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Showing 341–360 of 2058 publications.
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Lim, Michelle Su Anne; Portelli, Stefanie Suzanne; Padang, Ratnasari; Bannon, Paul Gerard; Hambly, Brett D.; Jeremy, Richmond William; Celermajer, David S.; Robertson, Elizabeth N.Background: Whilst a combination of genetically mediated vulnerability and hemodynamic insult is suspected to contribute to bicuspid aortic valve (BAV) aortopathy, the underlying pathophysiological mechanisms are poorly understood. Methods: Utilizing RT-qPCR, we compared the expression of 28 potentially relevant long non-coding RNA (lncRNA) in aortic tissue from BAV patients undergoing aortic surgery for aortopathy, to healthy controls. Relative lncRNA expression was measured using ??CT, with fold-change calculated as RQ=2???CT. Results: When comparing samples from BAV patients (n=29, males n=25; median age 58 years, Q1-Q3 5165, maximum aortic dimension 505 mm) with healthy controls (n=7; males n=4, P=.12; median age 39 years, Q1-Q3 18-47, P=.001), there were two differentially expressed lncRNA: TUG1 expression was significantly lower in BAV aortic tissue (RQ 0.59, 95% CI 0.500.69, P=.02), whilst MIAT expression was significantly higher (RQ 2.87, 95% CI 1.964.20, P=.01). Sensitivity analysis including only patients with normal BAV function showed similar trends of differential expression of TUG1 (RQ 0.69, 95% CI 0.50-0.90, P=.29) and MIAT (RQ 2.55, 95% CI 1.21-5.36, P=.29) compared to controls. Conclusions: LncRNA TUG1 and MIAT are differentially expressed in BAV aortopathy compared to healthy controls, independent of BAV hemodynamics. Aberrant lncRNA expression may be involved in the pathogenesis of BAV aortopathy 2022 Elsevier Inc.
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Strom, Jordan B.; Playford, David A.; Stewart, S.; Li, Stephanie; Shen, Changyu; Xu, Jiaman; Strange, G. A.Background While large scientific and medical evidence has demonstrated the increased risk of death and cardiovascular mortality in patients with severe AS, the independent contribution of moderate AS to an increased risk of death remains uncertain. Methods and findings We conducted a multicenter study including a cohort of 30,865 US patients and another cohort of 217,599 Australian patients with equivalent echocardiographic and aortic valve profiling over the same period (20032017). During a median 5.2 years (US) and 4.4 years (Australian) follow-up, the risk of death (hazard ratio) of patients with moderate AS as compared to those without AS was 1.66 (95%CI 1.521.80) and 1.37 (95%CI 1.341.41) in the US and Australian cohorts, even after adjusting this analysis for age and sex. This increased risk of death and cardiovascular mortality (odds ratio) in patients with moderate AS was consistent also across subgroups of left ventricular ejection fraction (LVEF) (subgroups of LVEF < 40%, 4049%, 5059%, and ? 60%: OR of moderate AS for CV mortality 2.0 [95%CI 1.42.7], 1.7 [95%CI 1.22.4], 1.5 [95%CI 1.11.9], and 1.4 [95%CI 1.21.6], respectively). Conclusions The findings of this study suggest that patients with moderate AS have a potential increased risk of death and cardiovascular mortality, regardless of age, sex, and LVEF. Hence, these data suggest the need to develop specific strategies to detect and treat individuals with moderate AS. : 2022 Strom et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Ali, Ziad A.; Escaned, Javier E.; Dudek, Dariusz; Radhakrishnan, Jai; Galougahi, Keyvan KarimiCoronary artery disease is highly prevalent in chronic kidney disease (CKD) and is a risk factor for contrast-associated acute kidney injury (CA-AKI), a complication of cardiovascular procedures that require contrast administration (e.g., coronary angiography, percutaneous coronary intervention [PCI]). CA-AKI has a major impact on morbidity, mortality, and healthcare resource utilization. The incidence of CA-AKI is particularly high in patients with pre-existing CKD, advanced age and comorbidities that increase the likelihood of CKD. The focus of the present review is to provide a brief overview on the assessment of the risk for and prevention of CA-AKI in patients undergoing angiography and PCI, including recognition of the important patient- and procedure-related factors that may contribute to CA-AKI. Preventive and treatment strategies, the mainstay of which is volume repletion by normal saline, are briefly discussed. The main focus of the review is placed on technical details of contrast minimization techniques, including ultra-low contrast angiography and zero-contrast PCI. Operator competence in such techniques is important to ensure that procedural challenges in patients with CKD, like vessel calcification, multivessel disease and complex anatomical subsets, are effectively addressed by PCI while minimizing the risk of CA-AKI. 2022. The Korean Society of Cardiology
