-
Circulation Mar 2024Device-detected atrial fibrillation (also known as subclinical atrial fibrillation or atrial high-rate episodes) is a common finding in patients with an implanted... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Device-detected atrial fibrillation (also known as subclinical atrial fibrillation or atrial high-rate episodes) is a common finding in patients with an implanted cardiac rhythm device and is associated with an increased risk of ischemic stroke. Whether oral anticoagulation is effective and safe in this patient population is unclear.
METHODS
We performed a systematic review of MEDLINE and Embase for randomized trials comparing oral anticoagulation with antiplatelet or no antithrombotic therapy in adults with device-detected atrial fibrillation recorded by a pacemaker, implantable cardioverter defibrillator, cardiac resynchronization therapy device, or implanted cardiac monitor. We used random-effects models for meta-analysis and rated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework (GRADE). The review was preregistered (PROSPERO CRD42023463212).
RESULTS
From 785 citations, we identified 2 randomized trials with relevant clinical outcome data: NOAH-AFNET 6 (Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes; 2536 participants) evaluated edoxaban, and ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; 4012 participants) evaluated apixaban. Meta-analysis demonstrated that oral anticoagulation with these agents reduced ischemic stroke (relative risk [RR], 0.68 [95% CI, 0.50-0.92]; high-quality evidence). The results from the 2 trials were consistent (I statistic for heterogeneity=0%). Oral anticoagulation also reduced a composite of cardiovascular death, all-cause stroke, peripheral arterial embolism, myocardial infarction, or pulmonary embolism (RR, 0.85 [95% CI, 0.73-0.99]; I=0%; moderate-quality evidence). There was no reduction in cardiovascular death (RR, 0.95 [95% CI, 0.76-1.17]; I=0%; moderate-quality evidence) or all-cause mortality (RR, 1.08 [95% CI, 0.96-1.21]; I=0%; moderate-quality evidence). Oral anticoagulation increased major bleeding (RR, 1.62 [95% CI, 1.05-2.50]; I²=61%; high-quality evidence).
CONCLUSIONS
The results of the NOAH-AFNET 6 and ARTESiA trials are consistent with each other. Meta-analysis of these 2 large randomized trials provides high-quality evidence that oral anticoagulation with edoxaban or apixaban reduces the risk of stroke in patients with device-detected atrial fibrillation and increases the risk of major bleeding.
Topics: Humans; Administration, Oral; Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Ischemic Stroke; Pyridines; Stroke; Thiazoles; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 37952187
DOI: 10.1161/CIRCULATIONAHA.123.067512 -
Chest Aug 2023Epinephrine is the most commonly used drug in out-of-hospital cardiac arrest (OHCA) resuscitation, but evidence supporting its efficacy is mixed. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epinephrine is the most commonly used drug in out-of-hospital cardiac arrest (OHCA) resuscitation, but evidence supporting its efficacy is mixed.
RESEARCH QUESTION
What are the comparative efficacy and safety of standard dose epinephrine, high-dose epinephrine, epinephrine plus vasopressin, and placebo or no treatment in improving outcomes after OHCA?
STUDY DESIGN AND METHODS
In this systematic review and network meta-analysis of randomized controlled trials, we searched six databases from inception through June 2022 for randomized controlled trials evaluating epinephrine use during OHCA resuscitation. We performed frequentist random-effects network meta-analysis and present ORs and 95% CIs. We used the the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate the certainty of evidence. Outcomes included return of spontaneous circulation (ROSC), survival to hospital admission, survival to discharge, and survival with good functional outcome.
