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Objective: A retrospective study of cases of endovascular treatment of dissection of the vertebral artery with subarachnoid hemorrhage was conducted., Material and Methods: Data were 11 cases of vertebral artery dissecting aneurysm (VADA) among 291 consecutive subarachnoid hemorrhage patients who underwent clipping or endovascular treatment at Ota Memorial Hospital. Classified into 4 patterns based on the location of the dissection and posterior inferior cerebellar artery (PICA): pre-PICA, post-PICA, involved PICA, and non-PICA. And one of the cases had bilateral vertebral artery dissection, and computational fluid dynamics analysis was included in the study., Results: Ruptured VADA occurred in 11 of the 291 patients (3.8%). Endovascular treatment was performed in 8 of these 11 patients. Postoperative diffusion-weighted imaging detected no high-intensity lesions and no postoperative ischemic complications or rebleeding occurred in any patient. In a case of bilateral VADA, computational fluid dynamics analysis of very low or high wall shear stress at the dissection, low aneurysm formation indicator, and high oscillatory shear index may be considered rupture factors., Conclusions: Treatment strategies for each branching pattern of PICA can prevent rupture and avoid ischemic complications. And prediction of the rupture side is important in patients with bilateral dissection to consider the appropriate treatment and timing., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hypertrophic cardiomyopathy (HCM) is a genetic disorder in which left ventricular outflow tract obstruction critically affects symptoms and prognosis. Traditionally, left ventricular outflow tract obstruction was primarily attributed to septal hypertrophy with systolic anterior motion of the mitral valve. However, recent evidence highlights significant contributions from the mitral valve and papillary muscle anomalies, as well as an apical-basal muscle bundle observed in HCM patients. Accurate morphological assessment is essential when considering septal reduction therapy. While transesophageal echocardiography and cardiac magnetic resonance are recommended for assessing the anomalous structures, four-dimensional computed tomography offers superior spatial resolution and multiplanar reconstruction capabilities. These features enable the evaluation of details of the morphological anomalies, such as the apical-basal muscle band, papillary muscle anomalies, subaortic stenosis, and right ventricular outflow tract obstruction. Based on the detailed assessment of these morphological features, four-dimensional computed tomography has been utilized for planning of surgical correction in a comprehensive HCM center. This approach facilitates the intervention strategies and may improve outcomes in septal reduction therapy for obstructive HCM., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim: Lower extremity artery disease (LEAD) is an increasingly common health problem that is associated with high mortality due to thrombotic and bleeding events. Growth differentiation factor-15 (GDF15), a stress-response cytokine belonging to the transforming growth factor-beta superfamily, is associated with cardiovascular disease and its outcomes. The aim of the present study was to examine the effect of serum GDF15 levels on clinical outcomes in patients with LEAD., Methods: We measured serum GDF15 levels in 200 patients with LEAD before their initial endovascular therapy. The primary endpoint was the all-cause mortality rate. The secondary endpoints, on the other hand, were thrombotic and bleeding events, such as cerebral infarction, acute coronary syndrome, acute limb ischemia, and Bleeding Academic Research Consortium types 3 and 5., Results: The serum GDF15 levels increased with advancing Fontaine class. Kaplan-Meier analysis revealed that the high-GDF15 group (≥ 2,275 pg/mL) had higher rates of all-cause deaths and thrombotic and bleeding events than the low-GDF15 group (＜2,275 pg/mL). Multivariate Cox proportional-hazards regression analysis revealed that GDF15 was an independent predictor of all-cause mortality and thrombotic and bleeding events after adjusting for confounding risk factors. When the ABC-AF-bleeding score was substituted for GDF15, similar results were obtained., Conclusion: Serum GDF15 levels were associated with all-cause mortality and thrombotic and bleeding events in patients with LEAD. Serum GDF15 is a potentially useful marker of clinical outcomes, specifically for tracking thrombotic and bleeding events in patients with LEAD.

Cigarette smoking is known to be the leading cause of chronic obstructive pulmonary disease (COPD). However, the detailed mechanisms have not been elucidated. PAF (platelet-activating factor), a potent inflammatory mediator, is involved in the pathogenesis of various respiratory diseases such as bronchial asthma and COPD. We focused on LPLAT9 (lysophospholipid acyltransferase 9), a biosynthetic enzyme of PAF, in the pathogenesis of COPD. LPLAT9 gene expression was observed in excised COPD lungs and single-cell RNA sequencing data of alveolar macrophages (AMs). LPLAT9 was predominant and upregulated in AMs, particularly monocyte-derived AMs, in patients with COPD. To identify the function of LPLAT9/PAF in AMs in the pathogenesis of COPD, we exposed systemic LPLAT9-knockout (LPALT9 -/- ) mice to cigarette smoke (CS). CS increased the number of AMs, especially the monocyte-derived fraction, which secreted MMP12 (matrix metalloprotease 12). Also, CS augmented LPLAT9 phosphorylation/activation on macrophages and, subsequently, PAF synthesis in the lung. The LPLAT9 -/- mouse lung showed reduced PAF production after CS exposure. Intratracheal PAF administration accumulated AMs by increasing MCP1 (monocyte chemoattractant protein-1). After CS exposure, AM accumulation and subsequent pulmonary emphysema, a primary pathologic change of COPD, were reduced in LPALT9 -/- mice compared with LPLAT9 +/+ mice. Notably, these phenotypes were again worsened by LPLAT9 +/+ bone marrow transplantation in LPALT9 -/- mice. Thus, CS-induced LPLAT9 activation in monocyte-derived AMs aggravated pulmonary emphysema via PAF-induced further accumulation of AMs. These results suggest that PAF synthesized by LPLAT9 has an important role in the pathogenesis of COPD.

Cardioembolic stroke is a serious disease with poor prognosis, whose main embolic source is the left atrial appendage (LAA). Left atrial (LA) strain evaluated by the two-dimensional (2D) speckle tracking technique has been proposed. However, the commonly used peak LA strain reflects only LA reservoir function. The LA strain also includes indicators of the other LA functions, such as booster pump function, which reflects active contraction of the LA. This study aimed to investigate whether a newly developed parameter, the left atrial strain time integral (LASTI), can evaluate LAA dysfunction more accurately in patients with acute stroke. We measured LA strain using a 2D speckle tracking method in 168 patients with acute stroke and 20 age-matched control subjects. LASTI was calculated as the area under the LA strain curve in one cardiac cycle. LAA dysfunction was defined as LAA thrombus and/or severe spontaneous echo contrast by transesophageal echocardiography. LASTI was significantly lower in patients with LAA dysfunction than those without. LASTI was a better correlation with LAA blood flow velocity measured by transesophageal echocardiography than peak LA strain. Multivariate logistic regression analysis showed that LASTI was an independent predictor of LAA dysfunction after adjustment for conventional risk factors. LASTI can be a feasible parameter for predicting LAA dysfunction in patients with acute stroke., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

The number of patients who underwent transcatheter aortic valve implantation (TAVI) with the potential for reintervention is steadily increasing; however, there is a risk of sinus sequestration (SS) during a redo TAVI. The prevalence, predictors, and risk stratification of the risk for SS remain uncertain. We analyzed computed tomography acquired from 263 patients who underwent TAVI between 2021 and 2022: balloon-expandable valve (BEV) (71%) and self-expandable valve (SEV) (29%). Patients were considered at risk for SS if they met the following: (1) BEV frame > sinotubular junction (STJ) or SEV neocommissure greater than the STJ and (2) valve-to-STJ <2 mm. The risk of left, right, and any SS in 51%, 50%, and 65%, respectively, did not differ between BEV and SEV. The predictors of any SS were the height of the left and right coronary cusp (odds ratio [OR] 0.81 and 0.71, cutoff 18.6 and 19.2 mm, respectively) and STJ minus the annulus diameter (OR 0.65, cutoff 3.7 mm) in BEV, and STJ diameter (OR 0.47, cutoff 27.6 mm) in SEV. The number of predictors stratified the risk of any SS: low risk with BEV at 0 predictors (14% at risk of SS), intermediate risk at 1 predictor (65%), high risk at 2 or 3 predictors (81% and 95%), and low risk with SEV at 0 predictors (33%) versus high risk at 1 predictor (91%). In conclusion, 2/3 of patients who underwent TAVI were at risk of SS. The height of the coronary cusp and the STJ diameter were associated with and adequately stratified the risk of SS., Competing Interests: Declaration of Competing Interest Dr. Takamisawa is the clinical proctor of TAVI (Edwards Lifesciences, Irvine, California and Medtronic, Minneapolis, Minnesota). The remaining authors have no competing interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Motion correction (MC) affects myocardial blood flow (MBF) measurements in 82 Rb PET myocardial perfusion imaging (MPI); however, frame-by-frame manual MC of dynamic frames is time-consuming. This study aims to develop an automated MC algorithm for time-activity curves used in compartmental modeling and compare the predictive value of MBF with and without automated MC for significant coronary artery disease (CAD). Methods: In total, 565 patients who underwent PET-MPI were considered. Patients without angiographic findings were split into training ( n = 112) and validation ( n = 112) groups. The automated MC algorithm used simplex iterative optimization of a count-based cost function and was developed using the training group. MBF measurements with automated MC were compared with those with manual MC in the validation group. In a separate cohort, 341 patients who underwent PET-MPI and invasive coronary angiography were enrolled in the angiographic group. The predictive performance in patients with significant CAD (≥70% stenosis) was compared between MBF measurements with and without automated MC. Results: In the validation group ( n = 112), MBF measurements with automated and manual MC showed strong correlations ( r = 0.98 for stress MBF and r = 0.99 for rest MBF). The automatic MC took less time than the manual MC (<12 s vs. 10 min per case). In the angiographic group ( n = 341), MBF measurements with automated MC decreased significantly compared with those without (stress MBF, 2.16 vs. 2.26 mL/g/min; rest MBF, 1.12 vs. 1.14 mL/g/min; MFR, 2.02 vs. 2.10; all P < 0.05). The area under the curve (AUC) for the detection of significant CAD by stress MBF with automated MC was higher than that without (AUC, 95% CI, 0.76 [0.71-0.80] vs. 0.73 [0.68-0.78]; P < 0.05). The addition of stress MBF with automated MC to the model with ischemic total perfusion deficit showed higher diagnostic performance for detection of significant CAD (AUC, 95% CI, 0.82 [0.77-0.86] vs. 0.78 [0.74-0.83]; P = 0.022), but the addition of stress MBF without MC to the model with ischemic total perfusion deficit did not reach significance (AUC, 95% CI, 0.81 [0.76-0.85] vs. 0.78 [0.74-0.83]; P = 0.067). Conclusion: Automated MC on 82 Rb PET-MPI can be performed rapidly with excellent agreement with experienced operators. Stress MBF with automated MC showed significantly higher diagnostic performance than without MC., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