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Zhang, Wei; Chen, Yi; Hu, Leixiao; Xia, Jiahui; Ye, Xiaofei; Cheng, Yibang; Wang, Ying; Guo, Qianhui; Li, Yan; Lowres, Nicole; Freedman, Ben Ben; Wang, JiguangAims Incidence of atrial fibrillation is highly associated with age and cardiovascular co-morbidities. Given this relationship, we hypothesized that the dynamic changes resulting in an increase in the CHA<inf>2</inf>DS<inf>2</inf>-VAS<inf>C</inf> score over time would improve the efficiency of predicting incident atrial fibrillation on repeated screening after a negative test. Methods and results We investigated in an analysis of the AF-CATCH trial [quarterly vs. annual electrocardiogram (ECG) screening for atrial fibrillation in older Chinese individuals] data, the association between the changes in the CHA<inf>2</inf>DS<inf>2</inf>-VAS<inf>C</inf> score from baseline to end-of-study visit and the risk of incident atrial fibrillation. Participants without a history of atrial fibrillation and with a sinus rhythm at baseline were randomized to the annual (usual) or quarterly 30 s (intensive) single-lead ECG screening groups. During a median follow-up of 2.1 years in 6806 participants, the incidence rate of atrial fibrillation increased from 4.2 per 1000 person-years in participants with a change in the CHA<inf>2</inf>DS<inf>2</inf>-VAS<inf>C</inf> score of 0 to 6.4 and 25.8 per 1000 person-years in participants with a change in the CHA<inf>2</inf>DS<inf>2</inf>-VAS<inf>C</inf> score of 1 and ?2, respectively. A change in the CHA<inf>2</inf>DS<inf>2</inf>-VAS<inf>C</inf> score of ?2 was associated with a significantly elevated risk of incident atrial fibrillation. Conclusions Patients with substantial changes in the CHA<inf>2</inf>DS<inf>2</inf>-VAS<inf>C</inf> score were more likely to develop incident atrial fibrillation, and regular re-assessments of cardiovascular risk factors in the elderly are probably worthwhile to improve the detection of atrial fibrillation. The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved.
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Brida, Margarita; Chessa, Massimo; Celermajer, David S.; Li, Wei; Geva, Tal; Khairy Dr, Paul; Griselli, Massimo; Gatzoulis, Michael A.; Gatzoulis, Michael AthanasiosAtrial septal defects (ASDs) represent the most common congenital heart defect diagnosed in adulthood. Although considered a simple defect, challenges in optimal diagnostic and treatment options still exist due to great heterogeneity in terms of anatomy and time-related complications primarily arrhythmias, thromboembolism, right heart failure and, in a subset of patients, pulmonary arterial hypertension (PAH). Atrial septal defects call for tertiary expertise where all options may be considered, namely catheter vs. surgical closure, consideration of pre-closure ablation for patients with atrial tachycardia and suitability for closure or/and targeted therapy for patients with PAH. This review serves to update the clinician on the latest evidence, the nuances of optimal diagnostics, treatment options, and long-term follow-up care for patients with an ASD. The Author(s) 2021.
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Chau, Katrina; Welsh, Mikala; Makris, Angela; Hennessy, AnnemarieRecent advances have been made in understanding the nature of placental dysfunction causing preeclampsia, and other hypertensive disorders of pregnancy. The contribution of animal studies in the understanding of the effects of inadequate placentation on blood pressure and other target organs will be explored in this review. This will include technical aspects of animal studies in pregnancy, as well as the translation of data regarding newly discovered pathological pathways, in particular the angiogenic pathway, into targets in clinical practice. 2021, Crown.
