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This study aimed to evaluate the association between the atherogenic index of plasma (AIP), which has been suggested as a novel marker for atherosclerosis, and coronary artery calcification (CAC) progression according to the baseline coronary artery calcium score (CACS). We included 12,326 asymptomatic Korean adults who underwent at least two CAC evaluations from December 2012 to August 2016. Participants were stratified into four groups according to AIP quartiles, which were determined by the log of (triglyceride/high-density lipoprotein cholesterol). Baseline CACSs were divided into three groups: 0, 1 − 100, and > 100. CAC progression was defined as a difference ≥ 2.5 between the square roots (√) of the baseline and follow-up CACSs (Δ√transformed CACS). Annualized Δ√transformed CACS was defined as Δ√transformed CACS divided by the inter-scan period. During a mean 3.3-year follow-up period, the overall incidence of CAC progression was 30.6%. The incidences of CAC progression and annualized Δ√transformed CACS were markedly elevated with increasing AIP quartile in participants with baseline CACSs of 0 and 1 − 100, but not in those with a baseline CACS > 100. The AIP level was associated with the annualized Δ√transformed CACS in participants with baseline CACSs of 0 (β = 0.016; P P 100 (β = 0.032; P = 0.385). After adjusting for traditional risk factors, the AIP was significantly associated with CAC progression in those with baseline CACS ≤ 100. The AIP has value for predicting CAC progression in asymptomatic adults without heavy baseline CAC.

Background and aims The new visceral adiposity index (NVAI) is an indirect marker of visceral adipose tissue recently developed using a Korean population. Here we examined the association of NVAI with coronary artery calcification and arterial stiffness in asymptomatic Korean patients. Methods and results We analyzed data from 60,938 asymptomatic Korean adults. Odds ratios and 95% confidence intervals (CIs) for coronary artery calcification score (CACS) > 100 and brachial–ankle pulse wave velocity (baPWV) ≥14 m/s were calculated across NVAI tertiles using multiple logistic regression analysis. Receiver operating characteristic (ROC) and area under the curve (AUC) analyses were used to assess the ability of NVAI to predict moderate to high risk of cardiovascular disease. The prevalence of moderate and high risk of cardiovascular disease increased significantly as the NVAI tertile increased. The odds ratio (95% CI) of the highest NVAI tertile for CACS >100 was 5.840 (5.101–6.686) for men and 18.916 (11.232–31.855) for women, after adjusting for confounders. All NVAI AUC values were significantly higher than the AUC values for other visceral adiposity markers. Conclusions This study provides the evidence that NVAI is independently and positively associated with coronary calcification and arterial stiffness in asymptomatic Korean adults.

Background Mismatches between the severity of coronary stenosis and the presence of ischemia by invasive fractional flow reserve (FFR) are frequently reported. Purpose To investigate whether plaque characteristics as evaluated with coronary computed tomography angiography (CCTA) may explain this discordance in nonobstructive versus obstructive coronary artery disease (CAD). Methods From the CREDENCE trial, 612 patients with suspected CAD at 13 sites (64±10 years, 70% men) underwent CCTA with semi-automated whole heart quantification and invasive coronary angiography with 3-vessel FFR measurements. Obstructive CAD was visually defined as ≥50% stenosis. The primary endpoint of coronary vessel-specific ischemia was defined as FFR ≤0.80. Generalized estimating equations were calculated to evaluate the effect of plaque characteristics on coronary vessel-specific ischemia. Interactions were tested by obstructive CAD, adjusted for age. Results Among 1,686 vessels, ischemia was present in 436 (26%) vessels. In both nonobstructive and obstructive CAD, the majority of plaque characteristics were associated with coronary vessel-specific ischemia (p≤0.005, Figure 1). In nonobstructive CAD, odds for ischemia were significantly higher for total percent atheroma volume (PAV, p Conclusion Our findings reveal that ischemia by FFR is documented in the setting of both nonobstructive and obstructive CAD on CCTA. Detection of atherosclerotic plaque characteristics associated with ischemia can potentially improve diagnostic certainty and guide management of symptomatic patients with nonobstructive CAD. Figure 1. Odds ratios for ischemia. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health - National Heart, Lung, and Blood Institute

Background Evolving evidence suggests unique sex-specific mechanisms underlying coronary artery disease (CAD). However, it remains unknown if certain coronary atherosclerotic features confer a higher risk for ischemia in women versus men. Purpose To determine the association between coronary atherosclerotic features on coronary computed tomography angiography (CCTA) and ischemia by invasive fractional flow reserve (FFR) in women versus men. Methods Secondary analysis of the CREDENCE trial, including patients referred for nonemergent invasive coronary angiography (ICA). All patients underwent CCTA with semi-automatic quantification of coronary atherosclerosis, as well as ICA with FFR interrogation of all major epicardial arteries ≥2 mm. Generalized estimating equations were calculated to assess the association between coronary atherosclerotic features and invasive vessel-specific ischemia (FFR ≤0.80). Sex interactions were tested, adjusted for age. Results From 612 patients (mean age 64±10 years, 30% women) with 1,686 analyzed vessels, a total of 436 (26%) vessels were ischemic. Women were significantly older than men (p30% stenosis (p=0.030), noncalcified PAV Conclusion Our results support a prominent influence of coronary atherosclerotic features that uniquely impact ischemic risk among women more so than men. These data support the role of CCTA for providing valuable information to guide management of symptomatic women. Figure 1. Ischemic risk in women vs. men Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health - National Heart, Lung, and Blood Institute

OBJECTIVES This study sought to explore sex-based differences in total and compositional plaque volume (PV) progression.BACKGROUND It is unclear whether sex has an impact on PV progression in patients with coronary artery disease (CAD).METHODS The 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.RESULTS Of 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 mm(3) [interquartile range (IQR): 0 to 121.8 mm(3)] vs. 56.7 mm(3) [IQR: 6.8 to 152.1 mm(3)] 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 (b = 2.83; p = 0.004) but slower noncalcified PV progression (b = -3.39; p = 0.008) and less development of high-risk plaques (b = -0.18; p = 0.049) than in men.CONCLUSIONS The compositional PV progression differed according to sex, suggesting that comprehensive plaque evaluation may contribute to further refining of risk stratification according to sex. (c) 2020 by the American College of Cardiology Foundation.

Background Atherosclerotic plaques in the left circumflex artery (LCx) are associated with a lower risk of future events than plaques in the right coronary artery (RCA) and left anterior descending artery (LAD). High risk plaque subtypes including necrotic core and fibrofatty plaque can be evaluated on computed coronary tomography angiography (CCTA) by Hounsfield Unit (HU) density. To date, little is known regarding differences in high risk plaque composition between major epicardial vessels. Purpose The aim of this analysis was to compare plaque extent and composition between the three coronary arteries. Methods This is a secondary analysis of baseline scans from the PARADIGM study which enrolled consecutive patients with suspected coronary artery disease undergoing serial CCTA at a scan interval of ≥2 years. Plaque quantification by composition was performed in the three coronary arteries based on fixed HU thresholds: high risk subtypes consisting of necrotic core ( Results From 1,271 patients (mean age 60.3±9.3 years; 57% men; median ASCVD score 9.3%), 3,813 vessels were analyzed. The prevalence of any plaque was lowest in the LCx, as was the prevalence of high risk plaque (Figure; P Conclusion Prevalence of any plaque as well as high risk plaque subtypes was significantly higher in the LAD and RCA than in the LCx. Also, high risk plaque subtypes made up significantly the lowest proportion in the LCx, whereas calcified plaque made up the largest proportion in the LCx. These data support a different atherogenic milieu contributing to the variable risk patterns between the epicardial coronary arteries. Figure 1. Prevalence of (high risk) plaque Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science and ICT (MSIT) (Grant no. 2012027176).

