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Showing 501–520 of 2058 publications.
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Tran, Derek L.; Celermajer, David S.; Ayer, Julian Ganesh J.; Grigg, Leeanne Elizabeth; Clendenning, Carley; Hornung, Tim S.; Justo, Robert N.; Davis, Glen Macartney; d'Udekem, Yves A.; Cordina, Rachael LouiseBackground: People with a Fontan circulation usually have moderately impaired exercise performance, although a subset have high physical performance (Super-Fontan), which may represent a low-risk phenotype. Methods: People with a Super-Fontan phenotype were defined as achieving normal exercise performance [?80% predicted peak oxygen uptake (VO<inf>2</inf>) and work rate] during cardiopulmonary exercise testing (CPET) and were identified from the Australian and New Zealand Fontan Registry. A Fontan control group that included people with impaired exercise performance (<80% predicted VO<inf>2</inf> or work rate) was also identified based on a 1:3 allocation ratio. A subset of participants were prospectively recruited and completed a series of physical activity, exercise self-efficacy, and health-related quality of life questionnaires. Results: Sixty CPETs (Super-Fontan, n = 15; control, n = 45) were included. A subset (Super-Fontan, n = 10; control, n = 13) completed a series of questionnaires. Average age was 29 8 years; 48% were males. Exercise capacity reflected by percent predicted VO<inf>2</inf> was 67 17% in the entire cohort. Compared to the Super-Fontan phenotype, age at Fontan completion was higher in controls (4.0 2.9 vs. 7.2 5.3 years, p = 0.002). Only one (7%) person in the Super-Fontan group had a dominant right ventricle compared to 15 (33%) controls (p = 0.043). None of those in the Super-Fontan group were obese, while almost a quarter (22%) of controls were obese based on body mass index (p = 0.046). Lung function abnormalities were less prevalent in the Super-Fontan group (20 vs. 70%, p = 0.006). Exercise self-efficacy was greater in the Super-Fontan group (34.2 3.6 vs. 27.9 7.2, p = 0.02). Self-reported sports participation and physical activity levels during childhood and early adulthood were higher in the Super-Fontan group (p < 0.05). The total average time spent participating in structured sports and physical activity was 4.3 2.6 h/wk in the Super-Fontan group compared to 2.0 3.0 h/wk in controls, p = 0.003. There were no differences in self-reported current total physical activity score or health-related quality of life between groups (p ? 0.05). Conclusions: The Super-Fontan phenotype is associated with a healthy weight, lower age at Fontan completion, better exercise self-efficacy, and higher overall levels of sport and physical activity participation during physical development. 2021 Tran, Celermajer, Ayer, Grigg, Clendenning, Hornung, Justo, Davis, d'Udekem and Cordina.
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Zink, Matthias Daniel H.; Mischke, Karl G.; Keszei, Andr P.; Rummey, Christian; Freedman, Ben Ben; Neumann, Gabriele; Tolksdorf, Alina; Frank, Friederike; Wienstrr, Jan; Kuth, Nicole; Schulz, Jg B.; Marx, NikolausAims: Current guidelines recommend opportunistic screening for atrial fibrillation (AF) but the prognosis of individuals is unclear. The aim of this investigation is to determine prevalence and 1-year outcome of individuals with screen-detected AF. Methods and results: We performed a prospective, pharmacy-based single time point AF screening study in 7107 elderly citizens (?65 years) using a hand-held, single-lead electrocardiogram (ECG) device. Prevalence of AF was assessed, and data on all-cause death and hospitalization for cardiovascular (CV) causes were collected over a median follow-up of 401 (372; 435) days. Mean age of participants was 74 5.9 years, with 58% (N = 4130) of female sex. Automated heart rhythm analyses identified AF in 432 (6.1%) participants, with newly diagnosed AF in 3.6% of all subjects. During follow-up, 62 participants (0.9%) died and 390 (6.0%) were hospitalized for CV causes. Total mortality was 2.3% in participants with a screen-detected AF and 0.8% in subjects with a normal ECG [hazard ratio (HR) 2.94; 95% confidence interval (CI) 1.49-5.78; P = 0.002]; hospitalization for CV causes occurred in 10.6% and 5.5%, respectively (HR 2.08; 95% CI 1.52-2.84; P < 0.001). Compared with subjects without a history of AF at baseline and a normal ECG, participants with newly diagnosed or known AF had a significantly higher mortality risk with HRs of 2.64 (95% CI 1.05-6.66; P = 0.04) and 2.68 (95% CI 1.44-4.97; P = 0.002), respectively. After multivariable adjustment, screen-detected AF remained a significant predictor of death or hospitalization for CV causes. Conclusion: Pharmacy-based, automated AF screening in elderly citizens identified subjects with unknown AF and an excess mortality risk over the next year. 2020 The Author(s).