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Bonnitcha, Paul D.; Sullivan, David R.; Fitzpatrick, Michael; Ireland, Andrea; Nguyen, Van Long; Koay, Yen Chin; OSullivan, John F.Asymmetric dimethylguanidino valeric acid (ADGV), asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are three arginine metabolites which have utility in the assessment of cardiovascular disease, renal disease and non-alcoholic fatty liver disease (NAFLD). Translation of these research metabolomic markers into routine clinical use requires the development of robust assays with appropriately assessed preanalytical variables and traceable clinical reference intervals. A hydrophilic interaction liquid chromatography (HILIC) tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of ADGV, ADMA and SDMA was developed. Sample stability and collection conditions were scrutinised to determine any preanalytical factors that could affect quantification under routine laboratory conditions. Patient samples from 120 males and 120 females were used to derive preliminary reference intervals. All three analytes were quantifiable in human plasma using unique MS/MS transitions. The analytes were stable for up to a week once separated from red cells, though reduced stability was observed upon extraction of the analytes from plasma. The assay was linear for concentration of ADGV between 1.6 nmol/L and 200 nmol/L and for ADMA and SDMA between 0.1 ?mol/L and 4.0 ?mol/L. The accuracy for all analytes was 97103% and interday and intraday imprecisions (coefficients of variation) were less than 10%. ADGV concentrations were noted to be lower in the female reference population when compared to males. The analytical method shows excellent performance and is sufficiently robust to be used in the clinical investigation of cardiovascular disease and NAFLD. 2022 Royal College of Pathologists of Australasia
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Offen, Sophie M.; Playford, David A.; Strange, G. A.; Stewart, S.; Celermajer, David S.Background: The prevalence and prognostic impact of tricuspid regurgitation (TR) remain incompletely characterized. Methods: The distribution of TR severity was analyzed in 439,558 adults (mean age, 62.1 17.8 years; 51.5% men) being investigated for heart disease, from 2000 to 2019, by 25 centers contributing to the National Echocardiography Database of Australia. Survival status and cause of death were ascertained in all adults from the National Death Index of Australia. The relationship between TR severity and mortality was examined. Results: Of those studied, 311,604 (70.9%) had no/trivial TR; 94,172 (21.4%), mild TR; 26,056 (5.9%), moderate TR; and 7,726 (1.8%), severe TR. During a median 4.1 years (interquartile range, 2.2-7.0 years) of follow-up, 109,004 died (49% from cardiovascular causes). Moderate or greater TR was associated with older age and female sex (P <.001). Individuals with moderate and severe TR had a 2.0- to 3.2-fold increased risk of all-cause long-term mortality after adjustment for age and sex compared with those with no/trivial TR (P <.001 for both comparisons). Even those with mild TR had a significantly increased risk for mortality (hazard ratio [HR] = 1.29; 95% CI, 1.27-1.31). In fully adjusted models, including for RV systolic pressure, atrial fibrillation, and significant left heart disease, there remained a 1.24- to 2.65-fold increased risk of mortality with mild (HR = 1.24; 95% CI, 1.23-1.26), moderate (HR = 1.72; 95% CI, 1.68-1.75), or severe TR (HR = 2.65; 95% CI, 2.57-2.73), compared with those with no/trivial TR (P <.001 for all). Conclusions: Tricuspid regurgitation is a common condition in adults referred for echocardiography. Moreover, even in the presence of other cardiac disease, increasing grades of TR are independently associated with increasing risks of cardiovascular and all-cause mortality. Furthermore, we show that even mild TR is independently associated with a significant increase in mortality. 2022 American Society of Echocardiography
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Radial First in Primary Percutaneous Coronary InterventionEnsuring At-Risk Groups Aren't Left BehindToomath, Shamus C.; Arnott, Clare; Patel, Sanjay[No abstract available]
