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Purpose: Coronary inflammation is postulated as a driver of atherosclerosis and dysfunctional arterial healing which may trigger stent failure. Pericoronary adipose tissue (PCAT) attenuation, detected on computer tomography coronary angiography (CTCA), is an emerging non-invasive marker of coronary inflammation. This propensity matched study assessed the utility of both lesion specific (PCAT Lesion ) and standardized PCAT attenuation as assessed in the proximal RCA (PCAT RCA ) as a predictor of stent failure in patients undergoing elective percutaneous coronary intervention. This is the first study to our knowledge that assesses the association of PCAT with stent failure., Methods: Patients undergoing CTCA assessment for coronary artery disease with subsequent stent insertion within 60 days and repeat coronary angiography for any clinical reason within 5 years were included in the study. Stent failure was defined as binary restenosis of >50 % on quantitative coronary angiography analysis or stent thrombosis. Both PCAT Lesion and PCAT RCA was assessed utilizing semi-automated proprietary software on baseline CTCA. Patients with stent failure were propensity matched utilizing age, sex, cardiovascular risk factors and procedural characteristics., Results: One hundred and fifty-one patients met inclusion criteria. Of these, 26 (17.2 %) had study-defined failure. A significant difference in PCAT Lesion attenuation between patients with and without failure was observed (-79.0 ± 12.6 vs. -85.9 ± 10.3HU, p = 0.035). There was no significant difference in PCAT RCA attenuation between the two groups (-79.5 ± 10.1 vs -81.0 ± 12.3HU, p = 0.50). Univariate regression analysis showed PCAT Lesion attenuation was independently associated with stent failure (OR 1.06, 95 % CI 1.01-1.12, P = 0.035)., Conclusions: Patients with stent failure exhibit significantly increased PCAT Lesion attenuation at baseline. These data suggest that baseline plaque inflammation may be an important driver for coronary stent failure., Competing Interests: Conflict of interest All authors report no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Subclinical leaflet thrombosis (LT) may occur following surgical and transcatheter aortic valve replacement. Computed tomography (CT) has become an established imaging modality to diagnose subclinical LT following bioprosthetic aortic valve replacement. Even so, there is a limited (but growing) experience in utilizing CT imaging for this indication. This review emphasizes a systematic approach to acquiring and analysing CT imaging for subclinical LT, highlighting evidence surrounding clinical sequelae of subclinical LT and anti-thrombotic implications following diagnosis., Competing Interests: Declaration of Competing Interest JL has received institutional core laboratory contracts with Edwards Lifesciences, Medtronic, Abbott, Boston Scientific, PI Cardia, and Conformal. PMH is a shareholder of Neumann Medical Ltd. RPG has received personal fees from Boston Scientific, Medtronic, and Abbott Vascular. The remaining authors have nothing to disclose in relation to this article., (Copyright © 2022 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

The relationship between reading ability and health, known as health literacy, broadly reflects the skills and competencies required to operate within the healthcare environment. It is only recently that we have seen attempts to conceptualize health literacy in the context of medication use by using terms such as medication literacy. Health literacy changes over one's lifetime and is dependent on factors such as numeracy, education, income, gender and country. Low health literacy and low medication literacy have been identified as significant risk factors for poor health outcomes of adults and children. With an evaluation of common tools used to assess health literacy and medication literacy, the aim of this review is to describe the shared responsibility between patients and healthcare providers for the communication of health and medication information. Key strategies and interventions to improve two-way communication between patients and healthcare providers are highlighted, with a focus on how health literacy can impact child health outcomes., (© 2021 British Pharmacological Society.)

Background: There are well-recognized benefits of behavioral interventions that include exercise for children and adolescents with obesity. However, such behavioral weight management programs may precipitate unintended consequences. It is unclear if different exercise modalities impact eating behaviors differently in youth with obesity., Objectives: The purpose of this study was to examine the effects of aerobic, resistance, and combined aerobic and resistance exercise training on eating attitudes and behaviors (uncontrolled eating, restrained eating, emotional eating, external eating and food craving) among adolescents with overweight and obesity., Methods: N  = 304 (70% female) adolescents with overweight and obesity participated in the 6-month Healthy Eating Aerobic and Resistance Training in Youth (HEARTY) randomized controlled trial. All participants were inactive post-pubertal adolescents (15.6 ± 1.4 years) with a mean BMI = 34.6 ± 4.5 kg/m 2 . The Food Craving Inventory (food cravings), Dutch Eating Behavior Questionnaire (restrained eating, emotional eating, external eating), and the Three-Factor Eating Questionnaire (uncontrolled eating) were used to assess eating attitudes and behaviors., Results: All exercise groups showed within-group decreases in external eating and food cravings. Participants randomized to the Combined training group and were more adherent showed the greatest improvements in eating behaviors and cravings., Conclusions: A 6-month exercise intervention produced improvements in disordered eating behaviors and food cravings, but effects may be gender and modality-specific. Findings highlight the need to tailor exercise intervention to participant characteristics for the promotion of healthier eating and weight management outcomes in youth with obesity., Clinical Trial Registration # and Date: ClinicalTrials.Gov NCT00195858, September 12, 2005., Competing Interests: The author declares that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (© 2022 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Backround: Dabigatran is a direct thrombin inhibitor used to treat cardiac arrhythmias, and rates of non-adherence to dabigatran in Polish populations are high. The current study examined how a pharmacist-led intervention of counselling with pictogram-enhanced medication instructions, and smartphone medication reminders, can improve adherence to dabigatran., Methods: A 3-month pharmacist-led intervention was conducted in community pharmacies in Poland on 325 men and women filling a dabigatran prescription for the first time. Participating pharmacies were assigned into the Control Group (n = 172 patients) or the Intervention Group (n = 153 patients). The primary outcome of this prospective study was self-reported medication adherence assessed at 3 time points (day 7, day 21, and day 90) after initiation of dabigatran., Results: Patients in the Intervention Group were significantly more adherent (mean days on Dabigatan/week) than the Control Group at 7 days (6.0 ± 0.9 vs 5.4 ± 1.1, p < 0.0001), 21 days (5.6 ± 1.0 vs 4.9 ± 1.3, p < 0.0001), and 90 days (5.5 ± 1.3 vs 4.4 ± 2.0, p < 0.0001), respectively. The percentage of patients in the Intervention Group who reported taking dabigatran twice/day as prescribed was significantly higher than the Control Group at 7 days (82.7% vs 71.4%, p = 0.0311), at 21 days (84.4% vs 58%, p < 0.0001), and at 90 days (78.4% vs 39.7%, p < 0.0001), respectively. The proportion of patients fully adherent (every day, twice/day) at 90 days was significantly higher in the Intervention Group than in the Control Group (26.1% vs 13.2%, p = 0.0145)., Conclusions: Our findings support the role for interventions in community pharmacies in Poland to improve medication adherence, thus providing evidence for the efficacy of a pharmacist-led pictogram and smartphone-based program to support optimal dabigatran treatment., (© 2022. The Author(s).)

