Eligibility and Cost-Utility Analysis of Dapagliflozin in Patients with Heart Failure Across the Whole Spectrum of Ejection Fraction in South Korea.

BACKGROUND: The DAPA-HF and DELIVER trials demonstrated the clinical benefits of dapagliflozin in heart failure (HF) patients across the entire ejection fraction (EF) spectrum. However, further investigation is needed for the real-world application of dapagliflozin in HF patients. This study examines the proportion of real-world HF patients eligible for dapagliflozin and evaluates the cost-effectiveness of adding dapagliflozin to current HF therapy. METHODS: Data from the nationwide prospective registry, the Korean Acute Heart Failure (KorAHF) registry, were used to determine dapagliflozin eligibility based on the enrollment criteria of the DAPA-HF/DELIVER trials. A cost-utility analysis was conducted using a Markov model to assess the cost-effectiveness of dapagliflozin by comparing it to the standard of care. RESULTS: Out of 5178 KorAHF patients, 48.7% met the enrollment criteria of the DAPA-HF/DELIVER trials, while 89.5% met the label criteria (US Food and Drug Administration, European Medicines Agency, and Korean Ministry of Food and Drug Safety). Eligibility was highest among HF patients with preserved EF (55.3% vs. HF with mildly reduced EF and HF with reduced EF 46.4%). Dapagliflozin proved to be cost-effective, with an incremental cost-effectiveness ratio (ICER) of 4557 US dollar (US$) per quality-adjusted life year, which falls below the US$18,182 willingness-to-pay threshold. The cost-effectiveness benefit was more pronounced in patients with a left ventricular EF (LVEF) ≤ 40% (ICER US$3279 for LVEF ≤ 40% vs. US$8383 for LVEF > 40%). CONCLUSIONS: Discrepancies in dapagliflozin eligibility were observed between real-world data and clinical trial results. The addition of dapagliflozin to HF therapy proved to be highly cost-effective across the entire EF spectrum.

Real-World Eligibility and Cost-Effectiveness Analysis of Empagliflozin for Heart Failure in Korea.

BACKGROUND: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. METHODS: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). RESULTS: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). CONCLUSION: There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843.

Erratum: Assessment of Disease Severity and Quality of Life in Patients with Atopic Dermatitis from South Korea.

This corrects the article on p. 419 in vol. 34, PMID: 36478424.

Assessment of Disease Severity and Quality of Life in Patients with Atopic Dermatitis from South Korea.

BACKGROUND: Data illustrating the impact of atopic dermatitis (AD) on lives of adults with AD in South Korea are limited. OBJECTIVE: To assess the AD disease severity and its impact on quality of life (QoL) in patients with AD from South Korea. METHODS: Patients with AD utilizing the specialist dermatology services of major hospitals in South Korea were assessed for disease severity using Eczema Area and Severity Index (EASI) score, for QoL using Dermatology Life Quality Index (DLQI) (for QoL), and for comorbidities and treatment experience via retrospective review of 12-month medical records. Clinical and sociodemographic characteristics were also measured. RESULTS: Of the 1,163 patients, 695 (59.8%) were men (mean age [years]±standard deviation: 31.6±12.1). Overall, 52.9% (n=615) patients had moderate-to-severe disease (EASI>7). The QoL of 72.3% (n=840) patients was affected moderately-to-severely (DLQI score: 6~30). Systemic immunosuppressants were used ≥1 over past 12 months in 51.9% (n=603) patients, and the most commonly used were cyclosporines (45.7%, n=531) and systemic corticosteroids (40.5%, n=471). Approximately, 10.8% (n=126) patients consulted or received treatment for AD-related eye problem. Of these, 40% (n=50) patients reported poor, very poor, or completely blind status; approximately, 16.7% patients (n=192) reported having depression or anxiety; and 35.5% (n=410) reported suicidal ideation or suicidal attempt. CONCLUSION: A large proportion of patients had moderate-to-severe AD, a compromised QoL, and ocular or mental health comorbidities, indicating a high disease burden despite systemic treatment. These findings highlight the importance of a holistic approach for the evaluation and treatment of patients with AD.

Longitudinal Quantitative Assessment of Coronary Atherosclerotic Plaque Burden Related to Serum Hemoglobin Levels.

