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European Heart Journal Mar 2018
2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed...
Topics: Fibrinolytic Agents; Humans; Peripheral Arterial Disease; Risk Factors; Vascular Surgical Procedures
PubMed: 28886620
DOI: 10.1093/eurheartj/ehx095 -
Biological Psychiatry Apr 2023The past decade has seen an explosion in the identification of genetic causes of neurodevelopmental disorders, including Mendelian, de novo, and somatic factors. These... (Review)
Review
The past decade has seen an explosion in the identification of genetic causes of neurodevelopmental disorders, including Mendelian, de novo, and somatic factors. These discoveries provide opportunities to understand cellular and molecular mechanisms as well as potential gene-gene and gene-environment interactions to support novel therapies. Stem cell-based models, particularly human brain organoids, can capture disease-associated alleles in the context of the human genome, engineered to mirror disease-relevant aspects of cellular complexity and developmental timing. These models have brought key insights into neurodevelopmental disorders as diverse as microcephaly, autism, and focal epilepsy. However, intrinsic organoid-to-organoid variability, low levels of certain brain-resident cell types, and long culture times required to reach maturity can impede progress. Several recent advances incorporate specific morphogen gradients, mixtures of diverse brain cell types, and organoid engraftment into animal models. Together with nonhuman primate organoid comparisons, mechanisms of human neurodevelopmental disorders are emerging.
Topics: Animals; Humans; Induced Pluripotent Stem Cells; Brain; Neurodevelopmental Disorders; Autistic Disorder; Organoids
PubMed: 36759260
DOI: 10.1016/j.biopsych.2023.01.012 -
European Heart Journal Oct 2019The presence of a patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions; however, the subject remains controversial and no... (Review)
Review
The presence of a patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions; however, the subject remains controversial and no official statements have been published. This interdisciplinary paper, prepared with involvement of eight European scientific societies, aims to review the available trial evidence and to define the principles needed to guide decision making in patients with PFO. In order to guarantee a strict process, position statements were developed with the use of a modified grading of recommendations assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements of particular management options were weighed and graded according to predefined scales. Despite being based often on limited and non-randomised data, while waiting for more conclusive evidence, it was possible to conclude on a number of position statements regarding a rational general approach to PFO management and to specific considerations regarding left circulation thromboembolism. For some therapeutic aspects, it was possible to express stricter position statements based on randomised trials. This position paper provides the first largely shared, interdisciplinary approach for a rational PFO management based on the best available evidence.
Topics: Consensus; Foramen Ovale, Patent; Humans; Ischemia; Practice Guidelines as Topic; Risk Assessment; Thromboembolism; Treatment Outcome
PubMed: 30358849
DOI: 10.1093/eurheartj/ehy649 -
Journal of the American College of... Jul 2014In the PROTECT AF (Watchman Left Atrial Appendage Closure Technology for Embolic Protection in Patients With Atrial Fibrillation) trial that evaluated patients with... (Comparative Study)
Comparative Study Randomized Controlled Trial
Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial.
BACKGROUND
In the PROTECT AF (Watchman Left Atrial Appendage Closure Technology for Embolic Protection in Patients With Atrial Fibrillation) trial that evaluated patients with nonvalvular atrial fibrillation (NVAF), left atrial appendage (LAA) occlusion was noninferior to warfarin for stroke prevention, but a periprocedural safety hazard was identified.
OBJECTIVES
The goal of this study was to assess the safety and efficacy of LAA occlusion for stroke prevention in patients with NVAF compared with long-term warfarin therapy.
METHODS
This randomized trial further assessed the efficacy and safety of the Watchman device. Patients with NVAF who had a CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and previous stroke/transient ischemic attack) score ≥2 or 1 and another risk factor were eligible. Patients were randomly assigned (in a 2:1 ratio) to undergo LAA occlusion and subsequent discontinuation of warfarin (intervention group, n = 269) or receive chronic warfarin therapy (control group, n = 138). Two efficacy and 1 safety coprimary endpoints were assessed.
