Relationship Between Coronary Artery Calcium and Atherosclerosis Progression Among Patients With Suspected Coronary Artery Disease

BackgroundAmong symptomatic patients, it remains unclear whether a coronary artery calcium (CAC) score alone is sufficient or misses a sizeable burden and progressive risk associated with obstructive and nonobstructive atherosclerotic plaque.ObjectivesAmong patients with low to high CAC scores, our aims were to quantify co-occurring obstructive and nonobstructive noncalcified plaque and serial progression of atherosclerotic plaque volume.MethodsA total of 698 symptomatic patients with suspected coronary artery disease (CAD) underwent serial coronary computed tomographic angiography (CTA) performed 3.5 to 4.0 years apart. Atherosclerotic plaque was quantified, including by compositional subgroups. Obstructive CAD was defined as ≥50% stenosis. Multivariate linear regression models were used to measure atherosclerotic plaque progression by CAC scores. Cox proportional hazard models estimated CAD event risk (median of 10.7 years of follow-up).ResultsAcross baseline CAC scores from 0 to ≥400, total plaque volume ranged from 30.4 to 522.4 mm³ (P < 0.001) and the prevalence of obstructive CAD increased from 1.4% to 49.1% (P < 0.001). Of those with a 0 CAC score, 97.9% of total plaque was noncalcified. Among patients with baseline CAC <100, nonobstructive CAD was prevalent (40% and 89% in CAC scores of 0 and 1-99), with plaque largely being noncalcified. On the follow-up coronary CTA, volumetric plaque growth (P < 0.001) and the development of new or worsening stenosis (P < 0.001) occurred more among patients with baseline CAC ≥100. Progression varied compositionally by baseline CAC scores. Patients with no CAC had disproportionate growth in noncalcified plaque, and for every 1 mm³ increase in calcified plaque, there was a 5.5 mm³ increase in noncalcified plaque volume. By comparison, patients with CAC scores of ≥400 exhibited disproportionate growth in calcified plaque with a volumetric increase 15.7-fold that of noncalcified plaque. There was a graded increase in CAD event risk by the CAC with rates from 3.3% for no CAC to 21.9% for CAC ≥400 (P < 0.001).ConclusionsCAC imperfectly characterizes atherosclerotic disease burden, but its subgroups exhibit pathogenic patterns of early to advanced disease progression and stratify long-term prognostic risk.     

Myocardial Flow Reserve and Coronary Calcification in Prognosis of Patients With Suspected Coronary Artery Disease

ObjectivesThe aim of this analysis is to examine the incremental prognostic value of coronary artery calcium (CAC) score and myocardial flow reserve (MFR) in patients with suspected coronary artery disease (CAD) undergoing positron emission tomography (PET) myocardial perfusion imaging (MPI).BackgroundAdvances in cardiac PET and computed tomography imaging enabled the simultaneous acquisition of anatomic and physiological data for patients suspected of CAD.MethodsConsecutive patients who underwent PET MPI and CAC score calculation at King Abdulaziz Cardiac Center, Riyadh, Saudi Arabia, between May 2011 and May 2018 were included in the study. MPI and CAC images were obtained in the same setting. The primary endpoint of the study was a composite of cardiac death and nonfatal myocardial infarction. Cox proportional hazard regression was used to assess the incremental prognostic value of CAC and MFR by sequentially adding the variables to a model that included clinical and PET variables.ResultsA total of 4,008 patients (mean age 59.7 ± 11.6 years, 55% women) were included in the analysis. Risk factors were prevalent (77.6% hypertension, 58.1% diabetes). In total, 35.9% of the cohort had CAC of 0, 16.5% had CAC ≥400, and 43.9% had MFR <2. Over a median follow up of 1.9 years, 130 (3.2%) patients had cardiac death/nonfatal myocardial infarction. CAC and MFR score added incremental prognostic value over clinical and perfusion variables (base model: c-index 0.8137; Akaike information criterion [AIC]: 1,865.877; p = 0.0011; CAC model: c-index = 0.8330; AIC: 1,850.810; p = 0.045 vs. base model; MFR model: c-index = 0.8279; AIC: 1,859.235; p = 0.024). Combining CAC and MFR did not enhance risk prediction (c-index = 0.8435; AIC: 1,846.334; p = 0.074 vs. MFR model; p = 0.21 vs. CAC model.)ConclusionsIn this large cohort of patients referred for PET MPI, both CAC and MFR independently added incremental prognostic value over clinical and MPI variables. Although combining both may have synergetic prognostic effect, this relation was not shown in multivariable model of this analysis.     

