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

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

Arterial Stiffness is Associated with False-Positive ST-Segment Depression in Supine Bicycle Exercise Stress Echocardiography.

Background: Although exercise stress electrocardiography (ECG) is a popular tool for detecting coronary artery disease (CAD), the induced ST-depression without coronary artery stenosis (FST) remains a challenge for accurate diagnosis. Exercise-induced ST depression is related to poor prognosis even in non-obstructive disease; however, its determinants have not been fully defined. We sought to investigate whether ventriculo-vascular interactional indexes such as arterial stiffness index, exercise hemodynamic parameters and echocardiographic left ventricular (LV) functional parameters were related to FST. Methods: In the current study, 609 participants who underwent both supine bicycle exercise echocardiography and brachial-ankle pulse wave velocity (baPWV) measurement without exercise-induced regional wall motion abnormalities (RWMA) were analyzed. Referral reasons for stress test were CAD detection or evaluation of patency of previous revascularization. Stepwise graded supine bicycle exercise was performed with simultaneous ECG recording and echocardiography after full conventional resting echocardiography. The FST was defined as newly developed > 1 mm ST depression without RWMA during exercise. Results: The median age of the study participants was 65 (59.0-70.5) years, and 222 (37%) patients were women. Among them, 103 (17%) patients showed FST during the exercise or recovery phase. The prevalence of FST did not differ between sexes. Older age, higher pulmonary arterial systolic pressure (PASP), left atrial volume index, baPWV and ankle brachial index at rest and hypertensive response, higher heart rate and rate-pressure product at peak exercise were significantly associated with FST. In multivariate analysis, higher peak heart rate, PASP, and baPWV were independently related to FST. Conclusions: Stress-induced RWMA in addition to ECG should be evaluated to detect CAD in patients with higher baPWV and PASP. FST might be linked to subclinical myocardial ischemia through arterial stiffness and diastolic dysfunction.

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

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

Impact of aortic atheroma and distensibility on diastolic function and prognosis in patients with ischemic stroke.

BACKGROUND: Patients with ischemic stroke are vulnerable to heart failure with preserved ejection fraction (HFpEF) because these conditions share common risk factors. Although evaluation of the ascending aorta, aortic arch, and proximal descending thoracic aorta is an essential step to determine the source of the causative embolism, the relationship between the degree of aortic atheroma and left ventricular (LV) diastolic function has not been extensively investigated. METHODS: We analyzed the transesophageal and transthoracic echocardiography in ischemic stroke patients. Patients with previous coronary artery disease, valvular heart disease of more than moderate degree, and an LV ejection fraction of less than 50% were excluded. The relationships between the grade of the aortic atheroma, aortic stiffness indexes, and diastolic functional indexes were evaluated. RESULTS: In 295 patients, the atheroma grade was significantly correlated with aortic stiffness index, ratio of mitral annular and inflow velocities (E/e'), left atrial volume index, and LV diastolic elastance. With further adjustment for age, hypertension, diabetes, estimated glomerular filtration rate, left atrial volume index, and LV mass index, the significance of the atheroma grade was attenuated. In the subgroup analysis, the atheroma grade was significantly and independently related to E/e' in women (ß = 0.181, p = 0.032), but not in men. However, atheroma grade was not associated with poor clinical outcomes in either sex. CONCLUSIONS: Aortic atheroma grade was significantly and independently related to LV diastolic function, especially in women. This suggests that aortic atheroma is an index of arterial stiffness and a potential risk factor for HFpEF through ventricular-vascular interactions, especially in women.

Retinal photograph-based deep learning predicts biological age, and stratifies morbidity and mortality risk.