Background: Instantaneous wave-free ratio (iFR) can reliably assess the physiological significance of coronary artery disease (CAD). Previous studies have demonstrated its interchangeability with other non-hyperaemic pressure ratios (NHPR), but there is no data exploring whether this association is maintained in patients with severe aortic stenosis (AS)., Methods: Forty-two patients (67 lesions) with severe AS were recruited and underwent invasive pressure-wire assessment. Data were extracted to calculate iFR, resting Pd/Pa, diastolic pressure ratios (DPR and dPR), and Diastolic Hyperaemia-Free Ratio (DFR). iFR was then compared with other NHPR to determine agreement and accuracy., Results: Mean aortic gradient and dimensionless index were 44.3 ± 11.6 mmHg and 0.23 ± 0.04, respectively. Of the 67 vessels, 57% were LAD, 15% LCx, 13% RCA and 12% other. There was strong positive correlation between iFR and all other NHPR, including Pd/Pa (r = 0.91, p < 0.001), DPR (r = 0.99, p < 0.001), dPR (r = 0.97, p < 0.001) and DFR (r = 0.98, p < 0.001). While Bald-Altman analysis demonstrated that Pd/Pa and DFR were numerically different from iFR, ROC analyses demonstrated iFR ≤0.89 was accurately identified by all NHPRs; Pd/Pa (AUC = 0.965, 95% CI [0.928-0.994]), DPR (AUC = 1.000, 95% CI [1.000-1.000]), dPR (AUC = 0.974, 95% CI [0.937-1.000]), DFR (AUC = 0.989, 95% CI [0.968-1.000])., Conclusion: In patients with severe AS, all the included NHPR in this analysis accurately predicted iFR < 0.89. These data should reassure clinicians that use of alternative NHPR to iFR is reasonable when assessing the physiological significance of CAD in patients with severe AS., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Robert P Gooley has received consultancy fees from Boston Scientific Inc. Other authors have no conflict of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Computed tomography coronary angiography (CTCA) is an established imaging modality widely used for diagnosing coronary artery stenosis with expanding potential for comprehensive assessment of coronary artery disease (CAD). Lesion-based analyses of high-risk plaques (HRP) on CTCA may aid further in prognostication presenting with stable chest pain. We conduct qualitative and quantitative assessments to identify HRPs that are associated with acute coronary syndrome (ACS) on a medium to long term follow-up., Methods: Retrospective cohort study of patients who underwent CTCA for suspected CAD. Obstructive stenosis (OS) is defined as ≥50% and the presence of HRP and its constituents: positive-remodelling (PR), low-attenuation-plaque (LAP; <56 HU), very-low-attenuation-plaque (vLAP; <30 HU) and spotty-calcification (SC) were recorded. A cross-sectional quantitative analysis of HRP was performed at the site of minimum-luminal-area (MLA). The primary endpoint was fatal or non-fatal ACS on follow-up., Results: A total of 1,257 patients were included (mean age 61±14 years old and 51% male) with a median follow-up of 7.24 years (interquartile range 5.5 to 7.7 years). The occurrence of ACS was significantly higher in HRP (+) patients compared to HRP (-) patients and patients with no plaques (20.5% vs. 1.6% vs. 0.4%, log-rank test P<0.001). ACS was more frequent in HRP (+)/OS (+) patients (20.7%) compared to HRP (+)/OS (-) patients (8.6%), HRP (-)/OS (+) patients (1.8%) and HRP (-)/OS (-) patients (1.0%). OS, cross-sectional plaque area (PA) and the presence of vLAP identified those HRP lesions that were more likely to cause future ACS. Cross-sectional LAP area (<56 HU) in HRP lesions added incremental prognostic value to OS in predicting ACS (P=0.008)., Conclusions: The presence of OS and the LAP area at the site of MLA identify the HRP lesions that have the greatest association with development of future ACS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-21-763/coif). DW serves as an unpaid editorial board member of Cardiovascular Diagnosis and Therapy from February 2021 to January 2023, and DW received honoraria for lectures from Eli-Lilly, Pfizer and Boehringer. The other authors have no conflicts of interest to declare., (2022 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Background: Non-invasive computed tomography (CT)-derived fractional flow reserve (FFR CT ) is computed from standard coronary CT angiography (CTA) datasets and provides accurate vessel-specific ischaemia assessment of coronary artery disease (CAD). To date, the technique and its diagnostic performance has not been verified in the Australian clinical context. The aim of this study was to describe and compare the diagnostic performance of FFR CT and CTA for the detection of vessel-specific ischaemia as determined by invasive fractional flow reserve (FFR) in the Australian patient population., Methods: One-hundred-and-nine patients (219 vessels) referred for clinically mandated invasive angiography were retrospectively assessed. Each patient underwent research mandated CTA and FFR CT within 3 months of invasive angiography and invasive FFR assessment. Independent core laboratory assessments were made to determine visual CTA stenosis, FFR CT and invasive FFR values. FFR CT values were matched with the corresponding invasive FFR measurement taken at the given wire position. Visual CTA stenosis ≥50%, FFR CT values ≤0.8 and invasive FFR values ≤0.8 were considered significant for ischaemia., Results: Per vessel accuracy, sensitivity, specificity, positive predictive value and negative predictive value of FFR CT were 80.4%, 80.0%, 80.6%, 64.9% and 90.0% respectively. Corresponding values for CTA were 75.1%, 87.1%, 69.2%, 58.1% and 91.7% respectively. In receiver operating characteristic curve analysis, FFR CT demonstrated superior area under the curve (AUC) compared with CTA in both per vessel (0.87 vs 0.77, p=0.004) and per patient analysis (0.86 vs 0.74, p=0.011). Per vessel AUC of combined CTA and FFR CT was superior to CTA alone (0.89 vs 0.77, p<0.0001)., Conclusion: In this cohort of Australian patients, the diagnostic performance of FFR CT was found to be comparable to existing international literature, with demonstrated improvement in performance compared with CTA alone for the detection of vessel-specific ischaemia., (Copyright © 2022 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background Exercise stress testing for cardiovascular assessment in kidney transplant candidates has been shown to be a feasible alternative to pharmacologic methods. Exercise stress testing allows the additional assessment of exercise capacity, which may have prognostic value for long-term cardiovascular outcomes in pre-transplant recipients. This study aimed to evaluate the prognostic value of exercise capacity on long-term cardiovascular outcomes in kidney transplant candidates. Methods and Results We retrospectively evaluated exercise capacity in 898 consecutive kidney transplant candidates between 2013 and 2020 who underwent symptom-limited exercise stress echocardiography for pre-transplant cardiovascular assessment. Exercise capacity was measured by age- and sex-predicted metabolic equivalents (METs). The primary outcome was incident major adverse cardiovascular events, defined as cardiac death, non-fatal myocardial infarction, and stroke. Cox proportional hazard multivariable modeling was performed to define major adverse cardiovascular events predictors with transplantation treated as a time-varying covariate. A total of 429 patients (48%) achieved predicted METs. During follow-up, 93 (10%) developed major adverse cardiovascular events and 525 (58%) underwent transplantation. Achievement of predicted METs was independently associated with reduced major adverse cardiovascular events (hazard ratio [HR] 0.49; [95% CI 0.29-0.82], P =0.007), as was transplantation (HR, 0.52; [95% CI 0.30-0.91], P =0.02). Patients achieving predicted METs on pre-transplant exercise stress echocardiography had favorable outcomes that were independent (HR, 0.78; [95% CI 0.32-1.92], P =0.59) and of similar magnitude to subsequent transplantation (HR, 0.97; [95% CI 0.42-2.25], P =0.95). Conclusions Achievement of predicted METs on pre-transplant exercise stress echocardiography confers excellent prognosis independent of and of similar magnitude to subsequent kidney transplantation. Future studies should assess the benefit on exercise training in this population.

Objective: To determine the association between prosthesis geometry with leaflet thrombosis (LT)., Background: Leaflet thrombosis following transcatheter aortic valve replacement (TAVR) is a recognised entity. The association between prosthesis geometry with LT is unclear but maybe a potential modifiable factor in its prevention., Methods: Patients who received an intra-annular TAVR prosthesis and were prospectively planned to undergo post-procedural computed tomography (CT) imaging were included. Leaflet thrombosis was defined as at least 50% restricted leaflet motion on CT. Prosthesis expansion and eccentricity was measured at prosthesis inflow, annulus and outflow levels. Prosthesis misalignment was defined as the average angle deviation between native and prosthesis leaflet commissure, greater than 30°., Results: Prevalence of LT was 13.7% in 117 patients. None of the patients with LT were on anticoagulation therapy. Patients with LT had reduced prosthesis annular expansion (89.4±5.2% vs 97.0±4.4%, p<0.01), greater prosthesis misalignment (81.3% vs 48.5%, p=0.02) and deeper implants (6.3±1.7 mm vs 4.3±1.5 mm, p<0.01). Threshold for the presence of LT on ROC analysis was an implant depth of 5.7 mm (AUC [area under curve]=0.81). Independent predictors of LT were annular under-expansion (Odds ratio [OR] 1.4, 95% confidence interval [CI] 1.2-1.7, p=0.03) prosthesis misalignment (OR 6.8, 95%CI 1.1-45.5, p=0.04) and implant depth (OR 1.9, 95%CI 1.1-3.2, p=0.03). Anticoagulation therapy was a protective factor (OR 0.2; 95%CI 0.1-0.4, p<0.01)., Conclusion: Geometrical predictors of LT post intra-annular TAVR were reduced prosthesis expansion at the annular level, lower implant depth and greater prosthesis misalignment. These factors may be important considerations during procedural planning for TAVR., (Copyright © 2021 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Olfaction contributes to feeding behaviour and is modulated by changes in dopamine levels. Methylphenidate (MPH) increases brain dopamine levels and has been shown to reduce appetite and promote weight loss in patients with attention deficit hyperactivity disorder. The objectives of this study were to test the effect of MPH on olfaction, appetite, energy intake, and body weight (BW) on individuals with obesity. In a randomized, double-blind study, 12 participants (age 28.9 ± 6.7 years) with a body mass index (BMI) of 36.1 ± 4.5 kg/m 2 were assigned to MPH (0.5 mg/kg) ( n  = 5) or placebo ( n  = 7) twice daily for 2 months. Appetite (visual analog scale), odour threshold (Sniffin' Sticks ® ), energy intake (food menu), and BW (DEXA scan) were measured at day 1 and day 60. MPH intake significantly increased odour threshold scores (6.3 ± 1.4 vs. 9.4 ± 2.1 and 7.9 ± 2.3 vs. 7.8 ± 1.9, respectively; p  = 0.029) versus placebo. There was a significantly greater suppression of appetite sensations (desire to eat ( p  = 0.001), hunger ( p  = 0.008), prospective food consumption ( p  = 0.003)) and an increase in fullness ( p  = 0.028) over time in the MPH versus placebo. MPH suppressed appetite and improved olfactory sensitivity in individuals with obesity. These data provide novel findings on the favourable effects of MPH on appetite and weight regulation in individuals living with obesity.