RESULTS
We included 18 trials (21,594 patients). Compared with placebo or no treatment, high-dose epinephrine (OR, 4.27; 95% CI, 3.68-4.97), standard-dose epinephrine (OR, 3.69; 95% CI, 3.32-4.10), and epinephrine plus vasopressin (OR, 3.54; 95% CI, 2.94-4.26) all increased ROSC. High-dose epinephrine (OR, 3.53; 95% CI, 2.97-4.20), standard-dose epinephrine (OR, 3.00; 95% CI, 2.66-3.38), and epinephrine plus vasopressin (OR, 2.79; 95% CI, 2.27-3.44) all increased survival to hospital admission as compared with placebo or no treatment. However, none of these agents may increase survival to discharge or survival with good functional outcome as compared with placebo or no treatment. Compared with placebo or no treatment, standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm (OR, 2.10; 95% CI, 1.21-3.63), but not in those with shockable rhythm (OR, 0.85; 95% CI, 0.39-1.85).
INTERPRETATION
Use of standard-dose epinephrine, high-dose epinephrine, and epinephrine plus vasopressin increases ROSC and survival to hospital admission, but may not improve survival to discharge or functional outcome. Standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm, but not those with shockable rhythm.
TRIAL REGISTRY
Center for Open Science: https://osf.io/arxwq.
Topics: Humans; Out-of-Hospital Cardiac Arrest; Network Meta-Analysis; Epinephrine; Vasopressins; Resuscitation; Cardiopulmonary Resuscitation; Emergency Medical Services
PubMed: 36736487
DOI: 10.1016/j.chest.2023.01.033 -
Heart (British Cardiac Society) Mar 2024In Fontan circulation, pulmonary arterial hypertension (PAH)-targeted therapies could improve the patients' exercise capacity. This study aimed to investigate the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
In Fontan circulation, pulmonary arterial hypertension (PAH)-targeted therapies could improve the patients' exercise capacity. This study aimed to investigate the effects of PAH agents on different exercise parameters in stable Fontan patients by synthesising evidence of randomised controlled trials (RCTs).
METHODS
A systematic search of PubMed, Cochrane Central Register of Controlled Trials and Web of Science databases, as well as of ClinicalTrials.gov, was performed. Primary outcomes were specific cardiopulmonary exercise test parameters: peak oxygen uptake (peak VO), peak heart rate (peak HR), the minute ventilation/produced carbon dioxide (VE/VCO) slope and the oxygen uptake, both measured at the anaerobic threshold (VO@AT).
RESULTS
Five RCTs were included in the analysis including 573 Fontan patients (mean age 21.2 years, 60% male). PAH-targeted therapies did not affect peak VO (mean difference (MD) 0.72, 95% CI -0.25 to 1.70) or peak HR (MD -0.67, 95% CI -3.81 to 2.47), but resulted in a small, significant improvement in VO@AT (standardised MD 0.24, 95% CI 0.02 to 0.47). VE/VCO slope at the anaerobic threshold was also reduced (MD -1.13, 95% CI -2.25 to -0.01).
CONCLUSIONS
Although PAH-targeted therapies did not affect exercise parameters at maximal effort, they induced slight improvements in indices of submaximal effort, measured at the anaerobic threshold. Pharmacological improvement of submaximal exercise seems to be a more suitable indicator of Fontan individuals' exercise capacity. Larger RCTs, recruiting specific subpopulations and focusing also on the anaerobic threshold, are warranted to draw more robust conclusions.
PROSPERO REGISTRATION NUMBER
CRD42022306674.
Topics: Male; Humans; Young Adult; Adult; Female; Fontan Procedure; Vasodilator Agents; Lung; Exercise Test; Familial Primary Pulmonary Hypertension; Oxygen; Oxygen Consumption; Randomized Controlled Trials as Topic
PubMed: 37918902
DOI: 10.1136/heartjnl-2023-323166 -
Ultrasound in Obstetrics & Gynecology :... Jul 2023A favorable postnatal prognosis in cases of pulmonary atresia/critical stenosis with intact ventricular septum (PA/CS-IVS) is generally equated with the possibility of... (Review)
Review
OBJECTIVE
A favorable postnatal prognosis in cases of pulmonary atresia/critical stenosis with intact ventricular septum (PA/CS-IVS) is generally equated with the possibility of achieving biventricular (BV) repair. Identification of fetuses that will have postnatal univentricular (UV) circulation is key for prenatal counseling, optimization of perinatal care and decision-making regarding fetal therapy. We aimed to evaluate the accuracy of published models for predicting postnatal circulation in PA/CS-IVS using a large internationally derived validation cohort.