Background It is unclear whether the annual progression of aortic valve calcification (AVC) is associated with the progression of coronary atherosclerosis. Purpose We explored the association between AVC and the total and compositional plaque volume (PV) progression. Methods We performed a prospective multinational registry of consecutive patients who underwent serial coronary computed tomography angiography (CTA) at ≥2-year intervals. AVC, and total and compositional PV at baseline and follow-up were quantitatively analyzed. Multivariate linear regression models were constructed. Results Overall, 594 patients (56% male, 61.5±9.7 years old) were included (mean coronary CTA interval, 3.9±1.5 years). At baseline, AVC was 30.9±117.3. Normalized total PV at baseline was 122.3±219.4mm3, encompassing 41.9±116.8mm3 of calcified PV and 80.4±131.5mm3 of non-calcified PV. After adjustment of age, sex, clinical risk factors, and drug use, AVC at baseline was independently associated with total and all compositional PVs (all p0.05) (Table, Figure). Conclusion The overall burden of coronary atherosclerosis is associated with AVC at baseline. However, the progression of AVC is associated only with the progression of calcified PV but not with that of total and non-calcified PV. Representative case Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The National Research Foundation (NRF) of Korea funded by the Ministry of Science and ICT (MSIT)

We investigated the optimal combinations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels for lowest mortality in participants not taking hypertensive medication at the study baseline using nationwide representative databases. Survival rates and hazard ratios (HRs) were calculated using Kaplan‐Meier curves and multivariable Cox regression analyses. The discriminatory ability for clinical outcomes was assessed by Harrell's C‐index analysis. A survival spline curve was presented, and Classification and Regression Tree (CART) analysis was performed. SBP ≥ 140 group and DBP ≥ 90 group had the highest risk of mortality. Within SBP

Background The current study aimed to examine the independent prognostic value of whole-heart atherosclerosis progression by serial coronary computed tomography angiography (CCTA) for major adverse cardiovascular events (MACE). Methods The multi-center PARADIGM study includes patients undergoing serial CCTA for symptomatic reasons, ≥2 years apart. Whole-heart atherosclerosis was characterized on a segmental level, with co-registration of baseline and follow-up CCTA, and summed to per-patient level. The independent prognostic significance of atherosclerosis progression for MACE (non-fatal myocardial infarction [MI], death, unplanned coronary revascularization) was examined. Patients experiencing interval MACE were not omitted. Results The study population comprised 1166 patients (age 60.5 ​± ​9.5 years, 54.7% male) who experienced 139 MACE events during 8.2 (IQR 6.2, 9.5) years of follow up (15 death, 5 non-fatal MI, 119 unplanned revascularizations). Whole-heart percent atheroma volume (PAV) increased from 2.32% at baseline to 4.04% at follow-up. Adjusted for baseline PAV, the annualized increase in PAV was independently associated with MACE: OR 1.23 (95% CI 1.08, 1.39) per 1 standard deviation increase, which was consistent in multiple subpopulations. When categorized by composition, only non-calcified plaque progression associated independently with MACE, while calcified plaque did not. Restricting to patients without events before follow-up CCTA, those with future MACE showed an annualized increase in PAV of 0.93% (IQR 0.34, 1.96) vs 0.32% (IQR 0.02, 0.90), P ​ Conclusions Whole-heart atherosclerosis progression examined by serial CCTA is independently associated with MACE, with a prognostic threshold of 1.0% increase in PAV per year.

OBJECTIVES This study sought to identify culprit lesion (CL) precursors among acute coronary syndrome (ACS) patients based on qualitative and quantitative computed tomography-based plaque characteristics.BACKGROUND Coronary computed tomography angiography (CTA) has been validated for patient-level prediction of ACS. However, the applicability of coronary CTA to CL assessment is not known.METHODS Utilizing the ICONIC (Incident COroNary Syndromes Identified by Computed Tomography) study, a nested casecontrol study of 468 patients with baseline coronary CTA, the study included ACS patients with invasive coronary angiography-adjudicated CLs that could be aligned to CL precursors on baseline coronary CTA. Separate blinded core laboratories adjudicated CLs and performed atherosclerotic plaque evaluation. Thereafter, the study used a boosted ensemble algorithm (XGBoost) to develop a predictive model of CLs. Data were randomly split into a training set (80%) and a test set (20%). The area under the receiver-operating characteristic curve of thismodel was compared with that of diameter stenosis (model 1), high-risk plaque features (model 2), and lesion-level features of CL precursors from the ICONIC study (model 3). Thereafter, the machine learning (ML) model was applied to 234 non-ACS patients with 864 lesions to determine model performance for CL exclusion.RESULTS CL precursors were identified by both coronary angiography and baseline coronary CTA in 124 of 234 (53.0%) patients, with a total of 582 lesions (containing 124 CLs) included in the analysis. The ML model demonstrated significantly higher area under the receiver-operating characteristic curve for discriminating CL precursors (0.774; 95% confidence interval [CI]: 0.758 to 0.790) compared with model 1 (0.599; 95% CI: 0.599 to 0.599; p < 0.01), model 2 (0.532; 95% CI: 0.501 to 0.563; p < 0.01), and model 3 (0.672; 95% CI: 0.662 to 0.682; p < 0.01). When applied to the non-ACS cohort, the ML model had a specificity of 89.3% for excluding CLs.CONCLUSIONS In a high-risk cohort, a boosted ensemble algorithm can be used to predict CL from non-CL precursors on coronary CTA. (c) 2020 by the American College of Cardiology Foundation.

Background: Hypertension (HTN), diabetes mellitus (DM), and dyslipidemia (DL) are well-known risk factors of cardiovascular disease (CVD), but not all patients develop CVDs. Studies have been limited investigating genetic risk of CVDs specific to individuals with metabolic diseases. This study aimed to identify disease-specific and/or common genetic loci associated with CVD susceptibility in chronic metabolic disease patients.Methods: We conducted a genome-wide association study (GWAS) of a multiple case-control design with data from the City Cohort within Health EXAminees subcohort of the Korean Genome and Epidemiology Study (KoGES_HEXA). KoGES_HEXA is a population-based prospective cohort of 173,357 urban Korean adults that had health examinations at medical centers. 42,393 participants (16,309 HTN; 5,314 DM; 20,770 DL) were analyzed, and each metabolic disease group was divided into three CVD case-controls: coronary artery disease (CAD), ischemic stroke (IS), and cardio-cerebrovascular disease (CCD). GWASs were conducted for each case-control group with 7,975,321 imputed single nucleotide polymorphisms using Phase 1/2 Asian panels from 1000 Genomes Project, by logistic regression and controlled for confounding variables. Genome-wide significant levels were implemented to identify important susceptibility loci.Results: Totaling 42,393 individuals, this study included 16,309 HTN (mean age [SD], 57.28 [7.45]; 816 CAD, 398 IS, and 1,185 CCD cases), 5,314 DM (57.79 [7.39]; 361 CAD, 153 IS, and 497 CCD cases), and 20,770 DL patients (55.34 [7.63]; 768 CAD, 295 IS, and 1,039 CCD cases). Six genome-wide significant CVD risk loci were identified, with relatively large effect sizes: 1 locus in HTN (HTN-CAD: 17q25.3/CBX8-CBX4 [OR, 2.607; P = 6.37 × 10−9]), 2 in DM (DM-IS: 4q32.3/MARCH1-LINC01207 [OR, 5.587; P = 1.34 × 10−8], and DM-CCD: 17q25.3/RPTOR [OR, 3.511; P = 1.99 × 10−8]), and 3 in DL (DL-CAD: 9q22.2/UNQ6494-LOC101927847 [OR, 2.282; P = 7.78 × 10−9], DL-IS: 3p22.1/ULK4 [OR, 2.162; P = 2.97 × 10−8], and DL-CCD: 2p22.2/CYP1B1-CYP1B1-AS1 [OR, 2.027; P = 4.24 × 10−8]).Conclusions: This study identified 6 susceptibility loci and positional candidate genes for CVDs in HTN, DM, and DL patients using an unprecedented study design. 1 locus (17q25.3) was commonly associated with CAD. These associations warrant validation in additional studies for potential therapeutic applications.

Author(s): Ferraro, Richard A; van Rosendael, Alexander R; Lu, Yao; Andreini, Daniele; Al-Mallah, Mouaz H; Cademartiri, Filippo; Chinnaiyan, Kavitha; Chow, Benjamin JW; Conte, Edoardo; Cury, Ricardo C; Feuchtner, Gudrun; de Araujo Goncalves, Pedro; Hadamitzky, Martin; Kim, Yong-Jin; Leipsic, Jonathon; Maffei, Erica; Marques, Hugo; Plank, Fabian; Pontone, Gianluca; Raff, Gilbert L; Villines, Todd C; Lee, Sang-Eun; Al'Aref, Subhi J; Baskaran, Lohendran; Cho, Iksung; Danad, Ibrahim; Gransar, Heidi; Budoff, Matthew J; Samady, Habib; Stone, Peter H; Virmani, Renu; Narula, Jagat; Berman, Daniel S; Chang, Hyuk-Jae; Bax, Jeroen J; Min, James K; Shaw, Leslee J; Lin, Fay Y | Abstract: AimsHigh-risk plaque (HRP) and non-obstructive coronary artery disease independently predict adverse events, but their importance to future culprit lesions has not been resolved. We sought to determine in patients prior to confirmed acute coronary syndrome (ACS) the association between lesion percent diameter stenosis (%DS), and the absolute number and prevalence of HRP. The secondary objective was to examine the relative importance of non-obstructive HRP in future culprit lesions.Methods and resultsWithin the ICONIC study, a nested case-control study of patients undergoing coronary computed tomographic angiography (coronary CT), we included ACS cases with culprit lesions confirmed by invasive coronary angiography and coregistered to baseline coronary CT. Quantitative CT was used to evaluate obstructive (≥50%) and non-obstructive (l50%) diameter stenosis, with HRP defined as ≥2 features of spotty calcification, positive remodelling, or low-attenuation plaque at baseline. A total of 234 patients with downstream ACS over 54 (interquartile range 5-525.5) days exhibited 198/898 plaques with HRP on coronary CT. While HRP was less prevalent in non-obstructive (19.7%, 161/819) than obstructive lesions (46.8%, 37/79, P l 0.001), non-obstructive plaque comprised 81.3% (161/198) of HRP lesions overall. Among the 128 patients with identifiable culprit lesion precursors, the adjusted hazard ratio (HR) was 1.85 [95% confidence interval (CI) 1.26-2.72] for HRP, with no interaction between %DS and HRP (P = 0.82). Compared to non-obstructive HRP lesions, obstructive lesions without HRP exhibited a non-significant HR of 1.41 (95% CI 0.61-3.25, P = 0.42).ConclusionsWhile HRP is more prevalent among obstructive lesions, non-obstructive HRP lesions outnumber those that are obstructive and confer risk clinically approaching that of obstructive lesions without HRP.