Background: Despite a potential role of hemoglobin in atherosclerosis, data on coronary plaque volume changes (PVC) related to serum hemoglobin levels are limited. Objectives: The authors sought to evaluate coronary atherosclerotic plaque burden changes related to serum hemoglobin levels using serial coronary computed tomographic angiography (CCTA). Methods: A total of 830 subjects (age 61 ± 10 years, 51.9% male) who underwent serial CCTA were analyzed. The median interscan period was 3.2 (IQR: 2.5-4.4) years. Quantitative assessment of coronary plaques was performed at both scans. All participants were stratified into 4 groups based on the quartile of baseline hemoglobin levels. Annualized total PVC (mm3/year) was defined as total PVC divided by the interscan period. Results: Baseline total plaque volume (mm3) was not different among all groups (group I [lowest]: 34.1 [IQR: 0.0-127.4] vs group II: 28.8 [IQR: 0.0-123.0] vs group III: 49.9 [IQR: 5.6-135.0] vs group IV [highest]: 34.3 [IQR: 0.0-130.7]; P = 0.235). During follow-up, serum hemoglobin level changes (Δ hemoglobin; per 1 g/dL) was related to annualized total PVC (ß = -0.114) in overall participants (P < 0.05). After adjusting for age, sex, traditional risk factors, baseline hemoglobin and creatinine levels, baseline total plaque volume, and the use of aspirin, beta-blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and statin, Δ hemoglobin significantly affected annualized total PVC in only the composite of groups I and II (ß = -2.401; P = 0.004). Conclusions: Serial CCTA findings suggest that Δ hemoglobin has an independent effect on coronary atherosclerosis. This effect might be influenced by baseline hemoglobin levels. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411).

Longitudinal quantitative assessment of coronary atherosclerosis related to normal systolic blood pressure maintenance in the absence of established cardiovascular disease.

BACKGROUND: Atherosclerosis-related adverse events are commonly observed even in conditions with low cardiovascular (CV) risk. Longitudinal data regarding the association of normal systolic blood pressure maintenance (SBPmaintain ) with coronary plaque volume changes (PVC) has been limited in adults without traditional CV disease. HYPOTHESIS: Normal SBPmaintain is important to attenuate coronary atherosclerosis progression in adults without baseline CV disease. METHODS: We analyzed 95 adults (56.7 ± 8.5 years; 40.0% men) without baseline CV disease who underwent serial coronary computed tomographic angiography with mean 3.5 years of follow-up. All participants were divided into two groups of normal SBPmaintain (follow-up SBP < 120 mm Hg) and ≥elevated SBPmaintain (follow-up SBP ≥ 120 mm Hg). Annualized PVC was defined as PVC divided by the interscan period. RESULTS: Compared to participants with normal SBPmaintain , those with ≥elevated SBPmaintain had higher annualized total PVC (mm3 /year) (0.0 [0.0-2.2] vs. 4.1 [0.0-13.0]; p < .001). Baseline total plaque volume (ß = .10) and the levels of SBPmaintain (ß = .23) and follow-up high-density lipoprotein cholesterol (ß = -0.28) were associated with annualized total PVC (all p < .05). The optimal cutoff of SBPmaintain for predicting plaque progression was 118.5 mm Hg (sensitivity: 78.2%, specificity: 62.5%; area under curve: 0.700; 95% confidence interval [CI]: 0.59-0.81; p < .05). SBPmaintain ≥ 118.5 mm Hg (odds ratio [OR]: 4.03; 95% CI: 1.51-10.75) and baseline total plaque volume (OR: 1.03; 95% CI: 1.01-1.06) independently influenced coronary plaque progression (all p < .05). CONCLUSION: Normal SBPmaintain is substantial to attenuate coronary atherosclerosis progression in conditions without established CV disease.

Fully automated quantification of cardiac chamber and function assessment in 2-D echocardiography: clinical feasibility of deep learning-based algorithms.

