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Frontiers in Pharmacology 2023Pulmonary arterial hypertension (PAH) is a rare and progressive disease. Some patients treated with phosphodiesterase type 5 inhibitors (PDE-5is) fail to reach...
Pulmonary arterial hypertension (PAH) is a rare and progressive disease. Some patients treated with phosphodiesterase type 5 inhibitors (PDE-5is) fail to reach treatment goals. As a novel soluble guanylate cyclase agonist, riociguat acts on the same pathway as PDE-5is but functions different mechanisms. Whether riociguat is more effective and safer than PDE-5is is ambiguous. We aimed to evaluate the efficacy and safety of switching from PDE-5is to riociguat among these patients. Original published articles were retrieved from PubMed/Medline, Embase, Web of Science, Open Grey and Google Scholar. Studies that assessed the World Health Organization functional class (WHO-FC), 6-min walking distance (6MWD), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), cardiac index (CI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were collected. Adverse events after switching were evaluated. Ten published studies were included. Compared to PDE-5is, riociguat significantly increased the 6MWD by 26.45 m weighted mean difference (WMD) = 26.45 m, 95% confidence intervals (CIs): 9.70-43.2 m, = 0.002) and improved mPAP (WMD = -3.53, 95% CIs: -5.62-1.44 mmHg, = 0.0009), PVR (WMD = -130.24 dyn·s·cm, 95% CI -187.43-73.05, 0.0001), CIs (WMD = 0.36 L/min·cm, 95% CIs: 0.25-0.47, 0.00001) and WHO-FC (OR = 0.11, 95% CIs: 0.08-0.16, < 0.0001) but not NT-proBNP. In addition, we did not observe the most common side effects during the replacement of riociguat for PDE-5is. PAH patients benefit from PDE-5is compared to riociguat, including in hemodynamic parameters, 6MWD, WHO-FC and biomarkers.
PubMed: 36778016
DOI: 10.3389/fphar.2023.1052546 -
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 -
Frontiers in Cardiovascular Medicine 2022There is little evidence of the effectiveness of switching from the endothelin receptor antagonists (ERAs) bosentan and ambrisentan to a novel ERA, macitentan, in...
BACKGROUND
There is little evidence of the effectiveness of switching from the endothelin receptor antagonists (ERAs) bosentan and ambrisentan to a novel ERA, macitentan, in patients with pulmonary arterial hypertension (PAH). Therefore, a systematic review and meta-analysis was performed to evaluate the efficacy and safety of patients with PAH switching from other ERAs to macitentan.
METHODS
We retrieved the relevant literature published before January 2022 for the meta-analysis from the PubMed, EMBASE, and Cochrane Library databases. Efficacy included changes in the 6-min walk distance (6MWD), World Health Organization functional class (WHO-FC), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, hemodynamics, echocardiography and survival.
RESULTS
Nine studies, consisting of 408 PAH patients, that met the inclusion criteria were included. The switch from bosentan or ambrisentan to macitentan effectively increased the 6MWD by 20.71 m (95% CI: 10.35-31.07, < 0.00001, = 0%). Six months after conversion, the tricuspid annular plane systolic excursion was found to improve from 19.0 ± 4.0 to 21.0 ± 5.0 mm in adults and from 16.00 ± 5.0 to 18.25 ± 4.8 mm in children. Ordinal logistic regression showed that the WHO-FC significantly improved by 0.412 (95% CI: 0.187-0.908, = 0.028). The switch did not show significant improvement in NT-proBNP levels. In addition, the switch was well tolerated.
CONCLUSION
The switch from bosentan or ambrisentan to macitentan significantly increased the 6MWD in PAH patients, improved the WHO-FC, and exerted safety benefits. The effects of the switch on NT-proBNP levels, hemodynamics, and echocardiography still need to be further confirmed.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021292554].
PubMed: 36568539
DOI: 10.3389/fcvm.2022.977110 -
European Journal of Pediatrics Jan 2023Infections with respiratory syncytial virus (RSV) can cause severe disease. In young children, RSV is the most common cause of lower respiratory tract illness and...
