mean MA area and circumference by 3D-TEE and CT were 11.3±2.7 versus 11.4±3.0 (P=0.67) and 124.1±15.6 versus 123.9±15.5 (P=0.79), respectively, with excellent correlation between modalities (r=0.84 and r=0.86; P<0.0001) and no systematic bias (-0.20±1.8 cm² [-3.7 cm²; 3.3 cm²], 0.37±9 mm [-18.0 mm; 17.27 mm]). Mean septal-to-lateral and inter-trigone distances by 3D-TEE and CT were 33.2±4.7 versus 32.5±4.4 (P=0.24) and 31.7±3.5 versus 32.6±3.6 (P=0.06), respectively, with good correlation (r=0.69 and r=0.71; P<0.0001) and no systematic bias (0.77±3.8 mm [-6.7 mm; 8.2 mm], -1.5±3.1 mm [-4.6 mm; 7.6 mm]). There was excellent intra- and interobserver agreement according to intraclass correlation coefficients >0.90 for all parameters. Conclusions--Similar to cardiac CT, 3D-TEE allows for D-shaped MA segmentation with no systematic difference in MA dimensions between modalities. This study supports the utilization of 3D-TEE as a complementary tool to CT assessment of the D-shaped MA to determine transcatheter mitral valve implantation size. [ABSTRACT FROM AUTHOR]

Background: Patients with significant (>=50%) left main disease (LMD) have a high risk of cardiovascular events, and guidelines recommend revascularization to improve survival. However, the impact of intermediate LMD (stenosis, 25%-49%) on outcomes is unclear. Methods: Randomized ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) participants who underwent coronary computed tomography angiography at baseline were categorized into those with (25%-49%) and without (<25%) intermediate LMD. The primary outcome was a composite of cardiovascular mortality, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. The primary quality of life outcome was the Seattle Angina Questionnaire summary score. Results: Among the 3699 participants who satisfied the inclusion criteria, 962 (26%) had intermediate LMD. Among invasive strategy participants with intermediate LMD on coronary computed tomography angiography, 49 (7.0%) had significant (>=50% stenosis) left main stenosis on invasive angiography. Patients with intermediate LMD had a higher risk of cardiovascular events in the unadjusted but not in the fully adjusted model compared with those without intermediate LMD. An invasive strategy increased procedural MI and decreased nonprocedural MI with no significant difference for other outcomes including the primary end point. There was no meaningful heterogeneity of treatment effect based on intermediate LMD status except for nonprocedural MI for which there was a greater absolute reduction with invasive management in the intermediate LMD group (-6.4% versus -2.0%; P interaction=0.049). The invasive strategy improved angina-related quality of life and the benefit was durable throughout follow-up without significant heterogeneity based on intermediate LMD status. Conclusions: In the ISCHEMIA trial, there was no meaningful heterogeneity of treatment benefit from an invasive strategy regardless of intermediate LMD status except for a greater absolute risk reduction in nonprocedural MI with invasive management in those with intermediate LMD. An invasive strategy increased procedural MI, reduced nonprocedural MI, and improved angina-related quality of life. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01471522. * Patients with significant (>=50%) left main disease (LMD) have a high risk of cardiovascular events, and guidelines recommend revascularization to improve survival. * The impact of intermediate LMD (25%-49% left main stenosis) is not known. * In the ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), 26% of participants had intermediate LMD (25%-49% left main stenosis) on coronary computed tomography angiography, and this was a marker for extensive atherosclerosis. * Invasive management increased procedural myocardial infarction, reduced nonprocedural myocardial infarction, and improved angina-related quality of life when compared with conservative management regardless of intermediate LMD status. * Invasive management resulted in a greater reduction in nonprocedural myocardial infarction compared with conservative management in those with intermediate LMD than in those without intermediate LMD. [ABSTRACT FROM AUTHOR]