An inter-hospital heart team conference based collaborative follow-up (FU) may facilitate outpatient cardiac rehabilitation (CR) programs, especially in hospitals without an outpatient CR center. Consecutive 145 patients with cardiovascular disease who received inpatient treatment at Yamagata University Hospital were divided into collaborative (n = 76) and same-hospital (n = 69) FU groups. In the collaborative FU group, patients received outpatient care at a university hospital and outpatient CR at different hospitals. In the same-hospital FU group, patients received outpatient care and outpatient CR at the same hospital other than the university hospital. The collaborative FU group held monthly 60-minute inter-hospital heart team conferences with CR specialists. No cardiovascular accidents occurred during the outpatient CR program in either group. Peak oxygen uptake VO 2 , anaerobic threshold, brain natriuretic peptide level, and left ventricular ejection fraction significantly improved in both groups. Kaplan-Meier analysis revealed no significant difference in prognosis between the collaborative and same-hospital FU groups (P = 0.246). Of the patients who had collaborative CR programs, 29 (38.2%) patients (37 consultations) were discussed at an inter-hospital heart team conference. Eighteen (48.6%) consultations were for issues related to continuing outpatient CR programs. Collaborative FU was as useful as same-hospital FU in terms of safety, efficacy, and prognosis in patients with cardiovascular disease. We conclude that regular inter-hospital heart team conferences are useful for facilitating collaboration among outpatient CR programs.

Some people overestimate the benefits of certain kinds of foods, such as organic foods, while others underestimate it. Previous studies have found that reducing people's self-assessed knowledge successfully moderated these extreme attitudes. In this study, we investigated interventions to reduce people's self-assessed knowledge and to moderate attitude extremity. We examined extreme attitudes toward organic foods and investigated the effects of implementing two intervention methods to moderate their attitude: (1) providing knowledge on organic food after asking them some questions and (2) simply providing them with knowledge. We conducted a two-factor mixed-design experiment with 653 college-educated Japanese women. In the first condition, before knowledge provision, participants were asked to answer questions about organic foods and were then informed of the correct answer and whether their answer was correct (Q&A Intervention). This step was based on an intervention conducted in a previous study to reduce their self-assessed factual knowledge. In the second condition, participants were simply provided with knowledge without being asked to answer any questions (Simple Intervention). The results showed that both intervention methods, on average, decreased the participants' self-assessed knowledge and attitude extremity. Therefore, simply providing knowledge may be effective in reducing their self-assessed factual knowledge and moderating their extreme attitudes toward organic foods., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Iwatani, Honda, Otaki and Ueda.)

Objective: The ideal type of hospital to care for adult congenital heart disease (ACHD) patients is not well known. Hospital competitiveness, clinical volume and market structure can influence clinical outcomes. We sought to understand how hospital competitiveness affects clinical outcomes in ACHD patients in the era prior to the Adult Congenital Heart Association accreditation program., Methods: Patient discharges with ACHD diagnosis codes were filtered between 2006-2011 from an all-payer inpatient healthcare database. Hospital-level data was linked to market structure patient flow. A common measure of market concentration used to determine market competitiveness-the Herfindahl-Hirschman Index (HHI)-was stratified into: more competitive (HHI ≤25th percentile), moderately competitive (HHI 25th to <75th percentile), and less competitive (HHI ≥75th percentile) hospital. Any complication, home discharge and mortality were analyzed with clustered mixed effects logistic regression. The combined impact of HHI and any complication on mortality by interaction was assessed., Results: A total of 67,434 patient discharges were isolated. More competitive hospitals discharged the least number of patients (N = 15,270, 22.6%) versus moderately competitive (N = 36,244, 53.7%) and less competitive (N = 15,920, 23.6%) hospitals. The adjusted odds of any complication or home discharge were not associated with hospital competitiveness strata. Compared to more competitive hospitals, mortality at moderately competitive hospitals (Adjusted Odds Ratio (AOR) 0.79, 95% CI: 0.66-0.94) and less competitive hospitals (AOR 0.79, 95% CI: 0.63-0.98) were lower (p = 0.025). Age, race, elective admission, transfer status, and payer mix were all significantly associated with adjusted odds of any complication, home discharge and mortality (p ≤ 0.05). Having any complication independently increased the adjusted odds of mortality more than 6-fold (p < 0.001), and this trend was independent of HHI strata. Failure to rescue an ACHD patient from mortality after having any complication is highest at less competitive hospitals. Sensitivity analysis which excluded the transfer status variable, showed that any complication (p = 0.047) and mortality (p = 0.01) were independently associated with HHI strata., Conclusions: Whether lower competition allow hospitals to focus more on quality of care is unknown. Hospital competitiveness and outcome seem to have an inverse trend relationship among ACHD patients. Since medical care is frequently provided away from the home area, hospital selection is an important issue for ACHD patients. Further research is needed to determine why competitiveness is linked to surgical outcomes in this population.

Background: Heart failure with preserved ejection fraction (HFpEF) is an increasing health problem associated with high morbidity and mortality rates. Several reports have shown an association between hypokalemia and clinical outcomes in patients with heart failure (HF). However, the association of hypokalemia with kidney function and clinical outcomes in patients with HFpEF remains unclear., Methods and results: We measured serum potassium levels and kidney function in 454 patients with HFpEF (mean age 76 years; 55% men) at admission. Hypokalemia (K + <3.5 mmol/L) and hyperkalemia (K + >5.0 mmol/L) were identified in 58 (12.7%) and 11 (2.4%) patients, respectively. Patients with hypokalemia showed renal tubular damage (RTD), defined as a urinary β 2 -microglobulin to creatinine ratio ≥300 μg/gCr, preserved estimated glomerular filtration rate (eGFR), and plasma volume expansion. Multivariate logistic analysis demonstrated that RTD, preserved eGFR, and plasma volume expansion were significantly associated with hypokalemia. During the median follow-up period of 1,000 days, 82 HF-related events occurred. Kaplan-Meier analysis showed that patients with hypokalemia had a higher rate of HF-related events than those without hypokalemia. Multivariate Cox proportional hazard regression analysis demonstrated that hypokalemia was significantly associated with HF-related events after adjusting for confounding factors., Conclusions: Hypokalemia is affected by kidney function, notably RTD, in patients with HFpEF. Hypokalemia is a risk factor for HF-related events in patients with HFpEF.

Left ventricular (LV) apical aneurysm is known to be associated with the life-threatening arrhythmic events in hypertrophic cardiomyopathy (HCM). However, the current 2014 ESC guideline has not included apical aneurysm as a major risk factor for sudden cardiac death and 2018 JCS guideline includes it only as a modulator, while it has been included as a new major risk marker in 2020 AHA/ACC guideline. Therefore, we sought to identify high-risk imaging characteristics in LV apex which is associated with a higher occurrence of ventricular tachycardia/fibrillation (VT/VF). In 99 consecutive Japanese HCM patients (median age, 65 years; 59 males) undergoing implantable cardioverter-defibrillator (ICD) implantation for primary prevention following cardiac magnetic resonance including late gadolinium enhancement (LGE), the occurrence of appropriate ICD interventions for VT/VF was evaluated for 6.2 (median) years after ICD implantation. Overall, appropriate ICD interventions occurred in 43% with annual rates of 7.0% for appropriate interventions. Kaplan-Meier analysis demonstrated that the presence of LV apical aneurysm was significantly associated with a higher occurrence of appropriate interventions (annual rates 18.9% vs. 6.4%, P = 0.013). Similarly, patients with high LV mid-to-apex pressure gradient (annual rates 14.9% vs. 6.2%, P = 0.022) and presence of apical LGE (annual rates 10.9% vs. 4.0%, P = 0.001) experienced appropriate interventions more frequently. An aneurysm, high-pressure gradient, and LGE in an apex are associated with VT/VF. These characteristics in apex should be kept in mind when implanting ICD in Japanese HCM patients as a primary prevention., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