METHODS
This was a systematic review of published uni- and multiparametric models for the prediction of postnatal circulation based on echocardiographic findings at between 20 and 28 weeks of gestation. Models were externally validated using data from the International Fetal Cardiac Intervention Registry. Sensitivity, specificity, predictive values, area under the receiver-operating-characteristics curves (AUCs) and proportion of cases with true vs predicted outcome were calculated.
RESULTS
Eleven published studies that reported prognostic parameters of postnatal circulation were identified. Models varied widely in terms of the main outcome (UV (n = 3), non-BV (n = 3), BV (n = 3), right-ventricle-dependent coronary circulation (n = 1) or tricuspid valve size at birth (n = 1)) and in terms of the included predictors (single parameters only (n = 6), multiparametric score (n = 4) or both (n = 1)), and were developed on small sample sizes (range, 15-38). Nine models were validated externally given the availability of the required parameters in the validation cohort. Tricuspid valve diameter Z-score, tricuspid regurgitation, ratios between right and left cardiac structures and the presence of ventriculocoronary connections (VCC) were the most commonly evaluated parameters. Multiparametric models including up to four variables (ratios between right and left structures, right ventricular inflow duration, presence of VCC and tricuspid regurgitation) had the best performance (AUC, 0.80-0.89). Overall, the risk of UV outcome was underestimated and that of BV outcome was overestimated by most models.
CONCLUSIONS
Current prenatal models for the prediction of postnatal outcome in PA/CS-IVS are heterogeneous. Multiparametric models for predicting UV and non-BV circulation perform well in identifying BV patients but have low sensitivity, underestimating the rate of fetuses that will ultimately have UV circulation. Until better discrimination can be achieved, fetal interventions may need to be limited to only those cases in which non-BV postnatal circulation is certain. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Pulmonary Atresia; Ventricular Septum; Constriction, Pathologic; Tricuspid Valve Insufficiency; Retrospective Studies
PubMed: 36776132
DOI: 10.1002/uog.26176 -
Resuscitation Dec 2023Extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence... (Meta-Analysis)
Meta-Analysis Review
Prognostic factors associated with favourable functional outcome among adult patients requiring extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A systematic review and meta-analysis.
BACKGROUND
Extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence from observational studies and clinical trials are conflicting and the factors influencing outcome have not been well established.
METHODS
We conducted a systematic review and meta-analysis summarizing the association between pre-ECPR prognostic factors and likelihood of good functional outcome among adult patients requiring ECPR for OHCA. We searched Medline and Embase databases from inception to February 28, 2023 and screened studies with two independent reviewers. We performed meta-analyses of unadjusted and adjusted odds ratios, adjusted hazard ratios and mean differences separately. We assessed risk of bias using the QUIPS tool and certainty of evidence using the GRADE approach.
FINDINGS
We included 29 observational and randomized studies involving 7,397 patients. Factors with moderate or high certainty of association with increased survival with favourable functional outcome include pre-arrest patient factors, such as younger age (odds ratio (OR) 2.13, 95% CI 1.52 to 2.99) and female sex (OR 1.37, 95% CI 1.11 to 1.70), as well as intra-arrest factors, such as shockable rhythm (OR 2.79, 95% CI 2.04 to 3.80), witnessed arrest (OR 1.68 (95% CI 1.16 to 2.42), bystander CPR (OR 1.55, 95% CI 1.19 to 2.01), return of spontaneous circulation (OR 2.81, 95% CI 2.19 to 3.61) and shorter time to cannulation (OR 1.14, 95% CI 1.17 to 1.69 per 10 minutes).