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Dunn, Louise L.; Kong, Stephanie M.Y.; Tumanov, Sergey; Chen, Weiyu; Cantley, James; Ayer, Anita; Maghzal, Ghassan J.; Midwinter, Robyn G.; Chan, Kim Hoe; Ng, Martin K.C.; Stocker, RolandOBJECTIVE: Hmox1 (heme oxygenase-1) is a stress-induced enzyme that catalyzes the degradation of heme to carbon monoxide, iron, and biliverdin. Induction of Hmox1 and its products protect against cardiovascular disease, including ischemic injury. Hmox1 is also a downstream target of the transcription factor HIF-1? (hypoxia-inducible factor-1?), a key regulator of the body's response to hypoxia. However, the mechanisms by which Hmox1 confers protection against ischemia-mediated injury remain to be fully understood. APPROACH AND RESULTS: Hmox1 deficient (Hmox1-/-) mice had impaired blood flow recovery with severe tissue necrosis and autoamputation following unilateral hindlimb ischemia. Autoamputation preceded the return of blood flow, and bone marrow transfer from littermate wild-type mice failed to prevent tissue injury and autoamputation. In wild-type mice, ischemia-induced expression of Hmox1 in skeletal muscle occurred before stabilization of HIF-1?. Moreover, HIF-1? stabilization and glucose utilization were impaired in Hmox1-/-mice compared with wild-type mice. Experiments exposing dermal fibroblasts to hypoxia (1% O2) recapitulated these key findings. Metabolomics analyses indicated a failure of Hmox1-/-mice to adapt cellular energy reprogramming in response to ischemia. Prolyl-4-hydroxylase inhibition stabilized HIF-1? in Hmox1-/-fibroblasts and ischemic skeletal muscle, decreased tissue necrosis and autoamputation, and restored cellular metabolism to that of wild-type mice. Mechanistic studies showed that carbon monoxide stabilized HIF-1? in Hmox1-/-fibroblasts in response to hypoxia. CONCLUSIONS: Our findings suggest that Hmox1 acts both downstream and upstream of HIF-1?, and that stabilization of HIF-1? contributes to Hmox1's protection against ischemic injury independent of neovascularization 2020 American Heart Association, Inc.
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Vaidya, Kaivan; Tucker, Bradley; Kurup, Rahul; Khandkar, Chinmay; Pandi?, Elvis; Barraclough, Jennifer Y.; Machet, Joshua; Misra, Ashish K.; Kavurma, Mary M.; Martez, Gonzalo J.; Rye, Kerry Anne; Cochran, Blake J.; Patel, SanjayBACKGROUND: Release of neutrophil extracellular traps (NETs) after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) is associated with periprocedural myocardial infarction, as a result of microvascular obstruction via proinflammatory and prothrombotic pathways. Colchicine is a well-established anti-inflammatory agent with growing evidence to support use in patients with coronary disease. However, its effects on post-PCI NET formation in ACS have not been explored. METHODS AND RESULTS: Sixty patients (40 ACS; 20 stable angina pectoris) were prospectively recruited and allocated to colchicine or no treatment. Within 24 hours of treatment, serial coronary sinus blood samples were collected during PCI. Isolated neutrophils from 10 patients with ACS post-PCI and 4 healthy controls were treated in vitro with colchicine (25 nmol/L) and stimulated with either ionomycin (5 ?mol/L) or phorbol 12-myristate 13-acetate (50 nmol/L). Extracellular DNA was quantified using Sytox Green and fixed cells were stained with Hoechst 3342 and anti-alpha tubulin. Baseline characteristics were similar across both treatment and control arms. Patients with ACS had higher NET release versus patients with stable angina pectoris (P<0.001), which was reduced with colchicine treatment (area under the curve: 0.58 versus 4.29; P<0.001). In vitro, colchicine suppressed unstimulated (P<0.001), phorbol 12-myristate 13-acetate-induced (P=0.009) and ionomycin-induced (P=0.002) NET formation in neutrophils isolated from patients with ACS post-PCI, but not healthy controls. Tubulin organization was impaired in neutrophils from patients with ACS but was restored by colchicine treatment. CONCLUSIONS: Colchicine suppresses NET formation in patients with ACS post-PCI by restoring cytoskeletal dynamics. These findings warrant further investigation in randomized trials powered for clinical end points. 2020 The Authors.