Discordance Between Coronary Artery Calcium Area and Density Predicts Long-Term Atherosclerotic Cardiovascular Disease Risk

BackgroundCoronary artery calcium (CAC) is commonly quantified as the product of 2 generally correlated measures: plaque area and calcium density.ObjectivesThe authors sought to determine whether discordance between calcium area and density has long-term prognostic importance in atherosclerotic cardiovascular disease (ASCVD) risk.MethodsThe authors studied 10,373 primary prevention participants from the CAC Consortium with CAC >0. Based on their median values, calcium area and mean calcium density were divided into 4 mutually exclusive concordant/discordant groups. Cox proportional hazards regression assessed the association of calcium area/density groups with ASCVD mortality over a median of 11.7 years, adjusting for traditional risk factors and the Agatston CAC score.ResultsThe mean age was 56.7 years, and 24% were female. The prevalence of plaque discordance was 19% (9% low calcium area/high calcium density, 10% high calcium area/low calcium density). Female sex (odds ratio [OR]: 1.48 [95% CI: 1.27-1.74]) and body mass index (OR: 0.81 [95% CI: 0.76-0.87], per 5 kg/m² higher) were significantly associated with high calcium density discordance, whereas diabetes (OR: 2.23 [95% CI: 1.85-3.19]) was most strongly associated with discordantly low calcium density. Compared to those with low calcium area/low calcium density, individuals with low calcium area/high calcium density had a 71% lower risk of ASCVD death (HR: 0.29 [95% CI: 0.09-0.95]).ConclusionsFor a given CAC score, high calcium density relative to plaque area confers lower long-term ASCVD risk, likely serving as an imaging marker of biological resilience for lesion vulnerability. Additional research is needed to define a robust definition of calcium area/density discordance for routine clinical risk prediction.     

Topological Data Analysis of Coronary Plaques Demonstrates the Natural History of Coronary Atherosclerosis

ObjectivesThis study sought to identify distinct patient groups and their association with outcome based on the patient similarity network using quantitative coronary plaque characteristics from coronary computed tomography angiography (CTA).BackgroundCoronary CTA can noninvasively assess coronary plaques quantitatively.MethodsPatients who underwent 2 coronary CTAs at a minimum of 24 months’ interval were analyzed (n = 1,264). A similarity Mapper network of patients was built by topological data analysis (TDA) based on the whole-heart quantitative coronary plaque analysis on coronary CTA to identify distinct patient groups and their association with outcome.ResultsThree distinct patient groups were identified by TDA, and the patient similarity network by TDA showed a closed loop, demonstrating a continuous trend of coronary plaque progression. Group A had the least coronary plaque amount (median 12.4 mm³ [interquartile range (IQR): 0.0 to 39.6 mm³]) in the entire coronary tree. Group B had a moderate coronary plaque amount (31.7 mm³ [IQR: 0.0 to 127.4 mm³]) with relative enrichment of fibrofatty and necrotic core (32.6% [IQR: 16.7% to 46.2%] and 2.7% [IQR: 0.1% to 6.9%] of the total plaque, respectively) components. Group C had the largest coronary plaque amount (187.0 mm³ [IQR: 96.7 to 306.4 mm³]) and was enriched for dense calcium component (46.8% [IQR: 32.0% to 63.7%] of the total plaque). At follow-up, total plaque volume, fibrous, and dense calcium volumes increased in all groups, but the proportion of fibrofatty component decreased in groups B and C, whereas the necrotic core portion decreased in only group B (all p < 0.05). Group B showed a higher acute coronary syndrome incidence than other groups (0.3% vs. 2.6% vs. 0.6%; p = 0.009) but both group B and C had a higher revascularization incidence than group A (3.1% vs. 15.5% vs. 17.8%; p < 0.001). Incorporating group information from TDA demonstrated increase of model fitness for predicting acute coronary syndrome or revascularization compared with that incorporating clinical risk factors, percentage diameter stenosis, and high-risk plaque features.ConclusionsThe TDA of quantitative whole-heart coronary plaque characteristics on coronary CTA identified distinct patient groups with different plaque dynamics and clinical outcomes. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411)     

