Comparison of Effectiveness Among Different Sodium-Glucose Cotransoporter-2 Inhibitors According to Underlying Conditions: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: To investigate the individual profile of each SGLT2 (sodium-glucose cotransoporter-2) inhibitor in patients with different backgrounds. METHODS AND RESULTS: This study included 21 placebo-controlled randomized controlled trials with a total of 96 196 participants, investigating empagliflozin, ertugliflozin, dapagliflozin, canagliflozin, and sotagliflozin. The primary efficacy end point was the composite of cardiovascular death and hospitalizations for heart failure. The secondary efficacy end points were all-cause death, cardiovascular death, hospitalizations for heart failure, kidney disease progression, and acute kidney injury. We conducted subgroup analyses based on the underlying comorbidities, including diabetes and chronic kidney disease. Safety end points were also assessed among SGLT2 inhibitors in the overall cohort. In the overall cohort, there were no significant differences in the primary efficacy outcome among the SGLT2 inhibitors, while empagliflozin (hazard ratio [HR], 0.70 [95% CI, 0.53-0.92]) and dapagliflozin (HR, 0.73 [95% CI, 0.56-0.96]) were associated with lower risk of acute kidney injury than sotagliflozin. The presence or absence of diabetes did not alter the results. In patients with chronic kidney disease, there were no differences in the efficacy outcomes among SGLT2 inhibitors, while in patients without chronic kidney disease, empagliflozin was associated with lower risk of the primary outcome compared with ertugliflozin (HR, 0.77 [95% CI, 0.60-0.98]). For safety outcomes, no significant differences were observed in amputation, urinary tract infection, genital infection, hypoglycemia, and diabetic ketoacidosis. CONCLUSIONS: The differences in reducing cardiovascular and kidney outcomes as well as safety profiles across SGLT2 inhibitors were not consistently significant, although empagliflozin might be preferred in patients without chronic kidney disease. Further investigations are needed to better understand the mechanism and clinical effectiveness of each SGLT2 inhibitor in certain populations.

Cardiac Reoperation or Transcatheter Mitral Valve Replacement for Patients With Failed Mitral Prostheses.

BACKGROUND: Evidence is limited regarding patient outcomes comparing redo surgical mitral valve replacement (redo SMVR) vs transcatheter mitral valve replacement (TMVR) for failed prostheses. OBJECTIVES: The goal of this study was to compare the outcomes of redo SMVR vs TMVR in patients with failed prostheses, as well as evaluate the association between case volume and outcomes. METHODS: Medicare beneficiaries aged ≥65 years who underwent redo SMVR or TMVR for failed mitral prostheses between 2016 and 2020 were included. The primary endpoint was mid-term (up to 3 years) major adverse cardiovascular events (MACE), including all-cause death, heart failure rehospitalization, stroke, or reintervention. Propensity score-matched analysis was used. RESULTS: A total of 4,293 patients were included (redo SMVR: 64%; TMVR: 36%). TMVR recipients were older, with a higher comorbidity burden. In matched cohort (n = 1,317 in each group), mid-term risk of MACE was similar (adjusted HR: 0.92; 95% CI: 0.80-1.04; P = 0.2). However, landmark analysis revealed a lower risk of MACE with TMVR in the first 6 months (adjusted HR: 0.75; 95% CI: 0.63-0.88; P < 0.001) albeit with a higher risk beyond 6 months (adjusted HR: 1.28; 95% CI: 1.04-1.58; P = 0.02). Increasing procedural volume was associated with decreased risk of mid-term MACE after redo SMVR (P = 0.001) but not after TMVR (P = 0.3). CONCLUSIONS: In this large cohort of Medicare beneficiaries with failed mitral prostheses, outcomes were similar between redo SMVR and TMVR at 3 years, with TMVR showing a lower initial risk but a higher risk of MACE after 6 months. These findings highlight the importance of striking a balance between surgical risk, anticipated longevity, and hospital expertise when selecting interventions.