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Molitor, Michael; Rudi, Wolf Stephan; Garlapati, Venkata S.; Finger, Stefanie; Scher, Rebecca L.; Kossmann, Sabine; Lagrange, Jy; Nguyen, Thanh Son; Wild, Johannes; Knopp, Tanja; Karbach, Susanne Helena; Knorr, Maike; Ruf, Wolfram; Mzel, Tomas F.; Wenzel, PhilipAims: Heart failure (HF) ensuing myocardial infarction (MI) is characterized by the initiation of a systemic inflammatory response. We aimed to elucidate the impact of myelomonocytic cells and their activation by angiotensin II on vascular endothelial function in a mouse model of HF after MI. Methods and results: HF was induced in male C57BL/6J mice by permanent ligation of the left anterior descending coronary artery. Compared to sham, HF mice had significantly impaired endothelial function accompanied by enhanced mobilization of Sca-1+c-Kit+ haematopoietic stem cells and Sca-1-c-Kit+ common myeloid and granulocyte-macrophage progenitors in the bone marrow as well as increased vascular infiltration of CD11b+Ly6G-Ly6Chigh monocytes and accumulation of CD11b+ F4/80+ macrophages, assessed by flow cytometry. Using mice with Cre-inducible expression of diphtheria toxin receptor in myeloid cells, we selectively depleted lysozyme M+ myelomonocytic cells for 10 days starting 28 days after MI. While the cardiac phenotype remained unaltered until 38 days post-MI, myeloid cell depletion attenuated vascular accumulation of Nox2+CD45+ cells, endothelial dysfunction, oxidative stress, and vascular expression of adhesion molecules and angiotensin II receptor type 1 (AT1R). Pharmacological blockade of this receptor for 4 weeks did not significantly alter cardiac function, but mimicked the effects of myeloid cell depletion: telmisartan (20 mg/kg/day, fed to C57BL/6J mice) diminished bone marrow myelopoesis and myeloid reactive oxygen species production, attenuated endothelial leucocyte rolling and vascular accumulation of CD11b+Ly6G-Ly6Chigh monocytes and macrophages, resulting in improved vascular function with less abundance of Nox2+CD45+ cells. Conclusion: Endothelial dysfunction in HF ensuing MI is mediated by inflammatory Nox2+ myeloid cells infiltrating the vessel wall that can be targeted by AT1R blockade. 2020 Published on behalf of the European Society of Cardiology. All rights reserved.
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Galougahi, Keyvan Karimi; Patel, Sanjay; Shlofmitz, Richard Alan; Maehara, Akiko; Kereiakes, Dean J.; Hill, Jonathan Michael; Stone, Gregg Whitney; Ali, Ziad A.Constituting a significant proportion of lesions treated with transcatheter interventions in the coronary arteries, moderate-to-severe calcification portends lower procedural success rates, increased periprocedural major adverse events, and unfavorable long-term clinical outcomes compared with noncalcific plaques. Adapted from the lithotripsy technology for treatment of nephrolithiasis, intravascular lithotripsy is a new technique for treatment of severely calcific lesions that uses acoustic shock waves in a balloon-based system to induce fracture in the calcium deposits to facilitate luminal gain and stent expansion. Herein, we summarize the physics and characteristics of the currently available intravascular lithotripsy system (Shockwave Medical, Santa Clara, CA), the clinical data on intravascular lithotripsy use in the coronary arteries, and future directions for adoption of the technique in percutaneous coronary intervention. 2021 Lippincott Williams and Wilkins. All rights reserved.