Background: Medical cannabis has been increasingly used in Canada after being sanctioned by Health Canada in 2001. Insomnia and sleep disorders are among the most common conditions for which patients report using cannabis. Current research shows cannabis may have a beneficial effect in sleep disorders and may improve patient-reported sleep scores., Methods: A retrospective chart review was conducted at Hybrid Pharm community pharmacy in Ottawa, Ontario, and included patients who were interested in, or already using, medical cannabis for sleep disorders. A qualitative, exploratory approach was taken to evaluate the descriptive efficacy and safety of medical cannabis when prescribed for insomnia or comorbid conditions. The comprehensive data collection also involved investigating the impact of cannabis on other medication used for insomnia., Results: A total of 38 patients were identified as having adequate follow-up documentation to assess the impact of medical cannabis. At time of data collection, 15 patients (39%) were able to reduce or completely discontinue a prescription medication indicated for sleep. On follow-up, 27 patients (71%) reported a subjective improvement in their sleep or related condition. Only 8 patients (21%) reported any adverse effects from medical cannabis use, and these were manageable and did not require discontinuation of cannabis., Conclusion: This study highlights the importance of a pharmacist's role in the management of cannabis-based therapy, including ongoing supportive care, follow-up and medication management. Can Pharm J (Ott) 2022;155:xx-xx., (© The Author(s) 2022.)

Background: Hypo-attenuated leaflet thickening (HALT) may occur following transcatheter aortic valve replacement (TAVR), however, it remains unclear if HALT is a predictor of haemodynamic valve deterioration (HVD)., Aim: To determine the impact of HALT on the occurrence of HVD., Methods: We prospectively evaluated 186 patients for the presence of HALT at a median of 6 weeks following TAVR (Interquartile-range [IQR] 4-12 weeks). HALT depth and area were measured. HVD encompassed any of the following: mean gradient ≥20 ​mmHg with an increase in gradient ≥10 ​mmHg from baseline, Doppler velocity index reduction ≥0.1 or new moderate-to-severe valvular regurgitation. Routine echocardiograms at discharge, one month and annually, were assessed by echo-cardiologists that were blinded to the HALT status., Results: LT prevalence was 17.7% (33/186). HVD was present in 8.6% (16/186) at a median follow-up of 2 years (IQR 1-3); two required valve re-intervention and five required anticoagulation. HALT was the only independent predictor of HVD on multivariate analysis (OR 33.3, 95%CI 7.4-125). Patients with HALT were more likely to develop HVD, require repeat valve intervention and have higher trans-valvular gradients at up to 3-year follow-up. Patients with HALT had a median cumulative thickness of 2.9 ​mm (IQR 1.9-4.7) and area of 64.2 ​mm 2 (IQR 40.9-91.6). Thresholds for HALT in predicting HVD were a cumulative depth of 2.4 ​mm (Specificity 94.1%, Sensitivity 75.0%, AUC ​= ​0.87) and cumulative area of 28 ​mm 2 (Specificity 92.2%, Sensitivity 81.3%, AUC ​= ​0.86)., Conclusion: HALT is an independent predictor of HVD, which exhibits specific depth and area thresholds to predict HVD. CT following TAVR may determine patients at risk of HVD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Robert Gooley receives Honoraria from Boston Scientific, Medtronic and Abbott Vascular. All the other authors report no conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)

(1) Introduction: Pharmacists are medical professionals who play an active role in the protection of public health. Since 2021, pharmacists with an appropriate certification have been authorised to administer vaccines against COVID-19. (2) Objective: The objective of this study was to ascertain the perceptions of patients about receiving vaccinations through community pharmacies. (3) Material and methods: This study was conducted in 2021. The research tool was an anonymous questionnaire published on the websites of patient organisations. Ultimately, 1062 patients participated in this study. (4) Results: This study shows that most of the respondents find community pharmacies more accessible than outpatient clinics (85.3%). Sixty-one percent of the respondents stated that getting vaccinated at pharmacies would be less time consuming than at outpatient clinics. Nearly every third respondent (29.5%) declared that they would get vaccinated if they received such a recommendation from a pharmacist. Fifty-six percent of the respondents were of the opinion that the administration of vaccines by pharmacists would relieve the burden on medical staff and the healthcare system. (5) Conclusions: Polish patients participating in the study have a positive attitude towards the implementation of vaccination services in community pharmacies as an effective way of combating infectious diseases.

An abnormal left ventricular contractile reserve is often seen in patients undergoing stress echocardiogram and may indicate the presence of obstructive coronary artery disease. The techniques and indexes used to identify abnormal left ventricular contractile response and its prognostic value in the absence of known causes has not been well studied. To describe the characteristics and clinical outcomes associated with an abnormal left ventricular contractile response, we performed a systematic review that identified 27 eligible studies. A diverse range of indices were utilised to measure left ventricular contractile reserve, most commonly Δleft ventricular ejection fraction in 11 studies. Dobutamine stress echocardiogram was the most commonly performed modality (19 studies) followed by exercise stress echocardiogram (4 studies), dipyridamole stress echocardiogram (2 studies), invasive hemodynamic measurement (1 study) and dobutamine stress magnetic resonance imaging (1 study). All but one study demonstrated a significant association between the absence of left ventricular contractile reserve and increased rate of cardiovascular events, cardiac death and all-cause mortality., (© 2022 Royal Australasian College of Physicians.)

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is functionally related to BDNF, and is associated with obesity and metabolic complications in adults, but limited research exists among adolescents. This study comparatively examined carriers and non-carriers of the BDNF Val66Met polymorphism on body composition, energy intake, and cardiometabolic profile among adolescents with obesity. The sample consisted of 187 adolescents with obesity; 99 were carriers of the homozygous Val (G/G) alleles and 88 were carriers of the Val/Met (G/A) or Met (A/A) alleles. Cardiometabolic profile and DNA were quantified from fasted blood samples. Body composition was assessed by magnetic resonance imaging (MRI). Compared to carriers of the homozygous Val (G/G) allele, carriers of the Val/Met (G/A) or Met/Met (A/A) variants exhibited significantly higher protein ( p = 0.01) and fat ( p = 0.05) intake, C-Reactive protein ( p = 0.05), and a trend toward higher overall energy intake ( p = 0.07), fat-free mass ( p = 0.07), and lower HDL-C ( p = 0.07) Results showed for the first time that among youth with obesity, carriers of the Val66Met BDNF Met-alleles exhibited significantly higher C-reactive protein and energy intake in the form of fat and protein compared to Val-allele carriers, thereby providing support for the possible role of BDNF in appetite, weight, and metabolic regulation during adolescence. Clinical Trial Registration: http://clinicaltrials.gov/, identifier NCT00195858., 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 © 2021 Goldfield, Walsh, Sigal, Kenny, Hadjiyannakis, De Lisio, Ngu, Prud’homme, Alberga, Doucette, Goldfield and Cameron.)

Low levels of brain derived-neurotrophic factor (BDNF) and excessive screen exposure are risk factors for neurocognitive deficits and obesity in youth, but the relationship between screen time and BDNF remains unknown. This study examined whether duration and/or type of sedentary screen time behaviour (TV viewing, video games, recreational computer use) are associated with serum BDNF levels in youth with obesity. The sample consisted of 250 inactive, postpubertal adolescents with obesity (172 females/78 males, aged 15.5 ± 1.4 years) at the baseline assessment of the Healthy Eating, Aerobic, Resistance Training in Youth Study. After controlling for self-reported age, sex, race, parental education, puberty stage, physical activity, and diet, higher total screen exposure was significantly associated with lower serum BDNF levels (β = -0.21, p  = 0.002). TV viewing was the only type of screen behaviour that was associated with BDNF levels (β = -0.22, p  = 0.001). Higher exposure to traditional forms of screen time was independently associated with lower serum BDNF levels, and this association appears to be driven primarily by TV viewing. Future intervention research is needed to determine whether limiting screen time is an effective way to increase BDNF and associated health benefits in a high-risk population of youth with obesity. Trial Registration: ClinicalTrials.Gov NCT00195858. Novelty: This study is the first to show that recreational screen time is inversely associated with serum BDNF levels. The inverse association between screen time and BDNF is driven primarily by TV viewing, indicating the type of screen might matter.