Overview of SARS-CoV-2 infection and vaccine associated myocarditis compared to non-COVID-19-associated myocarditis: A systematic review and meta-analysis.

BACKGROUND: Previous literature suggests that both SARS-CoV-2 infection and COVID-19 mRNA vaccine are associated with myocarditis, in which the incidence is higher in the infection group. COVID-19 mRNA vaccine-related myocarditis is noted to have a more benign course. Despite these findings, there is a need for a larger population systematic review that compares the outcomes to pre-pandemic acute myocarditis to better understand the extent of the current post-COVID state. METHODS: We performed a literature search with PubMed and EMBASE and identified studies investigating COVID-19 and its vaccinated population, and the population prior to the pandemic (control group) who had myocarditis. We performed a one-group meta-analysis of the incidence, baseline demographics, and outcomes of myocarditis for each group. RESULTS: The incidence in the SARS-CoV-2 infection group was 2.76 per thousand (95% CI, 0.85-8.92), 19.7 per million (95% CI, 12.3-31.6) in the vaccine group, and 0.861 per million (95% CI, 0.04-16.7) in the control group. The majority of patients were male, with the highest proportion in the vaccine group. The mean age was the youngest in the vaccine group (24.8, 95% CI, 19.1-30.6). The vaccine group had the lowest mortality (2.0%, 95% CI, 1.3-2.7) followed by the control and the SARS-CoV-2 infection group. The vaccine group had the lowest proportion of immunoglobulin and glucocorticoid use, mechanical circulatory support, and cardiogenic shock. CONCLUSION: Our study showed favorable outcomes of myocarditis in patients with COVID-19 mRNA vaccination, despite a higher incidence than pre-COVID controls. Further studies with standardized myocarditis diagnostic criteria assessing long-term outcomes are necessary.

Clinical Management of Brugada Syndrome: Commentary From the Experts.

Although there is consensus on the management of patients with Brugada Syndrome with high risk for sudden cardiac arrest, asymptomatic or intermediate-risk patients present clinical management challenges. This document explores the management opinions of experts throughout the world for patients with Brugada Syndrome who do not fit guideline recommendations. Four real-world clinical scenarios were presented with commentary from small expert groups for each case. All authors voted on case-specific questions to evaluate the level of consensus among the entire group in nuanced diagnostic and management decisions relevant to each case. Points of agreement, points of controversy, and gaps in knowledge are highlighted.

Anticoagulation in chronic thromboembolic pulmonary hypertension: A systematic review and meta-analysis.

INTRODUCTION: Life-long anticoagulation is the recommended management for chronic thromboembolic pulmonary hypertension (CTEPH). Evidence regarding the use of direct oral anticoagulants (DOAC) for CTEPH is yet to be established. We performed a systematic review and meta-analysis to clarify the outcomes of CTEPH in patients who used DOAC or vitamin K antagonists (VKA). METHODS: We reviewed literature in PubMed and EMBASE through March 2023. We included studies involving patients with CTEPH where DOAC and VKA were compared. We collected data including intervention history for CTEPH, bleeding events, recurrence of VTE (venous thromboembolism), and mortality. We performed a meta-analysis using the Mantel-Haenszel method with a fixed-effects model. RESULTS: We included one randomized clinical trial and six observational studies, with a total of 2969 patients. Six studies investigated major bleeding outcomes, and seven investigated all bleeding outcomes. There were no differences in major bleeding (RR 0.59, 95 % CI [0.34-1.02], I2 = 0 %) and all-bleeding (RR 0.87, 95 % CI [0.67-1.13], I2 = 0 %). Based on the five studies we included, DOAC was associated with a lower risk of mortality (RR 0.54, 95 % CI: 0.37-0.79, I2 = 5 %). However, a higher risk of recurrent pulmonary embolism (PE) was seen in three studies (RR 3.80, 95 % CI: [1.93-7.50], I2 = 11 %). No significant differences were noted in terms of VTE. CONCLUSION: DOAC compared to VKA was associated with a significantly lower mortality and higher risk of recurrent PE. Since most of the included studies are observational, we must consider the existence of multiple biases and confounding factors.