Fractional flow reserve derived from computed tomography angiography (FFRCT) is a noninvasive method for diagnosis of ischemic coronary lesions. To date, the diagnostic performance of FFRCT for lesions of intermediate stenosis severity remains unexamined.Among 407 vessels from 252 patients at 17 centers who underwent CT, FFRCT, invasive coronary angiography, and invasive FFR, we identified 150 vessels of intermediate stenosis by CT, defined as 30% to 69% stenosis. FFRCT, FFR, and CT were interpreted in blinded fashion by independent core laboratories. FFRCT and FFR 0.80 were considered hemodynamically significant, whereas CT stenosis ≥50% was considered obstructive. Diagnostic performance of FFRCT versus CT was assessed for accuracy, sensitivity, specificity, positive predictive values, and negative predictive values. Area under the receiver operating characteristic curve and net reclassification improvement were evaluated. For lesions of intermediate stenosis severity, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of FFRCT were 71%, 74%, 67%, 41%, and 90%, whereas accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of CT stenosis were 63%, 34%, 72%, 27%, and 78%. FFRCT demonstrated superior discrimination compared with CT stenosis on per-patient (area under the receiver operating characteristic curve, 0.81 versus 0.50; P=0.0001) and per-vessel basis (area under the receiver operating characteristic curve, 0.79 versus 0.53; P<0.0001). FFRCT demonstrated significant reclassification of CT stenosis for lesion-specific ischemia (net reclassification improvement, 0.45; 95% confidence interval, 0.25-0.65; P=0.01).FFRCT possesses high diagnostic performance for diagnosis of ischemic for lesions of intermediate stenosis severity. Notably, the high sensitivity and negative predictive value suggest the ability of FFRCT to effectively rule out intermediate lesions that cause ischemia. [ABSTRACT FROM AUTHOR]

The article discusses a study on the ability and practicability of 3DA to determine the optimal perpendicular valve projection for accurate positioning and deployment of valve prosthesis in transcatheter aortic valve replacement (TAVR) and compared the method with multidetector computed tomography (MDCT). Patient had MDC during the week before and 3DA at the start of TAVR. It suggests that the role of MDCT for patient selection, planning and conducting TAVR is well established.

Supplemental Digital Content is available in the text. Background: Although aortic valve replacement is associated with a major benefit in high-gradient (HG) severe aortic stenosis (AS), the results in low-gradient (LG, mean gradient <40 mm Hg) AS are conflicting. LG severe AS may be subdivided in classical low-flow (left ventricular ejection fraction <50%) and LG (CLF-LG); paradoxical low-flow (left ventricular ejection fraction ≥50% but stroke volume index <35 mL/m2) and LG; and normal-flow (left ventricular ejection fraction ≥50% and stroke volume index ≥35 mL/m2) and LG. The primary objective is to determine in the PARTNER 2 trial (The Placement of Aortic Transcatheter Valves) and registry the outcomes after aortic valve replacement of the 4 flow-gradient groups. Methods: A total of 3511 patients from the PARTNER 2 Cohort A randomized trial (n=1910) and SAPIEN 3 registry (n=1601) were included. The flow-gradient pattern was determined at baseline transthoracic echocardiography and classified as follows: (1) HG; (2) CLF-LG; (3) paradoxical low-flow-LG; and (4) normal-flow-LG. The primary end point for this analysis was the composite of (1) death; (2) rehospitalization for heart failure symptoms and valve prosthesis complication; or (3) stroke. Results: The distribution was HG, 2229 patients (63.5%); CLF-LG, 689 patients (19.6%); paradoxical low-flow-LG, 247 patients (7.0%); and normal-flow-LG, 346 patients (9.9%). The 2-year rate of primary end point was higher in CLF-LG (38.8%) versus HG: 31.8% (P =0.002) and normal-flow-LG: 32.1% (P =0.05) but was not statistically different from paradoxical low-flow-LG: 33.6% (P =0.18). There was no significant difference in the 2-year rates of clinical events between transcatheter aortic valve replacement versus surgical aortic valve replacement in the whole cohort and within each flow-gradient group. Conclusions: The LG AS pattern was highly prevalent (36.5%) in the PARTNER 2 trial and registry. CLF-LG was the most common pattern of LG AS and was associated with higher rates of death, rehospitalization, or stroke at 2 years compared with the HG group. Clinical outcomes were as good in the LG AS groups with preserved left ventricular ejection fraction compared with the HG group. [ABSTRACT FROM AUTHOR]

