-
Pulmonary Circulation 2021This systematic review of literature and online reports critically appraised incidence and prevalence estimates of pulmonary arterial hypertension and chronic...
Epidemiology of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: identification of the most accurate estimates from a systematic literature review.
This systematic review of literature and online reports critically appraised incidence and prevalence estimates of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension to identify the most accurate estimates. Medline® and Embase® databases were searched for articles published between 1 January 2003 and 31 August 2020. Studies were grouped according to whether they were registries (population-based estimates), clinical databases (hospital-based estimates) or claims/administrative databases. Registries were classified into systematic and non-systematic registries, according to whether every national centre participated. Of 7309 publications identified, 5414 were screened after removal of duplicates and 33 were included. Inclusion was based on study type, availability of a clear numerator (diagnosed population) and a population- or hospital-based denominator, or all primary data required to calculate estimates. Only the most recent publication from a database was included. Most studies were based on European data and very few included children. In adults, the range of estimates per million was approximately 20-fold for pulmonary arterial hypertension incidence (1.5-32) and prevalence (12.4-268) and of similar magnitude for chronic thromboembolic pulmonary hypertension incidence (0.9-39) and prevalence (14.5-144). Recent (≤5 years) national systematic registry data from centralised healthcare systems provided the following ranges in adult estimates per million: approximately 5.8 for pulmonary arterial hypertension incidence, 47.6-54.7 for pulmonary arterial hypertension prevalence, 3.1-6.0 for chronic thromboembolic pulmonary hypertension incidence and 25.8-38.4 for chronic thromboembolic pulmonary hypertension prevalence. These estimates were considered the most reliable and consistent for the scientific community to plan for resource allocation and improve detection rates.
PubMed: 33456755
DOI: 10.1177/2045894020977300 -
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 -
Pulmonary Circulation 2020Acute pulmonary embolism is the third most common cause of cardiovascular death. Pulmonary embolism increases right ventricular afterload, which causes right ventricular... (Review)
Review
Acute pulmonary embolism is the third most common cause of cardiovascular death. Pulmonary embolism increases right ventricular afterload, which causes right ventricular failure, circulatory collapse and death. Most treatments focus on removal of the mechanical obstruction caused by the embolism, but pulmonary vasoconstriction is a significant contributor to the increased right ventricular afterload and is often left untreated. Pulmonary thromboembolism causes mechanical obstruction of the pulmonary vasculature coupled with a complex interaction between humoral factors from the activated platelets, endothelial effects, reflexes and hypoxia to cause pulmonary vasoconstriction that worsens right ventricular afterload. Vasoconstrictors include serotonin, thromboxane, prostaglandins and endothelins, counterbalanced by vasodilators such as nitric oxide and prostacyclins. Exogenous administration of pulmonary vasodilators in acute pulmonary embolism seems attractive but all come with a risk of systemic vasodilation or worsening of pulmonary ventilation-perfusion mismatch. In animal models of acute pulmonary embolism, modulators of the nitric oxide-cyclic guanosine monophosphate-protein kinase G pathway, endothelin pathway and prostaglandin pathway have been investigated. But only a small number of clinical case reports and prospective clinical trials exist. The aim of this review is to give an overview of the causes of pulmonary embolism-induced pulmonary vasoconstriction and of experimental and human investigations of pulmonary vasodilation in acute pulmonary embolism.
PubMed: 32180938
DOI: 10.1177/2045894019899775 -
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 -
Heart Failure Clinics Jan 2023Main pulmonary vascular diseases (PVD) with precapillary pulmonary hypertension (PH) are pulmonary arterial and chronic thromboembolic PH. Guidelines recommend... (Meta-Analysis)
Meta-Analysis Review
Main pulmonary vascular diseases (PVD) with precapillary pulmonary hypertension (PH) are pulmonary arterial and chronic thromboembolic PH. Guidelines recommend supplemental oxygen therapy (SOT) for severely hypoxemic patients with PH, but evidence is scarce. The authors performed a systematic review and where possible meta-analyses on the effects of SOT on hemodynamics and exercise performance in patients with PVD. In PVD, short-term SOT significantly improved mean pulmonary artery pressure and exercise performance. There is growing evidence on the benefit of long-term SOT for selected patients with PVD regarding exercise capacity and maybe even survival.