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Freedman, Ben Ben; Kamel, Hooman; van Gelder, Isabelle C.; Schnabel, Renate B.Atrial fibrillation (AF) and stroke are inextricably connected, with classical Virchow pathophysiology explaining thromboembolism through blood stasis in the fibrillating left atrium. This conceptualization has been reinforced by the remarkable efficacy of oral anticoagulant (OAC) for stroke prevention in AF. A number of observations showing that the presence of AF is neither necessary nor sufficient for stroke, cast doubt on the causal role of AF as a villain in vascular brain injury (VBI). The requirement for additional risk factors before AF increases stroke risk; temporal disconnect of AF from a stroke in patients with no AF for months before stroke during continuous ECG monitoring but manifesting AF only after stroke; and increasing recognition of the role of atrial cardiomyopathy and atrial substrate in AF-related stroke, and also stroke without AF, have led to rethinking the pathogenetic model of cardioembolic stroke. This is quite separate from recognition that in AF, shared cardiovascular risk factors can lead both to non-embolic stroke, or emboli from the aorta and carotid arteries. Meanwhile, VBI is now expanded to include dementia and cognitive decline: research is required to see if reduced by OAC. A changed conceptual model with less focus on the arrhythmia, and more on atrial substrate/cardiomyopathy causing VBI both in the presence or absence of AF, is required to allow us to better prevent AF-related VBI. It could direct focus towards prevention of the atrial cardiomyopathy though much work is required to better define this entity before the balance between AF as villain or bystander can be determined. 2020 Oxford University Press. All rights reserved.
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Zhao, Yunduo Charles; Vatankhah, Parham; Goh, Tiffany; Wang, Jiaqiu; Chen, Xuanyi Valeria; Kashani, Moein Navvab; Zheng, Keke; Li, Zhiyong; Ju, Lining ArnoldPlatelet aggregation plays a central role in pathological thrombosis, preventing healthy physiological blood flow within the circulatory system. For decades, it was believed that platelet aggregation was primarily driven by soluble agonists such as thrombin, adenosine diphosphate and thromboxane A2. However, recent experimental findings have unveiled an intriguing but complementary biomechanical mechanism-the shear rate gradients generated from flow disturbance occurring at sites of blood vessel narrowing, otherwise known as stenosis, may rapidly trigger platelet recruitment and subsequent aggregation. In our Nature Materials 2019 paper [1], we employed microfluidic devices which incorporated micro-scale stenoses to elucidate the molecular insights underlying the prothrombotic effect of blood flow disturbance. Nevertheless, the rheological mechanisms associated with this stenotic microfluidic device are poorly characterized. To this end, we developed a computational fluid dynamics (CFD) simulation approach to systematically analyze the hemodynamic influence of bulk flow mechanics and flow medium. Grid sensitivity studies were performed to ensure accurate and reliable results. Interestingly, the peak shear rate was significantly reduced with the device thickness, suggesting that fabrication of microfluidic devices should retain thicknesses greater than 50 m to avoid unexpected hemodynamic aberration, despite thicker devices raising the cost of materials and processing time of photolithography. Overall, as many groups in the field have designed microfluidic devices to recapitulate the effect of shear rate gradients and investigate platelet aggregation, our numerical simulation study serves as a guideline for rigorous design and fabrication of microfluidic thrombosis models. This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Stavrakis, Stavros; Elkholey, Khaled; Lofgren, Marty M.; Abideen Asad, Zain Ul; Stephens, Lancer D.; Freedman, Ben BenBACKGROUND: American Indian adults have a higher risk of atrial fibrillation (AF) compared with other racial groups. We implemented opportunistic screening to detect silent AF in American Indian adults attending a tribal health system using a mobile, single-lead ECG device. METHODS AND RESULTS: American Indian patients aged ?50 years followed in a tribal primary care clinic with no history of AF underwent a 30-second ECG. A cardiologist overread all tracings to confirm the diagnosis of AF. After AF was confirmed, patients were