Intravascular Polarimetry in Patients With Coronary Artery Disease

ObjectivesThe aims of this first-in-human pilot study of intravascular polarimetry were to investigate polarization properties of coronary plaques in patients and to examine the relationship of these features with established structural characteristics available to conventional optical frequency domain imaging (OFDI) and with clinical presentation.BackgroundPolarization-sensitive OFDI measures birefringence and depolarization of tissue together with conventional cross-sectional optical frequency domain images of subsurface microstructure.MethodsThirty patients undergoing polarization-sensitive OFDI (acute coronary syndrome, n = 12; stable angina pectoris, n = 18) participated in this study. Three hundred forty-two cross-sectional images evenly distributed along all imaged coronary arteries were classified into 1 of 7 plaque categories according to conventional OFDI. Polarization features averaged over the entire intimal area of each cross section were compared among plaque types and with structural parameters. Furthermore, the polarization properties in cross sections (n = 244) of the fibrous caps of acute coronary syndrome and stable angina pectoris culprit lesions were assessed and compared with structural features using a generalized linear model.ResultsThe median birefringence and depolarization showed statistically significant differences among plaque types (p < 0.001 for both, one-way analysis of variance). Depolarization differed significantly among individual plaque types (p < 0.05), except between normal arteries and fibrous plaques and between fibrofatty and fibrocalcified plaques. Caps of acute coronary syndrome lesions and ruptured caps exhibited lower birefringence than caps of stable angina pectoris lesions (p < 0.01). In addition to clinical presentation, cap birefringence was also associated with macrophage accumulation as assessed using normalized SD.ConclusionsIntravascular polarimetry provides quantitative metrics that help characterize coronary arterial tissues and may offer refined insight into coronary arterial atherosclerotic lesions in patients.     

Dynamic Myocardial Perfusion CT for the Detection of Hemodynamically Significant Coronary Artery Disease

ObjectivesIn this international, multicenter study, using third-generation dual-source computed tomography (CT), we investigated the diagnostic performance of dynamic stress CT myocardial perfusion imaging (CT-MPI) in addition to coronary CT angiography (CTA) compared to invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR).BackgroundCT-MPI combined with coronary CTA integrates coronary artery anatomy with inducible myocardial ischemia, showing promising results for the diagnosis of hemodynamically significant coronary artery disease in single-center studies.MethodsAt 9 centers in Europe, Japan, and the United States, 132 patients scheduled for ICA were enrolled; 114 patients successfully completed coronary CTA, adenosine-stress dynamic CT-MPI, and ICA. Invasive FFR was performed in vessels with 25% to 90% stenosis. Data were analyzed by independent core laboratories. For the primary analysis, for each coronary artery the presence of hemodynamically significant obstruction was interpreted by coronary CTA with CT-MPI compared to coronary CTA alone, using an FFR of ≤0.80 and angiographic severity as reference. Territorial absolute myocardial blood flow (MBF) and relative MBF were compared using C-statistics.ResultsICA and FFR identified hemodynamically significant stenoses in 74 of 289 coronary vessels (26%). Coronary CTA with ≥50% stenosis demonstrated a per-vessel sensitivity, specificity, and accuracy for the detection of hemodynamically significant stenosis of 96% (95% CI: 91%-100%), 72% (95% CI: 66%-78%), and 78% (95% CI: 73%-83%), respectively. Coronary CTA with CT-MPI showed a lower sensitivity (84%; 95% CI: 75%-92%) but higher specificity (89%; 95% CI: 85%-93%) and accuracy (88%; 95% CI: 84%-92%). The areas under the receiver-operating characteristic curve of absolute MBF and relative MBF were 0.79 (95% CI: 0.71-0.86) and 0.82 (95% CI: 0.74-0.88), respectively. The median dose-length product of CT-MPI and coronary CTA were 313 mGy·cm and 138 mGy·cm, respectively.ConclusionsDynamic CT-MPI offers incremental diagnostic value over coronary CTA alone for the identification of hemodynamically significant coronary artery disease. Generalized results from this multicenter study encourage broader consideration of dynamic CT-MPI in clinical practice. (Dynamic Stress Perfusion CT for Detection of Inducible Myocardial Ischemia [SPECIFIC]; NCT02810795)     

Prognostic Implications of Plaque Characteristics and Stenosis Severity in Patients With Coronary Artery Disease