We aimed to compare the segmentation performance of the current prominent deep learning (DL) algorithms with ground-truth segmentations and to validate the reproducibility of the manually created 2D echocardiographic four cardiac chamber ground-truth annotation. Recently emerged DL based fully-automated chamber segmentation and function assessment methods have shown great potential for future application in aiding image acquisition, quantification, and suggestion for diagnosis. However, the performance of current DL algorithms have not previously been compared with each other. In addition, the reproducibility of ground-truth annotations which are the basis of these algorithms have not yet been fully validated. We retrospectively enrolled 500 consecutive patients who underwent transthoracic echocardiogram (TTE) from December 2019 to December 2020. Simple U-net, Res-U-net, and Dense-U-net algorithms were compared for the segmentation performances and clinical indices such as left atrial volume (LAV), left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), LV mass, and ejection fraction (EF) were evaluated. The inter- and intra-observer variability analysis was performed by two expert sonographers for a randomly selected echocardiographic view in 100 patients (apical 2-chamber, apical 4-chamber, and parasternal short axis views). The overall performance of all DL methods was excellent [average dice similarity coefficient (DSC) 0.91 to 0.95 and average Intersection over union (IOU) 0.83 to 0.90], with the exception of LV wall area on PSAX view (average DSC of 0.83, IOU 0.72). In addition, there were no significant difference in clinical indices between ground truth and automated DL measurements. For inter- and intra-observer variability analysis, the overall intra observer reproducibility was excellent: LAV (ICC = 0.995), LVEDV (ICC = 0.996), LVESV (ICC = 0.997), LV mass (ICC = 0.991) and EF (ICC = 0.984). The inter-observer reproducibility was slightly lower as compared to intraobserver agreement: LAV (ICC = 0.976), LVEDV (ICC = 0.982), LVESV (ICC = 0.970), LV mass (ICC = 0.971), and EF (ICC = 0.899). The three current prominent DL-based fully automated methods are able to reliably perform four-chamber segmentation and quantification of clinical indices. Furthermore, we were able to validate the four cardiac chamber ground-truth annotation and demonstrate an overall excellent reproducibility, but still with some degree of inter-observer variability.

Prognostic value of comprehensive intracoronary physiology assessment early after heart transplantation.

AIMS: We evaluated the long-term prognostic value of invasively assessing coronary physiology after heart transplantation in a large multicentre registry. METHODS AND RESULTS: Comprehensive intracoronary physiology assessment measuring fractional flow reserve (FFR), the index of microcirculatory resistance (IMR), and coronary flow reserve (CFR) was performed in 254 patients at baseline (a median of 7.2 weeks) and in 240 patients at 1 year after transplantation (199 patients had both baseline and 1-year measurement). Patients were classified into those with normal physiology, reduced FFR (FFR ≤ 0.80), and microvascular dysfunction (either IMR ≥ 25 or CFR ≤ 2.0 with FFR > 0.80). The primary outcome was the composite of death or re-transplantation at 10 years. At baseline, 5.5% had reduced FFR; 36.6% had microvascular dysfunction. Baseline reduced FFR [adjusted hazard ratio (aHR) 2.33, 95% confidence interval (CI) 0.88-6.15; P = 0.088] and microvascular dysfunction (aHR 0.88, 95% CI 0.44-1.79; P = 0.73) were not predictors of death and re-transplantation at 10 years. At 1 year, 5.0% had reduced FFR; 23.8% had microvascular dysfunction. One-year reduced FFR (aHR 2.98, 95% CI 1.13-7.87; P = 0.028) and microvascular dysfunction (aHR 2.33, 95% CI 1.19-4.59; P = 0.015) were associated with significantly increased risk of death or re-transplantation at 10 years. Invasive measures of coronary physiology improved the prognostic performance of clinical variables (χ2 improvement: 7.41, P = 0.006). However, intravascular ultrasound-derived changes in maximal intimal thickness were not predictive of outcomes. CONCLUSION: Abnormal coronary physiology 1 year after heart transplantation was common and was a significant predictor of death or re-transplantation at 10 years.

Comparative differences in the atherosclerotic disease burden between the epicardial coronary arteries: quantitative plaque analysis on coronary computed tomography angiography.

