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World Journal of Clinical Pediatrics Nov 2021Pulmonary hypertension (PH) has serious short- and long-term consequences. PH is gaining increasing importance in high risk groups such as Down syndrome (DS) as it...
BACKGROUND
Pulmonary hypertension (PH) has serious short- and long-term consequences. PH is gaining increasing importance in high risk groups such as Down syndrome (DS) as it influences their overall survival and prognosis. Hence, there is a dire need to collate the prevalence rates of PH in order to undertake definitive measures for early diagnosis and management.
AIM
To determine the prevalence of PH in children with DS.
METHODS
The authors individually conducted a search of electronic databases manually (Cochrane library, PubMed, EMBASE, Scopus, Web of Science). Data extraction and quality control were independently performed by two reviewers and a third reviewer resolved any conflicts of opinion. The words used in the literature search were "pulmonary hypertension" and "pulmonary arterial hypertension"; "Down syndrome" and "trisomy 21" and "prevalence". The data were analyzed by Comprehensive Meta-Analysis Software Version 2. Risk of bias assessment and STROBE checklist were used for quality assessment.
RESULTS
Of 1578 articles identified, 17 were selected for final analysis. The pooled prevalence of PH in these studies was 25.5%. Subgroup analysis was carried out for age, gender, region, year of publication, risk of bias and etiology of PH.
CONCLUSION
This review highlights the increasing prevalence of PH in children with DS. It is crucial for pediatricians to be aware of this morbid disease and channel their efforts towards earlier diagnosis and successful management. Community-based studies with a larger sample size of children with DS should be carried out to better characterize the epidemiology and underlying etiology of PH in DS.
PubMed: 34868894
DOI: 10.5409/wjcp.v10.i6.177 -
Pharmacological Research Nov 2017Numerous animal models of pulmonary hypertension are currently available. A systematic review and meta-analysis was performed of a number of experimental studies of... (Meta-Analysis)
Meta-Analysis Review
Numerous animal models of pulmonary hypertension are currently available. A systematic review and meta-analysis was performed of a number of experimental studies of disease induction based on several animal models. A meta-analysis was performed of 291 publications discussing the efficacy of 611 interventions to introduce disease pulmonary hypertension in 6126 animals. A meta-regression analysis was done to assess the effect of prolonged periods of disease induction on the outcomes. A random-effects meta-analysis was used to assess the impact of study characteristics and seek evidence of publication bias. A more pronounced worsening in hemodynamics or right ventricle hypertrophy was observed in animals exposed to Sugen combined with hypoxia, or left pneumonectomy followed by monocrotaline. Chronic hypoxia induced the poorest, but the most stable, response to disease induction with regard to elevated hemodynamic parameters, right ventricle hypertrophy and wall thickening. The greatest elevation of right ventricle systolic pressure was observed in animals exposed to isoflurane and the weakest to chloral hydrate. This result was true for different animal models and lengths of induction of pulmonary hypertension. Publication bias was found for all the crucial parameters. Development of pulmonary hypertension depends on the choice of animal model. Classic models, especially these related to chronic hypoxia, provoke a less severe response with regard to poorer hemodynamics and myocardial hypertrophy. The outcome of disease development can be strongly determined by the duration of induction, detailed experimental conditions and anesthesia procedure.