BackgroundAlthough the presence of ischemia is a key prognostic factor in patients with coronary artery disease, the presence of high-risk plaque characteristics (HRPC) is also associated with increased risk of cardiovascular events. Limited data exist regarding the prognostic implications of combined information on physiological stenosis severity assessed by fractional flow reserve (FFR) and plaque vulnerability by coronary computed tomography angiography (CTA)–defined HRPC.ObjectivesThe current study aimed to evaluate the: 1) association between physiological stenosis severity and coronary CTA-defined HRPC; and 2) prognostic implications of coronary CTA-defined HRPC according to physiological stenosis severity in patients with coronary artery disease.MethodsA total of 772 vessels (299 patients) evaluated by both coronary CTA and FFR were analyzed. The presence and number of HRPC (minimum lumen area <4 mm², plaque burden ≥70%, low attenuating plaque, positive remodeling, napkin-ring sign, or spotty calcification) were assessed using coronary CTA images. The risk of vessel-oriented composite outcome (VOCO) (a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death) at 5 years was compared according to the number of HRPC and FFR categories.ResultsThe proportion of lesions with ≥3 HRPC was significantly decreased according to the increase in FFR values (58.6%, 46.5%, 36.8%, 15.7%, and 3.5% for FFR ≤0.60, 0.61 to ≤0.70, 0.71 to ≤0.80, 0.81 to ≤0.90, and >0.90, respectively; overall p value <0.001). Both FFR and number of HRPC showed significant association with the estimated risk of VOCO (p = 0.008 and p = 0.023, respectively). In the FFR >0.80 group, lesions with ≥3 HRPC showed significantly higher risk of VOCO than those with <3 HRPC (15.0% vs. 4.3%; hazard ratio: 3.964; 95% confidence interval: 1.451 to 10.828; p = 0.007). However, there was no significant difference in the risk of VOCO according to HRPC in the FFR ≤0.80 group. By multivariable analysis, the presence of ≥3 HRPC was independently associated with the risk of VOCO in the FFR >0.80 group.ConclusionsPhysiological stenosis severity and the number of HRPC were closely related, and both components had significant association with the risk of clinical events. However, the prognostic implication of HRPC was different according to FFR. Integration of both physiological stenosis severity and plaque vulnerability would provide better prognostic stratification of patients than either individual component alone, especially in patients with FFR >0.80. (Clinical Implication of 3-vessel Fractional Flow Reserve [3V FFR-FRIENDS study]; NCT01621438)     

Bypass Grafting and Native Coronary Artery Disease Activity

ObjectivesThe aim of this study was to describe the potential of ¹⁸F-sodium fluoride (¹⁸F-NaF) positron emission tomography (PET) to identify graft vasculopathy and to investigate the influence of coronary artery bypass graft (CABG) surgery on native coronary artery disease activity and progression.BackgroundAs well as developing graft vasculopathy, CABGs have been proposed to accelerate native coronary atherosclerosis.MethodsPatients with established coronary artery disease underwent baseline ¹⁸F-NaF PET, coronary artery calcium scoring, coronary computed tomographic angiography, and 1-year repeat coronary artery calcium scoring. Whole-vessel coronary microcalcification activity (CMA) on ¹⁸F-NaF PET and change in calcium scores were quantified in patients with and without CABG surgery.ResultsAmong 293 participants (mean age 65 ± 9 years, 84% men), 48 (16%) underwent CABG surgery 2.7 years [IQR: 1.4-10.4 years] previously. Although all arterial and the majority (120 of 128 [94%]) of vein grafts showed no ¹⁸F-NaF uptake, 8 saphenous vein grafts in 7 subjects had detectable CMA. Bypassed native coronary arteries had 3 times higher CMA values (2.1 [IQR: 0.4-7.5] vs 0.6 [IQR: 0-2.7]; P < 0.001) and greater progression of 1-year calcium scores (118 Agatston unit [IQR: 48-194 Agatston unit] vs 69 [IQR: 21-142 Agatston unit]; P = 0.01) compared with patients who had not undergone CABG, an effect confined largely to native coronary plaques proximal to the graft anastomosis. In sensitivity analysis, bypassed native coronary arteries had higher CMA (2.0 [IQR: 0.4-7.5] vs 0.8 [IQR: 0.3-3.2]; P < 0.001) and faster disease progression (24% [IQR: 16%-43%] vs 8% [IQR: 0%-24%]; P = 0.002) than matched patients (n = 48) with comparable burdens of coronary artery disease and cardiovascular comorbidities in the absence of bypass grafting.ConclusionsNative coronary arteries that have been bypassed demonstrate increased disease activity and more rapid disease progression than nonbypassed arteries, an observation that appears independent of baseline atherosclerotic plaque burden. Microcalcification activity is not a dominant feature of graft vasculopathy.     

Coronary 18F-Sodium Fluoride Uptake Predicts Outcomes in Patients With Coronary Artery Disease

