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Background Patients with osteoporosis demonstrate increased vascular calcification but the effect of osteoporosis treatments on vascular calcification remains unclear. The present study aimed to examine whether coronary or aortic calcification are influenced by denosumab and alendronic acid treatment. Methods and Results In a double‐blind randomized controlled SALTIRE2 (Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis) trial, patients with aortic stenosis were randomized 2:1:2:1 to denosumab, placebo injection, alendronic acid, or placebo capsule. Participants underwent serial imaging with computed tomography and 18F‐sodium fluoride positron emission tomography for the assessment of vascular calcium burden and calcification activity, respectively. We report the prespecified secondary analyses of 24‐month change in coronary calcium score, and 12‐month changes in thoracic aorta calcium score, coronary and aortic 18F‐sodium fluoride activity. One hundred fifty patients with aortic stenosis (72±8 years; 21% female) were randomized to denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25). There were no differences in change in coronary calcium scores between placebo (16 [−64 to 148] Agatston units) and either denosumab (94 [0–212] Agatston units, P=0.24) or alendronic acid (34 [−62 to 134], P=0.99). There were no differences in change in thoracic aorta calcium scores between placebo (132 [22–512] Agatston units) and either denosumab (118 [11–340], P=0.75) or alendronic acid (116 [26–498] Agatston units, P=0.62). There were no differences in changes in coronary or aortic 18F‐sodium fluoride activity between treatment groups. Conclusions Neither alendronic acid nor denosumab are associated with changes in the activity or progression of coronary or aortic calcification. Osteoporosis treatments do not appear to have major impact on vascular calcification of atherosclerosis. registration https://www.clinicaltrials.gov; Unique identifier: NCT02132026.

Abstract Background Many patients are unsuitable for conventional femoral transcatheter aortic valve implantation (TAVI) but there is limited evidence as to which alternative approach has the best outcomes. We compared clinical outcomes in patients undergoing trans-subclavian (TS) or trans-apical (TA) TAVI. Methods This was a national retrospective observational study of patients undergoing surgical TAVI in Scotland between January 2013 and March 2020. The pre-operative patient characteristics, intraoperative details and post-operative outcomes were compared between TS and TA cohorts using data from the National Institute of Cardiovascular Outcomes Research (NICOR) registry. Results Among 1055 patients who underwent TAVI, TS or TA access was used in 50 (4.7%) and 90 (8.5%) patients respectively. Self-expanding Medtronic Evolut R valves were used in 84% of TS procedures, while balloon-expandable Edwards SAPIEN valves were used in all TA procedures. The TS group had a lower mean logistic EuroSCORE than the TA group (27.31 ± 19.44% vs 34.92 ± 19.61% p = 0.029). The TS approach was associated with a higher incidence of moderate postprocedural aortic regurgitation (12.5% vs 2.4%, p = 0.025). There was no significant difference in 30-day, 1-year or overall all-cause mortality. Conclusions Both trans-subclavian and trans-apical access are viable approaches for patients requiring non-transfemoral TAVI. Differences in peri-procedural indices reflect the disparate patient populations and factors governing prosthesis choice, and short- and long-term mortality was similar.

Background Important disparities in the treatment and outcomes of women and men with atrial fibrillation (AF) are well recognized. Whether introduction of direct oral anticoagulants has reduced disparities in treatment is uncertain. Methods and Results All patients who had an incident hospitalization from 2010 to 2019 with nonvalvular AF in Scotland were included in the present cohort study. Community drug dispensing data were used to determine prescribed oral anticoagulation therapy and comorbidity status. Logistic regression modeling was used to evaluate patient factors associated with treatment with vitamin K antagonists and direct oral anticoagulants. A total of 172 989 patients (48% women [82 833 of 172 989]) had an incident hospitalization with nonvalvular AF in Scotland between 2010 and 2019. By 2019, factor Xa inhibitors accounted for 83.6% of all oral anticoagulants prescribed, while treatment with vitamin K antagonists and direct thrombin inhibitors declined to 15.9% and 0.6%, respectively. Women were less likely to be prescribed any oral anticoagulation therapy compared with men (adjusted odds ratio [aOR], 0.68 [95% CI, 0.67–0.70]). This disparity was mainly attributed to vitamin K antagonists (aOR, 0.68 [95% CI, 0.66–0.70]), while there was less disparity in the use of factor Xa inhibitors between women and men (aOR, 0.92 [95% CI, 0.90–0.95]). Conclusions Women with nonvalvular AF were significantly less likely to be prescribed vitamin K antagonists compared with men. Most patients admitted to the hospital in Scotland with incident nonvalvular AF are now treated with factor Xa inhibitors and this is associated with fewer treatment disparities between women and men.