AIMS: Anatomic series commonly report the extent and severity of coronary artery disease (CAD), regardless of location. The aim of this study was to evaluate differences in atherosclerotic plaque burden and composition across the major epicardial coronary arteries. METHODS AND RESULTS: A total of 1271 patients (age 60 ± 9 years; 57% men) with suspected CAD prospectively underwent coronary computed tomography angiography (CCTA). Atherosclerotic plaque volume was quantified with categorization by composition (necrotic core, fibrofatty, fibrous, and calcified) based on Hounsfield Unit density. Per-vessel measures were compared using generalized estimating equation models. On CCTA, total plaque volume was lowest in the LCx (10.0 ± 29.4 mm3), followed by the RCA (32.8 ± 82.7 mm3; P < 0.001), and LAD (58.6 ± 83.3 mm3; P < 0.001), even when correcting for vessel length or volume. The prevalence of ≥2 high-risk plaque features, such as positive remodelling or spotty calcification, occurred less in the LCx (3.8%) when compared with the LAD (21.4%) or RCA (10.9%, P < 0.001). In the LCx, the most stenotic lesion was categorized as largely calcified more often than in the RCA and LAD (55.3% vs. 39.4% vs. 32.7%; P < 0.001). Median diameter stenosis was also lowest in the LCx (16.2%) and highest in the LAD (21.3%; P < 0.001) and located more distal along the LCx when compared with the RCA and LAD (P < 0.001). CONCLUSION: Atherosclerotic plaque, irrespective of vessel volume, varied across the epicardial coronary arteries; with a significantly lower burden and different compositions in the LCx when compared with the LAD and RCA. These volumetric and compositional findings support a diverse milieu for atherosclerotic plaque development and may contribute to a varied acute coronary risk between the major epicardial coronary arteries.

Variables Affecting Attitudes Toward Suicide Among the Adolescent Population.

Past research has supported the positive association between prosuicide attitudes and suicidal behavior. The aim of the present study was to determine the factor structure of adolescents' attitudes toward suicide and to explore correlates associated with their attitudes. A questionnaire was distributed to 1292 adolescents at eight middle schools to assess their demographic information, clinical variables, and attitudes toward suicide. After factor analysis, we reached a four-factor solution of the attitudes toward suicide. Significantly more females, nonreligious adolescents, those with a lower socioeconomic status, those with higher levels of depressive symptoms, and those with a history of suicidal ideation/plans had more understanding attitudes toward suicide. Depressive adolescents were also more permissive and believed that suicides were unpreventable and that loneliness led to suicide. In conclusion, adolescents' attitudes toward suicide were significantly associated with not only various sociodemographic correlates but also the severity of depressive symptoms and their own experiences of suicidality.

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.

Comparing the feasibility and accuracy of three-dimensional ultrasound to two-dimensional ultrasound and computed tomography angiography in the assessment of carotid atherosclerosis.

AIMS: Two-dimensional ultrasound (2D-US) is the mainstay imaging technique used to evaluate carotid atherosclerosis. An automated single sweep three-dimensional ultrasound (3D-US) technique became available. We evaluated the feasibility and accuracy of 3D-US in the assessment of carotid plaques compared to those of 2D-US. Carotid computed tomography angiography (CTA) was used as a reference. METHODS AND RESULTS: Among 126 stroke patients who underwent carotid 2D-US, 73 underwent 3D-US and carotid CTA. 3D-US was pursued when there were carotid plaques or when area stenosis was ≥ 20% by 2D-US. Both 2D- and 3D-US images of the carotid arteries were acquired using a dedicated ultrasound system that was equipped with the single sweep volumetric transducer. In total, 266 arteries from 73 patients were selected for comparison of the detection rate of carotid plaques between 2D- and 3D-US. Among the 73 patients, carotid CTA detected 139 plaques. 3D-US demonstrated a higher detection rate of carotid plaques than did 2D-US (108 plaques (77.9%) vs. 70 plaques (50.4%)) when using carotid CTA as a reference standard. Carotid plaque volume (PV) of 133 vessels from 73 patients were quantitatively evaluated using both 3D-US and carotid CTA. Plaque volume of carotid artery was comparable between 3D-US and CTA (148.5 ± 133.0 mm3 vs. 154.1 ± 134.6 mm3 , P = .998, R: 0.9825, P-value for r < .001). CONCLUSION: 3D-US using a single sweep technique was a feasible and accurate method of detecting arterial plaques and assessing plaque volume.

Longitudinal quantitative assessment of coronary plaque progression related to body mass index using serial coronary computed tomography angiography.