BackgroundReliable methods for predicting myocardial infarction in patients with established coronary artery disease are lacking. Coronary ¹⁸F-sodium fluoride (¹⁸F-NaF) positron emission tomography (PET) provides an assessment of atherosclerosis activity.ObjectivesThis study assessed whether ¹⁸F-NaF PET predicts myocardial infarction and provides additional prognostic information to current methods of risk stratification.MethodsPatients with known coronary artery disease underwent ¹⁸F-NaF PET computed tomography and were followed up for fatal or nonfatal myocardial infarction over 42 months (interquartile range: 31 to 49 months). Total coronary ¹⁸F-NaF uptake was determined by the coronary microcalcification activity (CMA).ResultsIn a post hoc analysis of data collected for prospective observational studies, the authors studied 293 study participants (age: 65 ± 9 years; 84% men), of whom 203 (69%) showed increased coronary ¹⁸F-NaF activity (CMA >0). Fatal or nonfatal myocardial infarction occurred only in patients with increased coronary ¹⁸F-NaF activity (20 of 203 with a CMA >0 vs. 0 of 90 with a CMA of 0; p < 0.001). On receiver operator curve analysis, fatal or nonfatal myocardial infarction prediction was highest for ¹⁸F-NaF CMA, outperforming coronary calcium scoring, modified Duke coronary artery disease index and Reduction of Atherothrombosis for Continued Health (REACH) and Secondary Manifestations of Arterial Disease (SMART) risk scores (area under the curve: 0.76 vs. 0.54, 0.62, 0.52, and 0.54, respectively; p < 0.001 for all). Patients with CMA >1.56 had a >7-fold increase in fatal or nonfatal myocardial infarction (hazard ratio: 7.1; 95% confidence interval: 2.2 to 25.1; p = 0.003) independent of age, sex, risk factors, segment involvement and coronary calcium scores, presence of coronary stents, coronary stenosis, REACH and SMART scores, the Duke coronary artery disease index, and recent myocardial infarction.ConclusionsIn patients with established coronary artery disease, ¹⁸F-NaF PET provides powerful independent prediction of fatal or nonfatal myocardial infarction.     

Sex Differences in Compositional Plaque Volume Progression in Patients With Coronary Artery Disease

ObjectivesThis study sought to explore sex-based differences in total and compositional plaque volume (PV) progression.BackgroundIt is unclear whether sex has an impact on PV progression in patients with coronary artery disease (CAD).MethodsThe study analyzed a prospective multinational registry of consecutive patients with suspected CAD who underwent 2 or more clinically indicated coronary computed tomography angiography (CTA) at ≥2-year intervals. Total and compositional PV at baseline and follow-up were quantitatively analyzed and normalized using the analyzed total vessel length. Multivariate linear regression models were constructed.ResultsOf the 1,255 patients included (median coronary CTA interval 3.8 years), 543 were women and 712 were men. Women were older (62 ± 9 years of age vs. 59 ± 9 years of age; p < 0.001) and had higher total cholesterol levels (195 ± 41 mg/dl vs. 187 ± 39 mg/dl; p = 0.002). Prevalence of hypertension, diabetes, and family history of CAD were not different (all p > 0.05). At baseline, men possessed greater total PV (31.3 mm³ [interquartile range (IQR): 0 to 121.8 mm³] vs. 56.7 mm³ [IQR: 6.8 to 152.1 mm³] p = 0.005), and there was an approximately 9-year delay in women in developing total PV than in men. The prevalence of high-risk plaques was greater in men than women (31% vs. 20%; p < 0.001). In multivariate analysis, after adjusting for age, clinical risk factors, medication use, and total PV at baseline, despite similar total PV progression rates, female sex was associated with greater calcified PV progression (β = 2.83; p = 0.004) but slower noncalcified PV progression (β = –3.39; p = 0.008) and less development of high-risk plaques (β = –0.18; p = 0.049) than in men.ConclusionsThe compositional PV progression differed according to sex, suggesting that comprehensive plaque evaluation may contribute to further refining of risk stratification according to sex. (NCT02803411).     

Risk Stratification With the Use of Coronary Computed Tomographic Angiography in Patients With Nonobstructive Coronary Artery Disease

ObjectivesThe purpose of this study was to develop a risk prediction model for patients with nonobstructive CAD.BackgroundAmong stable chest pain patients, most cardiovascular (CV) events occur in those with nonobstructive coronary artery disease (CAD). Thus, developing tailored risk prediction approaches in this group of patients, including CV risk factors and CAD characteristics, is needed.MethodsIn PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) computed tomographic angiography patients, a core laboratory assessed prevalence of CAD (nonobstructive 1% to 49% left main or 1% to 69% stenosis any coronary artery), degree of stenosis (minimal: 1% to 29%; mild: 30% to 49%; or moderate: 50% to 69%), high-risk plaque (HRP) features (positive remodeling, low-attenuation plaque, and napkin-ring sign), segment involvement score (SIS), and coronary artery calcium (CAC). The primary end point was an adjudicated composite of unstable angina pectoris, nonfatal myocardial infarction, and death. Cox regression analysis determined independent predictors in nonobstructive CAD.ResultsOf 2,890 patients (age 61.7 years, 46% women) with any CAD, 90.4% (n = 2,614) had nonobstructive CAD (mean age 61.6 yrs, 46% women, atherosclerotic cardiovascular disease [ASCVD] risk 16.2%). Composite events were independently predicted by ASCVD risk (hazard ratio [HR]: 1.03; p = 0.001), degree of stenosis (30% to 69%; HR: 1.91; p = 0.011), and presence of ≥2 HRP features (HR: 2.40; p = 0.008). Addition of ≥2 HRP features to: 1) ASCVD and CAC; 2) ASCVD and SIS; or 3) ASCVD and degree of stenosis resulted in a statistically significant improvement in model fit (p = 0.0036; p = 0.0176; and p = 0.0318; respectively). Patients with ASCVD ≥7.5%, any HRP, and mild/moderate stenosis had significantly higher event rates than those who did not meet those criteria (3.0% vs. 6.2%; p = 0.007).ConclusionsAdvanced coronary plaque features have incremental value over total plaque burden for the discrimination of clinical events in low-risk stable chest pain patients with nonobstructive CAD. This may be a first step to improve prevention in this cohort with the highest absolute risk for CV events.     