Introduction: Patients with family history of premature coronary artery disease (CAD) are at risk of CAD events at younger age. Risk factor based approaches and clinical evaluation are the commonly used methods of assessment. Recently it was shown up to 50% of individual presenting with their first myocardial infarction (MI) were considered "low risk" prior to that event. MI is often a result of plaque rupture preceded by progression of subclinical atherosclerosis. Therefore, detection of subclinical atherosclerosis may help target prevention of plaque progression. In this study, we assessed the predictive value of clinical risk factor, biomarkers and Framingham Risk Score (FRS) in predicting subclinical atherosclerosis in this population. Methods: From 230 referrals,182 individuals with a family history of premature CAD, Patients between the ages of 35 to 55 were enrolled in the Early Atherosclerosis Clinic at St. Paul's Hospital, Vancouver, Canada for evaluation of risk of CAD. Premature CAD was defined as CAD events in first-degree family members (male< 55, female< 65). Patients underwent clinical and risk factor evaluations as well as Cardiac CT or Calcium Score (CS) to assess presence of subclinical/clinical atherosclerosis if indicated by the treating physician. Results: In this pilot, 67 individuals (55% male, mean age 45.8 ± 6.0 years) completed evaluation, 31(46%) had evidence of subclinical atherosclerosis on CT coronary angiography or CT calcium score with a mean segment involvement score (SIS) of 3.1 and mean CS of 128. Aside from male sex and age, other risk factors and biomarkers including diabetes mellitus, hypertension, smoking history, total cholesterol, LDL-C, HDL-C, Cholesterol/HDL-C ratio and FRS were not significantly different between those with or without subclinical atherosclerosis (Table 1). Conclusions: In young individuals with a family history of premature CAD, risk factors, biomarkers, and FRS failed to identify patients with premature, subclinical atherosclerosis in this pilot study. Detection of subclinical atherosclerosis and early implementation of treatment with the aim of stabilizing plaques and stopping progression might prove vital in reducing events in these individuals. Further studies are warranted. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Diagnosis of coronary artery disease and management strategies have relied solely on the presence of diameter stenosis ≥50%. We assessed whether direct quantification of plaque burden (PB) and plaque characteristics assessed by coronary computed tomography angiography could provide additional value in terms of predicting rapid plaque progression. Methods and Results: From a 13-center, 7-country prospective observational registry, 1345 patients (60.4±9.4 years old; 57.1% male) who underwent repeated coronary computed tomography angiography >2 years apart were enrolled. For conventional angiographic analysis, the presence of stenosis ≥50%, number of vessel involved, segment involvement score, and the presence of high-risk plaque feature were determined. For quantitative analyses, PB and annual change in PB (△PB/y) in the entire coronary tree were assessed. Clinical outcomes (cardiac death, nonfatal myocardial infarction, and coronary revascularization) were recorded. Rapid progressors, defined as a patient with ≥median value of △PB/y (0.33%/y), were older, more frequently male, and had more clinical risk factors than nonrapid progressors (all P <0.05). After risk adjustment, addition of baseline PB improved prediction of rapid progression to each angiographic assessment of coronary artery disease, and the presence of high-risk plaque further improved the predictive performance (all P <0.001). For prediction of adverse outcomes, adding both baseline PB and △PB/y showed best predictive performance (C statistics, 0.763; P <0.001). Conclusions: Direct quantification of atherosclerotic PB in addition to conventional angiographic assessment of coronary artery disease might be beneficial for improving risk stratification of coronary artery disease. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02803411. [ABSTRACT FROM AUTHOR]