UNLABELLED
Infections with respiratory syncytial virus (RSV) can cause severe disease. In young children, RSV is the most common cause of lower respiratory tract illness and life-threatening infections most commonly occur in the first years of life. In adults, elderly and immunocompromised people are most vulnerable. Recently there has been an acceleration in the development of candidate RSV vaccines, monoclonal antibodies and therapeutics which are expected to become available in Europe within the next 2-10 years. Understanding the true burden of childhood RSV disease will become very important to support public health authorities and policy makers in the assessment of new therapeutic opportunities against RSV disease. A systematic literature search was performed to map local data on the burden of RSV disease and to evaluate available RSV surveillance systems. A group of 9 paediatric infectious diseases specialists participated in an expert panel. The purpose of this meeting was to evaluate and map the burden associated with RSV infection in children, including patient pathways and the epidemiological patterns of virus circulation in Belgium. Sources of information on the burden of RSV disease in Belgium are very limited. For the outpatient setting, it is estimated that 5-10% of young patients seen in primary care are referred to the hospital. Around 3500 children between 0 and 12 months of age are hospitalized for RSV-bronchiolitis every year and represent the majority of all hospitalizations. The current Belgian RSV surveillance system was evaluated and found to be insufficient. Knowledge gaps are highlighted and future perspectives and priorities offered.
CONCLUSION
The Belgian population-based RSV surveillance should be improved, and a hospital-led reporting system should be put in place to enable the evaluation of the true burden of RSV disease in Belgium and to improve disease management in the future.
WHAT IS KNOWN
• RSV bronchiolitis is a very important cause of infant hospitalization. • The burden of disease in the community is poorly studied and underestimated.
WHAT IS NEW
• This expert opinion summarizes knowledge gaps and offers insights that allow improvement of local surveillance systems in order to establish a future-proof RSV surveillance system.
Topics: Humans; Infant; Infant, Newborn; Belgium; Bronchiolitis; Hospitalization; Population Surveillance; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 36371521
DOI: 10.1007/s00431-022-04698-z -
Frontiers in Pediatrics 2022Meta-analysis of the impact on clinical outcome from transcatheter closure of Fontan fenestration.
BACKGROUND
Meta-analysis of the impact on clinical outcome from transcatheter closure of Fontan fenestration.
METHODS
Cochrane, Embase, MEDLINE, and Open-Gray were searched. Parameters such as changes in oxygen saturation, cavo-pulmonary pressure, maximum heart rate during exercise, exercise duration, and oxygen saturation after fenestration closure were pooled and statistical analysis performed.
RESULTS
Among 922 publications, 12 retrospective observational studies were included. The included studies involved 610 patients, of which 552 patients (90.5%) had a fenestration. Of those patients, 505 patients (91.5%) underwent attempt at trans-catheter closure. When it could be estimated, the pooled overall mean age at trans-catheter fenestration closure was 6.6 ± 7.4 years, and the mean follow-up time was 34.4 ± 10.7 months. There were 32 minor (6.3%) and 20 major (4.0%) complications during or after trans-catheter Fontan fenestration closure. The forest plots demonstrate that following fenestration closure, there was a significant increase in the mean arterial oxygen saturation of 7.9% (95% CI 6.4-9.4%, < 0.01). There was also a significant increase in the mean cavo-pulmonary pressure of 1.4 mmHg (95% CI 1.0-1.8 mmHg, < 0.01) following fenestration closure. The exercise parameters reported in 3 studies also favored closing the fenestration as well, yet the exercise duration increase of 1.7 min (95% CI 0.7-2.8 min, < 0.01) after fenestration closure is probably clinically insignificant.
CONCLUSION
Late closure of a Fontan fenestration has the impact of improving resting oxygen saturation, exercise oxygen saturation, and a modest improvement of exercise duration. These clinical benefits, however, may be at the expense of tolerating slightly higher cavo-pulmonary mean pressures.