referred to their primary care physician for initiation of anticoagulation. Patients seen over the same time period, who were not undergoing screening, served as controls. A total of 1019 patients received AF screening (mean age, 61.58.9 years, 62% women). Age and sex distribution of those screened was similar to the overall clinic population. New AF was diagnosed in 15 of 1019 (1.5%) patients screened versus 4 of 1267 (0.3%) patients who were not screened (mean difference, 1.2%; 95% CI, 0.3%2.2%, P=0.002). Eight of 15 with new screen-detected AF were aged <65 years. Those with screen-detected AF were slightly older and had a higher CHA<inf>2</inf> DS<inf>2</inf>-VASc score than those without AF. Fourteen of 15 patients diagnosed with new AF had a CHA<inf>2</inf> DS<inf>2</inf>-VASc score ?1 and initiated anticoagulation. CONCLUSIONS: Opportunistic, mobile single-lead ECG screening for AF is feasible in tribal clinics, and detects more AF than usual care, leading to appropriate initiation of anticoagulation. AF develops at a younger age in American Indian adults who would likely benefit from earlier AF screening. 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
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Di Bartolo, Belinda Ann; Cartland, Si; Genner, Scott W.; Cholan, Pradeep Manuneedhi; Vellozzi, Melissa A.; Rye, Kerry Anne; Kavurma, Mary M.Background and Aims. Apolipoprotein A-I (ApoA-I), the main component of high-density lipoprotein (HDL), not only promotes reverse cholesterol transport (RCT) in atherosclerosis but also increases insulin secretion in pancreatic ?-cells, suggesting that interventions which raise HDL levels may be beneficial in diabetes-associated cardiovascular disease (CVD). Previously, we showed that TNF-related apoptosis-inducing ligand (TRAIL) deletion in Apolipoprotein Eknockout (Apoe-/-) mice results in diabetes-accelerated atherosclerosis in response to a "Western"diet. Here, we sought to identify whether reconstituted HDL (rHDL) could improve features of diabetes-associated CVD in Trail-/-Apoe-/- mice. Methods and Results. Trail-/-Apoe-/- and Apoe-/- mice on a "Western"diet for 12 weeks received 3 weekly infusions of either PBS (vehicle) or rHDL (containing ApoA-I (20 mg/kg) and 1-palmitoyl-2-linoleoyl phosphatidylcholine). Administration of rHDL reduced total plasma cholesterol, triglyceride, and glucose levels in Trail-/-Apoe-/- but not in Apoe-/- mice, with no change in weight gain observed. rHDL treatment also improved glucose clearance in response to insulin and glucose tolerance tests. Immunohistological analysis of pancreata revealed increased insulin expression/production and a reduction in macrophage infiltration in mice with TRAIL deletion. Furthermore, atherosclerotic plaque size in Trail-/-Apoe-/- mice was significantly reduced associating with increased expression of the M2 macrophage marker CD206, suggesting HDL's involvement in the polarization of macrophages. rHDL also increased vascular mRNA expression of RCT transporters, ABCA1 and ABCG1, in Trail-/-Apoe-/- but not in Apoe-/- mice. Conclusions. rHDL improves features of diabetes-associated atherosclerosis in mice. These findings support the therapeutic potential of rHDL in the treatment of atherosclerosis and associated diabetic complications. More studies are warranted to understand rHDL's mechanism of action. 2021 Belinda A. Di Bartolo et al.
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Davanzo, Rene Hameau; Alarc, Alberto Fuensalida; Calqu, Jorge Quitral; Varela, Pablo Sepveda; Sepveda, Alejandro Martez; Herreros, Ram Corbal; Patel, Sanjay; Martez, Gonzalo J.Dual antiplatelet therapy is one of the cornerstones of modern percutaneous coronary interventions. The development of new therapeutic agents has significantly reduced ischemic events at the risk of increased bleeding complications. Therefore, efforts are currently focused on optimizing therapeutic algorithms to obtain the greatest anti-thrombotic benefit associated with the lowest risk of bleeding, that is, the greater net clinical benefit. A significant number of trials evaluating different drug combinations or adjustments in treatment duration have been completed. However, clinical translation of these results is often difficult due to the heterogeneity of the therapeutic approaches. The aim of this manuscript is to provide an updated review of the literature regarding the use of dual antiplatelet therapy in patients undergoing coronary angioplasty and stenting. 2021 Bentham Science Publishers.