Background: We assessed whether combinations of cardiometabolic risk factors independently predict coronary plaque progression (PP) and major adverse cardiovascular events in patients with stable coronary artery disease., Methods: Patients with known or suspected stable coronary artery disease (60.9±9.3 years, 55.4% male) undergoing serial coronary computed tomography angiographies (≥2 years apart), with clinical characterization and follow-up (N=1200), were analyzed from the PARADIGM study (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging). Plaque volumes measured in coronary segments (≥2 mm in diameter) were summed to provide whole heart plaque volume (mm 3 ) and percent atheroma volume (plaque volume/vessel volume×100; %) per patient at baseline and follow-up. Rapid PP was defined as a percent atheroma volume increase of ≥1.0%/y. Major adverse cardiovascular events included nonfatal myocardial infarction, death, and unplanned coronary revascularization., Results: In an interscan period of 3.2 years (interquartile range, 1.9), rapid PP occurred in 341 patients (28%). At multivariable analysis, the combination of cardiometabolic risk factors defined as metabolic syndrome predicted rapid PP (odds ratio, 1.51 [95% CI, 1.12-2.03]; P =0.007) together with older age, smoking habits, and baseline percent atheroma volume. Among single cardiometabolic variables, high fasting plasma glucose (diabetes or fasting plasma glucose >100 mg/dL) and low HDL-C (high-density lipoprotein cholesterol; <40 mg/dL in males and <50 mg/dL in females) were independently associated with rapid PP, in particular when combined (odds ratio, 2.37 [95% CI, 1.56-3.61]; P <0.001). In a follow-up of 8.23 years (interquartile range, 5.92-9.53), major adverse cardiovascular events occurred in 201 patients (17%). At multivariable Cox analysis, the combination of high fasting plasma glucose with high systemic blood pressure (treated hypertension or systemic blood pressure >130/85 mm Hg) was an independent predictor of events (hazard ratio, 1.79 [95% CI, 1.10-2.90]; P =0.018) together with family history, baseline percent atheroma volume, and rapid PP., Conclusions: In patients with stable coronary artery disease, the combination of hyperglycemia with low HDL-C is associated with rapid PP independently of other risk factors, baseline plaque burden, and treatment. The combination of hyperglycemia with high systemic blood pressure independently predicts the worse outcome beyond PP., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02803411., Competing Interests: Dr Chang receives funding from the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (grant No. 2012027176). Dr Min receives funding from GE Healthcare and serves on the scientific advisory board of Arineta and GE Healthcare. Dr Min also has an equity interest in and is an employee of Cleerly Inc. The other authors report no conflicts.

Background: Luminal stenosis, computed tomography-derived fractional-flow reserve (FFR CT ), and high-risk plaque features on coronary computed tomography angiography are all known to be associated with adverse clinical outcomes. The interactions between these variables, patient outcomes, and quantitative plaque volumes have not been previously described., Methods: Patients with coronary computed tomography angiography (n=4430) and one-year outcome data from the international ADVANCE (Assessing Diagnostic Value of Noninvasive FFR CT in Coronary Care) registry underwent artificial intelligence-enabled quantitative coronary plaque analysis. Optimal cutoffs for coronary total plaque volume and each plaque subtype were derived using receiver-operator characteristic curve analysis. The resulting plaque volumes were adjusted for age, sex, hypertension, smoking status, type 2 diabetes, hyperlipidemia, luminal stenosis, distal FFR CT , and translesional delta-FFR CT . Median plaque volumes and optimal cutoffs for these adjusted variables were compared with major adverse cardiac events, late revascularization, a composite of the two, and cardiovascular death and myocardial infarction., Results: At one year, 55 patients (1.2%) had experienced major adverse cardiac events, and 123 (2.8%) had undergone late revascularization (>90 days). Following adjustment for age, sex, risk factors, stenosis, and FFR CT , total plaque volume above the receiver-operator characteristic curve-derived optimal cutoff (total plaque volume >564 mm 3 ) was associated with the major adverse cardiac event/late revascularization composite (adjusted hazard ratio, 1.515 [95% CI, 1.093-2.099]; P =0.0126), and both components. Total percent atheroma volume greater than the optimal cutoff was associated with both major adverse cardiac event/late revascularization (total percent atheroma volume >24.4%; hazard ratio, 2.046 [95% CI, 1.474-2.839]; P <0.0001) and cardiovascular death/myocardial infarction (total percent atheroma volume >37.17%, hazard ratio, 4.53 [95% CI, 1.943-10.576]; P =0.0005). Calcified, noncalcified, and low-attenuation percentage atheroma volumes above the optimal cutoff were associated with all adverse outcomes, although this relationship was not maintained for cardiovascular death/myocardial infarction in analyses stratified by median plaque volumes., Conclusions: Analysis of the ADVANCE registry using artificial intelligence-enabled quantitative plaque analysis shows that total plaque volume is associated with one-year adverse clinical events, with incremental predictive value over luminal stenosis or abnormal physiology by FFR CT ., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02499679., Competing Interests: Dr Patel has received research grants from HeartFlow, Bayer, Janssen, and the National Heart, Lung, and Blood Institute; and has served on the advisory board for HeartFlow, Bayer, and Janssen. Dr Nørgaard has received unrestricted institutional research grants from Siemens and HeartFlow. Dr Fairbairn has served on the Speakers Bureau for HeartFlow. Dr Nieman has received institutional research support from Siemens Healthineers, HeartFlow, GE Healthcare, and Bayer Healthcare. Dr Hurwitz Koweek has received research support and speaking fees from HeartFlow and Siemens. Dr Pontone has received institutional research grant and honorarium as consultant/speaker from GE Healthcare, Bracco, Medtronic, Bayer, and HeartFlow. Dr Rabbat has served as a consultant for HeartFlow. Ms Mullen is an employee of and owns equity in HeartFlow. Dr De Bruyne has an institutional consulting relationship with Boston Scientific, Abbott Vascular, CathWorks, Siemens, GE Healthcare, and Coroventis Research; has received institutional research grants from Abbott Vascular, Coroventis Research, CathWorks, and Boston Scientific; and holds equities in Philips, Siemens, GE Healthcare, Edwards Lifesciences, HeartFlow, Opsens, and Celiad. Dr Rogers is employee of and owns equity in HeartFlow. Dr Leipsic has received an unrestricted research grant from GE Healthcare, has stock options and received consulting fees from HeartFlow and Circle CVI, and speaking fees from GE and Philips. Dr Ng is an employee of HeartFlow. The other authors report no conflicts.