Combination of rescue balloon pulmonary angioplasty and riociguat therapy for chronic thromboembolic pulmonary hypertension with nonsustained polymorphic ventricular tachycardia: A case report.

We encountered a case of frequent nonsustained polymorphic ventricular tachycardia (NSPVT) due to hemodynamically unstable chronic thromboembolic pulmonary hypertension (CTEPH). A 78-year-old woman was taking anticoagulants for CTEPH. She had refused specific treatment for CTEPH, including pulmonary vasodilators, because she was then asymptomatic. She fell and sustained a femoral neck fracture, and she was referred to our hospital in anticipation of a surgical repair. Her condition on admission was complicated by respiratory failure, and electrocardiogram monitoring showed frequent NSPVT. A right heart catheterization revealed high mean pulmonary artery pressure with severely reduced cardiac output. Pulmonary angiography showed bilateral stenosis and multiple obstructions. Because NSPVT was attributed to low cardiac output syndrome caused by CTEPH, rescue balloon pulmonary angioplasty (BPA) was performed, and riociguat treatment was initiated. Afterward, the NSPVT resolved. This case suggests that the combination of rescue BPA with riociguat therapy might be an immediate and effective treatment for patients with inoperable CTEPH and severe hemodynamic instability.

Short-Term DAPT and DAPT De-Escalation Strategies for Patients With Acute Coronary Syndromes: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Short-term (≤6 months) dual antiplatelet therapy (DAPT) and DAPT de-escalation become attractive for patients with acute coronary syndrome. METHODS: A systemic search identified randomized controlled trials that included patients with acute coronary syndrome treated using (1) standard DAPT (12 months) with clopidogrel, prasugrel (standard/low dose), or ticagrelor; (2) extended DAPT (≥18 months); (3) short-term DAPT (≤6 months) followed by P2Y12 inhibitor or aspirin; (4) 12-month DAPT with unguided de-escalation from potent P2Y12 inhibitors to low-dose potent P2Y12 inhibitor or clopidogrel at 1 month; and (5) guided selection DAPT with genotype or platelet function tests. The primary efficacy outcome (major adverse cardiovascular events) was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major or minor bleeding. RESULTS: This meta-analysis included 32 randomized controlled trials with 103 497 patients. While there were no differences in efficacy between short, unguided de-escalation and guided selection strategies, unguided de-escalation was associated with reduced risk of major adverse cardiovascular events compared with standard DAPT with clopidogrel or ticagrelor (hazard ratio [95% CI], 0.67 [0.49-0.93] and 0.68 [0.50-0.93]). Both short DAPT followed by P2Y12 inhibitor and unguided de-escalation were associated with reduced risks in safety compared with other strategies, including guided selection (hazard ratio [95% CI], 0.66 [0.47-0.93] and 0.48 [0.33-0.71]). Short DAPT followed by a P2Y12 inhibitor was associated with reduced risk of major bleeding and all-cause death compared with standard, extended DAPT (eg, versus DAPT with clopidogrel; hazard ratio [95% CI], 0.64 [0.42-0.97] and 0.60 [0.44-0.82]). By rankogram, unguided de-escalation strategy was the safest and most effective strategy in reducing major adverse cardiovascular events and major or minor bleeding while short DAPT followed by P2Y12 inhibitor was ranked the best for major bleeding and all-cause death. CONCLUSIONS: In patients with acute coronary syndrome, unguided de-escalation was associated with the lowest risk of major adverse cardiovascular events and major or minor bleeding outcomes, while short DAPT followed by P2Y12 inhibitor was associated with the lowest risk of major bleeding and all-cause death.

Network meta-analysis of temporary mechanical circulatory support in acute myocardial infarction cardiogenic shock.