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Othman, Farrah; Bailey, Brian P.; Collins, Nicholas J.; Lau, Edmund M.T.; Tanous, David J.; Rao, Karan; Celermajer, David S.; Cordina, Rachael LouiseBACKGROUND: Patent foramen ovale (PFO)-associated platypnea-orthodeoxia syndrome is characterized by dyspnea and hypoxemia when upright. The pathogenesis is thought to involve an increase in right atrial pressure or change in degree of right to left shunting with upright posture. METHODS AND RESULTS: We sought to characterize patients with platypnea-orthodeoxia syndrome related to PFO without pulmonary hypertension. We retrospectively reviewed databases at 3 tertiary referral hospitals in New South Wales, Australia from 2000 to 2019. Fourteen patients with a mean age of 6914 years had a PFO with wide tunnel separation. Mean New York Heart Association Classification was II (0.9) and 7 inpatients had been confined to bed (from postural symptoms). Baseline oxygen saturations supine were 93%5% and 84%6% upright. Two patients had a minor congenital heart defect and 4 had mild parenchymal lung disease with preserved lung function. The mean aortic root diameter was 37 6 mm and distance between aortic root and posterior atrial wall was 16 2 mm. Platypnea-orthodeoxia syndrome was preceded by surgery in 5 patients and 1 patient had mild pneumonia. Successful closure of the PFO using an Amplatzer device was performed in 11 of 14 patients. Post-closure, all patients had New York Heart Association Classification I (improvement 1.6 0.9, P<0.003) and semi-recumbent oxygen saturations increased by 13%8% (P<0.001, n=10). CONCLUSIONS: Platypnea-orthodeoxia syndrome is a debilitating condition, curable by PFO closure. Anatomical distortion of the atrial septum related to a dilated aortic root or shortening of the distance between the aortic root and posterior atrial wall may contribute to the syndrome. 2022 The Authors.
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Martinez, Chloe Anne; Jiramongkol, Yannasittha; Bal, Neha; Alwis, Imala D.; Nedoboy, Polina E.; Farnham, M. M. J.; White, Mark D.; Cistulli, Peter A.; Cook, Kristina M.The cellular response to hypoxia is regulated through enzymatic oxygen sensors, including the prolyl hydroxylases, which control degradation of the well-known hypoxia inducible factors (HIFs). Other enzymatic oxygen sensors have been recently identified, including members of the KDM histone demethylase family. Little is known about how different oxygen-sensing pathways interact and if this varies depending on the form of hypoxia, such as chronic or intermittent. In this study, we investigated how two proposed cellular oxygen-sensing systems, HIF-1 and KDM4A, KDM4B, and KDM4C, respond in cells exposed to rapid forms of intermittent hypoxia (minutes) and compared to chronic hypoxia (hours). We found that intermittent hypoxia increases HIF-1? protein through a pathway distinct from chronic hypoxia, involving the KDM4A, KDM4B, and KDM4C histone lysine demethylases. Intermittent hypoxia increases the quantity and activity of KDM4A, KDM4B, and KDM4C, resulting in a decrease in histone 3 lysine 9 (H3K9) trimethylation near the HIF1A locus. We demonstrate that this contrasts with chronic hypoxia, which decreases KDM4A, KDM4B, and KDM4C activity, leading to hypertrimethylation of H3K9 globally and at the HIF1A locus. Altogether, we found that demethylation of histones bound to the HIF1A gene in intermittent hypoxia increases HIF1A mRNA expression, which has the downstream effect of increasing overall HIF-1 activity and expression of HIF target genes. This study highlights how multiple oxygen-sensing pathways can interact to regulate and fine tune the cellular hypoxic response depending on the period and length of hypoxia. 2022 The Authors