Background: The clinical predictors and sequelae of leaflet thrombosis (LT) following transcatheter aortic valve replacement (TAVR) is still unclear. Therefore, our aim was to determine the clinical predictors and sequelae at mid-term follow-up of computed tomography (CT)-defined LT following TAVR., Methods and Results: We performed a prospective evaluation with a 320-multislice CT following TAVR for the presence of LT, defined as hypo-attenuated leaflet thickening (HALT). Four-dimensional CT image-rendering was performed to determine the presence of reduced leaflet motion (RELM). 172 patients [89 (51.7%) male, mean age 82.8 ± 5.7 years] treated with commercially available TAVR device (Lotus 54%, CoreValve 32% and Sapien 3 14%) were included, with median CT-scan at 6.0 weeks post-TAVR. Prevalence of HALT was 14.0% (24 cases) and RELM was 9.8% (17 cases). On multivariate analysis, patients with HALT were less prescribed oral anticoagulation (OAC) (OR 9.9), received larger TAVR prostheses (OR 5.7) and higher rates of moderate-severe para-valvular regurgitation (PVR) (OR 16.3). There was no difference in clinical outcomes at a median follow-up of 2.3 years. Patients with RELM had significantly higher transvalvular gradients after discharge when compared to those without RELM., Conclusions: Absence of OAC, large TAVR prostheses and moderate-severe PVR were predictors for LT. Transvalvular gradients were higher in patients that developed RELM but not HALT. Further studies are warranted to determine the long-term impact of LT on TAVR durability. Prevalence of different sub-types of CT-defined LT (HALT and RELM) and the clinical predictors of developing LT following TAVR. CT computed tomography, HALT hypo-attenuated leaflet thickening, LT leaflet thrombosis, RELM reduced leaflet motion, TAVR transcatheter aortic valve replacement., (© 2021. Crown.)

Background: Patients with severe aortic stenosis (AS) exhibit systemic endothelial dysfunction, which can be associated with myocardial ischaemia in absence of obstructive coronary disease. Transcatheter aortic valve replacement (TAVR) is used to treat severe AS in patients with high or prohibitive surgical risk. However, it remains unknown whether endothelial function recovers post-TAVR. We therefore sought to assess the early and late changes in flow-mediated dilation (FMD), a measure of endothelial function, following TAVR., Methods: Patients undergoing TAVR for severe AS had ultrasound assessment of brachial endothelial-independent and -dependent FMD. Measurements were performed pre-TAVR, at early follow-up (<48 h post-TAVR) and late follow-up (4-6 weeks post-TAVR)., Results: 27 patients (mean age 82.0 ± 7.0; 33.3% female) were recruited; 37.0% had diabetes mellitus and 59.3% had hypertension. Brachial artery FMD increased from 4.2 ± 1.6% (pre-TAVR) to 9.7 ± 3.5% at early follow-up (p < 0.0001). At late follow-up, improvement compared with early follow-up was sustained (8.7 ± 1.9%, p = 0.27). Resting brachial arterial flow velocities decreased significantly at late follow-up (11.24 ± 5.16 vs. 7.73 ± 2.79 cm/s, p = 0.003). Concordantly, at late follow-up, there was decrease in resting wall shear stress (WSS; 14.8 ± 7.8 vs. 10.6 ± 4.8dyne/cm2, p = 0.01), peak WSS (73.1 ± 34.1 vs. 58.8 ± 27.8dyne/cm2, p = 0.03) and cumulative WSS (3543 ± 1852 vs. 2504 ± 1089dyne·s/cm 2 , p = 0.002). Additionally, a favourable inverse correlation between cumulative WSS and FMD was restored at late follow-up (r = -0.21 vs. r = 0.49)., Conclusion: Endothelial function in patients with AS improves early post-TAVR and this improvement is sustained. This likely occurs as a result of improved arterial haemodynamics, leading to lower localised WSS and release of vasoactive mediators that may also alleviate myocardial ischaemia., Competing Interests: Declaration of Competing Interest RPG has received consultancy fees from Boston Scientific Inc. Other authors have no conflict of interest to declare., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The genetics of binge-eating disorder (BED) is an emerging topic, with dopaminergic genes being implicated in its etiology due to the role that dopamine (DA) plays in food reward sensitivity and self-regulation of eating behavior. However, no study to date has examined if DA genes influence response to behavioral treatment of BED., Objective: The primary objective of this study was to examine the ability of DA-associated polymorphisms to predict BED treatment response measured using binge frequency over 12 months. As secondary objectives, this study examined cross-sectional relationships between these polymorphisms and anthropometrics in women living with and without BED and obesity., Methods: Women aged 18-64 years old were genotyped for the DA-related SNPs DRD2/ANKK1 Taq1A (rs1800497) and COMT (rs4680), as well as the DA-related uVNTRs DAT-1 (SLC6A3) and MAO-A. A multi-locus DA composite score was formed from these 4 polymorphisms using genotypes known to have a functional impact resulting in modified DA signaling. Binge frequency (Eating Disorder Examination - Interview) and body composition (Tanita BC-418) were assessed in a pre-post analysis to examine genetic predictors of treatment response in women living with obesity and BED. Secondary data analysis was conducted on a cross-sectional comparison of three groups of women enrolled in trial group treatment for BED: women living with obesity and BED (n = 72), obesity without BED (n = 27), and normal-weight without BED (n = 45)., Results: There were no significant genotype × time interactions related to anthropometrics or binge frequency for any individual DA genotypes, or to the composite score reflecting DA availability. At baseline, there were no significant between-group differences in frequencies of DA-related alleles, nor were there associations between genotypes and anthropometrics., Conclusions: Our study found no evidence to suggest that the DRD2/ANKK1 Taq1A, COMT, MAO-A, or DAT-1 polymorphisms are associated with response to behavioral intervention for BED as measured by changes in binge frequency. Future studies should examine a greater variety of dopaminergic polymorphisms, other candidate genes that target other neurotransmitter systems, as well as examine their impact on both behavioral and pharmacological-based treatment for BED., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Carnosine, an over the counter food supplement, has been shown to improve glucose metabolism as well as cardiovascular risk factors in animal and human studies through its anti-inflammatory, antioxidative, antiglycating and chelating properties. The aim of this study is to establish if carnosine supplementation improves obesity, insulin sensitivity, insulin secretion, cardiovascular risk factors including arterial stiffness and endothelial function, and other risk factors related to diabetes and cardiovascular disease in the overweight and obese population., Methods and Analysis: Fifty participants will be recruited to be enrolled in a double-blind randomised controlled trial. Eligible participants with a body mass index (BMI) between 25 and 40 kg/m 2 will be randomly assigned to the intervention or placebo group. Following a medical review and oral glucose tolerance test to check eligibility, participants will then undergo testing. At baseline, participants will have anthropometric measurements (BMI, dual X-ray absorptiometry and peripheral quantitative CT scan), measurements of glucose metabolism (oral glucose tolerance test, intravenous glucose tolerance test and euglycaemic hyperinsulinaemic clamp), cardiovascular measurements (central blood pressure, endothelial function and arterial stiffness), a muscle and fat biopsy, physical activity measurement, liver fibroscan, cognitive function and questionnaires to assess dietary habits, sleep quality, depression, and quality of life. Following baseline assessments, participants will be randomised to either 2 g carnosine or placebo for 15 weeks. In the 15th week, all assessments will be repeated. The preplanned outcome metric is the change between baseline and follow-up measures., Ethics and Dissemination: This study is approved by the Human Research Ethics Committee of Monash Health and Monash University, Australia., Trial Registration Number: NCT02686996., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: High-risk plaques (HRP) detected on coronary computed tomography angiography (CTA) confer an increased risk of acute coronary syndrome (ACS). Pericoronary adipose tissue attenuation (PCAT) is a novel biomarker of coronary inflammation. This study aimed to evaluate the association of PCAT with HRP and subsequent ACS development in patients with stable coronary artery disease (CAD)., Methods: Patients with stable CAD who underwent coronary CTA from 2011 to 2016 and had available outcome data were included. We studied 41 patients with HRP propensity matched to 41 controls without HRP (60 ± 10 years, 67% males). PCAT was assessed using semi-automated software on a per-patient basis in the proximal right coronary artery (PCAT RCA ) and a per-lesion basis (PCAT Lesion ) around HRP in cases and the highest-grade stenosis lesions in controls., Results: PCAT RCA and PCAT Lesion were higher in HRP patients than controls (PCAT RCA : -80.7 ± 6.50 HU vs. -84.2 ± 8.09 HU, p = 0.03; PCAT Lesion : -79.6 ± 7.86 HU vs. -84.2 ± 10.3 HU, p = 0.04), and were also higher in men (PCAT RCA : -80.5 ± 7.03 HU vs. -86.1 ± 7.08 HU, p < 0.001; PCAT Lesion : -79.6 ± 9.06 HU vs. -85.2 ± 7.96 HU, p = 0.02). Median time to ACS was 1.9 years, within a median follow-up of 5.3 years. PCAT RCA alone was higher in HRP patients who subsequently presented with ACS (-76.8 ± 5.69 HU vs. -82.0 ± 6.32 HU, p = 0.03). In time-dependent analysis, ACS was associated with HRP and PCAT RCA ., Conclusions: PCAT attenuation is increased in stable CAD patients with HRP and is associated with subsequent ACS development. Further investigation is required to determine the clinical implications of these findings.