Automated Echocardiographic Detection of Severe Coronary Artery Disease Using Artificial Intelligence

ObjectivesThe purpose of this study was to establish whether an artificially intelligent (AI) system can be developed to automate stress echocardiography analysis and support clinician interpretation.BackgroundCoronary artery disease is the leading global cause of mortality and morbidity and stress echocardiography remains one of the most commonly used diagnostic imaging tests.MethodsAn automated image processing pipeline was developed to extract novel geometric and kinematic features from stress echocardiograms collected as part of a large, United Kingdom-based prospective, multicenter, multivendor study. An ensemble machine learning classifier was trained, using the extracted features, to identify patients with severe coronary artery disease on invasive coronary angiography. The model was tested in an independent U.S. study. How availability of an AI classification might impact clinical interpretation of stress echocardiograms was evaluated in a randomized crossover reader study.ResultsAcceptable classification accuracy for identification of patients with severe coronary artery disease in the training data set was achieved on cross-fold validation based on 31 unique geometric and kinematic features, with a specificity of 92.7% and a sensitivity of 84.4%. This accuracy was maintained in the independent validation data set. The use of the AI classification tool by clinicians increased inter-reader agreement and confidence as well as sensitivity for detection of disease by 10% to achieve an area under the receiver-operating characteristic curve of 0.93.ConclusionsAutomated analysis of stress echocardiograms is possible using AI and provision of automated classifications to clinicians when reading stress echocardiograms could improve accuracy, inter-reader agreement, and reader confidence.     

Coronary Calcium to Rule Out Obstructive Coronary Artery Disease in Patients With Acute Chest Pain

ObjectivesThis study aimed to evaluate the ability of coronary artery calcium (CAC) as an initial diagnostic tool to rule out obstructive coronary artery disease (CAD) in a very large registry of patients presenting to the emergency department (ED) with acute chest pain (CP) who were at low to intermediate risk for acute coronary syndrome (ACS).BackgroundIt is not yet well established whether CAC can be used to rule out obstructive CAD in the ED setting.MethodsWe included patients from the Baptist Health South Florida Chest Pain Registry presenting to the ED with CP at low to intermediate risk for ACS (Thrombolysis In Myocardial Infarction risk score ≤2, normal/nondiagnostic electrocardiography, and troponin levels) who underwent CAC and coronary computed tomography angiography (CCTA) procedures for evaluation of ACS. To assess the diagnostic accuracy of CAC testing to diagnose obstructive CAD and identify the need for coronary revascularization during hospitalization, we estimated sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV).ResultsOur study included 5,192 patients (mean age: 53.5 ± 10.8 years; 46% male; 62% Hispanic). Overall, 2,902 patients (56%) had CAC = 0, of which 135 (4.6%) had CAD (114 [3.9%] nonobstructive and 21 [0.7%] obstructive). Among those with CAC >0, 23% had obstructive CAD. Sensitivity, specificity, PPV, and NPV of CAC testing to diagnose obstructive CAD were 96.2%, 62.4%, 22.4%, and 99.3%, respectively. The NPV for identifying those who needed revascularization was 99.6%. Among patients with CAC = 0, 11 patients (0.4%) underwent revascularization, and the number needed to test with CCTA to detect 1 patient who required revascularization was 264.ConclusionsIn a large population presenting to ED with CP at low to intermediate risk, CAC = 0 was common. CAC = 0 ruled out obstructive CAD and revascularization in more than 99% of the patients, and <5% with CAC = 0 had any CAD. Integrating CAC testing very early in CP evaluation may be effective in appropriate triage of patients by identifying individuals who can safely defer additional testing and more invasive procedures.     