PubMed: 36268038
DOI: 10.3389/fped.2022.915045 -
Resuscitation Plus Dec 2022Calcium use during cardiac arrest has conflicting results in terms of efficacy. Therefore, we performed a systematic review evaluating the role of calcium administration... (Review)
Review
INTRODUCTION
Calcium use during cardiac arrest has conflicting results in terms of efficacy. Therefore, we performed a systematic review evaluating the role of calcium administration in cardiac arrest.
METHODS
We searched PubMed, Cochrane, and EMBASE for studies comparing calcium administration versus no calcium administration during cardiac arrest. The study was prospectively registered in PROSPERO (CRD42022316641) adhering to PRISMA guideline recommendations. The primary outcome was return of spontaneous circulation (ROSC) or survival at one hour. The secondary outcomes included survival to discharge or at 30 days, and favorable neurologic outcomes at 30 and 90 days. We planned to perform a random-effects meta-analysis of low risk of bias studies. We evaluated risk of bias with RoB-2 and ROBINS-I.
RESULTS
We identified 1,921 articles and included ten studies with 2509 patients. We were not able to perform a meta-analysis with low-risk of bias studies as only one study was found to be at low-risk of bias. However, for the primary outcome, the three RCTs included showed no benefit with calcium administration during cardiac arrest for ROSC. For the secondary outcomes, based on the most recent study and lower risk of bias, there was a neutral effect for survival to discharge or at 30 days and neurologic outcomes at 30 days. However, there was unfavorable neurologic outcomes at 90 days.
CONCLUSION
Based on our results, calcium administration in cardiac arrests shows no benefit and can cause harm. Further studies on this matter are likely not advisable.
PubMed: 36238582
DOI: 10.1016/j.resplu.2022.100315 -
Journal of Clinical Medicine Sep 2022Statins are lipid-lowering medications used for the prevention of cardiovascular disease (CVD), but the pleiotropic effects of statins might be beneficial in other... (Review)
Review
Statins are lipid-lowering medications used for the prevention of cardiovascular disease (CVD), but the pleiotropic effects of statins might be beneficial in other chronic diseases. This meta-analysis investigated the association between statin use and mortality in different chronic conditions. Eligible studies were real-world studies that compared all-cause mortality over at least 12 months between propensity score-matched statin users and non-users. Overall, 54 studies were included: 21 in CVD, 6 in chronic kidney disease, 6 in chronic inflammatory diseases, 3 in cancer, and 18 in other diseases. The risk of all-cause mortality was significantly reduced in statin users (hazard ratio: 0.72, 95% confidence interval: 0.66−0.76). The reduction in mortality risk was similar in CVD studies (0.73, 0.66−0.76) and non-CVD studies (0.70, 0.67−0.79). There were no significant differences in the risk reduction between cohorts with different diseases (p = 0.179). The greatest mortality reduction was seen in studies from Asia (0.61, 0.61−0.73) and the lowest in studies from North America (0.78, 0.73−0.83) and Australia (0.78, 0.62−0.97). There was a significant heterogeneity (I2 = 95%, tau2 = 0.029, p < 0.01). In conclusion, statin use was associated with a significantly reduced risk of all-cause mortality in real-world cohorts with CVD and non-CVD.
