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Pulmonary Circulation 2019Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal disease process in which pulmonary hypertension (PH) develops in the setting of malignancy. The purpose of...
Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal disease process in which pulmonary hypertension (PH) develops in the setting of malignancy. The purpose of this study is to present a detailed analysis of cases of PTTM reported in literature in the hopes of achieving more ante-mortem diagnoses. We conducted a systematic review of currently published and available cases of PTTM by searching the term "pulmonary tumor thrombotic microangiopathy" on the Pubmed.gov database. Seventy-nine publications were included consisting of 160 unique cases of PTTM. The most commonly reported malignancy was gastric adenocarcinoma (94 cases, 59%). Cough and dyspnea were reported in 61 (85%) and 102 (94%) cases, respectively. Hypoxemia was reported in 96 cases (95%). Elevation in D-dimer was noted in 36 cases (95%), presence of anemia in 32 cases (84%), and thrombocytopenia in 30 cases (77%). Common findings on chest computed tomography (CT) included ground-glass opacities (GGO) in 28 cases (82%) and nodules in 24 cases (86%). PH on echocardiography was noted in 59 cases (89%) with an average right ventricular systolic pressure of 71 mmHg. Common features of PTTM that are reported across the published literature include presence of dyspnea and cough, hypoxemia, with abnormal CT findings of GGO, nodules, and mediastinal/hilar lymphadenopathy, and PH. PTTM is a universally fatal disease process and this analysis provides a detailed examination of all the available published data that may help clinicians establish an earlier diagnosis of PTTM.
PubMed: 31032740
DOI: 10.1177/2045894019851000 -
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 -
The Lancet. Respiratory Medicine Aug 2015Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disorder associated with increased comorbid prevalence of cardiovascular diseases. We aimed to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disorder associated with increased comorbid prevalence of cardiovascular diseases. We aimed to quantify the magnitudes of association between overall and specific types of cardiovascular disease, major cardiovascular risk factors, and COPD.
METHODS
We searched Cochrane, Medline, and Embase databases for studies published between Jan 1, 1980, and April 30, 2015, on the prevalence of cardiovascular disease and its risk factors in patients with COPD versus matched controls or random samples from the general public. We assessed associations with random-effects meta-analyses. We studied heterogeneity and biases with random-effects meta-regressions, jackknife sensitivity analyses, assessment of funnel plots, and Egger tests.
FINDINGS
We identified 18,176 unique references and included 29 datasets in the meta-analyses. Compared with the non-COPD population, patients with COPD were more likely to be diagnosed with cardiovascular disease (odds ratio [OR] 2·46; 95% CI 2·02-3·00; p<0·0001), including a two to five times higher risk of ischaemic heart disease, cardiac dysrhythmia, heart failure, diseases of the pulmonary circulation, and diseases of the arteries. Additionally, patients with COPD reported hypertension more often (OR 1·33, 95% CI 1·13-1·56; p=0·0007), diabetes (1·36, 1·21-1·53; p<0·0001], and ever smoking (4·25, 3·23-5·60; p<0·0001). The associations between COPD and these cardiovascular disease types and cardiovascular disease risk factors were consistent and valid across studies. Enrolment period, age, quality of data, and COPD diagnosis partly explained the heterogeneity.
INTERPRETATION
The coexistence of COPD, cardiovascular disease, and major risk factors for cardiovascular disease highlights the crucial need for the development of strategies to screen for and reduce cardiovascular risks associated with COPD.
FUNDING
Canadian Institutes of Health Research.
Topics: Aged; Cardiovascular Diseases; Comorbidity; Female; Humans; Male; Middle Aged; Odds Ratio; Prevalence; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Risk Factors
PubMed: 26208998
DOI: 10.1016/S2213-2600(15)00241-6 -
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