The Natural History of Advanced Chronic Liver Disease Defined by Transient Elastography

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Coronary Artery Calcium for Risk Stratification of Sudden Cardiac Death: The Coronary Artery Calcium Consortium

BackgroundCoronary artery calcium (CAC) is a marker of plaque burden. Whether CAC improves risk stratification for incident sudden cardiac death (SCD) beyond atherosclerotic cardiovascular disease (ASCVD) risk factors is unknown.ObjectivesSCD is a common initial manifestation of coronary heart disease (CHD); however, SCD risk prediction remains elusive.MethodsThe authors studied 66,636 primary prevention patients from the CAC Consortium. Multivariable competing risks regression and C-statistics were used to assess the association between CAC and SCD, adjusting for demographics and traditional risk factors.ResultsThe mean age was 54.4 years, 33% were women, 11% were of non-White ethnicity, and 55% had CAC >0. A total of 211 SCD events (0.3%) were observed during a median follow-up of 10.6 years, 91% occurring among those with baseline CAC >0. Compared with CAC = 0, there was a stepwise higher risk (P trend < 0.001) in SCD for CAC 100 to 399 (subdistribution hazard ratio [SHR]: 2.8; 95% CI: 1.6-5.0), CAC 400 to 999 (SHR: 4.0; 95% CI: 2.2-7.3), and CAC >1,000 (SHR: 4.9; 95% CI: 2.6-9.9). CAC provided incremental improvements in the C-statistic for the prediction of SCD among individuals with a 10-year risk <7.5% (ΔC-statistic = +0.046; P = 0.02) and 7.5% to 20% (ΔC-statistic = +0.069; P = 0.003), which were larger when compared with persons with a 10-year risk >20% (ΔC-statistic = +0.01; P = 0.54).ConclusionsHigher CAC burden strongly associates with incident SCD beyond traditional risk factors, particularly among primary prevention patients with low-intermediate risk. SCD risk stratification can be useful in the early stages of CHD through the measurement of CAC, identifying patients most likely to benefit from further downstream testing.     

Biolimus-Coated Balloon in Small-Vessel Coronary Artery Disease: The BIO-RISE CHINA Study

BackgroundDrug-coated balloons are a safe and effective option for patients undergoing percutaneous coronary intervention, but prior randomized studies have exclusively used paclitaxel-coated devices.ObjectivesThe aim of this study was to assess for the first time the safety and efficacy of a novel biolimus-coated balloon (BCB) in patients with small-vessel coronary disease.MethodsIn a prospective trial conducted at 10 centers in China, 212 patients with small-vessel native coronary disease (reference vessel diameter 2.0-2.75 mm, lesion length ≤25 mm) were randomized to receive a BCB or an uncoated balloon. The primary endpoint was in-segment late lumen loss at 9 months.ResultsIn the per-protocol population, angiographic late lumen loss at 9 months was 0.16 ± 0.29 mm in the BCB group vs 0.30 ± 0.35 mm with the plain balloon (P = 0.001). Late luminal enlargement (positive remodeling) occurred in 29.7% of patients in the BCB group vs 9.8% of patients with plain balloons (P = 0.007). In the full analysis set population, after 12 months, target lesion failure rates were 6.7% in the BCB group vs 13.9% with the plain balloon (HR: 0.47; 95% CI: 0.19-1.16), and rates of the patient-oriented clinical outcome were 14.3% with the BCB vs 21.8% with the plain balloon (HR: 0.64; 95% CI: 0.33-1.24).ConclusionsIn this first-in-human study, a novel BCB showed superior efficacy to plain balloon angioplasty in patients with small-vessel coronary disease undergoing percutaneous coronary intervention. Positive vascular remodeling was more frequent, and there was a trend toward improved clinical outcomes. (A Randomized Trial of a Biolimus-Coated Balloon Versus POBA in Small Vessel Coronary Artery Disease [Brave]; NCT03769623)     

Simultaneous Hybrid Coronary Revascularization vs Conventional Strategies for Multivessel Coronary Artery Disease: A 10-Year Follow-Up