BACKGROUND: ageing is an important risk factor for a variety of human pathologies. Biological age (BA) may better capture ageing-related physiological changes compared with chronological age (CA). OBJECTIVE: we developed a deep learning (DL) algorithm to predict BA based on retinal photographs and evaluated the performance of our new ageing marker in the risk stratification of mortality and major morbidity in general populations. METHODS: we first trained a DL algorithm using 129,236 retinal photographs from 40,480 participants in the Korean Health Screening study to predict the probability of age being ≥65 years ('RetiAGE') and then evaluated the ability of RetiAGE to stratify the risk of mortality and major morbidity among 56,301 participants in the UK Biobank. Cox proportional hazards model was used to estimate the hazard ratios (HRs). RESULTS: in the UK Biobank, over a 10-year follow up, 2,236 (4.0%) died; of them, 636 (28.4%) were due to cardiovascular diseases (CVDs) and 1,276 (57.1%) due to cancers. Compared with the participants in the RetiAGE first quartile, those in the RetiAGE fourth quartile had a 67% higher risk of 10-year all-cause mortality (HR = 1.67 [1.42-1.95]), a 142% higher risk of CVD mortality (HR = 2.42 [1.69-3.48]) and a 60% higher risk of cancer mortality (HR = 1.60 [1.31-1.96]), independent of CA and established ageing phenotypic biomarkers. Likewise, compared with the first quartile group, the risk of CVD and cancer events in the fourth quartile group increased by 39% (HR = 1.39 [1.14-1.69]) and 18% (HR = 1.18 [1.10-1.26]), respectively. The best discrimination ability for RetiAGE alone was found for CVD mortality (c-index = 0.70, sensitivity = 0.76, specificity = 0.55). Furthermore, adding RetiAGE increased the discrimination ability of the model beyond CA and phenotypic biomarkers (increment in c-index between 1 and 2%). CONCLUSIONS: the DL-derived RetiAGE provides a novel, alternative approach to measure ageing.

MAFLD Predicts the Risk of Cardiovascular Disease Better than NAFLD in Asymptomatic Subjects with Health Check-Ups.

BACKGROUND AND AIM: Metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to compensate for the conventional concept of nonalcoholic fatty liver disease (NAFLD). We investigated the superiority of MAFLD versus NAFLD in predicting the risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: A total of 2,144 subjects without a history of ASCVD, who underwent a comprehensive medical health check-up, were selected for the study. The associations between fatty liver status and coronary risk surrogates, such as coronary artery calcium score (CACS), coronary artery disease, quantitative stenosis grade, and 10-year ASCVD risk, were analyzed. RESULTS: MAFLD and NAFLD were identified in 995 (46.4%) and 891 (41.6%) subjects, respectively. Subjects with MAFLD or NAFLD were more likely to be male and had a significantly higher prevalence of central obesity, obesity, hypertension, diabetes, and dyslipidemia (all, p < 0.05) than their counterparts. In terms of coronary risk surrogates, the MAFLD or NAFLD population had a significantly higher proportion of subjects with CACS > 100, coronary artery disease, higher grade of coronary artery stenosis, and higher 10-year ASCVD risk (all, p < 0.05) than their counterparts. Multivariable logistic regression models showed an independent association between MAFLD/NAFLD and coronary risk surrogates (all, p < 0.05). However, NAFLD only, defined as 'NAFLD, but not MAFLD,' was not associated with an increased coronary risk, compared to MAFLD. CONCLUSIONS: Although both MAFLD and NAFLD discriminated different ASCVD risks, MAFLD predicted the risk of ASCVD better than NAFLD in asymptomatic subjects who underwent medical health check-ups.

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

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

Effect of Renal and Left Ventricular Function on Serial Pulmonary Arterial Pressure Changes after Device Closure of Atrial Septal Defect.