Background: Coronary artery disease is common in patients with severe aortic stenosis. Computed tomography-derived fractional flow reserve (CT-FFR) is a clinically used modality for assessing coronary artery disease, however, its use has not been validated in patients with severe aortic stenosis. This study assesses the safety, feasibility, and validity of CT-FFR in patients with severe aortic stenosis., Methods: Prospectively recruited patients underwent standard-protocol invasive FFR and coronary CT angiography (CTA). CTA images were analyzed by central core laboratory (HeartFlow, Inc) for independent evaluation of CT-FFR. CT-FFR data were compared with FFR (ischemia defined as FFR ≤0.80)., Results: Forty-two patients (68 vessels) underwent FFR and CTA; 39 patients (92.3%) and 60 vessels (88.2%) had interpretable CTA enabling CT-FFR computation. Mean age was 76.2±6.7 years (71.8% male). No patients incurred complications relating to premedication, CTA, or FFR protocol. Mean FFR and CT-FFR were 0.83±0.10 and 0.77±0.14, respectively. CT calcium score was 1373.3±1392.9 Agatston units. On per vessel analysis, there was positive correlation between FFR and CT-FFR (Pearson correlation coefficient, R =0.64, P <0.0001). Sensitivity, specificity, positive predictive value, and negative predictive values were 73.9%, 78.4%, 68.0%, and 82.9%, respectively, with 76.7% diagnostic accuracy. The area under the receiver-operating characteristic curve for CT-FFR was 0.83 (0.72-0.93, P <0.0001), which was higher than that of CTA and quantitative coronary angiography ( P =0.01 and P <0.001, respectively). Bland-Altman plot showed mean bias between FFR and CT-FFR as 0.059±0.110. On per patient analysis, the sensitivity, specificity, positive predictive, and negative predictive values were 76.5%, 77.3%, 72.2%, and 81.0% with 76.9% diagnostic accuracy. The per patient area under the receiver-operating characteristic curve analysis was 0.81 (0.67-0.95, P <0.0001)., Conclusions: CT-FFR is safe and feasible in patients with severe aortic stenosis. Our data suggests that the diagnostic accuracy of CT-FFR in this cohort potentially enables its use in clinical practice and provides the foundation for future research into the use of CT-FFR for coronary evaluation pre-aortic valve replacement.

Background/purpose: Coronary artery disease (CAD) is common in patients undergoing transcatheter aortic valve replacement (TAVR), although its prognostic significance is questionable. Significant CAD stratified using SYNTAX score (SS) has been associated with greater mortality, yet it is unknown whether the functional impact of CAD also impacts outcomes in this cohort. DILEMMA score (DS) is a validated angiographic functional scoring tool that correlates with fractional flow reserve and instantaneous wave-free ratio. This study sought to assess the functional impact of CAD on outcomes in patients undergoing TAVR for severe aortic stenosis (AS)., Methods/materials: 229 patients were included in this analysis. Patients underwent angiographic DS and SS and were classified using predefined values. The primary endpoint was one-year all-cause mortality, with secondary endpoints of 30-day major adverse cardiac and cerebrovascular events (MACCE)., Results: The mean age was 83.9 ± 0.5 years (55.0% female), with 11.8% all-cause mortality. CAD defined by ≥30% stenosis in any vessel was not associated with adverse outcomes (HR = 1.08, p = 0.84). However, the risk of one-year mortality was greater in patients with either SS > 9 (20.8% vs. 9.4%, HR 2.34, p = 0.03) or DS > 2 (18.4% vs. 8.5%, HR = 2.28, p = 0.03). Both scoring systems were also associated with 30-day MACCE (both p < 0.05). After multivariate adjustment, independent predictors of one-year mortality were DS > 2 (HR = 2.29, p = 0.04), left ventricular ejection fraction <50% (HR 2.66, p = 0.04) and COPD (HR 2.43, p = 0.04)., Conclusion: Our results demonstrate that angiographic functional scoring is independently predictive of both 12-month mortality and 30-day MACCE following TAVR., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Hyperphosphatemia is associated with increased fibroblast growth factor 23 (FGF23), arterial calcification, and cardiovascular mortality. Effects of phosphate-lowering medication on vascular calcification and arterial stiffness in CKD remain uncertain., Methods: To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate >1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism., Results: A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m 2 ; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings., Conclusions: In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia., Clinical Trial Registry Name and Registration Number: Australian Clinical Trials Registry, ACTRN12610000650099., (Copyright © 2020 by the American Society of Nephrology.)

The use of fractional flow reserve (FFR) in guiding revascularisation improves patient outcomes and has been well-established in clinical guidelines. Despite this, the uptake of FFR has been limited, likely attributable to the perceived increase in procedural time and use of hyperaemic agents that can cause patient discomfort. This has led to the development of instantaneous wave-free ratio (iFR), an alternative non-hyperaemic pressure ratio (NHPR). Since its inception, the use of iFR has been supported by an increasing body of evidence and is now guideline recommended. More recently, other commercially available NHPRs including diastolic hyperaemia-free ratio and resting full-cycle ratio have emerged. Studies have demonstrated that these indices, in addition to mean distal coronary artery pressure to mean aortic pressure ratio, are mathematically analogous (with specific nuances) to iFR. Additionally, there is increasing data demonstrating the equivalent diagnostic performance of alternative NHPRs in comparison with iFR and FFR. These NHPRs are now integral within most current pressure wire systems and are commonly available in the catheter laboratory. It is therefore key to understand the fundamental differences and evidence for NHPRs to guide appropriate clinical decision-making., Competing Interests: Competing interests: ARI has received consulting fees from Boston Scientific and Canon Medical. SH has received speaker’s bureau and proctoring fees from Abbott Vascular and Boston Scientific. AB has received consultancy fees from Abbott Vascular and Boston Scientific., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Strengths and Difficulties Questionnaire (SDQ) is a brief measure of children's and adolescents' mental health. There are different versions of the questionnaire: a version for children and adolescents to complete by self-reporting, a version for parents and guardians to complete ("parent-rated"), and a version for teachers to complete. The purpose of this study was to examine the psychometric properties of the parent-rated SDQ with a nationally representative sample of Canadian children and adolescents., Data and Methods: Data are from cycle 1 (2007 to 2009), cycle 2 (2009 to 2011), cycle 3 (2012 to 2013) and cycle 4 (2014 to 2015) of the Canadian Health Measures Survey. Data include 7,451 Canadian children and adolescents aged 6 to 17 years (49.3% female). Parents and guardians completed the SDQ by reflecting on their child's behaviour over the past six months. Factorial validity was examined via confirmatory factor analysis, which included testing the original five-factor SDQ model and alternative three-factor and higher-order models. Reliability was assessed through composite reliability scores. Measurement invariance across subgroups was also assessed., Results: The original five-factor (i.e., emotional symptoms, conduct problems, peer problems, hyperactivity and prosocial behaviour) SDQ fit the data satisfactorily, demonstrated evidence of reliability, and was invariant across sex (male vs. female), age (children vs. adolescents) and survey language (English vs. French). The higher-order solution fit the data acceptably, and the three-factor solution did not fit the data well., Discussion: The original five-factor, parent-rated SDQ demonstrates evidence of factorial validity and reliability as a population measure of mental health difficulties among Canadian children and adolescents.