RESULTS
At 18 months, the rate of the first coprimary efficacy endpoint (composite of stroke, systemic embolism [SE], and cardiovascular/unexplained death) was 0.064 in the device group versus 0.063 in the control group (rate ratio 1.07 [95% credible interval (CrI): 0.57 to 1.89]) and did not achieve the prespecified criteria noninferiority (upper boundary of 95% CrI ≥1.75). The rate for the second coprimary efficacy endpoint (stroke or SE >7 days' postrandomization) was 0.0253 versus 0.0200 (risk difference 0.0053 [95% CrI: -0.0190 to 0.0273]), achieving noninferiority. Early safety events occurred in 2.2% of the Watchman arm, significantly lower than in PROTECT AF, satisfying the pre-specified safety performance goal. Using a broader, more inclusive definition of adverse effects, these still were lower in PREVAIL (Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) trial than in PROTECT AF (4.2% vs. 8.7%; p = 0.004). Pericardial effusions requiring surgical repair decreased from 1.6% to 0.4% (p = 0.027), and those requiring pericardiocentesis decreased from 2.9% to 1.5% (p = 0.36), although the number of events was small.
CONCLUSIONS
In this trial, LAA occlusion was noninferior to warfarin for ischemic stroke prevention or SE >7 days' post-procedure. Although noninferiority was not achieved for overall efficacy, event rates were low and numerically comparable in both arms. Procedural safety has significantly improved. This trial provides additional data that LAA occlusion is a reasonable alternative to warfarin therapy for stroke prevention in patients with NVAF who do not have an absolute contraindication to short-term warfarin therapy.
Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Cardiac Surgical Procedures; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Stroke; Treatment Outcome; Warfarin
PubMed: 24998121
DOI: 10.1016/j.jacc.2014.04.029 -
The New England Journal of Medicine Oct 2017We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention.
METHODS
In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months.
RESULTS
The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group.
CONCLUSIONS
Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).
Topics: Aged; Aspirin; Atherosclerosis; Cardiovascular Diseases; Double-Blind Method; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Rivaroxaban; Secondary Prevention
PubMed: 28844192
DOI: 10.1056/NEJMoa1709118 -
BMJ (Clinical Research Ed.) Jan 2019To examine the effect of regular breakfast consumption on weight change and energy intake in people living in high income countries. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To examine the effect of regular breakfast consumption on weight change and energy intake in people living in high income countries.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
PubMed, Ovid Medline, and CINAHL were searched for randomised controlled trials published between January 1990 and January 2018 investigating the effect of breakfast on weight or energy intake. ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform search portal were also searched in October 2018 to identify any registered yet unpublished or ongoing trials.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials from high income countries in adults comparing breakfast consumption with no breakfast consumption that included a measure of body weight or energy intake. Two independent reviewers extracted the data and assessed the risk of bias of included studies. Random effects meta-analyses of the effect of breakfast consumption on weight and daily energy intake were performed.
RESULTS
Of 13 included trials, seven examined the effect of eating breakfast on weight change, and 10 examined the effect on energy intake. Meta-analysis of the results found a small difference in weight favouring participants who skipped breakfast (mean difference 0.44 kg, 95% confidence interval 0.07 to 0.82), but there was some inconsistency across trial results (I=43%). Participants assigned to breakfast had a higher total daily energy intake than those assigned to skip breakfast (mean difference 259.79 kcal/day, 78.87 to 440.71; 1 kcal=4.18 kJ), despite substantial inconsistency across trial results (I=80%). All of the included trials were at high or unclear risk of bias in at least one domain and had only short term follow-ups (mean period seven weeks for weight, two weeks for energy intake). As the quality of the included studies was mostly low, the findings should be interpreted with caution.
CONCLUSION
This study suggests that the addition of breakfast might not be a good strategy for weight loss, regardless of established breakfast habit. Caution is needed when recommending breakfast for weight loss in adults, as it could have the opposite effect. Further randomised controlled trials of high quality are needed to examine the role of breakfast eating in the approach to weight management.
STUDY REGISTRATION
PROSPERO registration number CRD42017057687.
Topics: Body Weight; Breakfast; Energy Intake; Feeding Behavior; Humans; Randomized Controlled Trials as Topic
PubMed: 30700403
DOI: 10.1136/bmj.l42 -
European Journal of Vascular and... Mar 2018
Review
Editor's Choice - 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS).