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Dupuy, Alexander; Hagimola, Lejla; Mgaieth, Neil S.A.; Houlahan, Callum B.; Preketes-Tardiani, Renee Ellen; Coleman, Paul R.; Passam, Freda H.Microfluidic devices have an established role in the study of platelets and coagulation factors in thrombosis, with potential diagnostic applications. However, few microfluidic devices have assessed the contribution of neutrophils to thrombus formation, despite increasing knowledge of neutrophils importance in cardiovascular thrombosis. We describe a thromboinflammation model which uses straight channels, lined with fixed human umbilical vein endothelial cells, after treatment with tumour necrosis factor-alpha. Re-calcified whole blood is perfused over the endothelium at venous and arterial shear rate. Neutrophil adhesion, platelet and fibrin thrombus formation, is measured over time by the addition of fluorescent antibodies to a whole blood sample. Fixed endothelium retains surface expression of adhesion molecules ICAM-1 and E-Selectin. Neutrophils adhere preferentially to platelet thrombi on the endothelium. Inhibitors of neutrophil adhesion and anti-inflammatory agents, such as isoquercetin, decrease neutrophil adhesion. Our model offers the advantage of the use of (1) fixed endothelium, (2) whole blood, instead of isolated neutrophils, and (3) a small amount of blood (1 mL). The characteristics of this thromboinflammation model provide the potential for further development for drug screening and point-of-care applications. 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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Khandkar, Chinmay; Patel, Sanjay; Galougahi, Keyvan Karimi[No abstract available]
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Moore, Benjamin M.; Medi, Caroline; McGuire, Mark A.; Celermajer, David S.; Cordina, Rachael LouiseObjectives Long-term single-site ventricular pacing may adversely affect ventricular function, due to dyssynchronous systemic ventricular contraction. We sought to determine the incidence, predictors and outcomes of pacing-associated cardiomyopathy (PACM) in an adult congenital heart disease (ACHD) cohort. Methods We retrospectively identified all patients in our database with a permanent pacemaker from 2000 to 2019. Patients were followed for the primary endpoint of unexplained decline in systemic ventricular function (PACM) and the secondary endpoint of heart failure admission. Results Of 2073 patients in our database, 106 had undergone pacemaker implantation. Over a median follow-up of 9.4 years, 25 patients (24%) developed PACM, but only in those with ventricular pacing percentage (VP%) ?70%; PACM occurred in 0% of those with VP <70% and 47% of those with VP ?70% (p<0.001). High-burden ventricular pacing (?70%) remained predictive of PACM in transposition of the great arteries, tetralogy of Fallot and complex biventricular repair subgroups, but not in Fontan patients. Those with PACM were more likely to be admitted with heart failure (44% vs 15%, p=0.002). Cardiac resynchronisation therapy (CRT) upgrade was performed in 11 patients, with 9 responders (82%). Conclusions In a cohort of patients with ACHD followed long-term post-pacing, 24% developed cardiomyopathy that was significantly associated with a higher burden of ventricular pacing (VP ?70%). Given promising response rates to CRT, patients with ACHD expected to pace in the ventricle should be closely monitored for systemic ventricular decline. 2020 BMJ Publishing Group. All rights reserved.