BACKGROUND: The age of candidates for device closure of atrial septal defect (ASD) has been increasing. Thus, concerns exist about dyspnea aggravation or atrial fibrillation development after device closure due to augmentation of left ventricular (LV) and left atrial (LA) preload. This study aimed to examine patterns and determinants of serial pulmonary arterial pressure and left ventricular filling pressure changes after device closure of ASD. METHODS: Among the 86 consecutive patients who underwent percutaneous device closure of ASD, those with end-stage renal disease or those without pre- or postprocedural Doppler data were excluded. The clinical, transesophageal, and transthoracic echocardiographic findings of 78 patients were collected at baseline, one-day postprocedure, and one-year follow-up. RESULTS: The mean age of study patients was 49.8 ± 15.0 years, and the average maximal defect diameter and device size were 20.2 ± 6.0 mm and 23.8 ± 6.4 mm. Four patients (5.6%) underwent new-onset atrial fibrillation, and five patients (6.4%) took diuretics within one-year after closure. Some patients (n = 21; 27%) exhibited paradoxically increased tricuspid regurgitant velocity (TRV) one-day postprocedure; they also were older with lower e', glomerular filtration rate, and LV ejection fraction and a higher LA volume index. However, even in these patients, TRV deceased below baseline levels one-year later. Both E/e' and LA volume index significantly increased immediately after device closure, but all decreased one-year later. Larger defect size and higher TRV were significantly correlated with immediate E/e' elevation. CONCLUSION: In older, renal, diastolic, and systolic dysfunctional patients with larger LA and scheduled for larger device implantation, peri-interventional preload reduction therapy would be beneficial.

Effect of sarcomere and mitochondria-related mutations on myocardial fibrosis in patients with hypertrophic cardiomyopathy.

BACKGROUND: Myocardial fibrosis is an important prognostic factor in hypertrophic cardiomyopathy (HCM). However, the contribution from a wide spectrum of genetic mutations has not been well defined. We sought to investigate effect of sarcomere and mitochondria-related mutations on myocardial fibrosis in HCM. METHODS: In 133 HCM patients, comprehensive genetic analysis was performed in 82 nuclear DNA (33 sarcomere-associated genes, 5 phenocopy genes, and 44 nuclear genes linked to mitochondrial cardiomyopathy) and 37 mitochondrial DNA. In all patients, cardiovascular magnetic resonance (CMR) was performed, including 16-segmental thickness, late gadolinium enhancement (LGE), native and post-T1, extracellular volume fraction (ECV), and T2, along with echo-Doppler evaluations. RESULTS: Patients with sarcomere mutation (SM, n = 41) had higher LGE involved segment, % LGE mass, ECV and lower post-T1 compared to patients without SM (n = 92, all p < 0.05). When classified into, non-mutation (n = 67), only mitochondria-related mutation (MM, n = 24), only-SM (n = 36) and both SM and MM (n = 5) groups, only-SM group had higher ECV and LGE than the non-mutation group (all p < 0.05). In non-LGE-involved segments, ECV was significantly higher in patients with SM. Within non-SM group, patients with any sarcomere variants of uncertain significance had higher echocardiographic Doppler E/e' (p < 0.05) and tendency of higher LGE amount and ECV (p > 0.05). However, MM group did not have significantly higher ECV or LGE amount than non-mutation group. CONCLUSIONS: SMs are significantly related to increase in myocardial fibrosis. Although, some HCM patients had pathogenic MMs, it was not associated with an increase in myocardial fibrosis.

Impact of PRECISE-DAPT and DAPT Scores on Dual Antiplatelet Therapy Duration After 2nd Generation Drug-Eluting Stent Implantation.

PURPOSE: Determining the optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is an important clinical issue. We evaluated the effects of ischemia (by DAPT score) and bleeding (by PRECISE-DAPT score), as well as the impact of DAPT duration, on clinical outcomes. METHODS: From pooled analysis of four randomized clinical trials, 5131 patients undergoing second-generation DES implantation were randomized to short-duration (n = 2575; ≤ 6 months) or standard-duration (n = 2556; ≥ 12 months) DAPT groups. This population was further divided into four subgroups according to PRECISE-DAPT (high bleeding risk ≥ 25) and DAPT (high ischemic risk ≥ 2) scores. RESULTS: Net clinical outcomes (1.3% vs. 1.3%; p = 0.89) and ischemic events (5.0% vs. 4.5%; p = 0.44) did not differ between the two duration groups, although bleeding events were more frequent in patients with standard-duration DAPT (0.4% vs. 0.9%; p = 0.04). Standard-duration DAPT was associated with fewer ischemic events (6.9% vs. 4.0%; p = 0.02) and no increase in bleeding events only among patients at low bleeding risk and high ischemic risk. The other groups show no differences in net clinical outcomes, ischemic events, or bleeding events according to DAPT duration. CONCLUSION: Compared with short-duration DAPT, standard-duration DAPT was associated with similar net clinical outcomes and ischemic events, but more bleeding events at 12 months after second-generation DES implantation. However, standard-duration DAPT reduced ischemic events without increasing bleeding events among patients at low bleeding and high ischemic risk. When determining DAPT duration, considering both ischemic and bleeding risk can help optimize patient benefits. CLINICAL TRIAL REGISTRATION: EXCELLENT (NCT00698607), RESET (NCT01145079), IVUS-XPL (NCT01308281), OPTIMA-C (NCT03056118).