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Lam, Yuenting; Tan, Richard P.; Michael, Praveesuda Lorwattanapongsa; Yang, Nianji; Dunn, Louise L.; Cooke, John P.; Celermajer, David S.; Wise, Steven G.; Ng, Martin K.C.Endothelial dysfunction, hallmarked by an imbalance between vasoconstriction and vasorelaxation, is associated with diabetes. Thioredoxin Interacting protein (TXNIP), controlled by an exquisitely glucose sensitive gene, is increasingly recognized for its role in diabetes. However, the role of TXNIP in modulating diabetes-related endothelial dysfunction remains unclear. To elucidate the role of TXNIP, we generated two novel mouse strains; endothelial-specific TXNIP knockout (EKO) and a Tet-O inducible, endothelial-specific TXNIP overexpression (EKI). Hyperglycemia was induced by streptozotocin (STZ) treatment in floxed control (fl/fl) and EKO mice. Doxycycline (DOX) was given to EKI mice to induce endothelial TXNIP overexpression. The ablation of endothelial TXNIP improved glucose tolerance in EKO mice. Acetylcholine-induced, endothelium-dependent vasorelaxation was impaired in STZ-treated fl/fl mice while this STZ impaired vasorelaxation was attenuated in EKO mice. Hyperglycemia induction of NLRP3 and reductions in Akt and eNOS phosphorylation were also mitigated in EKO mice. Overexpression of endothelial TXNIP did not impair glucose tolerance in DOX-treated EKI mice, however induction of endothelial TXNIP led to impaired vasorelaxation in EKI mice. This was associated with increased NLRP3 and reduced Akt and eNOS activation. In conclusion, deletion of endothelial TXNIP is protective against and overexpression of endothelial TXNIP induces endothelial dysfunction; thus, endothelial TXNIP plays a critical role in modulating endothelial dysfunction. 2022
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Williams, Kate M.; Modi, Rakesh Narendra; Dymond, Andrew; Hoare, Sarah E.; Powell, Alison E.; Burt, Jenni A.; Edwards, Duncan A.H.; Lund, Jenny; Johnson, Rachel A.; Lobban, Trudie C.A.; Lown, Mark T.; Sweeting, Michael J.; Thom, Howard H.Z.; Kaptoge, Stephen K.; Fusco, Francesco; Morris, Stephen; Lip, Gregory Y.H.; Armstrong, N.; Cowie, Martin R.; Fitzmaurice, David Andrew; Freedman, Ben Ben; Griffin, Simon J.; Sutton, Stephen R.; Hobbs, FD Richard; McManus, R. J.; Mant, Jonathan W.F.; Safer Authorship Group, TheIntroduction Atrial fibrillation (AF) is a common arrhythmia associated with 30% of strokes, as well as other cardiovascular disease, dementia and death. AF meets many criteria for screening, but there is limited evidence that AF screening reduces stroke. Consequently, no countries recommend national screening programmes for AF. The Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) trial aims to determine whether screening for AF is effective at reducing risk of stroke. The aim of the pilot study is to assess feasibility of the main trial and inform implementation of screening and trial procedures. Methods and analysis SAFER is planned to be a pragmatic randomised controlled trial (RCT) of over 100 000 participants aged 70 years and over, not on long-term anticoagulation therapy at baseline, with an average follow-up of 5 years. Participants are asked to record four traces every day for 3 weeks on a hand-held single-lead ECG device. Cardiologists remotely confirm episodes of AF identified by the device algorithm, and general practitioners follow-up with anticoagulation as appropriate. The pilot study is a cluster RCT in 36 UK general practices, randomised 2:1 control to intervention, recruiting approximately 12 600 participants. Pilot study outcomes include AF detection rate, anticoagulation uptake and other parameters to incorporate into sample size calculations for the main trial. Questionnaires sent to a sample of participants will assess impact of screening on psychological health. Process evaluation and qualitative studies will underpin implementation of screening during the main trial. An economic evaluation using the pilot data will confirm whether it is plausible that screening might be cost-effective. Ethics and dissemination The London - Central Research Ethics Committee (19/LO/1597) and Confidentiality Advisory Group (19/CAG/0226) provided ethical approval. Dissemination will be via publications, patient-friendly summaries, reports and engagement with the UK National Screening Committee. Trial registration number ISRCTN72104369.