Topics: Animals; Disease Models, Animal; Hypertension, Pulmonary
PubMed: 28867639
DOI: 10.1016/j.phrs.2017.08.003 -
Internal and Emergency Medicine Apr 2024The evidence for the treatment of connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) mostly depends on subgroup or post hoc analysis of... (Meta-Analysis)
Meta-Analysis
The evidence for the treatment of connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) mostly depends on subgroup or post hoc analysis of randomized controlled trials (RCTs). Thus, we performed a meta-analysis of RCTs that reported outcomes for CTD-PAH. PubMed and EMBASE were searched for CTD-PAH treatment. The selected outcomes were functional class (FC) change, survival rates, 6-min walk distance (6-MWD), clinical worsening (CW), N-terminal prohormone BNP (NT-proBNP), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), right atrial pressure (RAP), and cardiac index (CI). The meta-analysis was conducted according to the PRISMA guidelines and registered in PROSPERO (CRD42020153560). Twelve RCTs conducted with 1837 patients were included. The diagnoses were systemic sclerosis in 59%, SLE in 20%, and other CTDs in 21%. The pharmacological interventions were epoprostenol, treprostinil, sildenafil, tadalafil, bosentan, macitentan, ambrisentan, riociguat, and selexipag. There was a significant difference between interventions and placebo in FC, 6MWD, CW, PVR, RAP, and CI that favored intervention. Our analysis showed a 39% reduction in the CW risk with PAH treatment. The short-term survival rates and mean serum NT-proBNP changes were similar between the study and control groups. Treatment for CTD-PAH had favorable effects on clinical and hemodynamic outcomes but not on survival and NT-proBNP levels. Different from the previous meta-analyses that focused on 6-MWD, time to clinical worsening, and CW as outcomes, this meta-analysis additionally reports the pooled analysis of change in FC, hemodynamic measurements (RAP, PVR, CI), and NT-proBNP, some of which have prognostic value for PAH.
Topics: Humans; Antihypertensive Agents; Connective Tissue Diseases; Peptide Fragments; Pulmonary Arterial Hypertension; Randomized Controlled Trials as Topic
PubMed: 38378970
DOI: 10.1007/s11739-024-03539-1 -
Frontiers in Cardiovascular Medicine 2022This study seeks to evaluate the diagnostic value of computed tomography (CT) in pulmonary hypertension.
OBJECTIVE
This study seeks to evaluate the diagnostic value of computed tomography (CT) in pulmonary hypertension.
METHOD
PubMed, Embase, Scopus, and Web of Science databases were searched to obtain the relevant English literature, and the retrieval time until June 2022. The quality of the included studies is evaluated using the QUADAS-2 tool. The quality of the included studies was assessed, followed by a meta-analysis, analyze heterogeneity, summarize sensitivity and specificity, draw the comprehensive subject working characteristics (sROC) curve, calculate the area under the curve and conduct subgroup analysis and sensitivity analysis to find the source of the heterogeneity.
RESULTS
A total of 12 articles were included, all with pulmonary artery diameter/liter aortic diameter >1 or 1 as the diagnostic criteria for pulmonary hypertension, and a total of 1,959 patients were included. Deek's funnel plot analysis suggests that there is no significant publication bias ( = 0.102). The combined sensitivity was 0.652 (95% CI: 0.579, 0.719), combined specificity was 0.830 (95% CI: 0.796, 0.880), positive likelihood ratio was 3.837 (95% CI: 3.215, 4.579), negative likelihood ratio was 0.419 (95% CI: 0.346, 0.507), diagnostic odds ratio was 9.157 (95% CI: 6.748, 12.427) and area under the summary receiver operating characteristic (SROC) curve was 0.84 (95% CI: 0.81, 0.87).
CONCLUSION
The CT examination of pulmonary artery diameter/aortic artery hypertension is worthy of clinical application.
PubMed: 36277788
DOI: 10.3389/fcvm.2022.966257 -
Therapeutic Apheresis and Dialysis :... Aug 2019In the general population and in heart disease, pulmonary hypertension (PH) is a strong and independent risk factor for mortality and adverse cardiovascular outcomes. We... (Meta-Analysis)
Meta-Analysis
In the general population and in heart disease, pulmonary hypertension (PH) is a strong and independent risk factor for mortality and adverse cardiovascular outcomes. We performed a systematic review and meta-analysis of longitudinal cohort studies of individuals with chronic kidney disease (CKD) of any-stage (also including end-stage kidney disease and kidney transplantation) stratified according to presence/absence of PH. Eighteen eligible studies (10 740 participants) were retrieved. PH had an overall pooled prevalence of 33% (95% CI 28-42) and portended a higher risk of all-cause mortality (RR 2.08; 1.06-4.08), cardiovascular mortality (RR 3.77; 2.46-5.78) and non-fatal cardiovascular events (RR 1.60; 1.28-1.99). PH is highly prevalent in CKD and end-stage kidney disease and may represent a novel factor for mortality and cardiovascular risk stratification, particularly in selected sub-categories. Future high-quality research is required to confirm the need for clinical attention on PH in the CKD setting.