AIMS: This study explored the coronary plaque volume change (PVC) according to the change of percent body mass index (BMI) and categorical BMI group using serial coronary computed tomography angiography (CCTA). METHODS AND RESULTS: A total of 1568 subjects who underwent serial CCTA with available BMI at baseline (CCTA1) and follow-up (CCTA2) were included. Median inter-scan period was 3.3 (interquartile range: 2.6-4.6) years. Quantitative assessment of coronary plaque was performed at both scans. All participants were categorized into three BMI (kg/m2) groups: normal: <25.0; overweight: 25.0-29.9; and obesity: ≥30.0. During follow-up, there were no significant differences in annualized PVC according to the 5% change of BMI in all BMI groups. Among 1424 (90.8%) subjects in the same BMI group at CCTA1 and CCTA2, a significant difference in annualized (PVC) was observed among the three groups. In 144 (9.2%) subjects with the change in their BMI group at CCTA2 compared their results at CCTA1, annualized PVC was not different compared with subjects in the same BMI group during follow-up. The percent change of BMI was not significantly related to the annualized PVC after adjusting confounding factors. Male gender [odds ratio (OR): 1.38; 95% confidence interval (CI): 1.05-1.81; P = 0.022], baseline plaque volume (OR: 1.07; 95% CI: 1.05-1.09; P < 0.001), and baseline overweight or obesity (OR: 1.35; 95% CI: 1.04-1.77; P = 0.027) were independently associated with coronary plaque progression. CONCLUSION: Over the near term, longitudinal small changes in BMI were not associated with changes in coronary plaque volume although baseline BMI was. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02803411.

Longitudinal assessment of coronary plaque volume change related to glycemic status using serial coronary computed tomography angiography: A PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging) substudy.

BACKGROUND: Data on the impact of glycemic status on coronary plaque progression have been limited. This study evaluated the association between glycemic status and coronary plaque volume change (PVC) using coronary computed tomography angiography (CCTA). METHODS: A total of 1296 subjects (61 ±â€¯9, 56.9% male) who underwent serial CCTA with available glycemic status were enrolled and analyzed from the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. The median inter-scan period was 3.2 (2.6-4.4) years. Quantitative assessment of coronary plaques was performed at both scans. All participants were categorized into the following groups according to glycemic status: normal, pre-diabetes (pre-DM), and diabetes mellitus (DM). RESULTS: During the follow-up, significant differences in PVC (normal: 51.3 ±â€¯83.3 mm3 vs. pre-DM: 51.0 ±â€¯84.3 mm3 vs. DM: 72.6 ±â€¯95.0 mm3; p < 0.001) and annualized PVC (normal: 14.9 ±â€¯24.9 mm3 vs. pre-DM: 15.7 ±â€¯23.8 mm3 vs. DM: 21.0 ±â€¯27.7 mm3; p = 0.001) were observed among the 3 groups. Compared with normal individuals, individuals with pre-DM showed no significant differences in the adjusted odds ratio (OR) for plaque progression (PP) (1.338, 95% confidence interval [CI] 0.967-1.853; p = 0.079). However, the adjusted OR for PP was higher in DM individuals than in normal individuals (1.635, 95% CI 1.126-2.375; p = 0.010). CONCLUSION: DM had an incremental impact on coronary PP, but pre-DM appeared to have no significant association with an increased risk of coronary PP after adjusting for confounding factors. CLINICAL TRIAL REGISTRATION: ClinicalTrials.govNCT02803411.

Three-Hour Delayed Imaging Improves Assessment of Coronary 18F-Sodium Fluoride PET.

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.

Demographics, treatment trends, and survival rate in incident pulmonary artery hypertension in Korea: A nationwide study based on the health insurance review and assessment service database.

Epidemiologic data regarding pulmonary arterial hypertension (PAH) have relied on registries from Western countries. We assessed the current status of PAH in the Korean population. The Health Insurance Review and Assessment Service (HIRA) claim database, which comprises nationwide medical insurance data of Koreans from 2008-2016, was assessed to determine the current status of PAH. Overall, 1,307 patients were newly diagnosed with PAH from 2008-2016 (0.0005%, annual incidence: 4.84 patients/1 million people/year). The mean age at diagnosis was 44±13 years (range 18-65) and patients were mostly women (n = 906, 69.3%). Cases of idiopathic PAH (51.6%) accounted for the largest proportion, followed by acquired PAH (APAH) associated with congenital heart disease (25.8%) and APAH with connective tissue disease (17.2%). Overall, 807 (61.7%) patients received a single PAH-specific treatment based on their last prescription, of which bosentan (50.6%) was the most frequently used. Only 240 (18.4%) patients received combination therapy, with the bosentan-beraprost combination (32.9%) being the most common. During the mean follow-up of 1.9 years, the 1-, 2-, 3-, and 5-year estimated survival rates were 85%, 62%, 54%, and 46%, respectively. The prevalence and incidence of PAH in the Korean population is currently comparable with that in previous registries. The 5-year survival rate was slightly higher in the Korean population than previously reported.