Key PointsQuestionAre atherosclerotic plaque measurements associated with physiologic measures of invasive fractional flow reserve? FindingsIn this analysis of the CREDENCE clinical trial that included 612 patients, nonobstructive and obstructive measures of atherosclerotic plaque were significantly associated with invasive fractional flow reserve. A comprehensive set of atherosclerotic plaque features improved the accuracy of classifying vessel-specific reduced fractional flow reserve vs rest/stress myocardial perfusion imaging measurements. MeaningUsing coronary computed tomographic angiography for detection of atherosclerotic plaque features associated with coronary physiology may improve diagnostic certainty and guide clinical management of symptomatic patients.ImportanceStress imaging has been the standard for diagnosing functionally significant coronary artery disease. It is unknown whether novel, atherosclerotic plaque measures improve accuracy beyond coronary stenosis for diagnosing invasive fractional flow reserve (FFR) measurement. ObjectiveTo compare the diagnostic accuracy of comprehensive anatomic (obstructive and nonobstructive atherosclerotic plaque) vs functional imaging measures for estimating vessel-specific FFR. Design, Setting, and ParticipantsControlled clinical trial of diagnostic accuracy with a multicenter derivation-validation cohort of patients referred for nonemergent invasive coronary angiography. A total of 612 patients (64 [10] years; 30% women) with signs and symptoms suggestive of myocardial ischemia from 23 sites were included. Patients were recruited from 2014 to 2017. Data analysis began in August 2018. InterventionsPatients underwent invasive coronary angiography with measurement of invasive FFR, coronary computed tomographic angiography (CCTA) quantification of atherosclerotic plaque and FFR by CT (FFR-CT), and semiquantitative scoring of rest/stress myocardial perfusion imaging (by magnetic resonance, positron emission tomography, or single photon emission CT). Multivariable generalized linear mixed models were derived and validated calculating the area under the receiver operating characteristics curve. Main Outcomes and MeasuresThe primary end point was invasive FFR of 0.80 or less. ResultsOf the 612 patients, the mean (SD) age was 64 (10) years, and 426 (69.9%) were men. An invasive FFR of 0.80 or less was measured in 26.5% of 1727 vessels. In the derivation cohort, CCTA vessel-specific factors associated with FFR 0.80 or less were stenosis severity, percentage of noncalcified atheroma volume, lumen volume, the number of lesions with high-risk plaque (>= 2 of low attenuation plaque, positive remodeling, napkin ring sign, or spotty calcification), and the number of lesions with stenosis greater than 30%. Fractional flow reserve-CT was not additive to this model including stenosis and atherosclerotic plaque. Significant myocardial perfusion imaging predictors were the summed rest and difference scores. In the validation cohort, the areas under the receiver operating characteristic curve were 0.81 for CCTA vs 0.67 for myocardial perfusion imaging (P

Background Accurate measurement of the maximum aortic diameter (Dmax) is crucial for patients with abdominal aortic aneurysm (AAA). Aortic computed tomography (CT) provides accurate Dmax values by three-dimensional (3-D) reconstruction but may cause nephrotoxicity because of contrast use and radiation hazard. We aimed to evaluate the accuracy of a novel semi-automated 3-D ultrasonography (3-D US) system compared with that of CT as a reference. Methods Patients with AAA (n = 59) or individuals with normal aorta (n = 18) were prospectively recruited in an outpatient setting. Two-dimensional ultrasonography (2-D US) and 3-D US images were acquired with a single-sweep volumetric transducer. The analysis was performed offline with a software. Dmax and the vessel area of the Dmax slice were measured with 2-D US, 3-D US, and CT. The lumen and thrombus areas of the Dmax slice were also measured in 40 patients with intraluminal thrombus. Vessel and thrombus volumes were measured using 3-D US and CT. Results The Dmax values from 3-D US demonstrated better agreement (R2 = 0.984) with the CT values than with the 2-D US values (R2 = 0.938). Overall, 2-D US underestimated Dmax compared with 3-D US (32.3 ± 12.1 mm vs. 35.1 ± 12.0 mm). The Bland-Altman analysis of the 3-D US values, revealed better agreement with the CT values (2 standard deviations [SD], 2.9 mm) than with the 2-D US values (2 SD, 5.4 mm). The vessel, lumen, and thrombus areas all demonstrated better agreement with CT than with 2-D US (R2 = 0.986 vs. 0.960 for the vessel, R2 = 0.891 vs. 0.837 for the lumen, and R2 = 0.977 vs. 0.872 for the thrombus). The thrombus volume assessed with 3-D US showed good correlation with the CT value (R2 = 0.981 and 2 SD in the Bland-Altman analysis: 13.6 cm3). Conclusions Our novel semi-automated 3-D US analysis system provides more accurate Dmax values than 2-D US and provides precise volumetric data, which were not evaluable with 2-D US. The application of the semi-automated 3-D US analysis system in abdominal aorta assessment is easy and accurate.

To determine whether the assessment of individual plaques is superior in predicting the progression to obstructive coronary artery disease (CAD) on serial coronary computed tomography angiography (CCTA) than per-patient assessment. From a multinational registry of 2252 patients who underwent serial CCTA at a ≥ 2-year inter-scan interval, patients with only non-obstructive lesions at baseline were enrolled. CCTA was quantitatively analyzed at both the per-patient and per-lesion level. Models predicting the development of an obstructive lesion at follow up using either the per-patient or per-lesion level CCTA measures were constructed and compared. From 1297 patients (mean age 60 ± 9 years, 43% men) enrolled, a total of 3218 non-obstructive lesions were identified at baseline. At follow-up (inter-scan interval: 3.8 ± 1.6 years), 76 lesions (2.4%, 60 patients) became obstructive, defined as > 50% diameter stenosis. The C-statistics of Model 1, adjusted only by clinical risk factors, was 0.684. The addition of per-patient level total plaque volume (PV) and the presence of high-risk plaque (HRP) features to Model 1 improved the C-statistics to 0.825 [95% confidence interval (CI) 0.823-0.827]. When per-lesion level PV and the presence of HRP were added to Model 1, the predictive value of the model improved the C-statistics to 0.895 [95% CI 0.893-0.897]. The model utilizing per-lesion level CCTA measures was superior to the model utilizing per-patient level CCTA measures in predicting the development of an obstructive lesion (p

BACKGROUND: The association of age with coronary plaque dynamics is not well characterized by coronary computed tomography angiography (CCTA). METHODS: From a multinational registry of patients who underwent serial CCTA, 1153 subjects (61 ± 5 years old, 61.1% male) were analyzed. Annualized volume changes of total, fibrous, fibrofatty, necrotic core, and dense calcification plaque components of the whole heart were compared by age quartile groups. Clinical events, a composite of all-cause death, acute coronary syndrome, and any revascularization after 30 days of the initial CCTA, were also analyzed. Random forest analysis was used to define the relative importance of age on plaque progression. RESULTS: With a 3.3-years' median interval between the two CCTA, the median annual volume changes of total plaque in each age quartile group was 7.8, 10.5, 10.8, and 12.1 mm3/year and for dense calcification, 2.5, 4.6, 5.4, and 7.1 mm3/year, both of which demonstrated a tendency to increase by age (p-for-trend = 0.001 and

Objectives The goal of this study was to investigate the association of stenosis and plaque features with myocardial ischemia and their prognostic implications. Background Various anatomic, functional, and morphological attributes of coronary artery disease (CAD) have been independently explored to define ischemia and prognosis. Methods A total of 1,013 vessels with fractional flow reserve (FFR) measurement and available coronary computed tomography angiography were analyzed. Stenosis and plaque features of the target lesion and vessel were evaluated by an independent core laboratory. Relevant features associated with low FFR (≤0.80) were identified by using machine learning, and their predictability of 5-year risk of vessel-oriented composite outcome, including cardiac death, target vessel myocardial infarction, or target vessel revascularization, were evaluated. Results The mean percent diameter stenosis and invasive FFR were 48.5 ± 17.4% and 0.81 ± 0.14, respectively. Machine learning interrogation identified 6 clusters for low FFR, and the most relevant feature from each cluster was minimum lumen area, percent atheroma volume, fibrofatty and necrotic core volume, plaque volume, proximal left anterior descending coronary artery lesion, and remodeling index (in order of importance). These 6 features showed predictability for low FFR (area under the receiver-operating characteristic curve: 0.797). The risk of 5-year vessel-oriented composite outcome increased with every increment of the number of 6 relevant features, and it had incremental prognostic value over percent diameter stenosis and FFR (area under the receiver-operating characteristic curve: 0.706 vs. 0.611; p = 0.031). Conclusions Six functionally relevant features, including minimum lumen area, percent atheroma volume, fibrofatty and necrotic core volume, plaque volume, proximal left anterior descending coronary artery lesion, and remodeling index, help define the presence of myocardial ischemia and provide better prognostication in patients with CAD. (CCTA-FFR Registry for Risk Prediction; NCT04037163 )