Contribution of sarcomere gene mutations to left atrial function in patients with hypertrophic cardiomyopathy.

BACKGROUND: Left atrial (LA) enlargement and dysfunction are related to clinical course in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate genetic contribution to LA structural and functional remodeling. METHODS: Two hundred twelve patients were consecutively enrolled, and echocardiography and extensive genetic analysis were performed. Cardiac magnetic resonance (CMR) was performed in 135 patients. Echocardiography was also performed in controls (n = 30). RESULTS: Patients with HCM had lower late-diastolic mitral annular velocity (a') and higher LA volume index (LAVI) than controls. Patients with pathogenic or likely pathogenic sarcomere gene mutations (PSM, n = 67, 32%) had higher LAVI and lower CMR-derived LA total emptying fraction (37.0 ± 18.5 vs. 44.2 ± 12.4%, p = 0.025). In patients without AF (n = 187), the PSM had lower a' (6.9 ± 2.0 vs. 7.8 ± 1.9 cm/s, p = 0.004) than others. The PSM had higher prevalence and amount of late gadolinium enhancement (LGE) in the left ventricle (LV). In multivariate analysis, PSM was significantly related to lower a' independent of E/e', LV mass index, and LAVI. However, the relation significantly attenuated after adjustment for the extent of LGE in the LV, suggesting common myopathy in the LV and LA. In addition, PSM was significantly related to lower LA total emptying fraction independent of age, E/e', s', LV ejection fraction, LV myocardial global longitudinal strain and %LGE mass. CONCLUSIONS: PSM was related to LA dysfunction independent of LV filling pressure and LAVI, suggesting its contribution to atrial myopathy in HCM.

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

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

Efficacy and Safety of Guideline-Recommended Risk Score-Directed Dual Antiplatelet Therapy After 2nd-Generation Drug-Eluting Stents.

BACKGROUND: Evaluate the safety and efficacy of guideline-recommended risk score-directed dual antiplatelet therapy (GD-DAPT) based on THE PRECISE-DAPT score after 2nd-generation drug-eluting stent (DES) implantation.Methods and Results:We analyzed 5,131 patients pooled from 4 clinical trials. Patients were divided into 3 groups according to current recommendations on the duration of DAPT and their actual DAPT duration: GD-DAPT (n=2,183), shorter DAPT (n=1,540), longer DAPT (n=1,408). The primary endpoint was the rate of net adverse clinical events (NACE) during the first 12 months. The secondary endpoints were ischemic or bleeding events. Overall, GD-DAPT did not affect NACE (1.2% vs. 1.2% for shorter DAPT and 1.7% for longer DAPT) or bleeding events (0.6% vs. 0.5% and 0.9%), and there were fewer ischemic events (2.8% vs. 4.4% and 4.0%, P=0.03) than with shorter DAPT. Especially in acute coronary syndrome (ACS) patients, GD-DAPT had fewer NACE (1.5% vs. 1.4% and 4.2%; P=0.006) and bleeding events (0.8% vs. 0.5% and 2.8%; P=0.001) than longer DAPT as well as fewer ischemic events (2.8% vs. 4.4% and 4.7%; P=0.03) than shorter DAPT. CONCLUSIONS: GD-DAPT did not affect NACE or bleeding events and reduced the number of ischemic events at 12 months compared with shorter DAPT. For ACS, GD-DAPT was associated with favorable outcomes compared with non-GD-DAPT. Therefore, GD-DAPT may optimize efficacy and safety.