Background: Onsite workstation-based CT-derived Fractional-Flow-Reserve (CT-FFR) is accurate in assessing hemodynamic-significance of coronary stenoses. We aim to describe the influence of operator expertise and luminal-segmentation technique on the diagnostic performance, precision and reproducibility of CT-FFR in identifying hemodynamically-significant stenosis (FFR≤0.8)., Methods: Forty-eight consecutive stable-patients (86 vessels) with suspected CAD underwent research indicated invasive-FFR and 320-detector CT-coronary-angiography (CTA). CT-FFR was derived using reduced-order model on standard desktop-computer. Semi-automated coronary luminal segmentation was performed using focused-technique with manual adjustments at regions of stenosis and calcification or comprehensive-technique with manual adjustments along the entire course of the vessel. CT-FFR analysis was performed using 3 blinded operators; core-laboratory engineer using focused-technique and radiographer and cardiologist using the comprehensive-technique. Diagnostic performance was assessed by area under receiver-operating-curve (AUC). Precision with invasive FFR was determined by Bland-Altman analysis, and reproducibility by intraclass-correlation-coefficient (ICC)., Results: Diagnostic performance was comparable among operators (Engineer: AUC = 0.88, Radiographer 0.84; Cardiologist 0.87; P = 0.59). Coronary luminal-segmentation time was shortest using focused technique (engineer 6:17 ± 2.43 min), compared with comprehensive technique (cardiologist 14.83 ± 7.09, radiographer 24.74 ± 12.65; P < 0.001). Use of focused technique was associated with widest limits of agreement (LOA) with FFR and moderate intra-operator reproducibility (engineer LOA -0.20-0.33; ICC 0.66), when compared with the comprehensive technique which demonstrated narrower LOA and excellent reproducibility [radiographer (LOA -0.17-0.20, ICC = 0.91) and cardiologist (LOA-0.15-0.23, ICC = -0.93)] CONCLUSION: A workstation-based CT-FFR technique was reproducible with high and comparable diagnostic performance among operators with different expertise. A comprehensive luminal segmentation technique was the most time-consuming and associated with the highest reproducibility and precision with FFR., Competing Interests: Declaration of competing interest Dr Ihdayhid has received honorarium from Canon Medical and Boston Scientific. Associate Professor Ko has received honorarium and speaker fees from Canon Medical, Medtronic, St Jude, Novartis, Pfizer, Bristol-Myers Squibb and Lilly., (Copyright © 2020. Published by Elsevier Inc.)

Severe aortic stenosis induces abnormalities in central aortic pressure, with consequent impaired organ and tissue perfusion. Relief of aortic stenosis by transcatheter aortic valve replacement (TAVR) is associated with both a short- and long-term hypertensive response. Counterintuitively, patients who are long-term normotensive post-TAVR have a worsened prognosis compared with patients with hypertension, yet the underlying mechanisms are not understood. We investigated immediate changes in invasively measured left ventricular and central aortic pressure post-TAVR in patients with severe aortic stenosis using aortic reservoir pressure, wave intensity analysis, and indices of aortic function. Fifty-four patients (mean age 83.6±6.2 years, 50.0% female) undergoing TAVR were included. We performed reservoir pressure and wave intensity analysis on invasively acquired pressure waveforms from the ascending aorta and left ventricle immediately pre- and post-TAVR. Following TAVR, there were increases in systolic, diastolic, mean, and pulse aortic pressures (all P <0.05). Post-TAVR reservoir pressure was unchanged (54.5±12.4 versus 56.6±14.0 mm Hg, P =0.30) whereas excess pressure increased 47% (29.0±10.9 versus 42.6±15.5 mm Hg, P <0.001). Wave intensity analysis (arbitrary units, au) demonstrated increased forward compression wave (64.9±35.5 versus 124.4±58.9, ×10 3 au, P <0.001), backward compression wave (11.6±5.5 versus 14.4±6.9, ×10 3 au, P =0.01) and forward expansion wave energies (43.2±27.3 versus 82.8±53.1, ×10 3 au, P <0.001). Subendocardial viability ratio improved with aortic function effectively unchanged post-TAVR. Increased central aortic pressure following TAVR relates to increased transmitted power and energy to the proximal aorta with increased excess pressure but unchanged reservoir pressure. These changes provide a potential mechanism for the improved prognosis associated with relative hypertension post-TAVR.

Background: To compare computed tomography coronary angiography (CTCA) with intravascular ultrasound (IVUS) in quantitative and qualitative plaque assessment., Methods: Patients who underwent IVUS and CTCA within 3 months for suspected coronary artery disease were retrospectively studied. Plaque volumes on CTCA were quantified manually and with automated-software and were compared to IVUS. High-risk plaque features were compared between CTCA and IVUS., Results: There were 769 slices in 32 vessels (27 patients). Manual plaque quantification on CTCA was comparable to IVUS per slice (mean difference of 0.06±0.07, p=0.44; Bland-Altman 95% limits of agreement -2.19-2.08 mm 3 , bias of -0.06mm 3 ) and per vessel (3.1mm 3 ± -2.85mm 3 , p=0.92). In contrast, there was significant difference between automated-software and IVUS per slice (2.3±0.09mm 3 , p<0.001; 95% LoA -6.78 to 2.25mm 3, bias of -2.2mm 3 ) and per vessel (33.04±10.3 mm 3 , p<0.01). The sensitivity, specificity, positive and negative predictive value of CTCA to detect plaques that had features of echo-attenuation on IVUS was 93.3%, 99.6%, 93.3% and 99.6% respectively. The association of ≥2 high-risk plaque features on CTCA with echo attenuation (EA) plaque features on IVUS was excellent (86.7%, 99.6%, 92.9% and 99.2%). In comparison, the association of high-risk plaque features on CTCA and plaques with echo-lucency on IVUS was only modest., Conclusion: Plaque volume quantification by manual CTCA method is accurate when compared to IVUS. The presence of at least two high-risk plaque features on CTCA is associated with plaque features of echo attenuation on IVUS., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Background: Quantitative flow ratio (QFR) is an estimate of fractional flow reserve (FFR) and is derived from 3-dimensional quantitative coronary angiography. The DILEMMA score is an angiographic technique developed to predict FFR. Unlike other diastolic indices such as instantaneous wave-free ratio (iFR), diastolic pressure ratio (dPR) and dPR 25-75 , neither QFR nor DILEMMA score require pressure wires. This study sought to compare the diagnostic performance of QFR, diastolic indices and DILEMMA score to predict FFR., Methods: Between January 2010 and December 2013, patients who underwent invasive coronary angiography and FFR assessments were retrospectively studied. iFR and dPR were derived from FFR pressure tracings. QFR was computed using commercial software., Results: Eighty-five lesions (25% FFR significant) were included in this study. Median FFR was 0.88 (0.81-0.92). QFR (r s =0.801), iFR (r s =0.710), dPR (r s =0.716), dPR 25-75 (r s =0.715) and DILEMMA score (r s =-0.623) significantly correlated with FFR (P<0.001). QFR ≤0.8 had a specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of 95%, 86%, 86% and 95% respectively of predicting significant FFR (P<0.001). Receiver-operating characteristic (ROC) analysis revealed the AUC to predict significant FFR for QFR (0.947), iFR (0.880), dPR (0.883), dPR 25-75 (0.880) and DILEMMA score (0.916) were not significantly different. However, QFR was a better predictor of FFR than iFR (0.947 vs. 0.770, P<0.01)., Conclusions: QFR had excellent correlation and accuracy as measured against FFR. When compared to other diastolic indices and DILEMMA score, QFR performed at least as well as the other indices. QFR predicts FFR better than it predicts iFR. QFR is a convenient tool to assess significance of coronary stenosis and a reliable alternative to pressure-wire based indices. Prospective studies are required to investigate the performance and cost-effectiveness of QFR when independently used to guide clinical decision making., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-179). DTLW currently serves on the editorial board for Cardiovascular Diagnosis and Therapy from Feb 2019–Jan 2021. The other authors have no conflicts of interest to declare., (2020 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Epicardial adipose tissue (EAT) is associated with cardiovascular risk. The longitudinal change in EAT volume (EATv) and density (EATd), and potential modulators of these parameters, has not been described. We prospectively recruited 90 patients with non-obstructive coronary atherosclerosis on baseline computed tomography coronary angiography (CTCA) performed for suspected coronary artery disease to undergo a repeat research CTCA. EATv in millilitres (mL) and EATd in Hounsfield units (HU) were analysed and multivariable regression analysis controlling for traditional cardiovascular risk factors (CVRF) performed to assess for any predictors of change. Secondary analysis was performed based on statin therapy. The median duration between CTCA was 4.3years. Mean EATv increased at follow-up (72 ± 33 mL to 89 ± 43 mL, p < 0.001) and mean EATd decreased (baseline -76 ± 6 HU vs. -86 ± 5 HU, p < 0.001). There were no associations between baseline variables of body mass index, age, sex, hypertension, hyperlipidaemia, diabetes or smoking on change in EATv or EATd. No difference in baseline, follow-up or delta EATv or EATd was seen in patients with (60%) or without baseline statin therapy. In this select group of patients, EATv consistently increased and EATd consistently decreased at long-term follow-up and these changes were independent of CVRF, age and statin use. Together with the knowledge of strong associations between EAT and cardiac disease, these findings may suggest that EAT is an independent parameter rather than a surrogate for cardiovascular risk.