Background: Preclinical studies and pilot patient studies have shown that chronic infarctions can be detected and characterized from cardiac magnetic resonance without gadolinium-based contrast agents using native-T1 maps at 3T. We aimed to investigate the diagnostic capacity of this approach for characterizing chronic myocardial infarctions (MIs) in a multi-center setting. Methods: Patients with a prior MI (n=105) were recruited at 3 different medical centers and were imaged with native-T1 mapping and late gadolinium enhancement (LGE) at 3T. Infarct location, size, and transmurality were determined from native-T1 maps and LGE. Sensitivity, specificity, receiver-operating characteristic metrics, and inter- and intraobserver variabilities were assessed relative to LGE. Results: Across all subjects, T1 of MI territory was 1621±110 ms, and remote territory was 1225±75 ms. Sensitivity, specificity, and area under curve for detecting MI location based on native-T1 mapping relative to LGE were 88%, 92%, and 0.93, respectively. Native-T1 maps were not different for measuring infarct size (native-T1 maps: 12.1±7.5%; LGE: 11.8±7.2%, P =0.82) and were in agreement with LGE ( R 2 =0.92, bias, 0.09±2.6%). Corresponding inter- and intraobserver assessments were also highly correlated (interobserver: R 2 =0.90, bias, 0.18±2.4%; and intraobserver: R 2 =0.91, bias, 0.28±2.1%). Native T1 maps were not different for measuring MI transmurality (native-T1 maps: 49.1±15.8%; LGE: 47.2±19.0%, P =0.56) and showed agreement ( R 2 =0.71; bias, 1.32±10.2%). Corresponding inter- and intraobserver assessments were also in agreement (interobserver: R 2 =0.81, bias, 0.1±9.4%; and intraobserver: R 2 =0.91, bias, 0.28±2.1%, respectively). While the overall accuracy for detecting MI with native-T1 maps at 3T was high, logistic regression analysis showed that MI location was a prominent confounder. Conclusions: Native-T1 mapping can be used to image chronic MI with high degree of accuracy, and as such, it is a viable alternative for scar imaging in patients with chronic MI who are contraindicated for LGE. Technical advancements may be needed to overcome the imaging confounders that currently limit native-T1 mapping from reaching equivalent detection levels as LGE.

OBJECTIVES This study explored whether the pattern of nonobstructive lesion progression into obstructive lesions would differ according to the presence of high-risk plaque (HRP).BACKGROUND It is still debatable whether HRP simply represents a certain phase during the natural history of coronary atherosclerotic plaques or if disease progression would differ according to the presence of HRP.METHODS Patients with nonobstructive coronary artery disease, defined as percent diameter stenosis (%DS) = 2 years. HRP was defined as lesions with >= 2 features of positive remodeling, spotty calcification, or low-attenuation plaque. Quantitative total and compositional percent atheroma volume (PAV) at baseline and annualized PAV change were compared between non-HRP and HRP lesions.RESULTS A total of 3,049 nonobstructive lesions were identified from 1,297 patients (mean age 60.3 +/- 9.3 years; 56.8% men). There were 2,624 non-HRP and 425 HRP lesions. HRP lesions had a greater total PAV and all noncalcified components of PAV and %DS at baseline compared with non-HRP lesions. However, the annualized total PAV changes were greater in non-HRP lesions than in HRP lesions. On multivariate analysis adjusted for clinical risk factors, drug use, change in lipid level, total PAV, %DS, and HRP, only the baseline total PAV and %DS independently predicted the development of obstructive lesions (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02 to 1.07, and HR: 1.07; 95% CI: 1.04 to 1.10, respectively, all p < 0.05), whereas the presence of HRP did not (p > 0.05).CONCLUSIONS The pattern of individual coronary atherosclerotic plaque progression differed according to the presence of HRP. Baseline PAV, not the presence of HRP features, was the most important predictor of lesions developing into obstructive lesions. (Progression of Atherosclerotic Plaque Determined By Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411) (c) 2020 by the American College of Cardiology Foundation.

BACKGROUND The impact of serum uric acid (SUA) on atherosclerosis has been suspected to be epiphenomenal owing to its close relationship with metabolic abnormalities. The aim of the present study was to evaluate the association between SUA levels and arterial stiffness in the absence of established cardiovascular (CV) disorders. METHODS The relationship between SUA levels and brachial-ankle pulse wave velocity (baPWV) was examined in 353 asymptomatic adults (57 ± 8 years, 11.9% men) without established CV disorders defined as systolic blood pressure (BP) ≥140 mmHg or diastolic BP ≥ 90 mmHg; total cholesterol ≥240 mg/dL; low-density lipoprotein cholesterol ≥160 mg/dL; high-density lipoprotein cholesterol

Background Atherogenic lipoprotein profile of plasma is an important risk factor for atherosclerosis. The atherogenic index of plasma (AIP) has been suggested as a novel marker for atherosclerosis. Hypothesis AIP is a useful marker of advanced subclinical coronary artery disease (CAD) in subjects without overt renal dysfunction. Methods A total of 6928 subjects with estimated glomerular filtration rate > 60 mL/minutes/1.73 m2 evaluated by coronary computed tomography angiography (CCTA) for health check‐up were included. The relation of AIP to advanced CAD (heavy coronary calcification, defined as coronary artery calcium score [CACS] >100 or obstructive coronary plaque [OCP], defined as plaque with >50% stenosis) was evaluated. Results All participants were stratified into four groups based on AIP quartiles. The prevalence of CACS >100 (group I [lowest] 4.7% vs group II 7.0% vs group III 8.8% vs group IV 10.0%) and OCP (group I 3.7% vs group II 6.4% vs group III 8.8% vs group IV 10.9%) (all P 100 (odds ratio [OR] 1.057, 95% confidence interval (CI) 1.010 to 1.106, P = .017; relative risk (RR) 1.048, 95% CI 1.009‐1.089, and P = .015) and OCP (OR 1.079, 95% CI 1.033‐1.127, P = .001; RR 1.069, 95% CI 1.031‐1.108, P 60 years, male sex, hypertension, diabetes mellitus, dyslipidaemia, obesity, and proteinuria. Conclusion AIP is independently associated with advanced subclinical CAD beyond traditional risk factors.

OBJECTIVES: To develop, demonstrate and evaluate an automated deep learning method for multiple cardiovascular structure segmentation. BACKGROUND: Segmentation of cardiovascular images is resource-intensive. We design an automated deep learning method for the segmentation of multiple structures from Coronary Computed Tomography Angiography (CCTA) images. METHODS: Images from a multicenter registry of patients that underwent clinically-indicated CCTA were used. The proximal ascending and descending aorta (PAA, DA), superior and inferior vena cavae (SVC, IVC), pulmonary artery (PA), coronary sinus (CS), right ventricular wall (RVW) and left atrial wall (LAW) were annotated as ground truth. The U-net-derived deep learning model was trained, validated and tested in a 70:20:10 split. RESULTS: The dataset comprised 206 patients, with 5.130 billion pixels. Mean age was 59.9 ± 9.4 yrs., and was 42.7% female. An overall median Dice score of 0.820 (0.782, 0.843) was achieved. Median Dice scores for PAA, DA, SVC, IVC, PA, CS, RVW and LAW were 0.969 (0.979, 0.988), 0.953 (0.955, 0.983), 0.937 (0.934, 0.965), 0.903 (0.897, 0.948), 0.775 (0.724, 0.925), 0.720 (0.642, 0.809), 0.685 (0.631, 0.761) and 0.625 (0.596, 0.749) respectively. Apart from the CS, there were no significant differences in performance between sexes or age groups. CONCLUSIONS: An automated deep learning model demonstrated segmentation of multiple cardiovascular structures from CCTA images with reasonable overall accuracy when evaluated on a pixel level.