Outcomes and Associated Factors of Discrepant Coronary and Carotid Atherosclerosis.

Some patients exhibit discrepancies in carotid and coronary artery atherosclerosis. This study aimed to define the characteristics and prognosis of these discrepant patients and determine the best strategy to detect pan-vascular atherosclerosis. A database of 5,022 consecutively registered patients who underwent both coronary angiography and carotid ultrasonography, along with clinical and blood laboratory tests, echocardiography, and pulse wave velocity (PWV), was analyzed. The development of cerebro-cardiovascular (CV) events during the follow-up period was also evaluated. A significant proportion of patients (n = 1,741, 35%) presented with a discrepancy between carotid artery plaque and coronary artery disease (CAD). In patients without carotid plaque, male sex (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.20-2.41; P = 0.003), older age (OR, 1.03; 95% CI, 1.01-1.04; P = 0.002), smoking history (OR, 1.58; 95% CI, 1.13-2.20; P = 0.008), lower high-density lipoprotein (HDL) -cholesterol level (OR, 0.97; 95% CI, 0.96-0.98; P < 0.001), and lower common carotid artery end-diastolic velocity (CCA-EDV) (OR, 0.97; 95% CI, 0.95-0.99; P = 0.005) were independently related to the presence of CAD. In patients without CAD, increased PWV was independently related to the presence of carotid plaque. In survival analysis, patients with isolated CAD had a higher probability of composite CV events; those with isolated carotid plaque had a higher probability of heart failure (HF) and mortality than their counterpart groups (P < 0.05). Even in patients without carotid artery plaque, careful coronary evaluation is needed in older or male patients with smoking history, lower HDL-cholesterol level, or lower CCA-EDV. Carotid plaque may be a potential risk factor for HF.

Clinical feasibility of catheter-directed selective intracoronary computed tomography angiography using an extremely low dose of iodine in patients with coronary artery disease.

OBJECTIVE: This study aimed to evaluate the clinical feasibility of catheter-directed selective computed tomography angiography (S-CTA) in patients with coronary artery disease (CAD). METHODS: We prospectively enrolled 65 patients diagnosed with CAD who underwent conventional computed tomography angiography (C-CTA). C-CTA was performed with 60-90 mL of contrast medium (370 mg iodine/mL), whereas S-CTA was performed with 15 mL of contrast medium and 17.19 mg iodine/mL. Luminal enhancement range, homogeneity of luminal enhancement, image quality, plaque volume (PV), and percent aggregate plaque volume (%APV) were measured. Paired Student's t test, Wilcoxon rank-sum test, and Pearson's correlation coefficient were used to compare two methods. RESULTS: Luminal enhancement was significantly higher on S-CTA than on C-CTA (324.4 ± 8.0 Hounsfield unit (HU) vs. 312.0 ± 8.0 HU, p < 0.0001 in the per-vessel analysis). Transluminal attenuation gradient showed a significantly slower reduction pattern on S-CTA than on C-CTA (-0.65 HU/10 mm vs. -0.89 HU/10 mm, p < 0.0001 in the per-vessel analysis). Image noise was significantly lower on S-CTA than on C-CTA (39.6 ± 10.0 HU vs. 43.9 ± 9.4 HU, p < 0.0001). There was excellent correlation between S-CTA and C-CTA with respect to PV and %APV (r = 0.99, r = 0.98, respectively). CONCLUSIONS: S-CTA might be useful in facilitating atherosclerotic plaque analysis and providing guidance for complex lesions such as chronic total occlusion, particularly in cases in which on-site procedure planning is required. KEY POINTS: • Selective computed tomography angiography (S-CTA) can serve as an intraprocedural computed tomography angiography protocol. • S-CTA was performed with low dose of iodine compared with conventional computed tomography angiography. • S-CTA enables on-site atherosclerotic plaque analysis.