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt.2020.01.09). HR reports grants from National Heart Foundation, grants from Royal Australasian College of Physician, grants from National Health and Medical Research Council, during the conduct of the study. SN reports grants from AstraZeneca, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron and LipoScience, personal fees from AstraZeneca, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, Boehringer Ingelheim, outside the submitted work. PP reports personal fees from ESPERION Therapeutics, Bayer, Boehringer Ingelheim, Merck, Pfizer, Astra Zeneca, grants from ABBOTT Vascular, outside the submitted work. The other authors have no conflicts of interest to declare.

Obstructive Sleep Apnea (OSA) is strongly associated with adverse cardiovascular events. In these patients, increased oxidative stress has been associated with accelerated coronary atherosclerosis. However, it is unclear if OSA is associated with significant coronary artery plaque burden. Our aim is to determine whether OSA and/or markers of hypoxemia are associated with coronary plaque burden (CPB). Patients who had coronary computed tomography angiography (CCTA) and a polysomnogram within 1 year of each other between 2011 and 2016 were analyzed. Apnea-Hypopnea Index (AHI) and hypoxemic burden (ODI3%, ODI4%, nadir SpO2, average spO 2 and time of spO 2  < 88%) were obtained from the polysomnogram. Total CPB was assessed using the prognostically validated CT-Leaman score (CT-LeSc). Significant CPB was defined as CT-LeSc ≥ 8.3. There were 119 patients with mean (± SD) age of 59 ± 12 years. Using logistical regression analysis; AHI, ODI4% and ODI3% were the only parameters associated with significant CPB. Severe OSA (AHI ≥ 30 events/h) was associated with significant CPB with adjusted OR of 3.21 (p = 0.010) independent of traditional cardiovascular risk factors. Mechanisms associated with apnea and hypopnea events (as measured by AHI, ODI3% and ODI4%), but not the severity of arterial desaturation (nadir SpO 2 , burden of SpO 2  < 88%) were associated with significant CPB.

Background: Despite the high prevalence of coronary bifurcation lesions in routine interventional cardiology practice, the best strategy for managing this challenging lesion subset remains debatable. Due to potential for complications, the routine practice of side-branch (SB) predilation is controversial., Methods: An electronic search was performed of online databases up until April 2018 for studies reporting periprocedural angiographic outcomes comparing provisional main-branch stenting with and without SB predilation. Random-effects model odds ratios (ORs) were calculated., Results: Eight studies were selected for a qualitative review, with 47.3% (1367/2890) of included subjects having angiographic outcomes following SB predilation reported. Of these, four studies included details of periangiographic outcomes comparing two groups. Bifurcation lesions stented without SB predilation demonstrated lower odds of requiring further SB intervention compared with lesions receiving upfront SB predilation (OR, 2.44; 95% confidence interval [CI], 1.71-3.47; I²=21%; P<.001). No difference was demonstrated regarding final SB TIMI flow <3, SB dissection, or intraprocedural SB occlusion. Although the odds of performing final kissing-balloon inflation were in favor of the group without SB predilation (OR, 1.62; 95% CI, 1.11-2.37; I²=61%; P=.01), there was no statistical difference in long-term major cardiovascular outcome (MACE) between the two groups (risk ratio, 1.29; 95% CI, 0.94-1.75; I²=11%; P=.33)., Conclusion: SB predilation during coronary bifurcation percutaneous coronary intervention did not alter overall procedural angiographic outcomes. However, SB predilation is associated with increased SB intervention, including increased requirement for SB stenting, without demonstrable long-term MACE benefit, compared with a standard strategy without SB predilation.

Background: Off-pump coronary artery bypass grafting (CABG) negates the requirement for extracorporeal circulation used with the traditional on-pump approach. However, off-pump CABG is technically more challenging and may theoretically lead to less complete revascularisation. Recent data suggests a prognostic benefit for traditional on-pump CABG, but the mechanism for this remains unclear. We hypothesised that the inferior outcomes with off-pump CABG could be driven by the need for repeat revascularisation, with this benefit only becoming clear at long-term follow-up. We therefore evaluated short, medium and long-term outcomes of patients undergoing revascularisation with on vs. off-pump CABG., Methods: Electronic databases were searched to identify suitable randomised controlled trials enrolling ≥100 patients in each arm. Clinical outcomes were extracted at 30-days, 12-months or >4years. The primary outcome was long-term all-cause death, while secondary outcomes included 30-day, 12-month and >4-year cardiac death, stroke, myocardial infarction or revascularisation., Results: Thirteen (13) studies comprising 13,234 patients were included. Off-pump CABG was associated with an increased risk of all-cause death (Odds Ratio [OR] 1.18, 95% confidence interval [CI] 1.02-1.32, p=0.01) and repeat bypass surgery (OR 2.57, 95%CI 1.23-5.39, p=0.01) at long-term follow-up. A significant, increased requirement for revascularisation in off-pump was seen at 12-month follow-up (OR 1.59, 95%CI 1.09-2.33, p=0.02). No differences were noted between groups at 30-days, 12-months and >4years for myocardial infarction or stroke., Conclusions: Off-pump CABG is associated with significantly higher rates of all-cause mortality rate at long-term follow-up. These outcomes demonstrate a temporal relationship that may be driven by a greater requirement for repeat revascularisation at 1- and 5-year follow-up., Study Registration: CRD42018102019 (PROSPERO)., (Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Computed tomography derived fractional flow reserve (FFR CT ) and computed tomography stress myocardial perfusion imaging (CTP) are techniques to assess haemodynamic significance of coronary stenosis. To compare the diagnostic performance of FFR CT and static rest/stress CTP in detecting fractional flow reserve (FFR) defined haemodynamically-significant stenosis (FFR ≤ 0.8). Fifty-one patients (96 vessels) with suspected coronary artery disease from a single institution planned for elective invasive-angiography prospectively underwent research indicated 320-detector-CT-coronary-angiography (CTA) and adenosine-stress CTP and invasive FFR. Analyses were performed in separate core-laboratories for FFR CT and CTP blinded to FFR results. Myocardial perfusion was assessed visually and semi-quantitatively by transmural perfusion ratio (TPR). Invasive FFR ≤ 0.8 was present in 33% of vessels and 49% of patients. FFR CT , visual CTP and TPR analysis was feasible in 96%, 92% and 92% of patients respectively. Overall per-vessel sensitivity, specificity and diagnostic accuracy for FFR CT were 81%, 85%, 84%, for visual CTP were 50%, 89%, 75% and for TPR were 69%, 48%, 56% respectively. Receiver-operating-characteristics curve analysis demonstrated larger per vessel area-under-curve (AUC) for FFR CT (0.89) compared with visual CTP (0.70; p < 0.001), TPR (0.58; p < 0.001) and CTA (0.70; p = 0.0007); AUC for CTA + FFR CT (0.91) was higher than CTA + visual CTP (0.77, p = 0.008) and CTA + TPR (0.74, p < 0.001). Per-patient AUC for FFR CT (0.90) was higher than visual CTP (0.69; p = 0.0016), TPR (0.56; p < 0.0001) and CTA (0.68; p = 0.001). Based on this selected cohort of patients FFR CT is superior to visually and semi-quantitatively assessed static rest/stress CTP in detecting haemodynamically-significant coronary stenosis as determined on invasive FFR.