We performed a network meta-analysis of 11 published randomized clinical trials examining the use of temporary mechanical circulatory support (MCS) devices in adults with acute myocardial infarction cardiogenic shock, including 1,053 total patients with an observed in-hospital or 30-day mortality of 40.4%. None of the temporary MCS devices was associated with lower in-hospital or 30-day mortality compared with initial medical therapy or any other MCS device, either individually or in combination. These data do not support the routine use of temporary MCS devices for the purpose of reducing short-term mortality in unselected patients with acute myocardial infarction cardiogenic shock.

Prevalence and Treatment of Arrhythmias in Patients With Transthyretin and Light-Chain Cardiac Amyloidosis.

Background: Various types of arrhythmia are observed in patients with cardiac amyloidosis, but the prevalence of arrhythmia has not been fully investigated. This study investigated the prevalence and treatment of arrhythmias in patients with cardiac amyloidosis before the introduction of new agents for amyloidosis, such as tafamidis. Methods and Results: Of 53 patients who were histologically diagnosed with cardiac amyloidosis at 10 centers in western Japan between 2009 and 2021, 43 who were diagnosed on the basis of immunohistochemical staining were evaluated in this study. Of these 43 patients, 13 had immunoglobulin light-chain (AL) amyloidosis and 30 had transthyretin (ATTR) amyloidosis; further, 27 had atrial tachyarrhythmia, 13 had ventricular tachyarrhythmia, and 17 had bradyarrhythmia. Atrial fibrillation (AF) was the most common arrhythmia in patients with cardiac amyloidosis (n=24; 55.8%), especially among those with ATTR amyloidosis (70.0% of ATTR vs. 23.1% of AL). Eleven (25.6%) patients were treated with a cardiac implantable device. All 3 patients with pacemakers were alive at the last follow-up (median 76.7 months; interquartile range [IQR] 4.8-146.4 months). Of the 8 patients who underwent AF ablation, there was no recurrence in 6 (75%) after a median of 39.3 months (IQR 19.8-59.3 months). Conclusions: The prevalence of various arrhythmias was high in patients with cardiac amyloidosis. AF occurred most frequently in patients with cardiac amyloidosis, especially among patients with ATTR.

Extracorporeal membrane oxygenation for COVID-19-associated acute respiratory distress syndrome: A nationwide analysis.

Extracorporeal membrane oxygenation (ECMO) has been used for COVID-19-associated acute respiratory distress syndrome (ARDS). We aimed to elucidate the association between ECMO and mortality in patients with COVID-19-associated ARDS in the nationwide setting. United States National Inpatient Sample was used to identify mechanically ventilated adults for COVID-19 with ARDS. We divided them into three groups according to the use of ECMO (i.e., no-ECMO, venovenous [VV]-ECMO, and venoarterial [VA]-ECMO). The primary outcome was in-hospital mortality, while the secondary outcomes included the length of hospital stay (LOS) and the total costs during hospitalization. We performed a stepwise logistic regression, adjusting for baseline characteristics, comorbidities, and severity. We included 68 795 (mean age [SD]: 63.5 [0.1]), 3280 (mean age [SD]: 48.7 [0.5]), and 340 (mean age [SD]: 43.3 [2.1]) patients who received no-, VV-, and VA-ECMO, respectively. The logistic regression analysis did not show significant associations between the use of VV-/VA-ECMO and mortality (adjusted odds ratio with no-ECMO as reference [95% confidence interval]: 1.03 [0.86-1.24] and 1.18 [0.64-2.15], respectively). While LOS was longest with VV-ECMO, the total costs were highest with VA-ECMO. In conclusion, our study found no association between the use of ECMO and mortality of COVID-19-associated ARDS in the nationwide setting.

Comparison of interventions for intermediate to high-risk pulmonary embolism: A network meta-analysis.