Objective: Inflammatory bowel disease (IBD) is closely related to stress and fatigue. Human herpesvirus 6B (HHV-6B) is reactivated by stress and fatigue and is associated with IBD. This study aimed to clarify the relationship between IBD and HHV-6B., Methods: Antibody titers to SITH-1, a protein specific to HHV-6B latent infection, were measured in 163 patients with IBD (107 with ulcerative colitis [UC] and 56 with Crohn's disease [CD]); clinical and endoscopic scores and depression scores of UC and CD were analyzed to examine the relationship between SITH-1 and IBD. The SITH-1 cut-off value was set as 1.96, according to known reports., Results: In patients with UC, C-reactive protein (CRP) level was significantly higher (1.5 vs 0.6 mg/L, P  = 0.006) and disease exacerbation within 6 months after entry was significantly more common in the SITH-1 (+) group (20% vs 0%, P  < 0.001). In the subanalysis comparing with and without UC exacerbation, the optimal cut-off value for SITH-1 to detect UC exacerbation was 3.44 (area under the curve: 0.81; 95% confidence interval: 0.72-0.90). CRP levels, SITH-1 levels, and disease activity scores by the clinical or endoscopic index were significantly higher in the exacerbation group than in the non-exacerbation group (2.6 vs 0.9 mg/L, P  = 0.03; 4.90 vs 1.71, P  < 0.001; 4 vs 3, P  = 0.03; 5 vs 3, P  = 0.02; respectively)., Conclusion: Patients with UC with high titers of SITH-1 have high disease activity and frequent disease exacerbation. SITH-1 can be associated with UC disease activity., (© 2023 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Pit latrines are the most common form of improved sanitation in many rapidly developing countries. However, they cause the highest amount of groundwater pollution among on-site sanitation (OSS) facilities. Many households in developing countries use groundwater as their main or sub-source, and pit latrines are not a sustainable solution. Thus, the conversion from pit latrines to septic tanks is required. We created two types of media, still images and a video, to illustrate the differences in functions and hygiene risks between pit latrines and septic tanks. Moreover, a survey was conducted in Sri Lanka to determine the media choice that would increase the people's preference for septic tanks as their next OSS, even weeks after the information is presented. The choice of the next OSS participants selected before they were presented with the images was the same as that currently in use, reflecting the belief that the problem of pit latrines was not currently apparent and need not be changed. However, a video presentation of the information made it possible for a larger group of people to choose the usage of septic tanks in the future, especially in suburban areas where the problems were likely to occur., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Purpose: To determine the association between low-attenuation plaque (LAP) burden at coronary CT angiography (CCTA) and plaque morphology determined with near-infrared spectroscopy intravascular US (NIRS-IVUS) and to compare the discriminative ability for NIRS-IVUS-verified high-risk plaques (HRPs) between LAP burden and visual assessment of LAP., Materials and Methods: This Health Insurance Portability and Accountability Act-compliant retrospective study included consecutive patients who underwent CCTA before NIRS-IVUS between October 2019 and October 2022 at two facilities. LAPs were visually identified as having a central focal area of less than 30 HU using the pixel lens technique. LAP burden was calculated as the volume of voxels with less than 30 HU divided by vessel volume. HRPs were defined as plaques with one of the following NIRS-IVUS-derived high-risk features: maximum 4-mm lipid core burden index greater than 400 (lipid-rich plaque), an echolucent zone (intraplaque hemorrhage), or echo attenuation (cholesterol clefts). Multivariable analysis was performed to evaluate NIRS-IVUS-derived parameters associated with LAP burden. The discriminative ability for NIRS-IVUS-verified HRPs was compared using receiver operating characteristic analysis., Results: In total, 273 plaques in 141 patients (median age, 72 years; IQR, 63-78 years; 106 males) were analyzed. All the NIRS-IVUS-derived high-risk features were independently linked to LAP burden ( P < .01 for all). LAP burden increased with the number of high-risk features ( P < .001) and had better discriminative ability for HRPs than plaque attenuation by visual assessment (area under the receiver operating characteristic curve, 0.93 vs 0.89; P = .02)., Conclusion: Quantification of LAP burden improved HRP assessment compared with visual assessment. LAP burden was associated with the accumulation of HRP morphology. Keywords: Coronary CT Angiography, Intraplaque Hemorrhage, Lipid-Rich Plaque, Low Attenuation Plaque, Near-Infrared Spectroscopy Intravascular Ultrasound Supplemental material is available for this article. See also the commentary by Ferencik in this issue.© RSNA, 2023., Competing Interests: Disclosures of conflicts of interest: H.T. No relevant relationships. H.M. No relevant relationships. S.C. No relevant relationships. S.H. No relevant relationships. H.O. No relevant relationships. K.I. No relevant relationships. D.I. No relevant relationships. K.K. No relevant relationships. A.S. No relevant relationships. T.H. No relevant relationships. Y.O. No relevant relationships. R.K. No relevant relationships. P.J.S. Grant to author's institution from Siemens Healthcare; NIH grants; software licenses from Cedars-Sinai; consulting fees from Synektik; JNC associate editor; president, Society of Nuclear Medicine & Molecular Imaging Cardiovascular Council. D.D. Royalties/licenses from Cedars-Sinai Medical Center; patents issued (US8885905B2). T.S. No relevant relationships., (© 2023 by the Radiological Society of North America, Inc.)

Introduction: Atrial fibrillation (AF) is a risk factor for reduced cerebral blood flow (CBF) and cognitive dysfunction, even in stroke-free patients. We aimed to test the hypothesis that CBF and hippocampal blood flow (HBF), measured with arterial spin labeling magnetic resonance imaging (MRI), improve after catheter ablation of AF to achieve sinus rhythm (SR)., Methods: A total of 84 stroke-free patients (63.1 ± 9.1 years; paroxysmal AF, n = 50; non-paroxysmal AF, n = 34) undergoing AF catheter ablation were included. MRI studies were done before, 3 months, and 12 months after the procedure with CBF and HBF measurements., Results: Baseline CBF and HBF values in 50 paroxysmal AF patients were used as controls. Baseline CBF was higher in patients with paroxysmal AF than with non-paroxysmal AF (100 ± 32% vs. 86 ± 28%, p = .04). Patients with non-paroxysmal AF had increased CBF 3 months after AF ablation (86 ± 28% to 99 ± 34%, p = .03). Differences in CBF and HBF were greater in the group with AF restored to SR (p < .01). Both CBF and HBF levels at 12 months were unchanged from the 3 months level. Successful rhythm control by catheter ablation was an independent predictor of an increase in CBF > 17.5%. The Mini-Mental State Examination score improved after ablation (p = .02)., Conclusion: SR restoration with catheter ablation was associated with improved CBF and HBF at 3 months, maintenance of blood flow, and improved cognitive function at 12 months., (© 2023 Wiley Periodicals LLC.)

Aims: Despite advances in heart failure (HF) treatment, HF with preserved ejection fraction (HFpEF) remains a health problem with a high mortality rate. HFpEF is composed of diverse phenogroups, of which patients with concomitant renal impairment have worse outcomes. Renal tubular damage (RTD) is associated with the development of HF and chronic kidney disease (CKD). However, the impact of RTD on HF progression in patients with HFpEF and CKD remains unclear. The aim of the present study was to examine whether RTD could predict HF-related events in patients with HFpEF and CKD., Methods and Results: We measured RTD markers, such as urinary β 2 -microglobulin to creatinine ratio (UBCR) and N-acetyl-β-d-glucosamidase (NAG) level, in 319 consecutive patients with HFpEF and CKD who were hospitalized for acute HF (49% females, mean age 76 ± 12). Based on previous reports, high UBCR and high NAG levels were defined as UBCR ≥300 μg/gCr and NAG >14.2 U/gCr, respectively. There were 91 HF-related events, defined as HF hospitalizations or HF deaths, during the median follow-up period of 5.2 years. The prevalence of high UBCR increased with advancing New York Heart Association functional class and albuminuria. Kaplan-Meier analysis demonstrated that patients with high UBCR had more HF-related events than those with normal or low UBCR. Multivariate Cox proportional hazards regression analyses demonstrated that high UBCR, but not high NAG level, was an independent predictor of HF-related events after adjusting for confounding risk factors in patients with HFpEF and CKD (hazard ratio, 2.60; 95% confidence interval, 1.52-4.72; P = 0.0009). UBCR significantly improved the C-statistic, with a significant net reclassification index and integrated discrimination improvement (0.738 vs. 0.684; P = 0.0244)., Conclusion: RTD, as assessed by a high UBCR, was associated with the severity and clinical outcomes of HFpEF and CKD, indicating that it could be a feasible marker for HF progression., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Lower extremity artery disease (LEAD) is an arterial occlusive disease associated with high morbidity and mortality. Estimated plasma volume status (ePVS), a marker of plasma volume expansion and contraction, is gaining attention in the field of cardiovascular diseases. However, the impact of ePVS on the clinical outcomes of patients with LEAD remains unclear. We calculated ePVS using two different formulas, Kaplan-Hakim (KH-ePVS) and Duarte (D-ePVS), in 288 patients (mean age, 73 years; 77% male) with LEAD who underwent the first endovascular therapy (EVT), and prospectively followed them up between 2014 and 2019. All patients were divided into two groups based on the median ePVS values. The primary endpoints were composite events, including all-cause death and major adverse limb events (death/MALE). The median follow-up duration was 672 days. There were 183, 40 and 65 patients in Fontaine classes II, III, and IV, respectively. The median KH-ePVS and D-ePVS was 5.96 and 5.09, respectively. The ePVS significantly increased with advancing Fontaine classes. Kaplan-Meier analysis demonstrated that the high ePVS group had higher rates of death/MALE than the low ePVS group. Multivariate Cox proportional hazard analysis revealed that each ePVS was an independent predictor for death/MALE after adjusting for confounding risk factors. The prognostic ability for death/MALE was significantly improved by adding ePVS to the basic predictors. ePVS was associated with LEAD severity and clinical outcomes, suggesting that ePVS could be an additional risk factor for death/MALE in patients with LEAD who underwent EVT. We demonstrated that the association between ePVS and the clinical outcomes of patients with LEAD. The prognostic ability for death/MALE was significantly improved by adding ePVS to the basic predictors. LEAD lower extremity artery disease, MALE major adverse limb events, PVS plasma volume status., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Heart failure (HF) is an increasing health problem associated with a high mortality rate. Growth differentiation factor (GDF) 15, a stress response cytokine belonging to the transforming growth factor-β superfamily, is associated with poor clinical outcomes in a broad spectrum of cardiovascular diseases. However, the prognostic usefulness of GDF15 in Japanese patients with HF remains unclear., Methods and results: We measured serum concentrations of GDF15 and B-type natriuretic peptide (BNP) in 1,201 patients with HF. All patients were prospectively followed for a median period of 1,309 days. In all, 319 HF-related events and 187 all-cause deaths occurred during the follow-up period. Kaplan-Meier analysis demonstrated that, among GDF15 tertiles, the highest tertile group had the greatest risk of HF-related events and all-cause mortality. Multivariate Cox proportional hazard regression analysis demonstrated that the serum GDF15 concentration was an independent predictor of HF-related events and all-cause deaths after adjusting for confounding risk factors. Serum GDF15 improved the prediction capacity for all-cause deaths and HF-related events with a significant net reclassification index and integrated discrimination improvement. Subgroup analysis in patients with HF with preserved ejection fraction also showed the prognostic usefulness of GDF15., Conclusions: Serum GDF15 concentrations were associated with HF severity and clinical outcomes, indicating that GDF15 could provide additional clinical information to track the health status of patients with HF.