Abstract Background Current 18F-NaF assessments of aortic valve microcalcification using 18F-NaF PET/CT are based on evaluations of end-diastolic or cardiac motion-corrected (ECG-MC) images, which are affected by both patient and respiratory motion. We aimed to test the impact of employing a triple motion correction technique (3 × MC), including cardiorespiratory and gross patient motion, on quantitative and qualitative measurements. Materials and methods Fourteen patients with aortic stenosis underwent two repeat 30-min PET aortic valve scans within (29 ± 24) days. We considered three different image reconstruction protocols; an end-diastolic reconstruction protocol (standard) utilizing 25% of the acquired data, an ECG-gated (four ECG gates) reconstruction (ECG-MC), and a triple motion-corrected (3 × MC) dataset which corrects for both cardiorespiratory and patient motion. All datasets were compared to aortic valve calcification scores (AVCS), using the Agatston method, obtained from CT scans using correlation plots. We report SUVmax values measured in the aortic valve and maximum target-to-background ratios (TBRmax) values after correcting for blood pool activity. Results Compared to standard and ECG-MC reconstructions, increases in both SUVmax and TBRmax were observed following 3 × MC (SUVmax: Standard = 2.8 ± 0.7, ECG-MC = 2.6 ± 0.6, and 3 × MC = 3.3 ± 0.9; TBRmax: Standard = 2.7 ± 0.7, ECG-MC = 2.5 ± 0.6, and 3 × MC = 3.3 ± 1.2, all p values ≤ 0.05). 3 × MC had improved correlations (R2 value) to the AVCS when compared to the standard methods (SUVmax: Standard = 0.10, ECG-MC = 0.10, and 3 × MC = 0.20; TBRmax: Standard = 0.20, ECG-MC = 0.28, and 3 × MC = 0.46). Conclusion 3 × MC improves the correlation between the AVCS and SUVmax and TBRmax and should be considered in PET studies of aortic valves using 18F-NaF.

Abstract Background First-phase ejection fraction (EF1; the ejection fraction measured during active systole up to the time of maximal aortic flow) measured by transthoracic echocardiography (TTE) is a powerful predictor of outcomes in patients with aortic stenosis. We aimed to assess whether cardiovascular magnetic resonance (CMR) might provide more precise measurements of EF1 than TTE and to examine the correlation of CMR EF1 with measures of fibrosis. Methods In 141 patients with at least mild aortic stenosis, we measured CMR EF1 from a short-axis 3D stack and compared its variability with TTE EF1, and its associations with myocardial fibrosis and clinical outcome (aortic valve replacement (AVR) or death). Results Intra- and inter-observer variation of CMR EF1 (standard deviations of differences within and between observers of 2.3% and 2.5% units respectively) was approximately 50% that of TTE EF1. CMR EF1 was strongly predictive of AVR or death. On multivariable Cox proportional hazards analysis, the hazard ratio for CMR EF1 was 0.93 (95% confidence interval 0.89–0.97, p = 0.001) per % change in EF1 and, apart from aortic valve gradient, CMR EF1 was the only imaging or biochemical measure independently predictive of outcome. Indexed extracellular volume was associated with AVR or death, but not after adjusting for EF1. Conclusions EF1 is a simple robust marker of early left ventricular impairment that can be precisely measured by CMR and predicts outcome in aortic stenosis. Its measurement by CMR is more reproducible than that by TTE and may facilitate left ventricular structure–function analysis.

Acquired ventricular wall ruptures can be life-threatening. Depending on the pathological features and anatomy, surgical repair can be technically challenging and may be associated with high morbidity and mortality. We present 3 successful percutaneous repairs of different ruptures that used a variety of techniques. (Level of Difficulty: Advanced.)