Topics: Diagnostic Techniques, Cardiovascular; Disease Management; Europe; Humans; Peripheral Arterial Disease; Practice Guidelines as Topic; Societies, Medical; Vascular Surgical Procedures
PubMed: 28851596
DOI: 10.1016/j.ejvs.2017.07.018 -
EuroIntervention : Journal of EuroPCR... Apr 2023Despite significant advances in pharmacological, electrophysiological and valve therapies for heart failure with reduced ejection fraction (HFrEF), the associated... (Review)
Review
Despite significant advances in pharmacological, electrophysiological and valve therapies for heart failure with reduced ejection fraction (HFrEF), the associated morbidity, mortality and healthcare costs remain high. With a constantly growing heart failure population, the existing treatment gap between current and advanced heart failure therapies (e.g., left ventricular [LV] assist devices, heart transplantation) reflects a large unmet need, calling for novel therapeutic approaches. Left ventricular remodelling and dilatation, with or without scar formation, is the hallmark of cardiomyopathy and is associated with poor prognosis. In the era of exciting advances in structural heart interventions, the advent of minimally invasive, device-based therapies directly targeting the LV geometry and promoting physical reverse remodelling has created a new frontier in the battle against heart failure. Interventional heart failure therapy is a rapidly emerging field, encompassing structural heart and minimally invasive hybrid procedures, with two left ventriculoplasty devices currently under investigation in pivotal clinical trials in the US. This review addresses the rationale for left ventriculoplasty, presents the prior surgical and percutaneous attempts in the field, provides an overview of the novel transcatheter left ventriculoplasty devices and their respective trials, and highlights potential challenges associated with establishing such device-based therapies in our armamentarium against heart failure.
Topics: Humans; Heart Failure; Stroke Volume; Cardiac Surgical Procedures; Cardiomyopathies; Ventricular Function, Left
PubMed: 37092265
DOI: 10.4244/EIJ-D-22-00544 -
Journal of the American College of... Feb 2022The right ventricular (RV)-pulmonary arterial (PA) coupling ratio relates the efficiency with which RV stroke work is transferred into the PA. Lower ratios indicate an...
BACKGROUND
The right ventricular (RV)-pulmonary arterial (PA) coupling ratio relates the efficiency with which RV stroke work is transferred into the PA. Lower ratios indicate an inadequate RV contractile response to increased afterload.
OBJECTIVES
This study sought to evaluate the prognostic significance of RV-PA coupling in patients with tricuspid regurgitation (TR) who were undergoing transcatheter tricuspid valve repair or replacement (TTVR).
METHODS
The study investigators calculated RV-PA coupling ratios for patients enrolled in the global TriValve registry by dividing the tricuspid annular plane systolic excursion (TAPSE) by the PA systolic pressure (PASP) from transthoracic echocardiograms performed before the procedure and 30 days after the procedure. The primary endpoint was all-cause mortality at 1-year follow-up.
RESULTS
Among 444 patients analyzed, their mean age was 76.9 ± 9.1 years, and 53.8% of the patients were female. The median TAPSE/PASP ratio was 0.406 mm/mm Hg (interquartile range: 0.308-0.567 mm/mm Hg). Sixty-three patients died within 1 year of TTVR, 21 with a TAPSE/PASP ratio >0.406 and 42 with a TAPSE/PASP ratio ≤0.406. In multivariable Cox regression analysis, a TAPSE/PASP ratio >0.406 vs ≤0.406 was associated with a decreased risk of all-cause mortality (HR: 0.57; 95% CI: 0.35-0.93; P = 0.023). In 234 (52.7%) patients with echocardiograms 30 days after TTVR, a decline in RV-PA coupling was independently associated with reduced odds of all-cause mortality (odds ratio [OR]: 0.42; 95% CI: 0.19-0.93; P = 0.032). The magnitude of TR reduction after TTVR (≥1+ vs <1+; OR: 2.53; 95% CI: 1.06-6.03; P = 0.037) was independently associated with a reduction in post-TTVR RV-PA coupling.
CONCLUSIONS
RV-PA coupling is a powerful, independent predictor of all-cause mortality in patients with TR undergoing TTVR. These data suggest that the TAPSE/PASP ratio can inform patient selection and prognostication following TTVR.
Topics: Aged; Cardiac Surgical Procedures; Echocardiography, Doppler; Female; Follow-Up Studies; Humans; Male; Postoperative Period; Pulmonary Artery; Pulmonary Wedge Pressure; Registries; Retrospective Studies; Stroke Volume; Tricuspid Valve; Tricuspid Valve Insufficiency; Ventricular Function, Left; Ventricular Function, Right
PubMed: 35115101
DOI: 10.1016/j.jacc.2021.11.031