Aims: Aortic diseases (ADs), including aortic dissection, aortic aneurysm, and aortic rupture, are fatal, with extremely high mortality rates. A body shape index (ABSI), an anthropometric measure calculated as waist circumference adjusted by height and weight, improves the predictive capacity for mortality. However, whether ABSI is a risk factor for AD-related mortality in the general population remains unclear., Methods: We used a nationwide database of 630,842 individuals (aged 40-75 years) who participated in the annual "Specific Health Check and Guidance in Japan" between 2008 and 2010., Results: During the follow-up period of 3.8 years, 159 AD-related deaths occurred, including 105 aortic dissections and 54 aortic aneurysm ruptures. The subjects were divided into three groups based on ABSI tertiles. Kaplan-Meier analysis demonstrated that the 3 rd tertile (with the highest ABSI) had the greatest risk among the three groups. Multivariate Cox proportional hazard regression analysis demonstrated that ABSI was significantly associated with AD-related death after adjusting for confounding risk factors. Neither waist circumference nor body mass index consistently predicted AD-related death in the multivariate model. The prediction capacity was significantly improved by the addition of ABSI to the confounding risk factors., Conclusions: We demonstrated for the first time that ABSI, a surrogate marker for abdominal visceral fat tissue, was associated with AD-related deaths in the general population, suggesting the importance of central adiposity in the development of AD.

Aims: Renal dysfunction is an independent predictor of adverse outcomes in patients with coronary artery disease (CAD). However, the prognostic impact of mid-term changes in renal dysfunction status remains unclear. This study aimed to investigate the impact of mid-term changes in renal dysfunction status on long-term clinical outcomes in CAD patients who underwent percutaneous coronary intervention (PCI)., Methods: We enrolled 382 consecutive patients with CAD who underwent PCI. Renal dysfunction was defined as a reduced estimated glomerular filtration rate (eGFR) of ＜60 mL/min/1.73m 2 . Renal dysfunction status was evaluated at baseline and 1-year follow-up after PCI. We divided the study population into three groups: persistent renal dysfunction, new-onset renal dysfunction, and no or improved renal dysfunction at 1-year follow-up as compared with on baseline. The endpoints of this study were composite events, including all-cause death, acute coronary syndrome, target vessel revascularization, and stroke., Results: At baseline, renal dysfunction was observed in 77 patients (20%). At the 1-year follow-up, new-onset renal dysfunction was observed in 46 patients (12%), and 59 patients (15%) had persistent renal dysfunction. Kaplan-Meier analysis revealed a significantly higher event rate in patients with persistent renal dysfunction and new-onset renal dysfunction (log-rank test, P=0.0003). In the multivariate Cox proportional hazards analysis, persistent renal dysfunction and new-onset renal dysfunction were independently associated with composite events after adjusting for confounding factors (adjusted hazard ratios 4.08 and 2.64, 95% confidence intervals 1.72-9.57 and 1.03-6.31, P=0.0016, P=0.0045, respectively)., Conclusion: Persistent and new-onset renal dysfunction at 1-year follow-up were associated with unfavorable outcomes in patients with CAD who underwent PCI.

Background: Despite a reduction in the rate of thrombotic events, ischemic heart disease (IHD) remains a key medical problem associated with high major bleeding and mortality in Asian patients with IHD. Growth differentiation factor (GDF)-15, a stress-response cytokine belonging to the transforming growth factor beta superfamily, is reportedly associated with poor clinical outcomes in Western patients with IHD. However, the clinical significance of GDF-15 in Asian patients with IHD has not yet been fully elucidated., Objectives: The aim of the present study was to examine the impact of serum GDF-15 on clinical outcomes in Japanese patients with IHD., Methods: Serum GDF-15 levels were evaluated in 632 consecutive patients with IHD. All patients were followed up for a median period of 2.8 years. The primary endpoint was the all-cause mortality rate. Secondary endpoints were major adverse cardiovascular events (MACE), heart failure (HF)-related rehospitalization, bleeding, and thrombotic events., Results: Serum GDF-15 levels were elevated in acute coronary syndrome, severe coronary artery disease, and the major Japanese version of the high bleeding risk criteria. Multivariate Cox proportional hazards regression analysis demonstrated that GDF-15 was an independent predictor of all-cause mortality, MACE, HF-related rehospitalizations, and bleeding events after adjusting for confounding risk factors but not for thrombotic events. Adding GDF-15 to risk factors significantly improved the net reclassification index and integrated discrimination improvement for all-cause deaths, MACE, HF-related rehospitalization, and bleeding events., Conclusions: Serum GDF-15 could be a feasible marker for major bleeding and adverse clinical outcomes in Japanese patients with IHD., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Background: Assessment of coronary artery calcium (CAC) by computed tomographic (CT) imaging provides an accurate measure of atherosclerotic burden. CAC is also visible in computed tomographic attenuation correction (CTAC) scans, always acquired with cardiac positron emission tomographic (PET) imaging., Objectives: The aim of this study was to develop a deep-learning (DL) model capable of fully automated CAC definition from PET CTAC scans., Methods: The novel DL model, originally developed for video applications, was adapted to rapidly quantify CAC. The model was trained using 9,543 expert-annotated CT scans and was tested in 4,331 patients from an external cohort undergoing PET/CT imaging with major adverse cardiac events (MACEs) (follow-up 4.3 years), including same-day paired electrocardiographically gated CAC scans available in 2,737 patients. MACE risk stratification in 4 CAC score categories (0, 1-100, 101-400, and >400) was analyzed and CAC scores derived from electrocardiographically gated CT scans (standard scores) by expert observers were compared with automatic DL scores from CTAC scans., Results: Automatic DL scoring required <6 seconds per scan. DL CTAC scores provided stepwise increase in the risk for MACE across the CAC score categories (HR up to 3.2; P < 0.001). Net reclassification improvement of standard CAC scores over DL CTAC scores was nonsignificant (-0.02; 95% CI: -0.11 to 0.07). The negative predictive values for MACE of zero CAC with standard (85%) and DL CTAC (83%) CAC scores were similar (P = 0.19)., Conclusions: DL CTAC scores predict cardiovascular risk similarly to standard CAC scores quantified manually by experienced operators from dedicated electrocardiographically gated CAC scans and can be obtained almost instantly, with no changes to PET/CT scanning protocol., Competing Interests: Funding Support and Author Disclosures This research was supported in part by grant R01HL089765 from the National Heart, Lung, and Blood Institute/National Institutes of Health (principal investigator, Piotr Slomka). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Pieszko was supported by a research scholarship from the Polish National Agency for Academic Exchange. Cedars-Sinai has a pending patent application on the use of convolutional long short-term memory for multislice medical image segmentation. Drs Berman, Slomka, and Van Kriekinge and Mr Kavanagh participate in software royalties for nuclear cardiology software at Cedars-Sinai Medical Center. Dr Slomka has received research grant support from Siemens Medical Systems. Dr Berman has served as a consultant for GE Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Xanthine oxidoreductase (XOR) is a rate-limiting enzyme for uric acid (UA) production and plays an important role in generating reactive oxygen species (ROS). Overproduction of ROS is reported to contribute to the pathophysiology of atrial fibrillation (AF), however, the prognostic impact of plasma XOR activity in patients with heart failure (HF) with AF is undetermined., Methods: We measured plasma XOR activity in 475 HF patients, including those with sinus rhythm (HF-SR, n = 211), and those with AF (HF-AF, n = 264). The type of AF included paroxysmal (n = 128) and persistent (n = 136) AF. All patients were prospectively followed up for a median period of 804 days., Results: HF-AF patients had significantly higher plasma XOR activity and serum UA levels compared with HF-SR patients. Both plasma XOR activity and serum UA levels were higher in patients with persistent AF than in those with SR and with paroxysmal AF. Multivariate linear regression analysis showed that persistent AF was independently associated with increased XOR activity. During the follow-up period, there were 79 major adverse cardiovascular events (MACEs). HF-AF patients with MACEs had higher plasma XOR activity compared with those without MACEs, while there were no significant differences in serum UA levels. Multivariate Cox proportional analysis showed that high XOR activity was an independent risk factor for MACEs after adjustment for confounding factors. Kaplan-Meier analysis revealed that the high XOR activity group had a higher risk of MACEs than the low XOR activity group. The prediction model was significantly improved by the addition of XOR activity to the basic predictors., Conclusions: HF-AF patients had significantly higher plasma XOR activity compared with HF-SR patients. Plasma XOR activity proved to be a reliable indicator for MACEs in HF-AF patients., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Precordial Doppler ultrasound technology can be utilized to confirm correct peripheral intravenous vascular (PIV) access in children during surgery. This study aimed to determine the minimally required dose of normal saline (NS) for confirming correct PIV access. Healthy children were randomly allocated to receive a 0.1 mL/kg, 0.3 mL/kg, or 0.5 mL/kg dose of NS injected via PIV access. Two independent raters judged the change in the recorded precordial Doppler sound test (S-test) before and after NS injection. Typically, rapid injection of NS increased the pitch of the heartbeat as the injection volume increased. Changes in blood flow velocity test (V-test) results were evaluated using a cut-off value of 1 cm/s. Both in the S- and V-tests, the detection rate of correct PIV access was lower with 0.1 mL/kg NS than with 0.3 mL/kg or 0.5 mL/kg. Logistic regression analysis showed that the positive results in both the S- and V-tests were significantly decreased with a 0.1 mL/kg NS; no significant difference was observed with a 0.3 mL/kg NS (reference dose: 0.5 mL/kg). These results suggest 0.3 mL/kg is the minimally required dose of NS for confirming correct PIV access. This study is registered with the University Hospital Medical Information Network (UMIN000041330)., (© 2023. The Author(s).)