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Quer, Giorgio; Freedman, Ben Ben; Steinhubl, Steven R.Aims Screening for asymptomatic atrial fibrillation (AF) could prevent strokes and save lives, but the AF burden of those detected can impact prognosis. New technologies enable continuous monitoring or intermittent electrocardiogram (ECG) snapshots, however, the relationship between AF detection rates and the burden of AF found with intermittent strategies is unknown. We simulated the likelihood of detecting AF using real-world 2-week continuous ECG recordings and developed a generalizable model for AF detection strategies. Methods From 1738 asymptomatic screened individuals, ECG data of 69 individuals (mean age 76.3, median burden 1.9%) and results with new AF found during 14 days continuous monitoring were used to simulate 30 seconds ECG snapshots one to four times daily for 14 days. Based on this simulation, 3566% of individuals with AF would be detected using intermittent screening. Twice-daily snapshots for 2 weeks missed 48% of those detected by continuous monitoring, but mean burden was 0.68% vs. 4% in those detected (P < 0.001). In a cohort of 6235 patients (mean age 69.2, median burden 4.6%) with paroxysmal AF during clinically indicated monitoring, simulated detection rates were 5376%. The Markovian model of AF detection using mean episode duration and mean burden simulated actual AF detection with <_9% error across the range of screening frequencies and durations. Conclusion Using twice-daily ECG snapshots over 2 weeks would detect only half of individuals discovered to have AF by continuous recordings, but AF burden of those missed was low. A model predicting AF detection, validated using real-world data, could assist development of optimized AF screening programmes. The Author(s) 2020.
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Shanmugalingam, Renuka; Wang, Xiaosuo; Motum, Penelope I.; Fulcher, Ian; Lee, Gaksoo; Kumar, Roshika; Hennessy, Annemarie; Makris, AngelaIntroduction: The benefit of aspirin in preventing preeclampsia is increasingly recognized; however, its mechanism of action remains unclear. Nonobstetric studies have described an anti-inflammatory effect of aspirin through the 15-epilipoxin-A4 pathway (aspirin-triggered lipoxin [ATL]). However, the antiinflammatory mechanism of aspirin in the prevention of preeclampsia remains unknown. Objective/Hypothesis: To examine (1) the difference in longitudinal endogenous lipoxin-A4 (En-Lipoxin-A4) concentration in low-risk (LR) and high-risk (HR) pregnancies, and (2) the effect of aspirin on endogenous ATL concentration and the associated effect on cytokine profile of HR women. Methods: Plasma from 220 HR women was collected at 12, 16, 20, 24, 28, 32, and 36 weeks of gestation. Adherence to aspirin was biochemically verified. Plasma En-Lipoxin-A4 and ATL concentrations were analyzed using liquid chromatography mass spectrometry, and cytokines, interleukin (IL)-10, tumor necrosis factor-?, interferon-?, IL-8, and IL-1?, with the high-sensitivity multibead Luminex assay. Results: HR women have up to 70% lower plasma concentration of En-Lipoxin-A4 (P < 0.001) than LR women. HR women with adequate aspirin adherence (HR-AA) (n = 82) had higher plasma concentration of ATL (P < .001), lower concentration of IL-8 from 16 to 36 weeks of gestation (P < .001), and increased IL-10 concentration from 16 to 28 weeks of gestation (P = .03) compared with high-risk women who were not on aspirin (HR-NA). HR-AA who did not develop preeclampsia had higher plasma En-lipoxin-A4 (P < .001), ATL (P = .02), and IL-10 concentrations (P < .001) with lower IL-8 concentration (P = .004) than HR women who developed preeclampsia. Discussion: Plasma concentration of En-Lipoxin-A4 is lower in HR women than in LR controls. Adequate adherence with aspirin results in an increase in ATL and IL-10 with reduced IL-8 plasma concentration. This study suggests a potential anti-inflammatory role of aspirin through the ATL pathway with prophylactic aspirin in HR pregnant women. The Author(s) 2020.