Aims In patients without obstructive coronary artery disease (CAD), we examined the prognostic value of risk factors and atherosclerotic extent. Methods and results Patients from the long-term CONFIRM registry without prior CAD and without obstructive (≥50%) stenosis were included. Within the groups of normal coronary computed tomography angiography (CCTA) (N = 1849) and non-obstructive CAD (N = 1698), the prognostic value of traditional clinical risk factors and atherosclerotic extent (segment involvement score, SIS) was assessed with Cox models. Major adverse cardiac events (MACE) were defined as all-cause mortality, non-fatal myocardial infarction, or late revascularization. In total, 3547 patients were included (age 57.9 ± 12.1 years, 57.8% male), experiencing 460 MACE during 5.4 years of follow-up. Age, body mass index, hypertension, and diabetes were the clinical variables associated with increased MACE risk, but the magnitude of risk was higher for CCTA defined atherosclerotic extent; adjusted hazard ratio (HR) for SIS >5 was 3.4 (95% confidence interval [CI] 2.3–4.9) while HR for diabetes and hypertension were 1.7 (95% CI 1.3–2.2) and 1.4 (95% CI 1.1–1.7), respectively. Exclusion of revascularization as endpoint did not modify the results. In normal CCTA, presence of ≥1 traditional risk factors did not worsen prognosis (log-rank P = 0.248), while it did in non-obstructive CAD (log-rank P = 0.025). Adjusted for SIS, hypertension and diabetes predicted MACE risk in non-obstructive CAD, while diabetes did not increase risk in absence of CAD (P-interaction = 0.004). Conclusion Among patients without obstructive CAD, the extent of CAD provides more prognostic information for MACE than traditional cardiovascular risk factors. An interaction was observed between risk factors and CAD burden, suggesting synergistic effects of both.

Contains fulltext : 220894.pdf (Publisher’s version ) (Closed access) AIMS: We aimed to compare semiquantitative coronary computed tomography angiography (CCTA) risk scores - which score presence, extent, composition, stenosis and/or location of coronary artery disease (CAD) - and their prognostic value between patients with and without diabetes mellitus (DM). Risk scores derived from general chest-pain populations are often challenging to apply in DM patients, because of numerous confounders. METHODS: Out of a combined cohort from the Leiden University Medical Center and the CONFIRM registry with 5-year follow-up data, we performed a secondary analysis in diabetic patients with suspected CAD who were clinically referred for CCTA. A total of 732 DM patients was 1:1 propensity-matched with 732 non-DM patients by age, sex and cardiovascular risk factors. A subset of 7 semiquantitative CCTA risk scores was compared between groups: 1) any stenosis ≥50%, 2) any stenosis ≥70%, 3) stenosis-severity component of the coronary artery disease-reporting and data system (CAD-RADS), 4) segment involvement score (SIS), 5) segment stenosis score (SSS), 6) CT-adapted Leaman score (CT-LeSc), and 7) Leiden CCTA risk score. Cox-regression analysis was performed to assess the association between the scores and the primary endpoint of all-cause death and non-fatal myocardial infarction. Also, area under the receiver-operating characteristics curves were compared to evaluate discriminatory ability. RESULTS: A total of 1,464 DM and non-DM patients (mean age 58 ± 12 years, 40% women) underwent CCTA and 155 (11%) events were documented after median follow-up of 5.1 years. In DM patients, the 7 semiquantitative CCTA risk scores were significantly more prevalent or higher as compared to non-DM patients (p ≤ 0.022). All scores were independently associated with the primary endpoint in both patients with and without DM (p ≤ 0.020), with non-significant interaction between the scores and diabetes (interaction p ≥ 0.109). Discriminatory ability of the Leiden CCTA risk score in DM patients was significantly better than any stenosis ≥50% and ≥70% (p = 0.003 and p = 0.007, respectively), but comparable to the CAD-RADS, SIS, SSS and CT-LeSc that also focus on the extent of CAD (p ≥ 0.265). CONCLUSION: Coronary atherosclerosis scoring with semiquantitative CCTA risk scores incorporating the total extent of CAD discriminate major adverse cardiac events well, and might be useful for risk stratification of patients with DM beyond the binary evaluation of obstructive stenosis alone.

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 Conclusion TyG index is an independent predictive marker for the progression of coronary atherosclerosis. Clinical registration ClinicalTrials.gov NCT02803411

Background and aims The Agatston coronary artery calcium score (CACS) method may fail to identify small or less dense coronary calcification that can be detected on coronary CT angiography (CCTA). We investigated the prevalence and prognostic importance of subtle calcified plaques on CCTA among individuals with CACS 0. Methods From the prospective multicenter CONFIRM registry, we evaluated patients without known CAD who underwent CAC scan and CCTA. CACS was categorized as 0, 1–10, 11–100, 101–400, and >400. Patients with CACS 0 were stratified according to the visual presence of coronary plaques on CCTA. Plaque composition was categorized as non-calcified (NCP), mixed (MP) and calcified (CP). The primary outcome was a major adverse cardiac event (MACE) which was defined as death and myocardial infarction. Results Of 4049 patients, 1741 (43%) had a CACS 0. NCP and subtle calcified plaques (MP or CP) were detected by CCTA in 110 patients (6% of CACS 0) and 64 patients (4% of CACS 0), respectively. During a 5.6 years median follow-up (IQR 5.1–6.2 years), 413 MACE events occurred (13%). Patients with CACS 0 and MP/CP detected by CCTA had similar MACE risk compared to patients with CACS 1–10 (p = 0.868). In patients with CACS 0, after adjustment for risk factors and symptom, MP/CP was associated with an increased MACE risk compared to those with entirely normal CCTA (HR 2.39, 95% CI [1.09–5.24], p = 0.030). Conclusions A small, but non-negligible proportion of patients with CACS 0 had identifiable coronary calcification, which was associated with increased MACE risk. Modifying CAC image acquisition and/or scoring methods could improve the detection of subtle coronary calcification.

OBJECTIVES: The aim of the current study was to explore the impact of plaque calcification in terms of absolute calcified plaque volume (CPV) and in the context of its percentage of the total plaque volume at a lesion and patient level on the progression of coronary artery disease. BACKGROUND: Coronary artery calcification is an established marker of risk of future cardiovascular events. Despite this, plaque calcification is also considered a marker of plaque stability, and it increases in response to medical therapy. METHODS: This analysis included 925 patients with 2,568 lesions from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry, in which patients underwent clinically indicated serial coronary computed tomography angiography. Plaque calcification was examined by using CPV and percent CPV (PCPV), calculated as (CPV/plaque volume) × 100 at a per-plaque and per-patient level (summation of all individual plaques). RESULTS: CPV was strongly correlated with plaque volume (r = 0.780; p < 0.001) at baseline and with plaque progression (r = 0.297; p < 0.001); however, this association was reversed after accounting for plaque volume at baseline (r = -0.146; p < 0.001). In contrast, PCPV was an independent predictor of a reduction in plaque volume (r = -0.11; p < 0.001) in univariable and multivariable linear regression analyses. Patient-level analysis showed that high CPV was associated with incident major adverse cardiac events (hazard ratio: 3.01: 95% confidence interval: 1.58 to 5.72), whereas high PCPV was inversely associated with major adverse cardiac events (hazard ratio: 0.529; 95% confidence interval: 0.229 to 0.968) in multivariable analysis. CONCLUSIONS: Calcified plaque is a marker for risk of adverse events and disease progression due to its strong association with the total plaque burden. When considered as a percentage of the total plaque volume, increasing PCPV is a marker of plaque stability and reduced risk at both a lesion and patient level. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411).

BACKGROUND Although significant stenosis and regurgitation can be observed on a single heart valve, studies on the outcome predictors for mixed valve disease are limited. The purpose of the current study was to investigate the fate and determinants of clinical outcomes in patients with mixed single mitral valve disease who have concomitant mitral stenosis (MS) and mitral regurgitation (MR). METHODS We retrospectively reviewed 82 consecutive patients with rheumatic heart disease who had both significant MS (MVA ≤ 1.5 cm2 ) and at least moderate MR, excluding patients with significant aortic valve stenosis or regurgitation. The primary endpoint was a composite of all-cause mortality during follow-up, mitral valve replacement, heart failure admission, and stroke. RESULTS There were 37 events (45.1%), 5 all-cause deaths (6.0%), and 32 mitral valve replacements (39.0%). In a multivariable Cox regression analysis, a transmitral mean pressure gradient (TMPG) over 6 mm Hg was the only independent echocardiographic predictor for events (hazard ratio 3.69, 95% confidential interval 1.31-10.44, P = .014), after adjusting for sex, age, symptoms, and the severity of MS and MR. The estimated 6-year event-free survival rate was significantly lower in patients with TMPG ≥ 6 mm Hg than in those with TMPG

Background Data on the relationship between the triglyceride glucose (TyG) index and coronary artery calcification (CAC) progression is limited. This longitudinal study evaluated the association of TyG index with CAC progression in asymptomatic adults. Methods We enrolled 12,326 asymptomatic Korean adults who had at least two CAC evaluations. The TyG index was determined using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). CAC progression was defined as a difference ≥ 2.5 between the square roots (√) of the baseline and follow-up coronary artery calcium score (CACS) (Δ√transformed CACS). Annualized Δ√transformed CACS was defined as Δ√transformed CACS divided by the inter-scan period. Results During a mean 3.3 years, the overall incidence of CAC progression was 30.6%. The incidence of CAC progression (group I [lowest]: 22.7% versus [vs.] group II: 31.7% vs. group III [highest]: 37.5%, P Conclusion The TyG index is an independent predictor of CAC progression, especially in adults without heavy baseline CAC.