Background: Myocardial perfusion imaging (MPI) is frequently used to provide risk stratification, but methods to improve the accuracy of these predictions are needed., Objectives: The authors developed an explainable deep learning (DL) model (HARD MACE [major adverse cardiac events]-DL) for the prediction of death or nonfatal myocardial infarction (MI) and validated its performance in large internal and external testing groups., Methods: Patients undergoing single-photon emission computed tomography MPI were included, with 20,401 patients in the training and internal testing group (5 sites) and 9,019 in the external testing group (2 different sites). HARD MACE-DL uses myocardial perfusion, motion, thickening, and phase polar maps combined with age, sex, and cardiac volumes. The primary outcome was all-cause mortality or nonfatal MI. Prognostic accuracy was evaluated using area under the receiver-operating characteristic curve (AUC)., Results: During internal testing, patients with normal perfusion and elevated HARD MACE-DL risk were at higher risk than patients with abnormal perfusion and low HARD MACE-DL risk (annualized event rate, 2.9% vs 1.2%; P < 0.001). Patients in the highest quartile of HARD MACE-DL score had an annual rate of death or MI (4.8%) 10-fold higher than patients in the lowest quartile (0.48% per year). In external testing, the AUC for HARD MACE-DL (0.73; 95% CI: 0.71-0.75) was higher than a logistic regression model (AUC: 0.70), stress total perfusion deficit (TPD) (AUC: 0.65), and ischemic TPD (AUC: 0.63; all P < 0.01). Calibration, a measure of how well predicted risk matches actual risk, was excellent in both groups (Brier score, 0.079 for internal and 0.070 for external)., Conclusions: The DL model predicts death or MI directly from MPI, by estimating patient-level risk with good calibration and improved accuracy compared with traditional quantitative approaches. The model incorporates mechanisms to explain to the physician which image regions contribute to the adverse event prediction., Competing Interests: Funding Support and Author Disclosures This research (principal investigator: Dr Slomka) was supported in part by grant R01HL089765 from the National Heart, Lung and Blood Institute of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Mr Kavanagh has participated in software royalties for QPS software at Cedars-Sinai Medical Center. Dr Einstein has served as a consultant to GE Healthcare and W.L. Gore & Associates; and his institution has received research support from GE Healthcare, Philips Healthcare, Toshiba America Medical Systems, Roche Medical Systems, and W.L. Gore & Associates. Dr Ruddy has received research grant support from GE Healthcare and Advanced Accelerator Applications. Dr Edward Miller has served as a consultant to GE Healthcare. Dr Dorbala has served as a consultant to GE Healthcare and Bracco Diagnostics; and her institution has received grant support from Astellas. Dr Di Carli has received research grant support from Spectrum Dynamics; and has received consulting honoraria from Sanofi and GE Healthcare. Dr Berman has participated in software royalties for QPS software at Cedars-Sinai Medical Center; and has served as a consultant to GE Healthcare. Dr Slomka has participated in software royalties for QPS software at Cedars-Sinai Medical Center; and has received research grant support from Siemens Medical Systems. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Artificial intelligence (AI) has high diagnostic accuracy for coronary artery disease (CAD) from myocardial perfusion imaging (MPI). However, when trained using high-risk populations (such as patients with correlating invasive testing), the disease probability can be overestimated due to selection bias. We evaluated different strategies for training AI models to improve the calibration (accurate estimate of disease probability), using external testing., Methods: Deep learning was trained using 828 patients from 3 sites, with MPI and invasive angiography within 6 months. Perfusion was assessed using upright (U-TPD) and supine total perfusion deficit (S-TPD). AI training without data augmentation (model 1) was compared to training with augmentation (increased sampling) of patients without obstructive CAD (model 2), and patients without CAD and TPD < 2% (model 3). All models were tested in an external population of patients with invasive angiography within 6 months (n = 332) or low likelihood of CAD (n = 179)., Results: Model 3 achieved the best calibration (Brier score 0.104 vs 0.121, p < 0.01). Improvement in calibration was particularly evident in women (Brier score 0.084 vs 0.124, p < 0.01). In external testing (n = 511), the area under the receiver operating characteristic curve (AUC) was higher for model 3 (0.930), compared to U-TPD (AUC 0.897) and S-TPD (AUC 0.900, p < 0.01 for both)., Conclusion: Training AI models with augmentation of low-risk patients can improve calibration of AI models developed to identify patients with CAD, allowing more accurate assignment of disease probability. This is particularly important in lower-risk populations and in women, where overestimation of disease probability could significantly influence down-stream patient management., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite advances in medicine, heart failure with preserved ejection fraction (HFpEF) remains an increasing health concern associated with a high mortality rate. Research has shown sex-based differences in the clinical characteristics of patients with HF; however, definitive biomarkers for poor clinical outcomes of HFpEF in women are unavailable. We focused on the albumin-to-globulin ratio (AGR), a biomarker for malnutrition and inflammation and investigated its usefulness as a predictor of clinical outcomes of HFpEF in women. We measured the AGR in consecutive 224 women with HFpEF and 249 men with HFpEF. There were 69 cardiac events in women with HFpEF and 69 cardiac events in men with HFpEF during the follow-up period. The AGR decreased with advancing New York Heart Association functional class in women with HFpEF. Patients were categorized into three groups based on AGR tertiles. Kaplan-Meier analysis showed that among the three groups, the risk for cardiac events and HF-associated rehospitalizations was the highest in the lowest tertile in women with HFpEF. Univariate and multivariate Cox proportional hazard regression analyses showed that after adjustment for confounding risk factors, the AGR was an independent predictor of cardiac events and HF-associated rehospitalizations in women with HFpEF, but not in men with HFpEF. The addition of AGR to the risk factors significantly improved the net reclassification and integrated discrimination indices in women with HFpEF. This is the first study that highlights the significant association between the AGR and the severity and clinical outcomes of HFpEF in women. Addition of AGR to the risk factors improved its prognostic value for clinical outcomes, which indicates that this variable may serve as a useful clinical biomarker for HFpEF in women., (© 2022. Springer Japan KK, part of Springer Nature.)

Artificial intelligence may improve accuracy of myocardial perfusion imaging (MPI) but will likely be implemented as an aid to physician interpretation rather than an autonomous tool. Deep learning (DL) has high standalone diagnostic accuracy for obstructive coronary artery disease (CAD), but its influence on physician interpretation is unknown. We assessed whether access to explainable DL predictions improves physician interpretation of MPI. Methods: We selected a representative cohort of patients who underwent MPI with reference invasive coronary angiography. Obstructive CAD, defined as stenosis ≥50% in the left main artery or ≥70% in other coronary segments, was present in half of the patients. We used an explainable DL model (CAD-DL), which was previously developed in a separate population from different sites. Three physicians interpreted studies first with clinical history, stress, and quantitative perfusion, then with all the data plus the DL results. Diagnostic accuracy was assessed using area under the receiver-operating-characteristic curve (AUC). Results: In total, 240 patients with a median age of 65 y (interquartile range 58-73) were included. The diagnostic accuracy of physician interpretation with CAD-DL (AUC 0.779) was significantly higher than that of physician interpretation without CAD-DL (AUC 0.747, P = 0.003) and stress total perfusion deficit (AUC 0.718, P < 0.001). With matched specificity, CAD-DL had higher sensitivity when operating autonomously compared with readers without DL results ( P < 0.001), but not compared with readers interpreting with DL results ( P = 0.122). All readers had numerically higher accuracy with CAD-DL, with AUC improvement 0.02-0.05, and interpretation with DL resulted in overall net reclassification improvement of 17.2% (95% CI 9.2%-24.4%, P < 0.001). Conclusion: Explainable DL predictions lead to meaningful improvements in physician interpretation; however, the improvement varied across the readers, reflecting the acceptance of this new technology. This technique could be implemented as an aid to physician diagnosis, improving the diagnostic accuracy of MPI., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: A vertebral artery-anterior spinal artery (VA-ASA) aneurysm is very rare. The authors report a case of successful coil embolization of a ruptured aneurysm of the VA-ASA., Observations: A 54-year-old man with World Federation of Neurosurgical Societies grade II subarachnoid hemorrhage presented with an aneurysm located at the region involving the origin of ASA on the VA. Endovascular treatment was chosen to prevent rerupture and preserve the perforating branches. The catheter shape was modified with steam forming to allow access to the aneurysm. Partial embolization was performed to preserve the ASA. The authors also prevented further rupture. On day 16, angiography showed thrombosis within the aneurysm and preserved blood flow in the ASA despite a neck remnant. The patient was discharged home with a modified Rankin Scale score of 0. Careful follow-up has been continued., Lessons: Endovascular coiling in the acute phase of rupture of a VA-ASA aneurysm achieved favorable results. The aneurysm could be safely treated by selecting the appropriate device and catheter geometry.