Genetic relevance and determinants of mitral leaflet size in hypertrophic cardiomyopathy.

BACKGROUND: Whether mitral leaflet elongation is a primary phenotype of hypertrophic cardiomyopathy (HCM) is controversial. We investigated the genetic relevance and determinants of mitral leaflet size by performing extensive gene analyses in patients with HCM. METHODS: Anterior mitral leaflet (AML) lengths were measured in HCM patients (n = 211) and age- and sex-matched controls (n = 30) using echocardiography with hemodynamic and chamber geometric assessments. We analyzed 82 nuclear DNA (8 sarcomeric genes, 74 other HCM-associated genes) and mitochondrial DNA. Cardiac magnetic resonance imaging (CMR) was performed in the 132 HCM patients. RESULTS: Average indexed AML was significantly longer for HCM than for controls (17.2 ± 2.3 vs. 13.3 ± 1.6 mm/m2, P <  0.001). Average AML length correlated with body surface area (BSA), left ventricular (LV) end-systolic volume (P <  0.001) and LV mass by CMR (P < 0.001). Average indexed AML by BSA of pure-apical HCM was significantly shorter than other typed HCM (16.6 ± 2.0 vs. 17.4 ± 2.4 mm/m2, P = 0.025). Indexed AML was independently correlated with left atrial wall stress. The thin filament mutation group showed larger average AML (31.9 ± 3.8 vs. 29.6 ± 3.8 mm, P = 0.045), but this was not significant with the indexed value. No difference in AML size among subgroups was observed based on the presence of sarcomere protein or mitochondria-related gene variants (P > 0.05). CONCLUSION: AML elongation was a unique finding of HCM. However, the leaflet size was more related to chamber geometry and hypertrophy pattern rather than genetic factors within overt HCM.

Association between triglyceride glucose index and arterial stiffness in Korean adults.

BACKGROUND: The triglyceride glucose (TyG) index has been suggested as a simple surrogate marker of insulin resistance. However, there are limited data regarding the association between the TyG index and arterial stiffness in adults. Therefore, we evaluated the relationship between the TyG index and arterial stiffness as measured based on brachial ankle pulse wave velocity (baPWV) in Korean adults. METHODS: A total of 3587 subjects were enrolled in this study. Anthropometric and cardiovascular risk factors were measured. The TyG index was calculated as ln[fasting triglycerides(mg/dl) × fasting glucose(mg/dl)/2], and the insulin resistance index of homeostasis model assessment (HOMA-IR) was estimated. Arterial stiffness was determined by measuring baPWV. RESULTS: The subjects were stratified into four groups based on the TyG index. There were significant differences in cardiovascular parameters among the groups; the mean baPWV increased significantly with increasing TyG index. According to the logistic regression analysis after adjusting for multiple risk factors, the odds ratio (95% CI) for increased baPWV (> 75th percentile) for the highest and lowest quartiles of the TyG index was 2.92 (1.92-4.44) in men and 1.84 (1.15-2.96) in women, and the odds ratio for increased baPWV for the highest and lowest quartiles of the HOMA-IR was 1.80 (1.17-2.78) in men and 1.46 (1.06-2.47) in women, respectively. CONCLUSION: The TyG index is more independently associated with increased arterial stiffness than HOMA-IR in Korean adults.

Relationship of insulin resistance estimated by triglyceride glucose index to arterial stiffness.