INTERPRETATION
The findings of this review confirm several clinical concepts wellestablished in the cardiac arrest literature and their applicability to the patient for whom ECPR is considered - that is, the impact of pre-existing patient factors, the benefit of timely and effective CPR, as well as the prognostic importance of minimizing low-flow time. We advocate for the thoughtful consideration of these prognostic factors as part of a risk stratification framework when evaluating a patient's potential candidacy for ECPR.
Topics: Adult; Humans; Female; Out-of-Hospital Cardiac Arrest; Cardiopulmonary Resuscitation; Prognosis; Odds Ratio; Extracorporeal Membrane Oxygenation; Retrospective Studies
PubMed: 37863420
DOI: 10.1016/j.resuscitation.2023.110004 -
Journal of Intensive Care Medicine May 2024During cardiopulmonary resuscitation, intravenous thrombolytics are commonly used for patients whose underlying etiology of cardiac arrest is presumed to be related to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
During cardiopulmonary resuscitation, intravenous thrombolytics are commonly used for patients whose underlying etiology of cardiac arrest is presumed to be related to pulmonary embolism (PE).
METHODS
We performed a systematic review and meta-analysis of the existing literature that focused on the use of thrombolytics for cardiac arrest due to presumed or confirmed PE. Outcomes of interest were return of spontaneous circulation (ROSC), survival to hospital discharge, neurologically-intact survival, and bleeding complications.
RESULTS
Thirteen studies with a total of 803 patients were included in this review. Most studies included were single-armed and retrospective. Thrombolytic agent and dose were heterogeneous between studies. Among those with control groups, intravenous thrombolysis was associated with higher rates of ROSC (OR 2.55, 95% CI = 1.50-4.34), but without a significant difference in survival to hospital discharge (OR 1.41, 95% CI = 0.79-2.41) or bleeding complications (OR 2.21, 0.95-5.17).
CONCLUSIONS
Use of intravenous thrombolytics in cardiac arrest due to confirmed or presumed PE is associated with increased ROSC but not survival to hospital discharge or change in bleeding complications. Larger randomized studies are needed. Currently, we recommend continuing to follow existing consensus guidelines which support use of thrombolytics for this indication.
Topics: Humans; Fibrinolytic Agents; Retrospective Studies; Pulmonary Embolism; Heart Arrest; Cardiopulmonary Resuscitation; Out-of-Hospital Cardiac Arrest
PubMed: 38037310
DOI: 10.1177/08850666231214754 -
The Western Journal of Emergency... Mar 2024Intra-arrest transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) have been introduced in adult patients with cardiac arrest (CA). Whether the...
INTRODUCTION
Intra-arrest transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) have been introduced in adult patients with cardiac arrest (CA). Whether the diagnostic performance of TTE or TEE is superior during resuscitation is unclear. We conducted a systematic review following PRISMA guidelines.
METHODS
We searched databases from PubMed, Embase, and Google Scholar and evaluated articles with intra-arrest TTE and TEE in adult patients with non-traumatic CA. Two authors independently screened and selected articles for inclusion; they then dual-extracted study characteristics and target conditions (pericardial effusion, aortic dissection, pulmonary embolism, myocardial infarction, hypovolemia, left ventricular dysfunction, and sonographic cardiac activity). We performed quality assessment using the Quality Assessment of Diagnostic Accuracy Studies Version 2 criteria.
RESULTS
A total of 27 studies were included: 14 studies with 2,145 patients assessed TTE; and 16 with 556 patients assessed TEE. A high risk of bias or applicability concerns in at least one domain was present in 20 studies (74%). Both TTE and TEE found positive findings in nearly one-half of the patients. The etiology of CA was identified in 13% (271/2,145), and intervention was performed in 38% (102/271) of patients in the TTE group. In patients who received TEE, the etiology was identified in 43% (239/556), and intervention was performed in 28% (68/239). In the TEE group, a higher incidence regarding the etiology of CA was observed, particularly for those with aortic dissection. However, the outcome of those with aortic dissection in the TEE group was poor.