Aims: Positron emission tomography (PET) myocardial perfusion imaging (MPI) is often combined with coronary artery calcium (CAC) scanning, allowing for a combined anatomic and functional assessment. We evaluated the independent prognostic value of quantitative assessment of myocardial perfusion and CAC scores in patients undergoing PET., Methods and Results: Consecutive patients who underwent Rb-82 PET with CAC scoring between 2010 and 2018, with follow-up for major adverse cardiovascular events (MACE), were identified. Perfusion was quantified automatically with total perfusion deficit (TPD). Our primary outcome was MACE including all-cause mortality, myocardial infarction (MI), admission for unstable angina, and late revascularization. Associations with MACE were assessed using multivariable Cox models adjusted for age, sex, medical history, and MPI findings including myocardial flow reserve.In total, 2507 patients were included with median age 70. During median follow-up of 3.9 years (interquartile range 2.1-6.1), 594 patients experienced at least one MACE. Increasing CAC and ischaemic TPD were associated with increased MACE, with the highest risk associated with CAC &gt; 1000 [adjusted hazard ratio (HR) 1.67, 95% CI 1.24-2.26] and ischaemic TPD &gt; 10% (adjusted HR 1.80, 95% CI 1.40-2.32). Ischaemic TPD and CAC improved overall patient classification, but ischaemic TPD improved classification of patients who experienced MACE while CAC mostly improved classification of low-risk patients., Conclusions: Ischaemic TPD and CAC were independently associated with MACE. Combining extent of atherosclerosis and functional measures improves the prediction of MACE risk, with CAC 0 identifying low-risk patients and regional ischaemia identifying high-risk patients in those with CAC &gt; 0., Competing Interests: Conflicts of interest: R.J.H.M. has received research support from Pfizer. D.S.B. participates in software royalties for QPS software at Cedars-Sinai Medical Center. P.J.S. participates in software royalties for QPS software at Cedars-Sinai Medical Center and received research support from Siemens., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Malnutrition, glomerular damage (GD), and renal tubular damage (RTD) are common morbidities associated with poor clinical outcomes in heart failure (HF) patients. However, the association between malnutrition and renal dysfunction and its impact on clinical outcomes in HF patients have not yet been fully elucidated. We assessed the nutritional status and renal function of 1061 consecutive HF patients. Malnutrition, GD, and RTD were defined as a controlling nutritional status (CONUT) score of ≥ 5, reduced eGFR or microalbuminuria, and levels of N-acetyl-beta-D-glucosamidase of > 14.2 U/gCr according to previous reports, respectively. Patients with RTD had a higher CONUT score and a lower prognostic nutritional index and geriatric nutritional risk index than those without. Multivariate logistic analysis demonstrated that RTD, but not GD, was significantly associated with malnutrition. There were 360 cardiac events during the median follow-up period of 688 days. Multivariate Cox proportional hazard regression analysis demonstrated that comorbid malnutrition and renal dysfunction, rather than simple malnutrition, were significantly associated with cardiac events in HF patients. We found a close relationship between malnutrition and renal dysfunction in HF patients. Comorbid malnutrition and renal dysfunction were risk factors for cardiac events in HF patients, suggesting the importance of managing and treating these., (© 2022. The Author(s).)

Background: A decrease in the activities of daily living (ADL) is an independent risk factor for cardiovascular disease. Although percutaneous coronary intervention (PCI) is known to prevent early mortality in patients with acute myocardial infarction (AMI), the relationship between ADL prior to myocardial infarction (MI), PCI implementation, and mortality in patients with AMI remains unknown. We investigated the impact of prehospital ADL on PCI implementation and on short- and long-term mortality in patients with AMI., Methods: We investigated the prehospital ADL in 1479 patients with AMI using data from the Yamagata AMI registry (period: 2015-2017). The patients were divided into three groups (preserved ADL, mildly impaired ADL, and severely impaired ADL) and their clinical characteristics were compared. Multivariate regression analysis was performed to elucidate the association of ADL prior to MI with the PCI implementation and mortality in patients with AMI., Results: Patients with impaired ADL were older, more likely to be female, less likely to have undergone PCI, and presented with higher acute mortality compared to those with preserved ADL. The proportion of patients with impaired ADL increased with age. Multivariate regression analysis showed that the lack of PCI implementation and prehospital ADL impairment were independent risk factors for acute death in patients with AMI after adjusting for confounding factors. Furthermore, univariate and multivariate analyses revealed that impaired ADL was associated with the PCI implementation. Cox proportional hazards analysis revealed that prehospital ADL impairment was an independent risk factor for long-term mortality in patients with AMI., Conclusions: Decreased levels of prehospital ADL were associated with lower PCI implementation and higher mortality in patients-especially older patients-with AMI., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Stress-only myocardial perfusion imaging (MPI) markedly reduces radiation dose, scanning time, and cost. We developed an automated clinical algorithm to safely cancel unnecessary rest imaging with high sensitivity for obstructive coronary artery disease (CAD)., Methods and Results: Patients without known CAD undergoing both MPI and invasive coronary angiography from REFINE SPECT were studied. A machine learning score (MLS) for prediction of obstructive CAD was generated using stress-only MPI and pre-test clinical variables. An MLS threshold with a pre-defined sensitivity of 95% was applied to the automated patient selection algorithm. Obstructive CAD was present in 1309/2079 (63%) patients. MLS had higher area under the receiver operator characteristic curve (AUC) for prediction of CAD than reader diagnosis and TPD (0.84 vs 0.70 vs 0.78, P &lt; .01). An MLS threshold of 0.29 had superior sensitivity than reader diagnosis and TPD for obstructive CAD (95% vs 87% vs 87%, P &lt; .01) and high-risk CAD, defined as stenosis of the left main, proximal left anterior descending, or triple-vessel CAD (sensitivity 96% vs 89% vs 90%, P &lt; .01)., Conclusions: The MLS is highly sensitive for prediction of both obstructive and high-risk CAD from stress-only MPI and can be applied to a stress-first protocol for automatic cancellation of unnecessary rest imaging., (© 2021. American Society of Nuclear Cardiology.)

Purpose: We sought to evaluate inter-scan and inter-reader agreement of coronary calcium (CAC) scores obtained from dedicated, ECG-gated CAC scans (standard CAC scan) and ultra-low-dose, ungated computed tomography attenuation correction (CTAC) scans obtained routinely during cardiac PET/CT imaging., Methods: From 2928 consecutive patients who underwent same-day 82 Rb cardiac PET/CT and gated CAC scan in the same hybrid PET/CT scanning session, we have randomly selected 200 cases with no history of revascularization. Standard CAC scans and ungated CTAC scans were scored by two readers using quantitative clinical software. We assessed the agreement between readers and between two scan protocols in 5 CAC categories (0, 1-10, 11-100, 101-400, and > 400) using Cohen's Kappa and concordance., Results: Median age of patients was 70 (inter-quartile range: 63-77), and 46% were male. The inter-scan concordance index and Cohen's Kappa for readers 1 and 2 were 0.69; 0.75 (0.69, 0.81) and 0.72; 0.8 (0.75, 0.85) respectively. The inter-reader concordance index and Cohen's Kappa (95% confidence interval [CI]) was higher for standard CAC scans: 0.9 and 0.92 (0.89, 0.96), respectively, vs. for CTAC scans: 0.83 and 0.85 (0.79, 0.9) for CTAC scans (p = 0.02 for difference in Kappa). Most discordant readings between two protocols occurred for scans with low extent of calcification (CAC score < 100)., Conclusion: CAC can be quantitatively assessed on PET CTAC maps with good agreement with standard scans, however with limited sensitivity for small lesions. CAC scoring of CTAC can be performed routinely without modification of PET protocol and added radiation dose., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: A pathophysiological interplay exists between plaque morphology and coronary physiology. Machine learning (ML) is increasingly being applied to coronary computed tomography angiography (CCTA) for cardiovascular risk stratification. We sought to assess the performance of a ML score integrating CCTA-based quantitative plaque features for predicting vessel-specific ischemia by invasive fractional flow reserve (FFR) and impaired myocardial blood flow (MBF) by positron emission tomography (PET)., Methods: This post-hoc analysis of the PACIFIC trial (Prospective Comparison of Cardiac Positron Emission Tomography/Computed Tomography [CT]' Single Photon Emission Computed Tomography/CT Perfusion Imaging and CT Coronary Angiography with Invasive Coronary Angiography) included 208 patients with suspected coronary artery disease who prospectively underwent CCTA' [ 15 O]H 2 O PET, and invasive FFR. Plaque quantification from CCTA was performed using semiautomated software. An ML algorithm trained on the prospective NXT trial (484 vessels) was used to develop a ML score for the prediction of ischemia (FFR≤0.80), which was then evaluated in 581 vessels from the PACIFIC trial. Thereafter, the ML score was applied for predicting impaired hyperemic MBF (≤2.30 mL/min per g) from corresponding PET scans. The performance of the ML score was compared with CCTA reads and noninvasive FFR derived from CCTA (FFR CT )., Results: One hundred thirty-nine (23.9%) vessels had FFR-defined ischemia, and 195 (33.6%) vessels had impaired hyperemic MBF. For the prediction of FFR-defined ischemia, the ML score yielded an area under the receiver-operating characteristic curve of 0.92, which was significantly higher than that of visual stenosis grade (0.84; P <0.001) and comparable with that of FFR CT (0.93; P =0.34). Quantitative percent diameter stenosis and low-density noncalcified plaque volume had the greatest ML feature importance for predicting FFR-defined ischemia. When applied for impaired MBF prediction, the ML score exhibited an area under the receiver-operating characteristic curve of 0.80; significantly higher than visual stenosis grade (area under the receiver-operating characteristic curve 0.74; P =0.02) and comparable with FFR CT (area under the receiver-operating characteristic curve 0.77; P =0.16)., Conclusions: An externally validated ML score integrating CCTA-based quantitative plaque features accurately predicts FFR-defined ischemia and impaired MBF by PET, performing superiorly to standard CCTA stenosis evaluation and comparably to FFR CT .