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Boriani, Giuseppe; Schnabel, Renate B.; Healey, Jeff S.; Les, Renato Delcio; Verbiest-van Gurp, Nicole; Lobban, Trudie C.A.; Camm, John A.; Freedman, Ben BenAim: A variety of consumer-facing wearables, devices and apps are marketed directly to consumers to detect atrial fibrillation (AF). However, their management is not defined. Our aim was to explore their role for AF screening via a survey. Methods and Results: An anonymous web-based survey was undertaken by 588 health care professionals (HCPs) (response rate 23.7%). Overall, 57% HCPs currently advise wearables/apps for AF detection in their patients: this was much higher for electrophysiologists and nurses/allied health professionals (7475%) than cardiologists (57%) or other physicians (3438%). Approximately 46% recommended handheld (portable) single-lead dedicated ECG devices, or, less frequently, wristband ECG monitors with similar differentials between HCPs. Only 1015% HCPs advised photoplethysmographic wristband monitors or smartphone apps. In over half of the HCP consultations for AF detected by wearables/apps, the decision to screen was entirely the patient's. About 45% of HCPs perceive a potential role for AF screening in people aged >65 years or in those with risk factors. Almost 70% of HCPs believed we are not yet ready for mass consumer-initiated screening for AF using wearable devices/apps, with patient anxiety, risk of false positives and negatives, and risk of anticoagulant-related bleeding perceived as potential disadvantages, and perceived need for appropriate management pathways. Conclusions: There is a great potential for appropriate use of consumer-facing wearables/apps for AF screening. However, it appears that there is a need to better define suitable individuals for screening and an appropriate mechanism for managing positive results before they can be recommended by HCPs. 2020 The Authors
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Bernier, Michel; Harney, Dylan James; Koay, Yen Chin; Diaz, Antonio; Singh, Abhishek K.; Wahl, Devin; Pulpitel, Tamara Jayne; Ali, Ahmed; Guiterrez, Vince; Mitchell, Sarah Jayne; Kim, Eun-young; MacH, John; Price, Nathan L.; Aon, Miguel Antonio; LeCouteur, David G.; Cogger, Victoria Carroll; Ferndez-Hernando, Carlos; OSullivan, John F.; Larance, Mark; Cuervo, Ana Maria; de Cabo, Rafael C.There is an unmet need and urgency to find safe and effective anti-obesity interventions. Our recent study in mice fed on obesogenic diet found that treatment with the alcohol aversive drug disulfiram reduced feeding efficiency and led to a decrease in body weight and an increase in energy expenditure. The intervention with disulfiram improved glucose tolerance and insulin sensitivity, and mitigated metabolic dysfunctions in various organs through poorly defined mechanisms. Here, integrated analysis of transcriptomic and proteomic data from mouse and rat livers unveiled comparable signatures in response to disulfiram, revealing pathways associated with lipid and energy metabolism, redox, and detoxification. In cell culture, disulfiram was found to be a potent activator of autophagy, the malfunctioning of which has negative consequences on metabolic regulation. Thus, repurposing disulfiram may represent a potent strategy to combat obesity. 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
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Li, Mengbo; Parker, Benjamin L.; Pearson, Evangeline; Hunter, Benjamin; Cao, Jacob Y.; Koay, Yen Chin; Guneratne, Oneka; James, David Ernest; Yang, Jean Yee Hwa; Lal, Sean P.; OSullivan, John F.Poor access to human left ventricular myocardium is a significant limitation in the study of heart failure (HF). Here, we utilise a carefully procured large human heart biobank of cryopreserved left ventricular myocardium to obtain direct molecular insights into ischaemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), the most common causes of HF worldwide. We perform unbiased, deep proteomic and metabolomic analyses of 51 left ventricular (LV) samples from 44 cryopreserved human ICM and DCM hearts, compared to age-, gender-, and BMI-matched, histopathologically normal, donor controls. We report a dramatic reduction in serum amyloid A1 protein in ICM hearts, perturbed thyroid hormone signalling pathways and significant reductions in oxidoreductase co-factor riboflavin-5-monophosphate and glycolytic intermediate fructose-6-phosphate in both; unveil gender-specific changes in HF, including nitric oxide-related arginine metabolism, mitochondrial substrates, and X chromosome-linked protein and metabolite changes; and provide an interactive online application as a publicly-available resource. 2020, The Author(s).
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Indo, Hiroko P.; Majima, Hideyuki J.; Terada, Masahiro; Suenaga, Shigeaki; Tomita, Kazuo; Higashibata, Akira; Ishioka, Noriaki; Kanekura, Takuro; Hawkins, Clare L.; Davies, Michael J.; St. Clair, Daret K.; Mukai, Chiaki N.An amendment to this paper has been published and can be accessed via a link at the top of the paper. 2020, The Author(s).