CONCLUSION
While TEE could identify more causes of CA than TTE, sonographic cardiac activity was reported much more in the TTE group. The impact of TTE and TEE on the return of spontaneous circulation and further survival was still inconclusive in the current dataset.
Topics: Adult; Humans; Echocardiography; Echocardiography, Transesophageal; Ventricular Dysfunction, Left; Resuscitation; Aortic Dissection
PubMed: 38596913
DOI: 10.5811/westjem.18440 -
Canadian Journal of Anaesthesia =... Aug 2023Perioperative pulmonary hypertension (PH) is an independent risk factor for morbidity and mortality in cardiac surgery. While inhaled prostacyclins (iPGIs) are an... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Perioperative pulmonary hypertension (PH) is an independent risk factor for morbidity and mortality in cardiac surgery. While inhaled prostacyclins (iPGIs) are an established treatment of chronic PH, data on the efficacy of iPGIs in perioperative PH are scarce.
METHODS
We searched PubMed, Embase, the Web of Science, CENTRAL, and the grey literature from inception until April 2021. We included randomized controlled trials investigating the use of iPGIs in adult and pediatric patients undergoing cardiac surgery with an increased risk of perioperative right ventricle failure. We assessed the efficacy and safety of iPGIs compared with placebo and other inhaled or intravenous vasodilators with random-effect meta-analyses. The primary outcome was mean pulmonary artery pressure (MPAP). Secondary outcomes included other hemodynamic parameters and mortality.
RESULTS
Thirteen studies were included, comprising 734 patients. Inhaled prostacyclins significantly decreased MPAP compared with placebo (standardized effect size, 0.46; 95% confidence interval [CI], 0.11 to 0.87; P = 0.01) and to intravenous vasodilators (1.26; 95% CI, 0.03 to 2.49; P = 0.045). Inhaled prostacyclins significantly improved the cardiac index compared with intravenous vasodilators (1.53; 95% CI, 0.50 to 2.57; P = 0.004). In contrast, mean arterial pressure was significantly lower in patients treated with iPGIs vs placebo (-0.39; 95% CI, -0.62 to 0.16; P = 0.001), but higher than in patients treated with intravenous vasodilators (0.81; 95% CI, 0.29 to 1.33; P = 0.002). With respect to hemodynamics, iPGIs had similar effects as other inhaled vasodilators. Mortality was not affected by iPGIs.
CONCLUSION
The results of this systematic review and meta-analysis show that iPGIs improved pulmonary hemodynamics with similar efficacy as other inhaled vasodilators, but caused a significant small decrease in arterial pressure when compared with placebo, indicating spill-over into the systemic circulation. These effects did not affect clinical outcomes.
STUDY REGISTRATION DATE
PROSPERO (CRD42021237991); registered 26 May 2021.
Topics: Adult; Humans; Child; Iloprost; Prostaglandins I; Administration, Inhalation; Vasodilator Agents; Hypertension, Pulmonary; Cardiac Surgical Procedures
PubMed: 37380903
DOI: 10.1007/s12630-023-02520-4 -
Critical Care Medicine Jun 2024Persistent pulmonary hypertension of the newborn (PPHN) is a life-threatening disease. Despite being considered the gold standard treatment scheme, inhaled nitric oxide... (Meta-Analysis)
Meta-Analysis Comparative Study
OBJECTIVES
Persistent pulmonary hypertension of the newborn (PPHN) is a life-threatening disease. Despite being considered the gold standard treatment scheme, inhaled nitric oxide (iNO) is not readily available in settings with limited resources. Therefore, in recent years, research on related drugs is being actively pursued. Herein, we aimed to use random-effects network meta-analysis to evaluate the efficacy and associated mortality of different PPHN therapies.