Topics: Cardiovascular Diseases; Humans; Hypertension, Pulmonary; Kidney Failure, Chronic; Renal Dialysis; Renal Insufficiency, Chronic; Risk Assessment
PubMed: 30565874
DOI: 10.1111/1744-9987.12777 -
Annals of the American Thoracic Society Jun 2023Transbronchial lung biopsies (TBLBs) are commonly performed by pulmonologists. Most providers consider pulmonary hypertension to be at least a relative contraindication... (Meta-Analysis)
Meta-Analysis
Transbronchial lung biopsies (TBLBs) are commonly performed by pulmonologists. Most providers consider pulmonary hypertension to be at least a relative contraindication to TBLB. This practice is based primarily on expert opinion, as there are very few patient outcomes data backing it. We performed a systematic review and meta-analysis of previously published studies to determine the safety of TBLB in patients with pulmonary hypertension. The MEDLINE, Embase, Scopus, and Google Scholar databases were searched for pertinent studies. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using MedCalc version 20.118 to calculate the weighted pooled relative risk of complications in patients with pulmonary hypertension. Nine studies with a total of 1,699 patients were included in the meta-analysis. On the basis of the Newcastle-Ottawa Scale, the risk of bias was low in the included studies. The overall weighted relative risk of bleeding with TBLB in patients with pulmonary hypertension was 1.01 (95% confidence interval, 0.71-1.45) compared with patients without pulmonary hypertension. Heterogeneity was low; therefore, the fixed-effects model was used. In a subgroup analysis of three studies, the overall weighted relative risk of significant hypoxia in patients with pulmonary hypertension was 2.06 (95% confidence interval, 1.12-3.76). Our results show that the patients with pulmonary hypertension do not have a significantly elevated risk of bleeding with TBLB compared with control subjects. We hypothesize that significant postbiopsy bleeding might be preferentially originating from bronchial artery circulation as opposed to pulmonary artery circulation, much like episodes of massive spontaneous hemoptysis. This hypothesis can explain our results, as in this scenario, elevated pulmonary arterial pressure would not be expected to have a bearing on the risk of post-TBLB bleeding. Most of the studies in our analysis included patients with mild to moderate pulmonary hypertension and it is not clear if our results can be extrapolated to patients with severe pulmonary hypertension. We noted that the patients with pulmonary hypertension were at a higher risk of developing hypoxia and needing a longer duration of mechanical ventilation with TBLB compared with control subjects. Further studies are needed to better understand the origin and pathophysiology of post-TBLB bleeding.
Topics: Humans; Hypertension, Pulmonary; Bronchoscopy; Biopsy; Lung Diseases; Hypoxia; Lung
PubMed: 36867520
DOI: 10.1513/AnnalsATS.202211-965OC -
Journal of Cardiovascular Development... Dec 2023Chronic obstructive pulmonary disease-associated pulmonary hypertension (PH-COPD) results in a significant impact on symptoms, quality of life, and survival. There is... (Review)
Review
Chronic obstructive pulmonary disease-associated pulmonary hypertension (PH-COPD) results in a significant impact on symptoms, quality of life, and survival. There is scant and conflicting evidence about the use of pulmonary hypertension (PH) specific therapy in patients with PH-COPD. PubMed, OVID, CINAHL, Cochrane, Embase, and Web of Science were searched using various MESH terms to identify randomized controlled trials (RCTs) or observational studies investigating PH-specific therapies in patients with severe PH-COPD, defined by mean pulmonary artery pressure (mPAP) of more than 35 mm Hg or pulmonary vascular resistance (PVR) of more than 5 woods units on right heart catheterization. The primary outcome was a change in mPAP and PVR. Secondary outcomes were changes in six-minute walk distance (6MWD), changes in the brain-natriuretic peptide (BNP), New York Heart Association (NYHA) functional class, oxygenation, and survival. Thirteen studies satisfied the inclusion criteria, including a total of 328 patients with severe PH-COPD. Out of these, 308 patients received some type of specific therapy for PH. There was a significant reduction in mPAP (mean difference (MD) -3.68, 95% CI [-2.03, -5.32], < 0.0001) and PVR (MD -1.40 Wood units, 95% CI [-1.97, -0.82], < 0.00001). There was a significant increase in the cardiac index as well (MD 0.26 L/min/m, 95% CI [0.14, 0.39], < 0.0001). There were fewer patients who had NYHA class III/lV symptoms, with an odds ratio of 0.55 (95% CI [0.30, 1.01], = 0.05). There was no significant difference in the 6MWD (12.62 m, 95% CI [-8.55, 33.79], = 0.24), PaO (MD -2.20 mm Hg, 95% CI [-4.62, 0.22], = 0.08), or BNP or NT-proBNP therapy (MD -0.15, 95% CI [-0.46, 0.17], = 0.36). The use of PH-specific therapies in severe PH-COPD resulted in a significant reduction in mPAP and PVR and increased CI, with fewer patients remaining in NYHA functional class III/IV. However, no significant difference in the 6MWD, biomarkers of right ventricular dysfunction, or oxygenation was identified, demonstrating a lack of hypoxemia worsening with treatment. Further studies are needed to investigate the use of PH medications in patients with severe PH-COPD.