Background: Blood glucose monitoring (BGM) is essential for glycemic control in diabetic therapy. Followingly, accurate sensors are required for both daily personal and clinical use. The frequency of sensor use in patients with diabetes facilitates the use of disposable components. However, BGM systems are not exempt from green innovation sustainability initiatives., Methods: Clinical study of a high-accuracy green design blood glucose monitor using an innovative optical transmission absorbance system was carried out. Venous blood samples were collected from 104 patients with type II diabetes. The heat resistance of sensor strips was evaluated by storing sensor strips at 25℃ and 60℃ for approximately 3 months. Accuracy of the BGM system was evaluated via the ISO 15197:2013 protocol., Results: The BGM system achieved ±7.1% accuracy in glycemic level measurement, with 84% of all measurements within ±5% of the reference values. Furthermore, the sensor strip demonstrated heat resistance for more than 3 months when stored at 60℃., Conclusions: A new, highly accurate BGM system was developed based on the latest optical measurement system, introducing a rare metal-free "green-strip." The developed BGM system achieved the highest reported accuracy in clinical research, using venous blood from patients with diabetes. The sensor strip also exhibited high heat resistance, reducing limitations on storage conditions.

Background: We aim to develop an explainable deep learning (DL) network for the prediction of all-cause mortality directly from positron emission tomography myocardial perfusion imaging flow and perfusion polar map data and evaluate it using prospective testing., Methods: A total of 4735 consecutive patients referred for stress and rest 82 Rb positron emission tomography between 2010 and 2018 were followed up for all-cause mortality for 4.15 (2.24-6.3) years. DL network utilized polar maps of stress and rest perfusion, myocardial blood flow, myocardial flow reserve, and spill-over fraction combined with cardiac volumes, singular indices, and sex. Patients scanned from 2010 to 2016 were used for training and validation. The network was tested in a set of 1135 patients scanned from 2017 to 2018 to simulate prospective clinical implementation., Results: In prospective testing, the area under the receiver operating characteristic curve for all-cause mortality prediction by DL (0.82 [95% CI, 0.77-0.86]) was higher than ischemia (0.60 [95% CI, 0.54-0.66]; P <0.001), myocardial flow reserve (0.70 [95% CI, 0.64-0.76], P <0.001) or a comprehensive logistic regression model (0.75 [95% CI, 0.69-0.80], P <0.05). The highest quartile of patients by DL had an annual all-cause mortality rate of 11.87% and had a 16.8 ([95% CI, 6.12%-46.3%]; P <0.001)-fold increase in the risk of death compared with the lowest quartile patients. DL showed a 21.6% overall reclassification improvement as compared with established measures of ischemia., Conclusions: The DL model trained directly on polar maps allows improved patient risk stratification in comparison with established methods for positron emission tomography flow or perfusion assessments.

Early detection and treatment of diseases through health checkups are effective in improving life expectancy. In this study, we compared the predictive ability for 5-year mortality between two machine learning-based models (gradient boosting decision tree [XGBoost] and neural network) and a conventional logistic regression model in 116,749 health checkup participants. We built prediction models using a training dataset consisting of 85,361 participants in 2008 and evaluated the models using a test dataset consisting of 31,388 participants from 2009 to 2014. The predictive ability was evaluated by the values of the area under the receiver operating characteristic curve (AUC) in the test dataset. The AUC values were 0.811 for XGBoost, 0.774 for neural network, and 0.772 for logistic regression models, indicating that the predictive ability of XGBoost was the highest. The importance rating of each explanatory variable was evaluated using the SHapley Additive exPlanations (SHAP) values, which were similar among these models. This study showed that the machine learning-based model has a higher predictive ability than the conventional logistic regression model and may be useful for risk assessment and health guidance for health checkup participants., (© 2022. The Author(s).)

Hyperhomocysteinemia was reported to enhance endoplasmic reticulum (ER) stress and subsequent apoptosis in several cells. However, the precise mechanisms of smoking susceptibility associated with hyperhomocysteinemia has not been fully elucidated. This study included 7- to 9-week-old C57BL6 male mice induced with hyperhomocysteinemia and were exposed to cigarette smoke (CS). A549 cells (human alveolar epithelial cell line) were cultured with homocysteine and were exposed to cigarette smoke extract (CSE) to observe cell viability and expression of proteins related to the ER stress. After 6 months of CS exposure, pulmonary emphysema was more severely induced in the group under the condition of hyperhomocysteinemia compared to that in the control group. The apoptotic A549 cells increased as homocysteine concentration increased and that was enhanced by CSE. Protein expression levels of ER stress markers were significantly increased after simultaneous stimulation. Notably, vitamin B12 and folate supplementation improved ER stress after simultaneous stimulation of A549 cells. In this study, we showed that hyperhomocysteinemia exacerbates CS exposure-induced emphysema in mice, suggesting that hyperhomocysteinemia and CS stimulation enhance ER stress and subsequent induced apoptosis in alveolar epithelial cells. It was suggested that there is a synergistic effect between homocysteine and CS., (© 2022. The Author(s).)

Aims: Optimal risk stratification with machine learning (ML) from myocardial perfusion imaging (MPI) includes both clinical and imaging data. While most imaging variables can be derived automatically, clinical variables require manual collection, which is time-consuming and prone to error. We determined the fewest manually input and imaging variables required to maintain the prognostic accuracy for major adverse cardiac events (MACE) in patients undergoing a single-photon emission computed tomography (SPECT) MPI., Methods and Results: This study included 20 414 patients from the multicentre REFINE SPECT registry and 2984 from the University of Calgary for training and external testing of the ML models, respectively. ML models were trained using all variables (ML-All) and all image-derived variables (including age and sex, ML-Image). Next, ML models were sequentially trained by incrementally adding manually input and imaging variables to baseline ML models based on their importance ranking. The fewest variables were determined as the ML models (ML-Reduced, ML-Minimum, and ML-Image-Reduced) that achieved comparable prognostic performance to ML-All and ML-Image. Prognostic accuracy of the ML models was compared with visual diagnosis, stress total perfusion deficit (TPD), and traditional multivariable models using area under the receiver-operating characteristic curve (AUC). ML-Minimum (AUC 0.798) obtained comparable prognostic accuracy to ML-All (AUC 0.799, P = 0.19) by including 12 of 40 manually input variables and 11 of 58 imaging variables. ML-Reduced achieved comparable accuracy (AUC 0.796) with a reduced set of manually input variables and all imaging variables. In external validation, the ML models also obtained comparable or higher prognostic accuracy than traditional multivariable models., Conclusion: Reduced ML models, including a minimum set of manually collected or imaging variables, achieved slightly lower accuracy compared to a full ML model but outperformed standard interpretation methods and risk models. ML models with fewer collected variables may be more practical for clinical implementation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Lower extremity artery disease (LEAD) is an arterial occlusive disease characterized by an insufficient blood supply to the lower limb arteries. The H 2 FPEF score, comprising Heavy, Hypertensive, atrial Fibrillation, Pulmonary hypertension, Elder, and Filling pressure, has been developed to identify patients at high risk of heart failure (HF) with preserved ejection fraction. This study assessed the impact of modified H 2 FPEF scores on chronic limb-threatening ischemia (CLTI) in patients with LEAD. Methods and Results: This study was a prospective observational study. Because the definition of obesity differs by race, we calculated the modified H 2 FPEF score using a body mass index >25 kg/m 2 to define obesity in 293 patients with LEAD who underwent first endovascular therapy. The primary endpoints were newly developed and recurrent CLTI. The secondary endpoint was a composite of events, including mortality and rehospitalization due to worsening HF and/or CLTI. The modified H 2 FPEF score increased significantly with advancing Fontaine classes. Multivariate Cox proportional hazard analysis revealed that the modified H 2 FPEF score was an independent predictor of newly developed and recurrent CLTI and composite events. The net reclassification index and integrated discrimination improvement were significantly improved by adding the modified H 2 FPEF score to the basic predictors. Conclusions: The modified H 2 FPEF score was associated with LEAD severity and future CLTI development, suggesting that it could be a feasible marker for patients with LEAD., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022, THE JAPANESE CIRCULATION SOCIETY.)

Background: Semiquantitative assessment of stress myocardial perfusion defect has been shown to have greater prognostic value for prediction of major adverse cardiac events (MACE) in women compared with men in single-center studies with conventional single-photon emission computed tomography (SPECT) cameras. We evaluated sex-specific difference in the prognostic value of automated quantification of ischemic total perfusion defect (ITPD) and the interaction between sex and ITPD using high-efficiency SPECT cameras with solid-state detectors in an international multicenter imaging registry (REFINE SPECT [Registry of Fast Myocardial Perfusion Imaging With Next-Generation SPECT])., Methods: Rest and exercise or pharmacological stress SPECT myocardial perfusion imaging were performed in 17 833 patients from 5 centers. MACE was defined as the first occurrence of death or myocardial infarction. Total perfusion defect (TPD) at rest, stress, and ejection fraction were quantified automatically by software. ITPD was given by stressTPD-restTPD. Cox proportional hazards model was used to evaluate the association between ITPD versus MACE-free survival and expressed as a hazard ratio., Results: In 10614 men and 7219 women, with a median follow-up of 4.75 years (interquartile range, 3.7-6.1), there were 1709 MACE. In a multivariable Cox model, after adjusting for revascularization and other confounding variables, ITPD was associated with MACE (hazard ratio, 1.08 [95% CI, 1.05-1.1]; P <0.001). There was an interaction between ITPD and sex ( P <0.001); predicted survival for ITPD<5% was worse among men compared to women, whereas survival among women was worse than men for ITPD≥5%, P <0.001., Conclusions: In the international, multicenter REFINE SPECT registry, moderate and severe ischemia as quantified by ITPD from high-efficiency SPECT is associated with a worse prognosis in women compared with men.