DATA SOURCES
We electronically searched the PubMed, Embase, and Cochrane Library for data up to January 27, 2023.
STUDY SELECTION
Randomized controlled trials involving neonates with PPHN assessing efficacy and mortality of various treatments.
DATA EXTRACTION
Details of study population, treatments, and outcomes were extracted.
DATA SYNTHESIS
Direct pairwise comparisons and a network meta-analysis was performed under random effects. The ranking probability was further assessed based on the surface under the cumulative ranking curve (SUCRA). We analyzed 23 randomized clinical trials involving 902 newborns with PPHN. Sixteen different treatment strategies were compared with each other and conventional therapy (CON). A median concentration of 10-20 parts per million (ppm) iNO (MNO) coupled with sildenafil orally administered at a dose of 1-3 mg/kg/dose every 6-8 hours (OSID) demonstrated the best efficacy (MNO + OSID vs. CON: odds ratio [OR] = 27.53, 95% CI, 2.36-321.75; SUCRA = 0.818, ranking first; moderate quality). OSID combined with milrinone administered IV also performed well in terms of efficacy (OSID + milrinone vs. CON: OR = 25.13, 95% CI = 1.67-377.78; SUCRA = 0.811, ranking second; low quality) and mortality reduction (CON vs. OSID + milrinone: OR = 25.13, 95% CI = 1.67-377.78; SUCRA = 0.786, ranking last; low quality).
CONCLUSIONS
MNO + OSID is the most effective PPHN treatment. If iNO is not available, OSID + milrinone is preferred.
Topics: Humans; Infant, Newborn; Persistent Fetal Circulation Syndrome; Nitric Oxide; Network Meta-Analysis; Sildenafil Citrate; Administration, Inhalation; Vasodilator Agents; Milrinone; Randomized Controlled Trials as Topic
PubMed: 38363176
DOI: 10.1097/CCM.0000000000006227 -
Animal Models and Experimental Medicine Feb 2024The maintenance dosage of selexipag is categorized as low, medium or high. In order to assess the efficacy and safety of different dosages of selexipag for the risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The maintenance dosage of selexipag is categorized as low, medium or high. In order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypertension (PAH), we performed a systematic review and meta-analysis.
METHODS
Studies assessing PAH risk stratification indices, such as the World Health Organization functional class (WHO-FC), six-minute walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, right atrial pressure (RAP), cardiac index (CI) and mixed venous oxygen saturation (SvO), were included.
RESULTS
Thirteen studies were included. Selexipag led to improvements in the 6MWD (MD: 24.20 m, 95% CI: 10.74-37.67), NT-proBNP (SMD: -0.41, 95% CI: -0.79-0.04), CI (MD: 0.47 L/min/m, 95% CI: 0.17-0.77) and WHO-FC (OR: 0.564, 95% CI: 0.457-0.697). Subgroup analysis demonstrated that all three dosages improved the 6MWD. A moderate dosage led to improvements in the CI (MD: 0.30 L/min/m, 95% CI: 0.15-0.46) and WHO-FC (OR: 0.589, 95% CI: 0.376-0.922). Within 6 months of treatment, only the WHO-FC and CI were significantly improved (OR: 0.614, 95% CI: 0.380-0.993; MD: 0.30 L/min/m, 95% CI: 0.16-0.45, respectively). More than 6 months of treatment significantly improved the 6MWD, WHO-FC and NT-proBNP (MD: 40.87 m, 95% CI: 10.97-70.77; OR: 0.557, 95% CI: 0.440-0.705; SMD: -0.61, 95% CI: -1.17-0.05, respectively).
CONCLUSIONS
Low, medium, and high dosages of selexipag all exhibited good effects. When treatment lasted for more than 6 months, selexipag exerted obvious effects, even in the low-dosage group. This finding is important for guiding individualized treatments.
Topics: Humans; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Acetamides; Pyrazines
PubMed: 37740617
DOI: 10.1002/ame2.12347