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Dennis, Mark R.; Howpage, Sashie; McGill, Margaret J.; Dutta, Shashwati; Koay, Yen Chin; Nguyen-Lal, Lisa; Lal, Sean P.; Wu, Ted; Ugander, Martin; Wang, Alexandra; Muz, Phillip A.; Wong, Jencia; Constantino, Maria Ines; OSullivan, John F.; Twigg, Stephen Morris; Puranik, RajeshAims: To identify biomarkers of cardiomyopathy in patients with type 2 diabetes mellitus (T2DM) using cardiovascular magnetic resonance (CMR) and to identify associations between functional status, metabolomic profile and myocardial fibrosis. Methods: In this prospective case control study, patients (n = 49) with T2DM without significant coronary artery disease, and matched controls (n = 18) underwent CMR, cardiopulmonary exercise testing, and plasma metabolomic analyses. Results: Patients with T2DM (n = 49, median [interquartile range] age 61 [5663] years, 61% male, diabetes duration 11 [720] years), historical HbA1c 7.6% (60 mmol/mol) (6.98.6) and matched controls (n = 18) were examined. Study patients had increased myocardial extracellular volume (ECV) (26.9 [23.830.0] vs 23.4 [22.425.5) %, p < 0.001). Increased ECV was associated with male sex (p = 0.04), time with T2DM (p = 0.02), reduced peak VO<inf>2</inf> (R2 = 0.48, p = 0.01), increased circulating choline (p = 0.002) and cysteamine (p = 0.002) both of which were also associated with reduced peak VO<inf>2</inf> (p < 0.025 and 0.014 respectively). Conclusions: Patients with well-controlled T2DM without significant coronary disease exhibit focal and diffuse myocardial fibrosis and diffuse myocardial fibrosis is associated with reduced exercise tolerance and metabolites. Plasma metabolites may provide mechanistic insights into diffuse myocardial fibrosis, and cardiopulmonary fitness. 2022
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Maclean, Jessica A.A.; Tomkins, Amelia J.; Sturgeon, Sharelle A.; Hofma, Benjamin R.; Alwis, Imala D.; Samson, Andre L.; Schoenwaelder, Simone M.; Jackson, Shaun P.Recanalization with restored cerebral perfusion is the primary goal of thrombolytic therapy in acute ischemic stroke. The identification of adjunctive therapies that can be safely used to enhance thrombolysis in stroke remains an elusive goal. We report here the development of a mouse in situ carotid artery thrombolysis (iCAT) stroke model involving graded cerebral ischemia to induce unihemispheric infarction after thrombotic occlusion of the common carotid artery (CCA). Electrolytic-induced thrombotic occlusion of the left CCA enabled real-time assessment of recanalization and rethrombosis events after thrombolysis with recombinant tissue-type plasminogen activator (rtPA). Concurrent transient stenosis of the right CCA induced unihemispheric hypoperfusion and infarction in the left middle cerebral artery territory. Real-time assessment of thrombolysis revealed recanalization rates ,30% in rtPA-treated animals with high rates of rethrombosis. Addition of the direct thrombin inhibitor argatroban increased recanalization rates to 50% and reduced rethrombosis. Paradoxically, this was associated with increased cerebral ischemia and stroke-related mortality (25%-42%). Serial analysis of carotid and cerebral blood flow showed that coadministration of argatroban with rtPA resulted in a marked increase in carotid artery embolization, leading to distal obstruction of the middle cerebral artery. Real-time imaging of carotid thrombi revealed that adjunctive anticoagulation destabilized platelet-rich thrombi at the vessel wall, leading to dislodgement of large platelet emboli. These studies confirm the benefits of anticoagulants in enhancing thrombolysis and large artery recanalization; however, at high levels of anticoagulation (?3-fold prolongation of activated partial thromboplastin time), this effect is offset by increased incidence of carotid artery embolization and distal middle cerebral artery occlusion. The iCAT stroke model should provide important new insight into the effects of adjunctive antithrombotic agents on real-time thrombus dynamics during thrombolysis and their correlation with stroke outcomes. 2022 by The American Society of Hematology.