PubMed: 36233511
DOI: 10.3390/jcm11195643 -
Animal Models and Experimental Medicine Oct 2022The association between blood eosinophil (EOS) counts and arterial/venous thrombosis is unclear. We aim to explore whether EOS count is a risk factor for thrombosis. We... (Meta-Analysis)
Meta-Analysis
The association between blood eosinophil (EOS) counts and arterial/venous thrombosis is unclear. We aim to explore whether EOS count is a risk factor for thrombosis. We searched several databases and preprint platforms using core terms 'eosinophil', 'myocardial infarction', 'ischemic stroke', and 'venous thromboembolism' (VTE), among others. Studies comparing the odds ratios (ORs) or risk ratios (RRs) of EOSs with the abovementioned diseases were eligible. Overall, 22 studies were included. A high EOS count was associated with acute coronary artery thrombosis events (OR: 1.23, 95% CI: 1.15-1.32), short-term cerebral infarction and mortality (RR: 2.87, 95% CI: 1.49-5.51). The short-term risk of VTE was more common in patients with EOS-related diseases (RR: 6.52, 95% CI: 2.42-17.54). For coronary artery disease, a high EOS count was a protective factor against 6-month to 1-year mortality (RR: 0.56, 95% CI: 0.45-0.69) but was associated with long-term mortality (RR: 1.64, 95% CI: 1.25-2.14). Therefore, we conclude that for coronary artery thrombosis, EOS count is not associated with AMI events in general population. It may be associated with NSTEMI and STEMI in CAD patients, but more studies are needed to confirm this. In addition, EOS count is associated with an increased risk of both short- and long-term mortality but is not predictive of the composite endpoints. For cerebral artery thrombosis, EOS count may be associated with cerebral infarction and could lead to an increased risk of poor short-term prognosis. For VTEs, EOS count was a risk factor for some patients, especially those with acute-phase EOS-related diseases.
Topics: Humans; Venous Thromboembolism; Venous Thrombosis; Myocardial Infarction; Coronary Thrombosis; Cerebral Infarction
PubMed: 36205251
DOI: 10.1002/ame2.12277 -
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 -
Circulation Aug 2022Clinical worsening (CW) is a composite end point commonly used in pulmonary arterial hypertension (PAH) trials. We aimed to assess the trial-level surrogacy of CW for... (Meta-Analysis)
Meta-Analysis
Assessment of Clinical Worsening End Points as a Surrogate for Mortality in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
BACKGROUND
Clinical worsening (CW) is a composite end point commonly used in pulmonary arterial hypertension (PAH) trials. We aimed to assess the trial-level surrogacy of CW for mortality in PAH trials, and whether the various CW components were similar in terms of frequency of occurrence, treatment-related relative risk (RR) reduction, and importance to patients.
METHODS
We searched MEDLINE, Embase, and the Cochrane Library (January 1990 to December 2020) for trials evaluating the effects of PAH therapies on CW. The coefficient of determination between the RR for CW and mortality was assessed by regression analysis. The frequency of occurrence, RR reduction, and importance to patients of the CW components were assessed.
RESULTS
We included 35 independent cohorts (9450 patients). PAH therapies significantly reduced CW events (RR, 0.64 [95% CI, 0.55-0.73]), including PAH-related hospitalizations (RR, 0.61 [95% CI, 0.47-0.79]), treatment escalation (RR, 0.57 [95% CI, 0.38-0.84]) and symptomatic progression (RR, 0.58 [95% CI, 0.48-0.69]), and modestly reduced all-cause mortality when incorporating deaths occurring after a primary CW-defining event (RR, 0.860 [95% CI, 0.742-0.997]). However, the effects of PAH-specific therapies on CW only modestly correlated with their effects on mortality (, 0.35 [95% CI, 0.10-0.59]; <0.0001), and the gradient in the treatment effect across component end points was large in the majority of trials. The weighted proportions of CW-defining events were hospitalization (33.5%) and symptomatic progression (32.3%), whereas death (6.7%), treatment escalation (5.6%), and transplantation/atrioseptostomy (0.2%) were infrequent. CW events were driven by the occurrence of events of major (49%) and mild-to-moderate (37%) importance to patients, with 14% of the events valued as critical.
CONCLUSIONS
PAH therapies significantly reduced CW events, but study-level CW is not a surrogate for mortality in PAH trials. Moreover, components of CW largely vary in frequency, response to therapy, and importance to patients and are thus not interchangeable.
REGISTRATION
URL: https://www.crd.york.ac.uk/PROSPERO; Unique identifier: CRD42020178949.
Topics: Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Randomized Controlled Trials as Topic; Regression Analysis
PubMed: 35862151
DOI: 10.1161/CIRCULATIONAHA.121.058635