PubMed: 38132665
DOI: 10.3390/jcdd10120498 -
American Journal of Cardiovascular... Jan 2024Pulmonary arterial hypertension (PAH) is a progressive, cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pulmonary arterial hypertension (PAH) is a progressive, cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent ventricular dilatation and failure. New therapeutic targets are being investigated for their potential roles in improving PAH patients' symptoms and reversing pulmonary vascular pathology.
METHOD
We aimed to address the available knowledge from the published randomized controlled trials (RCTs) regarding the role of Rho-kinase (ROCK) inhibitors, bone morphogenetic protein 2 (BMP2) inhibitors, estrogen inhibitors, and AMP-activated protein kinase (AMPK) activators on the PAH evaluation parameters. This systematic review (SR) was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CDR42022340658) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Overall, 5092 records were screened from different database and registries; 8 RCTs that met our inclusion criteria were included. The marked difference in the study designs and the variability of the selected outcome measurement tools among the studies made performing a meta-analysis impossible. However, the main findings of this SR relate to the powerful potential of the AMPK activator and the imminent antidiabetic drug metformin, and the BMP2 inhibitor sotatercept as promising PAH-modifying therapies. There is a need for long-term studies to evaluate the effect of the ROCK inhibitor fasudil and the estrogen aromatase inhibitor anastrozole in PAH patients. The role of tacrolimus in PAH is questionable. The discrepancy in the hemodynamic and clinical parameters necessitates defining cut values to predict improvement. The differences in the PAH etiologies render the judgment of the therapeutic potential of the tested drugs challenging.
CONCLUSION
Metformin and sotatercept appear as promising therapeutic drugs for PAH.
CLINICAL TRIALS REGISTRATION
This work was registered in PROSPERO (CDR42022340658).
Topics: Humans; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; AMP-Activated Protein Kinases; Familial Primary Pulmonary Hypertension; Estrogens; Metformin
PubMed: 37945977
DOI: 10.1007/s40256-023-00613-5 -
The Cochrane Database of Systematic... Oct 2019Persistent pulmonary hypertension of the newborn (PPHN) is a disease entity that describes a physiology in which there is persistence of increased pulmonary arterial... (Review)
Review
BACKGROUND
Persistent pulmonary hypertension of the newborn (PPHN) is a disease entity that describes a physiology in which there is persistence of increased pulmonary arterial pressure. PPHN is characterised by failure to adapt to a functional postnatal circulation with a fall in pulmonary vascular resistance. PPHN is responsible for impairment in oxygenation and significant neonatal mortality and morbidity. Prostanoids and their analogues may be useful therapeutic interventions due to their pulmonary vasodilatory and immunomodulatory effects.