BACKGROUND: Insulin resistance (IR) is an important risk factor for subclinical atherosclerosis. This study evaluated the relationship between the triglyceride glucose (TyG) index, which is a simple and reliable surrogate marker for IR, and arterial stiffness. METHODS: This study included 2560 Korean subjects without a previous history of coronary artery disease, stroke, and malignancies who participated in a community-based cohort study. Arterial stiffness was measured using the brachial-ankle pulse wave velocity (baPWV). RESULTS: All participants were stratified into four groups based on the quartile of the TyG index. The prevalence of metabolic syndrome and diabetes significantly increased with increasing TyG index quartile. The mean baPWV was significantly different among all groups (group I [lowest]: 1421 ± 242 vs. group II: 1480 ± 244 vs. group III: 1534 ± 260 vs. group IV [highest]: 1575 ± 279 cm/s; p < 0.001). The TyG index values were correlated with baPWV (r = 0.224, p < 0.001). Multiple regression analysis showed that age (ß = 0.410), male gender (ß = 0.051), increased blood pressure (ß = 0.266), and TyG index (ß = 0.158) were associated with baPWV (p < 0.05, respectively). TyG index was independently related to baPWV in both non-diabetics and diabetics. CONCLUSIONS: The TyG index is independently associated with arterial stiffness in a relatively healthy Korean population.

Rationale and design of the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry: A comprehensive exploration of plaque progression and its impact on clinical outcomes from a multicenter serial coronary computed tomographic angiography study.

BACKGROUND: The natural history of coronary artery disease (CAD) in patients with low-to-intermediate risk is not well characterized. Although earlier invasive serial studies have documented the progression of atherosclerotic burden, most were focused on high-risk patients only. The PARADIGM registry is a large, prospective, multinational dynamic observational registry of patients undergoing serial coronary computed tomographic angiography (CCTA). The primary aim of PARADIGM is to characterize the natural history of CAD in relation to clinical and laboratory data. DESIGN: The PARADIGM registry (ClinicalTrials.govNCT02803411) comprises ≥2,000 consecutive patients across 9 cluster sites in 7 countries. PARADIGM sites were chosen on the basis of adequate CCTA volume, site CCTA proficiency, local demographic characteristics, and medical facilities to ensure a broad-based sample of patients. Patients referred for clinically indicated CCTA will be followed up and enrolled if they had a second CCTA scan. Patients will also be followed up beyond serial CCTA performance to identify adverse CAD events that include cardiac and noncardiac death, myocardial infarction, unstable angina, target vessel revascularization, and CAD-related hospitalization. SUMMARY: The results derived from the PARADIGM registry are anticipated to add incremental insight into the changes in CCTA findings in accordance with the progression or regression of CAD that confer prognostic value beyond demographic and clinical characteristics.

Optimal boundary detection method and window settings for coronary atherosclerotic plaque volume analysis in coronary computed tomography angiography: comparison with intravascular ultrasound.

OBJECTIVE: To evaluate optimal methodology for quantitative plaque volume analysis by coronary CT angiography (QCT). METHODS: Fifty-one coronary artery segments were evaluated and contour measurements based on two different methods [(1) no gap, or (2) fixed 0.3-mm gap between inner and outer boundary] were compared with intravascular ultrasound (IVUS). In addition, three different window width (WW) and level (WL) settings [fixed (740/220) Hounsfield unit (HU), adjusted (155 % and 65 % of mean luminal intensity of the segment, and aorta adjusted (155 % and 65 % of mean luminal intensity of central aorta)] were used for semiautomated plaque volume analysis. RESULTS: For boundary detection, the no gap method led to underestimation compared with IVUS (105.4 ± 82.3 vs. 136.1 ± 72.8 mm(3), p < 0.001), while fixed 0.3-mm gap showed no difference between IVUS and QCT (136.1 ± 72.8 vs. 139.8 ± 93.9 mm(3), p = 0.50). Comparison of the three different window settings demonstrated that the aorta adjusted setting underestimated (120.5 ± 74.3 vs. 136.1 ± 72.8 mm(3), p = 0.003), while fixed setting showed the least mean difference compared with IVUS (3.8 ± 39.8 mm(3), p = 0.50). CONCLUSION: For plaque volumetric assessment, optimal results were obtained with fixed 0.3-mm gap with fixed HU setting (740/220). KEY POINTS: • Quantitative plaque volume analysis by coronary CT angiography has recently emerged. • Different boundary detection methods and window width and level settings were evaluated. • Fixed 0.3-mm gap with fixed HU setting (740/220) afforded optimal results.