BackgroundAlthough evidence is sufficient to confirm that hybrid coronary revascularization (HCR) is safe and effective in the short term, its value in the long run is debatable.ObjectivesThis study sought to compare the long-term outcomes of HCR with coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for multivessel disease.MethodsThree groups of patients, 540 each, receiving HCR, CABG, or PCI between June 2007 to September 2018, were matched using propensity score matching. Patients were stratified by EuroSCORE (European System for Cardiac Operative Risk Evaluation) II (low ≤0.9; 0.9 < medium <1.5; high ≥1.5) and SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (low ≤22; 22 < medium <33; high ≥33). Major adverse cardiac and cerebrovascular events (MACCE) and Seattle Angina Questionnaire (SAQ) scores were compared among the 3 groups.ResultsIn terms of MACCE and SAQ, HCR performed similarly to off-pump CABG but significantly outperformed PCI (P < 0.001). In the low-to-medium EuroSCORE II and medium-to-high SYNTAX score tertiles, MACCE rates in the HCR group were significantly lower than those in the PCI (EuroSCORE II: low, 30.7% vs 41.2%; P = 0.006; medium, 31.3% vs 41.7%; P = 0.013; SYNTAX score: medium, 27.6% vs 41.2%; P = 0.018; high, 32.4% vs 52.7%; P = 0.011) but were similar to those in the CABG group. In the high EuroSCORE II stratum, HCR had a lower MACCE rate than CABG (31.9% vs 47.0%; P = 0.041) and PCI (31.9% vs 53.7%; P = 0.015).ConclusionsCompared with conventional strategies, HCR provided satisfactory long-term outcomes in MACCE and functional status for multivessel disease.     

National Trends in Coronary Artery Disease Imaging: Associations With Health Care Outcomes and Costs

BackgroundIn 2016, the National Institute for Health and Care Excellence Clinical Guideline Number 95 (“Chest pain of recent onset”) (CG95) recommended coronary computed tomography angiography (CCTA) as the first-line test for possible angina.ObjectivesThe purpose of this study was to determine the impact of temporal trends in imaging use on outcomes for coronary artery disease (CAD) following the CG95 recommendations.MethodsInvestigations from 2012 to 2018 were extracted from a national database and linked to hospital admission and mortality registries. Growth rates were adjusted for population size, with image modality use, cardiovascular hospital admissions, and mortality compared using Kendall’s rank correlation. The impact of CG95 was assessed using an interrupted time-series analysis.ResultsA total of 1,909,314 investigations for CAD were performed, with an annualized per capita growth of 4.8%. Costs were £0.35 million/100,000 population/year with an increase of 2.8%/year mirroring inflation (2.5%/year). CG95 was associated with a rise in CCTA (exp[β]: 1.10; 95% CI: 1.03-1.18), no change in myocardial perfusion imaging, and a potential modest fall (exp[β]: 0.997; 95% CI: 0.993-1.00]) in invasive coronary angiography. There was an apparent trend between computed tomography angiography growth and invasive catheter angiography reduction across regions (Kendall Tau: −0.19; P = 0.08). CCTA growth was associated with a reduction in cardiovascular mortality (Kendall Tau: −0.21; P = 0.045), and ischemic heart disease deaths (Kendall Tau: −0.22; P = 0.042), with an apparent trend with reduced all-cause mortality (Kendall Tau: −0.19; P = 0.07).ConclusionsImaging investigations for CAD are increasing. Greater regional increases in CCTA were associated with fewer hospitalizations for myocardial infarction and a more rapid decline in CAD mortality.     

Impact of Coronary Artery Disease on Outcomes in Patients Undergoing Percutaneous Edge-to-Edge Repair

ObjectivesThe aim of this observational study was to evaluate the impact of concomitant coronary artery disease (CAD) on outcomes in patients undergoing percutaneous valve repair with the MitraClip system.BackgroundMitral valve regurgitation and CAD are often coexistent in elderly patients undergoing percutaneous mitral valve repair. The impact of CAD and revascularization on outcomes in this patient cohort, however, remains uncertain.MethodsIn 444 MitraClip patients, CAD severity was assessed, represented by the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SS), as well as the residual SS (rSS) and SYNTAX score II (SS-II). Patients were stratified according to CAD severity and SS-II values (SS ≤3 vs. SS >3 and SS-II ≤45 vs. SS-II >45) and according to remaining CAD burden into 2 groups (rSS = 0 vs. rSS >0) to compare 1-year all-cause mortality.ResultsHigher SS, rSS, and SS-II were associated with mortality (22% for SS >3 vs. 9.6% for SS ≤3 [p < 0.001], 31.4% for rSS >0 vs. 9.6% for rSS = 0 [p < 0.001], and 17.1% for SS-II > 45 vs. 11.2% for SS-II ≤45 [p = 0.044]). The rSS was an independent predictor of 1-year all-cause mortality (p = 0.001) in multivariate analysis.ConclusionsThe complexity of CAD, as assessed using the SS, is associated with outcomes in patients undergoing MitraClip procedures. The burden of residual CAD after percutaneous coronary intervention is an independent predictor of 1-year all-cause mortality. Patients undergoing complete revascularization had the most favorable outcomes independent of mitral regurgitation etiology.