Background/purpose: Biodegradable-polymer (BP) and polymer-free (PF) drug eluting stents (DES) were developed to reduce the risk of delayed arterial healing observed with durable-polymer (DP) platforms. Although trials demonstrate BP-DES and PF-DES are non-inferior to DP-DES, there is limited data directly comparing these technologies. We performed a meta-analysis to assess the efficacy and safety of BP-DES versus PF-DES for the treatment of coronary artery disease., Methods/materials: Electronic searches were performed identifying randomized trials comparing BP-DES with PF-DES. Co-primary efficacy endpoints were target vessel revascularization (TVR), target lesion revascularization (TLR) and angiographic in-stent late lumen loss (LLL). Co-secondary safety endpoints were all-cause death, myocardial infarction (MI) and stent thrombosis (ST)., Results: Of 208 studies, 5 met inclusion criteria including 1975 patients. At mean follow-up (14 ± 5 months), BP-DES were associated with significantly reduced rates of TVR (OR 0.58, 95%CI 0.37-0.92, p = 0.02), TLR (4.7% vs 9.5%) (OR 0.48, 95%CI 0.31-0.75, p = 0.001) and in-stent LLL (pooled mean difference -0.20 mm, 95%CI -0.24 to -0.16, p < 0.001). There was no difference in safety, including all-cause death (OR 1.24, 95%CI 0.68-2.28, p = 0.48), MI (OR 0.92, 95%CI 0.54-1.56, p = 0.75) or ST (OR 1.58, 95%CI 0.67-3.73, p = 0.30)., Conclusions: These data suggests that BP-DES are more efficacious when compared with PF-DES for the treatment of CAD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: We sought to assess the validity of the DILEMMA score against instantaneous wave-free ratio (iFR) and evaluate its utility in rationalizing the number of patients referred for invasive physiological assessment., Background: The DILEMMA score is a validated angiographic scoring tool incorporating minimal lumen diameter, lesion length and subtended myocardial area that has been shown to predict the functional significance of lesions as assessed by fractional flow reserve (FFR)., Methods: Patients in the DEFINE-FLAIR study who had coronary stenosis of intermediate severity were randomized to either FFR or iFR. DILEMMA score was calculated retrospectively on a subset of this cohort by operators blinded to FFR or iFR values., Results: Three hundred and forty-six lesions (181 assessed by FFR; 165 by iFR) from 259 patients (mean age 66.0 years, 79% male) were included. A DILEMMA score ≤ 2 had a negative predictive value of 96.3% and 95.7% for identifying lesions with FFR >0.80 and iFR >0.89, respectively. A DILEMMA score ≥ 9 had a positive predictive value of 88.9% and 100% for identifying lesions with FFR ≤0.80 and iFR ≤0.89, respectively. The receiver operating characteristic area under the curve values for DILEMMA score to predict FFR ≤0.80 and iFR ≤0.89 were 0.83 (95% CI 0.77-0.90) and 0.82 (0.75-0.89) respectively. A DILEMMA score ≤ 2 or ≥9 occurred in 172 of the 346 lesions (49.7%)., Conclusions: Using DILEMMA score in patients with coronary stenosis of intermediate severity may reduce the need for pressure wire use, offering potential cost-savings and minimizing the risks associated with invasive physiological lesion assessment., (© 2019 Wiley Periodicals, Inc.)

Background: Coronary computed tomography angiography (CCTA) is often avoided in elderly patients due to a presumption that a high proportion of patients will have heavily calcified plaque limiting an accurate assessment. We sought to assess the image quality, luminal stenosis and utility of CCTA in elderly patients with suspected coronary artery disease (CAD) and stable chest pain., Methods: Retrospective analysis of elderly patients (> 75 years) who underwent 320-detector row CCTA between 2012-2017 at MonashHeart. The CCTA was analysed for degree maximal coronary stenosis by CAD-RADS classification, image quality by a 5-point Likert score (1-poor, 2-adequate, 3-good, 4-very good, 5-excellent) and presence of artefact limiting interpretability., Results: 1011 elderly patients (62% females, 78.8 ± 3.3 years) were studied. Cardiovascular risk factor prevalence included: hypertension (65%), hyperlipidaemia (48%), diabetes (19%) and smoking (21%). The CCTA was evaluable in 68% of patients which included 52% with non-obstructive CAD (< 50% stenosis), 48% with obstructive CAD (> 50%) stenosis. Mean Likert score was 3.1 ± 0.6 corresponding to good image quality. Of the 323 (32%) of patients with a non-interpretable CCTA, 80% were due to calcified plaque and 20% due to motion artefact. Male gender ( P = 0.009), age ( P = 0.02), excess motion ( P < 0.01) and diabetes mellitus ( P = 0.03) were associated with non-interpretable CCTA., Conclusion: Although CCTA is a feasible non-invasive tool for assessment of elderly patients with stable chest pain, clinicians should still be cautious about referring elderly patients for CCTA. Patients who are male, diabetic and >78 years of age are significantly less likely to have interpretable scans.

Background: Familial hypercholesterolemia (FH) is a common underdiagnosed autosomal dominant lipid disorder carrying a significant risk of premature coronary artery disease. The aim of this study was to evaluate the awareness and knowledge of heterozygous FH of healthcare providers in coronary care units (CCUs)., Methods: Medical staff working in CCUs in 4 sizable metropolitan health networks in Melbourne, Australia, were requested to complete a structured anonymised questionnaire with regard to FH. The results were tabulated and analysed with the Statistical Package for the Social Sciences version 23 (IBM, New York, NY)., Results: A total of 121 participants (67% response rate) completed the survey. Some 76% claimed to be at least modestly familiar with FH, and more than half of them adequately described FH; however, only 16% and 43%, respectively, were aware of the prevalence of FH and existence of lipid guidelines. In regard to epidemiological knowledge and update in the management of FH in CCUs, knowledge was suboptimal. In regard to FH care, General Practitioners were rated by 72% of participants as the first most efficient healthcare provider in the management of FH, and cardiologists were rated by 54% of participants as the second most efficient healthcare provider in the management of FH. Some 36% of respondents advocated a form of alert system in laboratory reports to facilitate the diagnosis of FH., Conclusions: This survey identified substantial gaps in the knowledge and awareness of FH among healthcare providers involved in the management of acute coronary syndrome. Focused education and clinical training are warranted to raise awareness of FH among healthcare providers working in CCUs., (Crown Copyright © 2019 Published by Elsevier Inc. on behalf of the Canadian Cardiovascular Society.)

Background: Familial hypercholesterolemia (FH) is a common monogenic hereditary lipid disorder characterised by increased serum low-density lipoprotein cholesterol (LDL-cholesterol) concentrations and high risk of premature atherosclerotic cardiovascular disease. The prevalence of FH identified in a tertiary hospital laboratory was investigated by performing an opportunistic screen for index cases., Methods: The prevalence of likely FH based on LDL-cholesterol thresholds >4.9 mmol/L as employed by the Dutch Lipid Clinic Network Criteria (DLCNC) score was evaluated retrospectively in a single tertiary hospital laboratory over a six-month period (July to December 2016)., Results: 4943 lipid profiles screened, 106 patients (mean age 53.2 ± 12.9 and 41% male) had LDL-cholesterol of >4.9 mmol/L after exclusion of 5 patients (0.1%) with secondary causes. Possible (n = 90) and probable/definite (n = 16) FH according to DLCNC score was seen in 1.8% and 0.4% of the overall screened population, respectively., Conclusions: Point prevalence of screening for FH in patients undergoing lipid profile testing in a tertiary hospital laboratory was comparable with prevalence of FH in general population (based on 1 in 200-250). This supports the benefit of establishing an efficient "alert system" in conjunction with a trigger "reflex testing" to facilitate further formal FH scoring and exclusion of possible secondary causes of hyperlipidemia in potential index FH.

Objectives: The genetics of binge-eating disorder (BED) is an emerging topic and one candidate pathway, namely the fat mass and obesity-associated (FTO) gene, may be implicated because of its role in food reward sensitivity and self-regulation of eating. The aims of this study were to examine the independent effects of variants of FTO on binge frequency in women with and without BED and to examine the moderating role of interpersonal attachment in this association., Methods: Secondary data analysis was conducted on a cross-sectional comparison of three groups of women in a trial of group treatment for BED: BED with obesity (n = 73), BED without obesity (n = 55), and normal weight without BED (n = 50). Women were genotyped for five of the most common FTO single-nucleotide polymorphisms, rs9939609, rs8050136, rs3751812, rs1421085, and rs1121980, which have been related to body mass index and energy intake. Binge frequency (Eating Disorder Examination), body composition (bioelectric impedance), and attachment (Attachment Style Questionnaire) were assessed., Results: There were no significant between-group differences for frequencies of FTO alleles, nor were there any significant anthropometric associations. The FTO × attachment interaction was significant whereby, relative to a low-risk FTO genotype, individuals with a high-risk genotype for the SNP rs1421085 and high-avoidant attachment had higher mean binge frequency than those with high genetic risk but low-avoidant attachment (β = -7.96; t = -2.07; P = 0.042)., Conclusions: FTO genotypes associated with risk for obesity and loss of control of eating, specifically rs1421085, may interact with insecure attachment in a way that may exacerbate binge eating among women with BED., (Copyright © 2018. Published by Elsevier Inc.)