Background Rapid coronary plaque progression (RPP) is associated with incident cardiovascular events. To date, no method exists for the identification of individuals at risk of RPP at a single point in time. This study integrated coronary computed tomography angiography–determined qualitative and quantitative plaque features within a machine learning (ML) framework to determine its performance for predicting RPP. Methods and Results Qualitative and quantitative coronary computed tomography angiography plaque characterization was performed in 1083 patients who underwent serial coronary computed tomography angiography from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry. RPP was defined as an annual progression of percentage atheroma volume ≥1.0%. We employed the following ML models: model 1, clinical variables; model 2, model 1 plus qualitative plaque features; model 3, model 2 plus quantitative plaque features. ML models were compared with the atherosclerotic cardiovascular disease risk score, Duke coronary artery disease score, and a logistic regression statistical model. 224 patients (21%) were identified as RPP. Feature selection in ML identifies that quantitative computed tomography variables were higher‐ranking features, followed by qualitative computed tomography variables and clinical/laboratory variables. ML model 3 exhibited the highest discriminatory performance to identify individuals who would experience RPP when compared with atherosclerotic cardiovascular disease risk score, the other ML models, and the statistical model (area under the receiver operating characteristic curve in ML model 3, 0.83 [95% CI 0.78–0.89], versus atherosclerotic cardiovascular disease risk score, 0.60 [0.52–0.67]; Duke coronary artery disease score, 0.74 [0.68–0.79]; ML model 1, 0.62 [0.55–0.69]; ML model 2, 0.73 [0.67–0.80]; all P P =0.128). Conclusions Based on a ML framework, quantitative atherosclerosis characterization has been shown to be the most important feature when compared with clinical, laboratory, and qualitative measures in identifying patients at risk of RPP.

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.\ud \ud Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.\ud \ud Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response.\ud \ud Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56–0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro–brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil–assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12–60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting.\ud \ud Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.\ud \ud Clinical trial registered with www.clinicaltrials.gov (NCT01560624).

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 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.

Background Diastolic blood pressure has a J-curve relation with coronary heart disease and death, but it is debating whether a J-curve association exists in general population. We aimed to assess the relation of blood pressure to mortality, and whether their association is interacted with presence of high coronary artery calcium (CAC). Methods The KOICA registry is a retrospective, multicenter observational study designed to investigate the effectiveness and prognostic value of CAC score for primary prevention of cardiovascular disease in asymptomatic Korean adults. The association between CAC score and blood pressure was assessed. Patients were divided into 2 groups according to the baseline CACS (> 300 and ≤ 300), and all-cause mortality was assessed. Results The study population composed 48903 subjects with a mean age of 54 ± 9. There were 425 (0.9%) deaths during follow-up. At baseline, SBP (systolic blood pressure) more than 110 mmHg and DBP (diastolic blood pressure) more than 80 mmHg was associated with increased risk for CACS > 300. In patients with baseline CACS ≤ 300, all-cause mortality was increased in patients with SBP of 110-119 mmHg (HR 1.47, p = 0.023), 130-139 mmHg (HR 1.72, p = 0.002) and ≥ 140 mmHg (HR 1.47, p = 0.042) compared to SBP of 120-129 mmHg, whereas DBP did not predict all-cause mortality. In contrast, SBP was not associated to all-cause mortality in patients with CACS > 300, whereas DBP < 60 mmHg (HR 3.53, p =0.018) and 70-79 mmHg (HR 2.21, p = 0.042) was associated with increased risk for all-cause mortality compared to DBP of 80-89 mmHg. Conclusion Low DBP was associated with increased risk for all-cause mortality in subjects with high CAC score, suggesting high-risk for coronary artery disease. However, this J-curve relation was not shown in the population with low CAC score.

Background and Objectives We aim to explore the additional discriminative accuracy of a deep learning (DL) algorithm using repeated-measures data for identifying people at high risk for cardiovascular disease (CVD), compared to Cox hazard regression. Methods Two CVD prediction models were developed from National Health Insurance Service-Health Screening Cohort (NHIS-HEALS): a Cox regression model and a DL model. Performance of each model was assessed in the internal and 2 external validation cohorts in Koreans (National Health Insurance Service-National Sample Cohort; NHIS-NSC) and in Europeans (Rotterdam Study). A total of 412,030 adults in the NHIS-HEALS; 178,875 adults in the NHIS-NSC; and the 4,296 adults in Rotterdam Study were included. Results Mean ages was 52 years (46% women) and there were 25,777 events (6.3%) in NHIS-HEALS during the follow-up. In internal validation, the DL approach demonstrated a C-statistic of 0.896 (95% confidence interval, 0.886–0.907) in men and 0.921 (0.908–0.934) in women and improved reclassification compared with Cox regression (net reclassification index [NRI], 24.8% in men, 29.0% in women). In external validation with NHIS-NSC, DL demonstrated a C-statistic of 0.868 (0.860–0.876) in men and 0.889 (0.876–0.898) in women, and improved reclassification compared with Cox regression (NRI, 24.9% in men, 26.2% in women). In external validation applied to the Rotterdam Study, DL demonstrated a C-statistic of 0.860 (0.824–0.897) in men and 0.867 (0.830–0.903) in women, and improved reclassification compared with Cox regression (NRI, 36.9% in men, 31.8% in women). Conclusions A DL algorithm exhibited greater discriminative accuracy than Cox model approaches. Trial Registration ClinicalTrials.gov Identifier: NCT02931500

Author(s): Wang, Nan; Christodoulou, Anthony G; Xie, Yibin; Wang, Zhenjia; Deng, Zixin; Zhou, Bill; Lee, Sangeun; Fan, Zhaoyang; Chang, Hyukjae; Yu, Wei; Li, Debiao | Abstract: PurposeTo develop a dynamic contrast-enhanced (DCE) MRI method capable of high spatiotemporal resolution, 3D carotid coverage, and T1-based quantification of contrast agent concentration for the assessment of carotid atherosclerosis using a newly developed Multitasking technique.Methods5D imaging with 3 spatial dimensions, 1 T1 recovery dimension, and 1 DCE time dimension was performed using MR Multitasking based on low-rank tensor modeling, which allows direct T1 quantification with high spatiotemporal resolution (0.7 mm isotropic and 595 ms, respectively). Saturation recovery preparations followed by 3D segmented fast low angle shot readouts were implemented with Gaussian-density random 3D Cartesian sampling. A bulk motion removal scheme was developed to improve image quality. The proposed protocol was tested in phantom and human studies. In vivo scans were performed on 14 healthy subjects and 7 patients with carotid atherosclerosis. Kinetic parameters including area under the concentration versus time curve (AUC), vp , Ktrans , and ve were evaluated for each case.ResultsPhantom experiments showed that T1 measurements using the proposed protocol were in good agreement with reference value ( R 2 = 0.96 ). In vivo studies demonstrated that AUC, vp , and Ktrans in the patient group were significantly higher than in the control group (0.63 ± 0.13 versus 0.42 ± 0.12, P l 0.001; 0.14 ± 0.05 versus 0.11 ± 0.03, P = 0.034; and 0.13 ± 0.04 versus 0.08 ± 0.02, P l 0.001, respectively). Results from repeated subjects showed good interscan reproducibility (intraclass correlation coefficient: vp , 0.83; Ktrans , 0.87; ve , 0.92; AUC, 0.94).ConclusionMultitasking DCE is a promising approach for quantitatively assessing the vascularity properties of the carotid vessel wall.

OBJECTIVES:This study sought to describe the impact of statins on individual coronary atherosclerotic plaques. BACKGROUND:Although statins reduce the risk of major adverse cardiovascular events, their long-term effects on coronary atherosclerosis remain unclear. METHODS:We performed a prospective, multinational study consisting of a registry of consecutive patients without history of coronary artery disease who underwent serial coronary computed tomography angiography at an interscan interval of ≥2 years. Atherosclerotic plaques were quantitatively analyzed for percent diameter stenosis (%DS), percent atheroma volume (PAV), plaque composition, and presence of high-risk plaque (HRP), defined by the presence of ≥2 features of low-attenuation plaque, positive arterial remodeling, or spotty calcifications. RESULTS:Among 1,255 patients (60 ± 9 years of age; 57% men), 1,079 coronary artery lesions were evaluated in statin-naive patients (n = 474), and 2,496 coronary artery lesions were evaluated in statin-taking patients (n = 781). Compared with lesions in statin-naive patients, those in statin-taking patients displayed a slower rate of overall PAV progression (1.76 ± 2.40% per year vs. 2.04 ± 2.37% per year, respectively; p = 0.002) but more rapid progression of calcified PAV (1.27 ± 1.54% per year vs. 0.98 ± 1.27% per year, respectively; p 50% DS were not different (1.0% vs. 1.4%, respectively; p > 0.05). Statins were associated with a 21% reduction in annualized total PAV progression above the median and 35% reduction in HRP development. CONCLUSIONS:Statins were associated with slower progression of overall coronary atherosclerosis volume, with increased plaque calcification and reduction of high-risk plaque features. Statins did not affect the progression of percentage of stenosis severity of coronary artery lesions but induced phenotypic plaque transformation. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411).