Acute pulmonary embolism (PE) carries an increased risk of death. Using transthoracic echocardiography (TTE) to assist diagnosis and risk stratification is recommended in current guidelines. However, its utilization in real-world clinical practice is unknown. We conducted a retrospective observational study to delineate the prevalence of inpatient TTE use following confirmed acute PE, identify predictors for its use and its impact on patient's outcome.Clinical details of consecutive patients (2000 to 2012) from two tertiary-referral hospitals were retrieved from dedicated PE databases. All-cause and cause-specific mortality was tracked from a state-wide death registry.In total, 2306 patients were admitted with confirmed PE, of whom 687 (29.8%) had inpatient TTE (39.3% vs 14.4% between sites, P

Renal cell carcinoma (RCC) is the most common primary malignancy of the kidney and one of the most lethal genitourinary malignancies. Clear-cell renal cell carcinoma (ccRCC) has an extremely poor prognosis because of a high potential for tumor growth, vascular invasion, metastasis and recurrence. Unfortunately, the mechanism of RCC growth and metastasis is not well understood. In this report, we for the first time demonstrated ubiquitin protein ligase E3C (UBE3C) as a driving factor for RCC growth and metastasis. UBE3C expression was increased in ccRCC tissues compared with adjacent normal tissues. ccRCC patients with high UBE3C protein expression in tumors were associated with significantly worse postoperative survival. Knockdown of UBE3C expression in ACHN cells inhibited cell proliferation, migrations and invasiveness in vitro while overexpression of UBE3C in 786-O cells exerted the opposite effects. UBE3C up-regulated β-catenin protein levels and promoted β-catenin nuclear accumulation, leading to the activation of the Wnt/β-catenin signal pathway in RCC cells. Collectively, these observations suggest that UBE3C plays an important role in RCC development and progression, and UBE3C may be a novel target for prevention and treatment of ccRCC.

Background: The increasing use of intracardiac echocardiography (ICE) in the ablation of premature ventricular complexes (PVCs) has raised questions about its true efficacy and safety. Methods: This retrospective study collected the periprocedural complications and PVC burden post ablation. The risk factors of PVC recurrence was further explored. Results: The study included patients treated without ICE (control group, n = 451) and with ICE (ICE group, n = 155) from May 2019 to July 2022. The ICE group demonstrated significantly lower fluoroscopy times and X-ray doses. There were no major complications in the ICE group, and the difference in the occurrence of periprocedural complications between the groups was not statistically significant (p = 0.072). The long-term success rates were similar for the control and ICE groups (89.6% and 87.1%, respectively). The origin of PVCs was identified as the independent factor for ablation success. Conclusions: The use of ICE did not confer an advantage with regard to long-term success in PVCs ablation. To thoroughly evaluate the safety and effectiveness of ICE in PVCs ablation, a prospective, multicenter, randomized study is warranted. [ABSTRACT FROM AUTHOR]

Introduction. Further evidence is required to understand the impact of preexisting and newly diagnosed diabetes mellitus (DM) on atrial fibrillation (AF) recurrence and major adverse cardiac and cerebrovascular events (MACCEs) following catheter ablation. Materials and Methods. Data from 1,685 patients (1,406 without DM vs. 279 with DM) who underwent AF catheter ablation between 2015 and 2019 were analyzed. These participants were prospectively monitored for incidents of AF recurrence and MACCE over an average period of 58.1 months. Results. A higher incidence of AF recurrence (24.6% vs. 34.4%) and a greater frequency of MACCE (6.5% vs. 9.3%) were observed among DM patients. Kaplan–Meier curves indicated that DM significantly increased the rates of AF recurrence, with a hazard ratio (HR) of 1.506 and a 95% confidence interval (CI) of 1.165–1.948 (p = 0.0003). This association persisted in the propensity‐matched cohort. DM was independently predictive of AF recurrence after adjusting for potential risks using Cox regression analysis. Notably, new‐onset DM was also found to be an independent predictor of AF recurrence. Similarly, DM was an independent risk of MACCE (HR [95% CI], 2.273 [1.120–4.615], p = 0.023). Conclusions. Both existing DM and newly diagnosed DM were identified as independent risk factors for AF recurrence following ablation; they also significantly impacted MACCE outcomes. This study underscores the urgent need for careful management of DM among individuals undergoing AF ablation in order to reduce the likelihood of arrhythmic relapse. This analysis utilized data from a prospective observational study registered in the Chinese Clinical Trial Registry on July 20, 2014 (ChiCTR-OCH-14004674). [ABSTRACT FROM AUTHOR]