Background: Explainable artificial intelligence (AI) can be integrated within standard clinical software to facilitate the acceptance of the diagnostic findings during clinical interpretation., Objectives: This study sought to develop and evaluate a novel, general purpose, explainable deep learning model (coronary artery disease-deep learning [CAD-DL]) for the detection of obstructive CAD following single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI)., Methods: A total of 3,578 patients with suspected CAD undergoing SPECT MPI and invasive coronary angiography within a 6-month interval from 9 centers were studied. CAD-DL computes the probability of obstructive CAD from stress myocardial perfusion, wall motion, and wall thickening maps, as well as left ventricular volumes, age, and sex. Myocardial regions contributing to the CAD-DL prediction are highlighted to explain the findings to the physician. A clinical prototype was integrated using a standard clinical workstation. Diagnostic performance by CAD-DL was compared to automated quantitative total perfusion deficit (TPD) and reader diagnosis., Results: In total, 2,247 patients (63%) had obstructive CAD. In 10-fold repeated testing, the area under the receiver-operating characteristic curve (AUC) (95% CI) was higher according to CAD-DL (AUC: 0.83 [95% CI: 0.82-0.85]) than stress TPD (AUC: 0.78 [95% CI: 0.77-0.80]) or reader diagnosis (AUC: 0.71 [95% CI: 0.69-0.72]; P < 0.0001 for both). In external testing, the AUC in 555 patients was higher according to CAD-DL (AUC: 0.80 [95% CI: 0.76-0.84]) than stress TPD (AUC: 0.73 [95% CI: 0.69-0.77]) or reader diagnosis (AUC: 0.65 [95% CI: 0.61-0.69]; P < 0.001 for all). The present model can be integrated within standard clinical software and generates results rapidly (<12 seconds on a standard clinical workstation) and therefore could readily be incorporated into a typical clinical workflow., Conclusions: The deep-learning model significantly surpasses the diagnostic accuracy of standard quantitative analysis and clinical visual reading for MPI. Explainable artificial intelligence can be integrated within standard clinical software to facilitate acceptance of artificial intelligence diagnosis of CAD following MPI., Competing Interests: Funding Support and Author Disclosures This research was supported in part by National Heart, Lung, and Blood Institute/National Institutes of Health grant R01HL089765 (principal investigator: Piotr Slomka). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Drs Berman and Slomka and Mr Kavanagh participated in software royalties for QPS software at Cedars-Sinai Medical Center. Dr Slomka has received research grant support from Siemens Medical Systems. Drs Berman, Dorbala, Einstein, and Edward Miller are consultants for GE Healthcare. Dr Einstein is a consultant for W.L. Gore & Associates. Dr Dorbala is a consultant for Bracco Diagnostics; and has received a grant through her institution from Astellas. Dr Di Carli has received research grant support from Spectrum Dynamics; and he is a consultant for Sanofi and GE Healthcare. Dr Ruddy has received research grant support from GE Healthcare and Advanced Accelerator Applications. Dr Einstein has received research support through his institution from GE Healthcare, Philips Healthcare, Toshiba America Medical Systems, Roche Medical Systems, and W.L. Gore & Associates. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: We hypothesized early post-stress left ventricular ejection fraction reserve (EFR) on solid-state-SPECT is associated with major cardiac adverse events (MACE)., Methods: 151 patients (70 ± 12 years, male 50%) undergoing same-day rest/regadenoson stress 99m Tc-sestamibi solid-state SPECT were followed for MACE. Rest imaging was performed in the upright and supine positions. Early stress imaging was started 2 minutes after the regadenoson injection in the supine position and followed by late stress acquisition in the upright position. Total perfusion deficit (TPD) and functional parameters were quantified automatically. EFR, ∆end-diastolic volume (EDV), and end-systolic volume (ESV) were calculated as the difference between stress and rest values in the same position. EFR < 0%, ∆EDV ≥ 5 ml, or ∆ESV ≥ 5 ml was defined as abnormal., Results: During the follow-up (mean 3.2 years), 28 MACE occurred (19%). In Kaplan-Meier analysis, there was a significantly decreased event-free survival in patients with early EFR < 0% (P = 0.004). Similarly, there was a decreased event-free survival in patients with ∆ESV ≥ 5 ml at early stress (P = 0.003). However, EFR, ∆EDV, and ∆ESV at late stress were not associated with MACE-free survival. Cox proportional hazards model adjusting for clinical information and stress TPD demonstrated that EFR, ∆EDV, and ∆ESV at early stress were significantly associated with MACE (P < 0.05 for all)., Conclusions: Reduced early post-stress EFR on vasodilator stress solid-state SPECT is associated with MACE., (© 2021. American Society of Nuclear Cardiology.)

Purpose: We sought to evaluate the diagnostic performance for coronary artery disease (CAD) of myocardial blood flow (MBF) quantification with 18 F-flurpiridaz PET using motion correction (MC) and residual activity correction (RAC)., Methods: In total, 231 patients undergoing same-day pharmacologic rest and stress 18 F-flurpiridaz PET from Phase III Flurpiridaz trial (NCT01347710) were studied. Frame-by-frame MC was performed and RAC was accomplished by subtracting the rest residual counts from the dynamic stress polar maps. MBF and myocardial flow reserve (MFR) were derived with a two-compartment early kinetic model for the entire left ventricle (global), each coronary territory, and 17-segment. Global and minimal values of three territorial (minimal vessel) and segmental estimation (minimal segment) of stress MBF and MFR were evaluated in the prediction of CAD. MBF and MFR were evaluated with and without MC and RAC (1: no MC/no RAC, 2: no MC/RAC, 3: MC/RAC)., Results: The area-under the receiver operating characteristics curve (AUC [95% confidence interval]) of stress MBF with MC/RAC was higher for minimal segment (0.89 [0.85-0.94]) than for minimal vessel (0.86 [0.81-0.92], p = 0.03) or global estimation (0.81 [0.75-0.87], p < 0.0001). The AUC of MFR with MC/RAC was higher for minimal segment (0.87 [0.81-0.93]) than for minimal vessel (0.83 [0.76-0.90], p = 0.014) or global estimation (0.77 [0.69-0.84], p < 0.0001). The AUCs of minimal segment stress MBF and MFR with MC/RAC were higher compared to those with no MC/RAC (p < 0.001 for both) or no MC/no RAC (p < 0.0001 for both)., Conclusions: Minimal segment MBF or MFR estimation with MC and RAC improves the diagnostic performance for obstructive CAD compared to global assessment., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Single nucleotide polymorphisms (SNPs) in nitric oxide synthase 3 ( NOS3 ) are associated with cardiovascular risk factors. However, it is not clear whether the NOS3 SNP is a genetic risk factor for cardiovascular diseases. Methods and Results: This prospective cohort study included 2,726 subjects aged ≥40 years who participated in a community-based health checkup. We genotyped 639 SNPs, including 2 NOS3 SNPs (rs1799983 and rs1808593). All subjects were monitored prospectively over a median follow-up period of 16.0 years, with the endpoint being cardiovascular events, including cardiovascular death and/or non-fatal myocardial infarction. Kaplan-Meier analysis demonstrated that both rs1799983 GT/TT and rs1808593 GG carriers had a higher risk of the endpoint than non-carriers. Univariate and multivariate Cox proportional hazard regression analyses revealed that both rs1799983 GT/TT and rs1808593 GG were independently associated with cardiovascular events after adjusting for confounding risk factors. The net reclassification index and integrated discrimination index were significantly improved by the addition of NOS3 SNPs as cardiovascular risk factors. Conclusions: NOS3 gene polymorphisms could be genetic risk factors for cardiovascular events in the general Japanese population, and could be used to facilitate the early identification of individuals at high risk of cardiovascular events., Competing Interests: None., (Copyright © 2022, THE JAPANESE CIRCULATION SOCIETY.)

Background: Obese patients constitute a substantial proportion of patients referred for SPECT myocardial perfusion imaging (MPI), presenting a challenge of increased soft tissue attenuation. We investigated whether automated quantitative perfusion analysis can stratify risk among different obesity categories and whether two-view acquisition adds to prognostic assessment., Methods: Participants were categorized according to body mass index (BMI). SPECT MPI was assessed visually and quantified automatically; combined total perfusion deficit (TPD) was evaluated. Kaplan-Meier and Cox proportional hazard analyses were used to assess major adverse cardiac event (MACE) risk. Prognostic accuracy for MACE was also compared., Results: Patients were classified according to BMI: BMI < 30, 30 ≤ BMI < 35, BMI ≥ 35. In adjusted analysis, each category of increasing stress TPD was associated with increased MACE risk, except for 1% ≤ TPD < 5% and 5% ≤ TPD < 10% in patients with BMI ≥ 35. Compared to visual analysis, single-position stress TPD had higher prognostic accuracy in patients with BMI < 30 (AUC .652 vs .631, P < .001) and 30 ≤ BMI < 35 (AUC .660 vs .636, P = .027). Combined TPD had better discrimination than visual analysis in patients with BMI ≥ 35 (AUC .662 vs .615, P = .003)., Conclusions: Automated quantitative methods for SPECT MPI interpretation provide robust risk stratification in the obese population. Combined stress TPD provides additional prognostic accuracy in patients with more significant obesity., (© 2020. American Society of Nuclear Cardiology.)