Objectives This study aimed to determine the rate and extent of plaque progression (PP), changes in plaque features, and clinical predictors of PP in patients with diabetes mellitus (DM). Background The natural history of coronary PP in patients with DM is not well established. Methods A total of 1,602 patients (age 61.3 ± 9.0 years; 60.3% men; median scan interval 3.8 years) who underwent serial coronary computed tomography angiography over a period of at least 24 months were enrolled and analyzed from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) trial. Study endpoints were changes in plaque features in diabetics with PP and risk factors for PP by serial coronary computed tomography angiography between patients with and without DM. PP was defined if plaque volume at follow-up minus plaque volume at baseline was >0. Results DM was an independent risk factor for PP (84.6%; 276 of 326 patients with PP) in multivariate analysis (odds ratio [OR]: 1.526; 95% confidence interval [CI]: 1.100 to 2.118; p = 0.011). Independent risk factors for PP in patients with DM were male sex (OR: 1.485; 95% CI: 1.003 to 2.199; p = 0.048) and mean plaque burden at baseline ≥75% (OR: 3.121; 95% CI: 1.701 to 5.725; p ≤0.001). After propensity matching, percent changes in overall plaque volume (30.3 ± 36.9% in patients without DM and 36.0 ± 29.7% in those with DM; p = 0.032) and necrotic core volume (−7.0 ± 35.8% in patients without DM and 21.5 ± 90.5% in those with DM; p = 0.007) were significantly greater in those with DM. The frequency of spotty calcification, positive remodeling, and burden of low-attenuation plaque were significantly greater in patients with DM. Conclusions People with DM experience greater PP, particularly significantly greater progression in adverse plaque, than those without DM. Male sex and mean plaque burden >75% at baseline were identified as independent risk factors for PP.

Coronary 18F-sodium fluoride (18F-NaF) PET identifies ruptured plaques in patients with recent myocardial infarction and localizes to atherosclerotic lesions with active calcification. Most studies to date have performed the PET acquisition 1 h after injection. Although qualitative and semiquantitative analysis is feasible with 1-h images, residual blood-pool activity often makes it difficult to discriminate plaques with 18F-NaF uptake from noise. We aimed to assess whether delayed PET performed 3 h after injection improves image quality and uptake measurements. Methods: Twenty patients (67 ± 7 y old, 55% male) with stable coronary artery disease underwent coronary CT angiography (CTA) and PET/CT both 1 h and 3 h after the injection of 266.2 ± 13.3 MBq of 18F-NaF. We compared the visual pattern of coronary uptake, maximal background (blood pool) activity, noise, SUVmax, corrected SUVmax (cSUVmax), and target-to-background (TBR) ratio in lesions defined by CTA on 1-h versus 3-h 18F-NaF PET. Results: On 1-h PET, 26 CTA lesions with 18F-NaF PET uptake were identified in 12 (60%) patients. On 3-h PET, we detected 18F-NaF PET uptake in 7 lesions that were not identified on 1-h PET. The median cSUVmax and TBRs of these lesions were 0.48 (interquartile range [IQR], 0.44-0.51) and 1.45 (IQR, 1.39-1.52), respectively, compared with -0.01 (IQR, -0.03-0.001) and 0.95 (IQR, 0.90-0.98), respectively, on 1-h PET (both P < 0.001). Across the entire cohort, 3-h PET SUVmax was similar to 1-h PET measurements (1.63 [IQR, 1.37-1.98] vs. 1.55 [IQR, 1.43-1.89], P = 0.30), and the background activity was lower (0.71 [IQR, 0.65-0.81] vs. 1.24 [IQR, 1.05-1.31], P < 0.001). On 3-h PET, TBR, cSUVmax, and noise were significantly higher (respectively: 2.30 [IQR, 1.70-2.68] vs. 1.28 [IQR, 0.98-1.56], P < 0.001; 0.38 [IQR, 0.27-0.70] vs. 0.90 [IQR, 0.64-1.17], P < 0.001; and 0.10 [IQR, 0.09-0.12] vs. 0.07 [IQR, 0.06-0.09], P = 0.02). Median cSUVmax and TBR increased by 92% (range, 33%-225%) and 80% (range, 20%-177%), respectively. Conclusion: Blood-pool activity decreases on delayed imaging, facilitating the assessment of 18F-NaF uptake in coronary plaques. Median TBR increases by 80%, leading to the detection of more plaques with significant uptake than are detected using the standard 1-h protocol. A greater than 1-h delay may improve the detection of 18F-NaF uptake in coronary artery plaques.

Data on the impact of optimal glycemic control (OGC) on the progression of coronary artery calcification, an important marker for future adverse cardiovascular events in individuals with diabetes are limited.We investigated 1637 asymptomatic adults with diabetes (56 ± 8 years, 88.8% men) and no history of coronary artery disease or stroke, who underwent serial coronary artery calcium (CAC) screening. The median inter-scan period was 3.0 (2.0-4.4) years. The change in CAC was compared base on OGC status. OGC was defined as a follow-up hemoglobin A1C (HbA1C) of7.0%, and CAC progression was defined by a square root (√) transformed difference between the baseline and follow-up CAC scores (Δ √transformed CAC) of ≥2.5.Despite no significant difference in the baseline CAC scores, the incidence of CAC progression was lower in the OGC group than in the non-OGC group (45.4% vs. 51.7%; p 0.013). The two groups differed in the Δ √transformed (OGC, 3.8 ± 6.4; non-OGC, 4.7 ± 6.9; p = 0.016) and annualized Δ √transformed CAC (OGC, 1.1 ± 2.4; non-OGC, 1.4 ± 2.6; p = 0.010) scores. Subgroup analysis showed that OGC significantly reduced the risk of CAC progression in patients aged65 years and in: smokers, and patients with a body mass index of25 kg/mOGC attenuated the progression of coronary artery calcification in asymptomatic patients with diabetes.

BACKGROUND Arterial stiffening is a major contributing factor in the development of cardiovascular disease in patients with end-stage renal disease (ESRD). However, there is no gold standard for evaluating arterial stiffness. This study aimed to evaluate the newly developed speckle-tracking carotid strain imaging method in assessing arterial stiffness in patients with ESRD. METHODS In total, 85 patients with normal renal function (controls) and 36 with ESRD were enrolled in this single-center study. Carotid B-mode ultrasonography was performed for all patients. Arterial stiffness indices and strain parameters of the common carotid arteries were analyzed. Values were compared between the groups, and multivariate linear regression analysis was performed to assess the impact of ESRD on carotid strain. RESULTS There were no differences in the intima-media thickness, β stiffness index, and arterial compliance, but arterial distensibility was lower, and the elastic modulus and pulse wave velocity β (PWV) were higher among patients with ESRD (all p < 0.05), whether assessed in the longitudinal or transverse plane. Both longitudinal and transverse strain rates were reduced in patients with ESRD (all p < 0.05). In multivariate analyses, ESRD independently reduced both transverse radial strain and strain rate (all p < 0.05), and the transverse circumferential strain and strain rate (p < 0.05). However, all conventional aortic stiffness indices and longitudinal strain parameters were not associated with ESRD. CONCLUSIONS Speckle-tracking carotid strain ultrasonography was successfully performed in both normal subjects and patients with ESRD. Multidirectional carotid strain analyses may provide more value than conventional aortic stiffness indices for risk stratification in patients with ESRD.

BACKGROUND: Coronary computed tomography angiography (CTA) allows quantification of stenosis. However, such quantitative analysis is not part of clinical routine. We evaluated the feasibility of utilizing deep learning for quantifying coronary artery disease from CTA. METHODS: A total of 716 diseased segments in 156 patients (66 ± 10 years) who underwent CTA were analyzed. Minimal luminal area (MLA), percent diameter stenosis (DS), and percent contrast density difference (CDD) were measured using semi-automated software (Autoplaque) by an expert reader. Using the expert annotations, deep learning was performed with convolutional neural networks using 10-fold cross-validation to segment CTA lumen and calcified plaque. MLA, DS and CDD computed using deep-learning-based approach was compared to expert reader measurements. RESULTS: There was excellent correlation between the expert reader and deep learning for all quantitative measures (r=0.984 for MLA; r=0.957 for DS; and r=0.975 for CDD, p

The optimal blood pressure (BP) guidelines in Asian populations have not been determined. We compared all-cause and cardiovascular mortality based on the Joint National Committee 7 (JNC7) and 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. The National Health Insurance System-National Health Screening Cohort (NHIS-HEALS) and Korea National Health and Nutrition Examination Survey (KNHANES) were utilized. BPs were classified into three groups according to each guideline, and survival rates were analyzed with Kaplan-Meier curves and log-rank tests. Hazard ratios (HRs) were calculated using multivariable cox regression analyses, and the discriminatory ability for clinical outcomes was assessed by Harrell&rsquo, s C-indexes. The JNC7 guidelines demonstrated a linear association between BP levels and survival outcomes. Adjusted HRs from the JNC7 guidelines differentiated the hypertension group (&ge, 140/90) from the pre (130/80&ndash, 139/89) and normal (&lt, 130 and &lt, 80) BP groups in clinical outcomes. In contrast, the 2017 ACC/AHA guidelines showed inconsistent survival outcomes according to BP classification (normal: &lt, 120 and &lt, 80, elevated: 120&ndash, 129, and &lt, 80, and HTN: &ge, 130/80). According to Harrell&rsquo, s C-indexes, the JNC7 guidelines had greater discrimination ability in survival outcomes in the NHIS-HEALS dataset. Our results suggest that the JNC7 guidelines are more appropriate than the 2017 ACC/AHA guidelines in Korean populations.