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Von-Lewinski, Dirk; Benedikt, Martin; Alber, Hannes Franz W.; Debrauwere, Jan P.; Smits, Pieter Cornelis; es, Istv Ferenc; Kiss, Rert Gabor; Merkely, Ba Peter; Nagy, Gergely Gygy; Ptaszynski, Pawel Andrzej; Za?ebski, MacIej; Kubica, Julia Maria; Kleinrok, Andrzej; Coats, Andrew J.S.; Wallner, MarkusPatients with acute myocardial infarction are at high risk for developing heart failure due to scar development. Although regenerative approaches are evolving, consistent clinical benefits have not yet been reported. Treatment with dutogliptin, a second-generation DPP-4 inhibitor, in co-administration with filgrastim (G-CSF) has been shown to enhance endogenous repair mechanisms in experimental models. The REC-DUT-002 trial was a phase 2, multicenter, double-blind placebo-controlled trial which explored the safety, tolerability, and efficacy of dutogliptin and filgrastim in patients with ST-elevation Myocardial Infarction (STEMI). Patients (n = 47, 56.1 10.7 years, 29% female) with STEMI, reduced left ventricular ejection fraction (EF ? 45%) and successful revascularization following primary PCI were randomized to receive either study treatment or matching placebo. Cardiac magnetic resonance imaging (cMRI) was performed within 72 h post-PCI and repeated after 3 months. The study was closed out early due to the SARS-CoV-2 pandemic. There was no statistically significant difference between the groups with respect to serious adverse events (SAE). Predefined mean changes within cMRI-derived functional and structural parameters from baseline to 90 days did not differ between placebo and treatment (left ventricular end-diastolic volume: +13.7 mL vs. +15.7 mL; LV-EF: +5.7% vs. +5.9%). Improvement in cardiac tissue health over time was noted in both groups: full-width at half-maximum late gadolinium enhancement (FWHM LGE) mass (placebo: ?12.7 g, treatment: ?19.9 g; p = 0.23). Concomitant treatment was well tolerated, and no safety issues were detected. Based on the results, the FDA and EMA have already approved an adequately powered large outcome trial. 2022 by the authors.
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McKenzie, Kirsty; Lowres, Nicole; Orchard, Jessica Joan; Hespe, Charlotte Mary; Freedman, Ben Ben; Giskes, KatrinaBackground: Current Australian and European guidelines recommend opportunistic screening for atrial fibrillation (AF) among patients ?65 years, but general practitioners (GPs) report time constraints as a major barrier to achieving this. Patient self-screening stations in GP waiting rooms may increase screening rates and case detection of AF, but the acceptability of patient self-screening from the practice staff perspective, and the usability by patients, is unknown. Objective: To determine staff perspectives on AF self-screening stations and factors impacting acceptability, usability by patients, and sustainability. Methods: We performed semi-structured interviews with 20 general practice staff and observations of 22 patients while they were undertaking self-screening. Interviews were coded and data analyzed using an iterative thematic analysis approach. Results: GPs indicated high levels of acceptance of self-screening, and reported little impact on their workflow. Reception staff recognized the importance of screening for AF, but reported significant impacts on their workflow because some patients were unable to perform screening without assistance. Patient observations corroborated these findings and suggested some potential ways to improve usability. Conclusion: AF self-screening in GP waiting rooms may be a viable method to increase opportunistic screening by GPs, but the impacts on reception workflow need to be mitigated for the method to be upscaled for more widespread screening. Furthermore, more age-appropriate station design may increase patient usability and thereby also reduce impact on reception workflow. 2022 Heart Rhythm Society
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Luk, Alison W.S.; Mitchell, Lachlan; Koay, Yen Chin; OSullivan, John F.; OConnor, Helen T.; Hackett, Daniel A.; Holmes, Andrew J.Diet, exercise and the gut microbiome are all factors recognised to be significant contributors to cardiometabolic health. However, diet and exercise interventions to modify the gut microbiota to improve health are limited by poor understanding of the interactions between them. In this pilot study, we explored dietexercisemicrobiome dynamics in bodybuilders as they represent a distinctive group that typically employ well-defined dietary strategies and exercise regimes to alter their body composition. We performed longitudinal characterisation of diet, exercise, the faecal microbial community composition and serum metabolites in five bodybuilders during competition preparation and post-competition. All participants reduced fat mass while conserving lean mass during competition preparation, corresponding with dietary energy intake and exercise load, respectively. There was individual variability in food choices that aligned to individualised gut microbial community compositions throughout the study. However, there was a common shift from a high protein, low carbohydrate diet during pre-competition to a more macronutrient-balanced diet post-competition, which was associated with similar changes in the gut microbial diversity across participants. The circulating metabolite profiles also reflected individuality, but a subset of metabolites relating to lipid metabolism distinguished between pre- and post-competition. Changes in the gut microbiome and circulating metabolome were distinct for each individual, but showed common patterns. We conclude that further longitudinal studies will have greater potential than cross-sectional studies in informing personalisation of diet and exercise regimes to enhance exercise outcomes and improve health. 2022 by the authors.