Background: Coronary artery calcification is a marker of underlying atherosclerotic vascular disease. The absence of coronary artery calcification is associated with a low prevalence of obstructive coronary artery disease (CAD), but it cannot be ruled out completely. We sought to develop a clinical tool that can be added to Agatston score of zero to rule out obstructive CAD with high accuracy., Methods: We developed a clinical score retrospectively from a cohort of 4903 consecutive patients with an Agatston score of zero. Patients with prior diagnosis of CAD, coronary percutaneous coronary intervention, or surgical revascularization were excluded. Obstructive CAD was defined as any epicardial vessel diameter narrowing of ≥50%. The score was validated using an external cohort of 4290 patients with an Agatston score of zero from a multinational registry., Results: The score consisted of 7 variables: age, sex, typical chest pain, dyslipidemia, hypertension, family history, and diabetes mellitus. The model was robust with an area under the curve of 0.70 (95% CI, 0.65-0.76) in the derivation cohort and 0.69 (95% CI, 0.65-0.72) in the validation cohort. Patients were divided into 3 risk groups based on the score: low (≤6), intermediate (7-13), and high (≥14). Patients who score ≤6 have a negative likelihood ratio of 0.42 for obstructive CAD, whereas those who score ≥14 have a positive likelihood ratio of >5.5 for obstructive CAD. The outcome was ruled out in >98% of patients with a score ≤6 in the validation cohort., Conclusions: We developed a score that may be used to identify the likelihood of obstructive CAD in patients with an Agatston score of zero, which may be used to direct the need for additional testing. However, the results of this retrospective analysis are hypothesis generating and before clinical implementation should be validated in a trial with a prospectively collected data.