Aims The long-term prognostic value of coronary computed tomography angiography (CCTA)-identified coronary artery disease (CAD) has not been evaluated in elderly patients (≥70 years). We compared the ability of coronary CCTA to predict 5-year mortality in older vs. younger populations. Methods and results From the prospective CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry, we analysed CCTA results according to age 50%); (ii) segment involvement score (SIS): number of segments with plaque. Cox-proportional hazard models assessed the relationship between CCTA findings and time to mortality. At a mean 5.6 ± 1.1 year follow-up, CCTA-identified CAD predicted increased mortality compared with patients with a normal CCTA in both Conclusion The presence and extent of CAD is a meaningful stratifier of long-term mortality and MACE in patients aged

Coronary artery calcium (CAC) is an established surrogate marker for coronary atherosclerotic disease (CAD) burden. The CAC score is also an independent predictor of adverse events with significant incremental prognostic value over traditional/clinical risk stratification algorithms. The objective of this study was to examine the prognostic ability of Machine learning (ML) based algorithms to predict multi-class CAC (0: normal; 1–100: low risk CAD; 101–400 Intermediate risk CAD; >400 severe/high risk CAD) from available electronic health record (EHR) data. A retrospective observation study of 60,923 asymptomatic patients with clinically evaluated CAC score along with sixty five clinical and laboratory parameters were included in developing the ML algorithm (data split into 70% [training] and 30% [test]). In addition, a separate cohort of 7,552 patients was used to externally validate the developed ML algorithm. Classification performance was assessed using the area under the receiver operating curve (AUC). The prediction algorithm derived from the ML method showed high predictive value for CAC risk category.

Numerical simulations on the pulsatile flow in stenosed tubes were conducted to investigate the effect of trapezium shape of stenosis on the flow field around stenoses. Four trapezium shapes of stenoses were considered by varying contraction, plateau, and expansion parts of stenoses for different stenosis area reduction ratios. The Galerkin finite element method based on the P2P1 mixed element was employed to solve the axisymmetric incompressible Navier-Stokes equations and the continuity equation. The proposed numerical method was validated by solving a benchmark problem of stenotic flow. It was found that the average pressure profile along the centerline was more affected by the contraction shape than the expansion shape. It was also revealed that the average wall shear stress of mild contraction was greater than that of sudden contraction around the stenotic region. Furthermore, the pressure drop across the stenosis was found to be associated with the form drag experienced by the stenosis.

Our objective was to assess the prognostic value of symptom typicality in patients without obstructive coronary artery disease (CAD), determined by coronary computed tomographic angiography (CCTA). We identified 4215 patients without prior history of CAD and without obstructive CAD (

Objectives The purpose of this study was to develop and validate a simple-to-use nomogram for prediction of 5-, 10-, and 15-year survival among asymptomatic adults. Background Simple-to-use prognostication tools that incorporate robust methods such as coronary artery calcium scoring (CACS) for predicting near-, intermediate- and long-term mortality are warranted. Methods In a consecutive series of 9,715 persons (mean age: 53.4 ± 10.5 years; 59.3% male) undergoing CACS, we developed a nomogram using Cox proportional hazards regression modeling that included: age, sex, smoking, hypertension, dyslipidemia, diabetes, family history of coronary artery disease, and CACS. We developed a prognostic index (PI) summing the number of risk points corresponding to weighted covariates, which was used to configure the nomogram. Validation of the nomogram was assessed by discrimination and calibration applied to a separate cohort of 7,824 adults who also underwent CACS. Results A total of 936 and 294 deaths occurred in the derivation and validation sets at a median follow-up of 14.6 years (interquartile range: 13.7 to 15.5 years) and 9.4 years (interquartile range: 6.8 to 11.5 years), respectively. The developed model effectively predicted 5-, 10-, and 15-year probability of survival. The PI displayed high discrimination in the derivation and validation sets (C-index 0.74 and 0.76, respectively), indicating suitable external performance of our nomogram model. The predicted and actual estimates of survival in each dataset according to PI quartiles were similar (though not identical), demonstrating improved model calibration. Conclusions A simple-to-use nomogram effectively predicts 5-, 10- and 15-year survival for asymptomatic adults undergoing screening for cardiac risk factors. This nomogram may be considered for use in clinical care.

We investigated whether quantification of global left ventricular (LV) strain by tissue tracking-CMR (TT-CMR) can estimate the infarct size and clinical outcomes in patients with acute myocardial infarction (MI). We retrospectively registered 247 consecutive patients (58 ± 12 years; male, 81%) who underwent 1.5-T CMR within 1 month after ST-segment elevation MI (median, 4 days; interquartile range, 3–6 days), and 20 age- and sex-matched controls (58 ± 11 years; male, 80%). TT-CMR analysis was applied to cine-images to measure global LV radial, circumferential and longitudinal peak strains (GRS, GCS and GLS, respectively). Adverse cardiac events were defined as cardiac death and hospitalization for heart failure. During the follow-up (median, 7.8 years), 20 patients (8.1%) experienced adverse events. LV myocardial deformation was significantly decreased in MI patients compared to controls and closely related to the infarct size. The GRS, GCS and GLS were all significant predictors of adverse cardiac events. In particular, a GLS > −14.1% was independently associated with a > 5-fold increased risk for adverse events, even after adjustment for the LV ejection fraction and infarct size. TT-CMR-derived LV strain is significantly related to the infarct size and adverse events. GLS measurement provides strong prognostic information in MI patients. • TT-CMR provides reliable quantification of LV strain in MI patients. • TT-CMR allows prediction of the infarct size and adverse events. • In particular, GLS by TT-CMR had independent prognostic value in MI patients.

Background: We aimed to investigate the characteristics and echocardiographic changes in patients with severe mitral stenosis (MS) who maintained sinus rhythm (SR) for at least 10 years after successful percutaneous mitral balloon valvuloplasty (PMV). Methods: We retrospectively reviewed 107 patients who had successful PMV and follow-up echocardiography for at least 10 years without mitral valve surgery. Preprocedural, immediate postprocedural (PMV), and long-term follow-up echocardiography (at least 10 years after PMV) data were reviewed. Results: The mean follow-up time after PMV was 15 ± 4 years for SR patients (n = 50) and 16 ± 4 years (p = 0.172) for atrial fibrillation (AF) patients (n = 57). The left atrial diameter was significantly decreased in SR patients in the follow-up echocardiography images compared to its pre-PMV value (46.7 ± 6.3 vs. 43.3 ± 6.2 mm, respectively), whereas it was significantly increased in patients with AF (53.9 ± 7.1 vs. 58.1 ± 8.7 mm). In multivariate analysis, preprocedural AF (odds ratio [OR] 14.50, p = 0.001) and LA diameter ≥50 mm (OR 8.81, p < 0.001) were independently associated with increased risk for the presence of AF after successful PMV. Conclusion: Very long-term maintenance of SR after successful PMV was associated with preprocedural SR and LA diameter < 50 mm.

Emergency medical service (EMS) occurs in a high-pressure and error-prone environment, where paramedics must provide prompt decisions in care while recording information with limited time, incomplete data, restricted resources, and competing priorities. The EMS requires cooperative workflows between patients or caregivers, paramedics and medical centers in the community. In a conventional EMS, they have difficulties in obtaining causes of emergencies and personal medical histories, which are important for a rapid and proper response. We analyzed the requirement of a smart EMS (SEMS) system and derived the key components in connected care environments leveraging information and communication technology. A survey of paramedics (n=113) revealed that a SEMS system using IoT technology should integrate personal lifelogs, electronic medical records, and patient monitoring in ambulances into pre-hospital care recording systems. It also addressed context-awareness in the EMS accelerates first responder's activities, while supporting personalized care not only at the scene of the emergency but also during the entire hospital stay. Based on requirement analysis, we designed and implemented SEMS using health information standards to provide interoperability between devices and systems. As an application of SEMS, an example service is introduced: lifelog-connected EMS for stroke patients with a real-time location service for managing timeline of treatment.