Topics: Humans; Pulmonary Circulation; Vascular Diseases; Hypertension, Pulmonary; Pulmonary Artery; Hemodynamics; Oxygen
PubMed: 36922056
DOI: 10.1016/j.hfc.2022.11.001 -
Pulmonary Circulation Jul 2022Pulmonary thromboembolic events have been linked to coronavirus disease 2019 (COVID-19), but their incidence and long-term sequelae remain unclear. We performed a... (Review)
Review
Pulmonary thromboembolic events have been linked to coronavirus disease 2019 (COVID-19), but their incidence and long-term sequelae remain unclear. We performed a systematic literature review to investigate the incidence of pulmonary embolism (PE), microthrombi, thrombosis in situ (thromboinflammatory disease), and chronic thromboembolic pulmonary hypertension (CTEPH) during and after COVID-19. PubMed and the World Health Organization Global Research Database were searched on May 7, 2021. Hospital cohort and database studies reporting data for ≥1000 patients and autopsy studies reporting data for ≥20 patients were included. Results were summarized descriptively. We screened 1438 records and included 41 references (32 hospital/database studies and 9 autopsy studies). The hospital/database studies reported the incidence of PE but not CTEPH, microthrombi, or thromboinflammatory disease. PE incidence varied widely (0%-1.1% of outpatients, 0.9%-8.2% of hospitalized patients, and 1.8%-18.9% of patients in intensive care). One study reported PE events occurring within 45 days after hospital discharge (incidence in discharged patients: 0.2%). Segmental arteries were generally the most common location for PE. In autopsy studies, PE, thromboinflammatory disease, and microthrombi were reported in 6%-23%, 43%-100%, and 45%-84% of deceased patients, respectively. Overall, the included studies mostly focused on PE during the acute phase of COVID-19. The results demonstrate the challenges of identifying and characterizing vascular abnormalities using current protocols (e.g., visual computed tomography reads). Further research is needed to detect subtle pulmonary vascular abnormalities, distinguish thromboinflammatory disease from PE, optimize treatment, and assess the incidence of long-term sequelae after COVID-19.
PubMed: 35942076
DOI: 10.1002/pul2.12113 -
Animal Models and Experimental Medicine Feb 2022Circular RNAs (circRNAs) are endogenous RNAs with a covalently closed single-stranded transcript. They are a novel class of genomic regulators that are linked to many... (Review)
Review
Circular RNAs (circRNAs) are endogenous RNAs with a covalently closed single-stranded transcript. They are a novel class of genomic regulators that are linked to many important development and disease processes and are being pursued as clinical and therapeutic targets. Using the most powerful RNA sequencing and bioinformatics techniques, a large number of circRNAs have been identified and further functional studies have been performed. It is known that circRNAs act as potential biomarkers, sponges for microRNAs (miRNAs) and RNA-binding proteins (RBPs), and regulators of mRNA transcription. They also participate in the translation of peptides or proteins. Many types of circRNAs are dysregulated in plasma or lung tissues, and they may be involved in regulating the proliferation and apoptosis of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs), leading to pulmonary vascular remodeling in pulmonary hypertension (PH). One possible mechanism is that circRNAs can regulate the function of PAECs and PASMCs by acting as miRNA sponge. However, other potential mechanisms of action of circRNAs are still being actively explored in PH. This paper presents a systematic review of the biogenesis, biological characterization, relevant underlying functions, and future perspectives for studies of circRNAs in the pathogenesis of PH.
Topics: Computational Biology; Endothelial Cells; Humans; Hypertension, Pulmonary; MicroRNAs; RNA, Circular
PubMed: 35229989
DOI: 10.1002/ame2.12208 -
Resuscitation Plus Jun 2023To perform a systematic review of administration of calcium compared to no calcium during cardiac arrest. (Review)
Review
AIM
To perform a systematic review of administration of calcium compared to no calcium during cardiac arrest.
METHODS
The search included Medline (PubMed), Embase, Cochrane, Web of Science, and CINAHL Plus and was conducted on September 30, 2022. The population included adults and children in any setting with cardiac arrest. The outcomes included return of spontaneous circulation, survival, survival with favourable neurologic outcome to hospital discharge and 30 days or longer, and quality of life outcome. Cochrane Risk of Bias 2 and ROBINS-I were performed to assess risk of bias for controlled and observational studies, respectively.
RESULTS
The systematic review identified 4 studies on 3 randomised controlled trials on 554 adult out-of-hospital cardiac arrest (OHCA) patients, 8 observational studies on 2,731 adult cardiac arrest patients, and 3 observational studies on 17,449 paediatric in-hospital cardiac arrest (IHCA) patients. The randomised controlled and observational studies showed that routine calcium administration during cardiac arrest did not improve the outcome of adult OHCA or IHCA or paediatric IHCA. The risk of bias for the adult trials was low for one recent trial and high for two earlier trials, with randomization as the primary source of bias. The risk of bias for the individual observational studies was assessed to be critical due to confounding. The certainty of evidence was assessed to be moderate for adult OHCA and low for adult and paediatric IHCA. Heterogeneity across studies precluded any meaningful meta-analyses.
CONCLUSIONS
This systematic review found no evidence that routine calcium administration improves the outcomes of cardiac arrest in adults or children.PROSPERO Registration: CRD42022349641.
PubMed: 37025978
DOI: 10.1016/j.resplu.2023.100379 -
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