Background: Coronary 18 F-fluoride positron emission tomography identifies ruptured and high-risk atherosclerotic plaque. The optimal method to identify, to quantify, and to categorize increased coronary 18 F-fluoride uptake and determine its reproducibility has yet to be established. This study aimed to optimize the identification, quantification, categorization, and scan-rescan reproducibility of increased 18 F-fluoride activity in coronary atherosclerotic plaque., Methods: In a prospective observational study, patients with multi-vessel coronary artery disease underwent serial 18 F-fluoride positron emission tomography. Coronary 18 F-fluoride activity was visually assessed, quantified, and categorized with reference to maximal tissue to background ratios. Levels of agreement for both visual and quantitative methods were determined between scans and observers., Results: Thirty patients (90% male, 20 patients with stable coronary artery disease, and 10 with recent type 1 myocardial infarction) underwent paired serial positron emission tomography-coronary computed tomography angiography imaging within an interval of 12±5 days. A mean of 3.7±1.8 18 F-fluoride positive plaques per patient was identified after recent acute coronary syndrome, compared with 2.4±2.3 positive plaques per patient in stable coronary artery disease. The bias in agreement in maximum tissue to background ratio measurements in visually positive plaques was low between observers (mean difference, -0.01; 95% limits of agreement, -0.32 to 0.30) or between scans (mean difference, 0.06; 95% limits of agreement, -0.49 to 0.61). Good agreement in the categorization of focal 18 F-fluoride uptake was achieved using visual assessment alone (κ=0.66) and further improved at higher maximum tissue to background ratio values., Conclusions: Coronary 18 F-fluoride activity is a precise and reproducible metric in the coronary vasculature. The analytical performance of 18 F-fluoride is sufficient to assess the prognostic utility of this radiotracer as a noninvasive imaging biomarker of plaque vulnerability., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02110303 and NCT02278211.

Bioprostheses are prone to structural valve degeneration, resulting in limited long-term durability. A significant challenge when comparing the durability of different types of bioprostheses is the lack of a standardized terminology for the definition of a degenerated valve. This issue becomes especially important when we try to compare the degeneration rate of surgically inserted and transcatheter bioprosthetic valves. This document, by the VIVID (Valve-in-Valve International Data), proposes practical and standardized definitions of valve degeneration and provides recommendations for the timing of clinical and imaging follow-up assessments accordingly. Its goal is to improve the quality of research and clinical care for patients with deteriorated bioprostheses by providing objective and strict criteria that can be utilized in future clinical trials. We hope that the adoption of these criteria by both the cardiological and surgical communities will lead to improved comparability and interpretation of durability analyses., (© 2018 American Heart Association, Inc.)

Background: Age-adjusted coronary artery disease (CAD) burden identified on coronary computed tomography angiography predicts major adverse cardiovascular event (MACE) risk; however, it seldom contributes to clinical decision making because of a lack of nomographic data. We aimed to develop clinically pragmatic age- and sex-specific nomograms of CAD burden using coronary computed tomography angiography and to validate their prognostic use., Methods and Results: Patients prospectively enrolled in phase I of the CONFIRM registry (Coronary CT Angiography Evaluation for Clinical Outcomes) were included (derivation cohort: n=21,132; 46% female) to develop CAD nomograms based on age-sex percentiles of segment involvement score (SIS) at each year of life (40-79 years). The relationship between SIS age-sex percentiles (SIS%) and MACE (all-cause death, myocardial infarction, unstable angina, and late revascularization) was tested in a nonoverlapping validation cohort (phase II, CONFIRM registry; n=3030, 44% female) by stratifying patients into 3 SIS% groups (≤50th, 51-75th, and >75th) and comparing annualized MACE rates and time to MACE using multivariable Cox proportional hazards models adjusting for Framingham risk and chest pain typicality. Age-sex percentiles were well fitted to second-order polynomial curves (men: R 2 =0.86±0.12; women: R 2 =0.86±0.14). Using the nomograms, there were 1576, 965, and 489 patients, respectively, in the ≤50th, 51-75th, and >75th SIS% groups. Annualized event rates were higher among patients with greater CAD burden (2.1% [95% confidence interval: 1.7%-2.7%], 3.9% [95% confidence interval: 3.0%-5.1%], and 7.2% [95% confidence interval: 5.4%-9.6%] in ≤50th, 51-75th, and >75th SIS% groups, respectively; P <0.001). Adjusted MACE risk was significantly increased among patients in SIS% groups above the median compared with patients below the median (hazard ratio [95% confidence interval]: 1.9 [1.3-2.8] for 51-75th SIS% group and 3.4 [2.3-5.0] for >75th SIS% group; P <0.01 for both)., Conclusions: We have developed clinically pragmatic age- and sex-specific nomograms of CAD prevalence using coronary computed tomography angiography findings. Global plaque burden measured using SIS% is predictive of cardiac events independent of traditional risk assessment., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01443637., (© 2017 American Heart Association, Inc.)