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Hall-Beauvais, Alexandra Van; Poganik, Jesse Richard; Huang, Kuangting; Parvez, Saba; Zhao, Yi; Lin, Hongyu; Liu, Xuyu; Long, Marcus John Curtis; Aye, YimonStudying electrophile signaling is marred by difficulties in parsing changes in pathway flux attributable to on-target, vis-vis off-target, modifications. By combining bolus dosing, knockdown, and Z-REXa tool investigating on-target/on-pathway electrophile signaling, we document that electrophile labeling of one zebrafish-Keap1-paralog (zKeap1b) stimulates Nrf2-driven antioxidant response (AR) signaling (like the human-ortholog). Conversely, zKeap1a is a dominant-negative regulator of electrophile-promoted Nrf2-signaling, and itself is nonpermissive for electrophile-induced Nrf2-upregulation. This behavior is recapitulated in human cells, wherein following electrophile treatment: (1) zKeap1b-transfected cells are permissive for augmented AR-signaling through reduced zKeap1bNrf2 binding; (2) zKeap1a-transfected cells are non-permissive for AR-upregulation, as zKeap1aNrf2 binding capacity remains unaltered; (3) 1:1 ZKeap1a:zKeap1b-transfected cells show no Nrf2-release from the Keap1-complex, rendering these cells unable to upregulate AR. We identified a zKeap1a-specific point-mutation (C273I) responsible for zKeap1as behavior. Human-Keap1(C273I), of known diminished Nrf2-regulatory capacity, dominantly muted electrophile-induced Nrf2-signaling. These studies highlight divergent and interdependent electrophile signaling behaviors, despite conserved electrophile sensing. 2022, eLife Sciences Publications Ltd. All rights reserved.
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Anderson, Christopher A.J.; Suna, Jessica M.; Keating, Shelley E.; Cordina, Rachael Louise; Tran, Derek L.; Ayer, Julian Ganesh J.; Coombes, Jeff S.Background: While exercise training is beneficial in the prevention and management of many chronic diseases, the role of exercise training in children and adolescents with congenital heart disease is less understood. We sought to determine the safety and efficacy of exercise training in children and adolescents with congenital heart disease. Methods: We conducted a systematic search of the following databases: PubMed, CINAHL, EMBASE, Web of Science and SportDiscus. We included randomised controlled trials that incorporated an exercise intervention compared with a non-exercising comparator group and examined safety and efficacy in children and adolescents with congenital heart disease. A descriptive analysis of the included trials was then conducted. Results: A total of 9 articles from 6 trials (642 participants with varying conditions and disease severity) were included. Significant variability of study participants and outcomes were observed across the trials. No adverse events linked to the exercise interventions were stated. The articles reported numerous positive changes to clinically relevant fitness measures. Exercise capacity improved with exercise training in 3 of 4 trials in which it was measured. Cardiorespiratory fitness showed improvements in 3 of 4 trials. Neuromuscular fitness increased in 1 of 2 trials. Physiological and metabolic parameters were improved, and negative changes were not observed to several clinically important measures (e.g. muscular oxygenation, cardiac measures) in 2 of 2 trials. Physical activity increased in 1 of 3 trials. No articles reported on changes in measures of body composition. Outcomes are varied with little consensus on measurements or assessment methods. Conclusions: Exercise training appears to be safe and efficacious for improving physical fitness in children and adolescents with congenital heart disease who have been appropriately screened by their medical team. However, the certainty of the evidence for these findings is low to moderate. 2022