Feasibility of Coronary 18F-Sodium Fluoride Positron-Emission Tomography Assessment With the Utilization of Previously Acquired Computed Tomography Angiography.

BACKGROUND: We assessed the feasibility of utilizing previously acquired computed tomography angiography (CTA) with subsequent positron-emission tomography (PET)-only scan for the quantitative evaluation of 18F-NaF PET coronary uptake. METHODS AND RESULTS: Forty-five patients (age 67.1±6.9 years; 76% males) underwent CTA (CTA1) and combined 18F-NaF PET/CTA (CTA2) imaging within 14 [10, 21] days. We fused CTA1 from visit 1 with 18F-NaF PET (PET) from visit 2 and compared visual pattern of activity, maximal standard uptake (SUVmax) values, and target to background ratio (TBR) measurements on (PET/CTA1) fused versus hybrid (PET/CTA2). On PET/CTA2, 226 coronary plaques were identified. Fifty-eight coronary segments from 28 (62%) patients had high 18F-NaF uptake (TBR >1.25), whereas 168 segments had lesions with 18F-NaF TBR ≤1.25. Uptake in all lesions was categorized identically on coregistered PET/CTA1. There was no significant difference in 18F-NaF uptake values between PET/CTA1 and PET/CTA2 (SUVmax, 1.16±0.40 versus 1.15±0.39; P=0.53; TBR, 1.10±0.45 versus 1.09±0.46; P=0.55). The intraclass correlation coefficient for SUVmax and TBR was 0.987 (95% CI, 0.983-0.991) and 0.986 (95% CI, 0.981-0.992). There was no fixed or proportional bias between PET/CTA1 and PET/CTA2 for SUVmax and TBR. Cardiac motion correction of PET scans improved reproducibility with tighter 95% limits of agreement (±0.14 for SUVmax and ±0.15 for TBR versus ±0.20 and ±0.20 on diastolic imaging; P<0.001). CONCLUSIONS: Coronary CTA/PET protocol with CTA first followed by PET-only allows for reliable and reproducible quantification of 18F-NaF coronary uptake. This approach may facilitate selection of high-risk patients for PET-only imaging based on results from prior CTA, providing a practical workflow for clinical application.

End-Stage Renal Disease Impairs the Multidirectional Movements of the Common Carotid Artery: Assessment Using Dimensional Speckle-Tracking Carotid Strain Ultrasonography.

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, ß stiffness index, and arterial compliance, but arterial distensibility was lower, and the elastic modulus and pulse wave velocity ß (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.

Accurate Risk Assessment of Patients with Pathologic T3aN0M0 Renal Cell Carcinoma.

To develop a more precise risk-stratification system by investigating the prognostic impact of tumor growth within fatty tissues surrounding the kidney and/or renal vein. We conducted a retrospective review of the medical records of 211 patients with a pathologic diagnosis of T3aN0M0RCC among 4,483 renal cell carcinoma (RCC) patients from February 1988 to December 2015 according to the number of T3a pathologies-extrarenal fat invasion (EFI) and/or renal venous invasion (RVI). During a mean follow-up duration of 38.8 months, the patients with both pathologies (EFI + RVI) had lower recurrence free survival (RFS) rate than those with only a single pathology (p = 0.001). Using multivariable Cox regression analysis, the presence of both factors was shown to be an independent predictor of RFS (HR = 1.964, p = 0.032); cancer specific survival rate was not different among patients with EFI and/or RVI. Patients with pathologic T3aN0M0 RCC presenting with both EFI and RVI were at an increased risk of recurrence following nephrectomy. Therefore, pathologic T3a RCC could be sub-divided into those with favorable and unfavorable disease according to presence of EFI and/or RVI pathologies.

Quantification of Coronary Atherosclerosis in the Assessment of Coronary Artery Disease.

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