OBJECTIVES
Primary objective• To determine the efficacy and safety of prostanoids and their analogues (iloprost, treprostinil, and beraprost) in decreasing mortality and the need for extracorporeal membrane oxygenation (ECMO) among neonates with PHSecondary objective• To determine the efficacy and safety of prostanoids and their analogues (iloprost, treprostinil, and beraprost) in decreasing neonatal morbidity (necrotizing enterocolitis (NEC), chronic lung disease (CLD), retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), length of hospital stay, and duration of mechanical ventilation) and improving neurodevelopmental outcomes among neonates with PHComparisons• Prostanoids and their analogues at any dosage or duration used to treat PPHN versus 'standard treatment without these agents', placebo, or inhaled nitric oxide (iNO) therapy• Prostanoids and their analogues at any dosage or duration used to treat refractory PPHN as an 'add-on' therapy to iNO versus iNO alone SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 9), MEDLINE via PubMed (1966 to 16 September 2018), Embase (1980 to 16 September 2018), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 16 September 2018). We also searched clinical trials databases, conference proceedings of the Pediatric Academic Societies (1990 to 16 September 2018), and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. We contacted authors who have published in this field as discerned from the reference lists of identified clinical trials and review authors' personal files.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials evaluating prostanoids or their analogues (at any dose, route of administration, or duration) used in neonates at any gestational age less than 28 days' postnatal age for confirmed or suspected PPHN.
DATA COLLECTION AND ANALYSIS
We used the standard methods of Cochrane Neonatal to conduct a systematic review and to assess the methodological quality of included studies (neonatal.cochrane.org/en/index.html). Three review authors independently assessed the titles and abstracts of studies identified by the search strategy and obtained full-text versions for assessment if necessary. We designed forms for trial inclusion or exclusion and for data extraction. We planned to use the GRADE approach to assess the quality of evidence.
MAIN RESULTS
We did not identify any eligible neonatal trials evaluating prostanoids or their analogues as sole agents in the treatment of PPHN.
AUTHORS' CONCLUSIONS
Implications for practiceCurrently, no evidence shows the use of prostanoids or their analogues as pulmonary vasodilators and sole therapeutic agents for the treatment of PPHN in neonates (age 28 days or less).Implications for researchThe safety and efficacy of different preparations and doses and routes of administration of prostacyclins and their analogues in neonates must be established. Well-designed, adequately powered, randomized, multi-center trials are needed to address the efficacy and safety of prostanoids and their analogues in the treatment of PPHN. These trials should evaluate long-term neurodevelopmental and pulmonary outcomes, in addition to short-term outcomes.
PubMed: 31573068
DOI: 10.1002/14651858.CD012963.pub2 -
Chest May 2024Pulmonary hypertension (PH) is a key complication in interstitial lung disease (ILD), with recent therapeutic advances.
BACKGROUND
Pulmonary hypertension (PH) is a key complication in interstitial lung disease (ILD), with recent therapeutic advances.
RESEARCH QUESTION
What are the diagnostic evaluation, epidemiologic features, associated factors, prognostic significance, and outcome measures in interventional trials for PH in patients with ILD in the current literature?
STUDY DESIGN AND METHODS
Ovid MEDLINE, Embase, and CENTRAL databases were searched for original research evaluating PH in participants with ILD of any cause. The definition of PH was based on the investigators' criteria.
RESULTS
Three hundred two studies were included, with varying diagnostic evaluations used to define PH. Commonly used diagnostic tests were right heart catheterization (RHC; 56%) and transthoracic echocardiography (TTE; 50%). The pooled prevalence for PH in general populations with ILD was 36% (95% CI, 30%-42%) using RHC and 34% (95% CI, 29%-38%) using TTE. Lower diffusion capacity of the lungs for carbon monoxide, worse oxygenation status, reduced exercise capacity, increased pulmonary artery to aorta ratio and pulmonary artery diameter, and elevated serum brain natriuretic peptide consistently were associated with the presence of PH in at least 60% of reported studies. The presence of PH was associated with increased symptom burden and worse prognosis. Outcome measures in interventional trials of PH in ILD focused on changes in pulmonary vascular hemodynamics and 6-min walk distance.
INTERPRETATION
PH is a common complication in ILD with significant health impacts. A standardized definition with prospective evaluation of risk-stratified assessments for PH using identified associated risk factors is warranted. Our findings provide an evidence base for validation as surrogate end points in future PH interventional trials in ILD.
TRIAL REGISTRY
International Prospective Register of Systematic Reviews; No.: CRD42021255394; URL: https://www.crd.york.ac.uk/prospero/.
PubMed: 38821182
DOI: 10.1016/j.chest.2024.04.025