BACKGROUND: Multiple interventions, including catheter-directed therapy (CDT), systemic thrombolysis (ST), surgical embolectomy (SE), and therapeutic anticoagulation (AC) have been used to treat intermediate to high-risk pulmonary embolism (PE), but the most effective and safest treatment remains unclear. Our study aimed to investigate the efficacy and safety outcomes of each intervention. METHODS: We queried PubMed and EMBASE in January 2023 and performed a network meta-analysis of observational studies and randomized controlled trials (RCT), including high or intermediate-risk PE patients, and comparing AC, CDT, SE, and ST. The primary outcomes were in-hospital mortality and major bleeding. The secondary outcomes included long-term mortality (≥6 months), recurrent PE, minor bleeding, and intracranial hemorrhage. RESULTS: We identified 11 RCTs and 42 observational studies involving 157,454 patients. CDT was associated with lower in-hospital mortality than ST (odds ratio [OR] [95% confidence interval (CI)]: 0.41 [0.31-0.55]), AC (OR [95% CI]: 0.33 [0.20-0.53]), and SE (OR [95% CI]: 0.61 [0.39-0.96]). Recurrent PE in CDT was lower than ST (OR [95% CI]: 0.66 [0.50-0.87]), AC (OR [95% CI]: 0.36 [0.20-0.66]), and trended lower than SE (OR [95% CI]: 0.71 [0.40-1.26]). Notably, ST had higher major bleeding risks than CDT (OR [95% CI]: 1.51 [1.19-1.91]) and AC (OR [95% CI]: 2.21 [1.53-3.19]). By rankogram analysis, CDT presented the highest p-score in in-hospital mortality, long-term mortality, and recurrent PE. CONCLUSION: In this network meta-analysis of observational studies and RCTs involving patients with intermediate to high-risk PE, CDT was associated with improved mortality outcomes compared to other therapies, without significant additional bleeding risk.

Use of Perioperative Extracorporeal Membranous Oxygenation in Pulmonary Endarterectomy Cases: A Systematic Review and Meta-Analysis.

Introduction: Pulmonary endarterectomy (PEA) is known to be a curative intervention for chronic thromboembolic pulmonary hypertension (CTEPH). Its complications include endobronchial bleeding, persistent pulmonary arterial hypertension, right ventricular failure, and reperfusion lung injury. Extracorporeal membranous oxygenation (ECMO) is a perioperative salvage method for PEA. Although risk factors and outcomes have been reported in several studies, overall trends remain unknown. We performed a systematic review and study-level meta-analysis to understand the outcomes of ECMO utilization in the perioperative period of PEA. Methods: We performed a literature search with PubMed and EMBASE on 11/18/2022. We included studies including patients who underwent perioperative ECMO in PEA. We collected data including baseline demographics, hemodynamic measurements, and outcomes such as mortality and weaning of ECMO and performed a study-level meta-analysis. Results: Eleven studies with 2632 patients were included in our review. ECMO insertion rate was 8.7% (225/2,625, 95% CI 5.9-12.5) in total, VV-ECMO was performed as the initial intervention in 1.1% (41/2,625, 95% CI 0.4-1.7) (Figure 3), and VA-ECMO was performed as an initial intervention in 7.1% (184/2,625, 95% CI 4.7-9.9). Preoperative hemodynamic measurements showed higher pulmonary vascular resistance, mean pulmonary arterial pressure, and lower cardiac output in the ECMO group. Mortality rates were 2.8% (32/1238, 95% CI: 1.7-4.5) in the non-ECMO group and 43.5% (115/225, 95% CI: 30.8-56.2) in the ECMO group. The proportion of patients with successful weaning of ECMO was 72.6% (111/188, 95% CI: 53.4-91.7). Regarding complications of ECMO, the incidence of bleeding and multi-organ failure were 12.2% (16/79, 95% CI: 13.0-34.8) and 16.5% (15/99, 95% CI: 9.1-28.1), respectively. Conclusion: Our systematic review showed a higher baseline cardiopulmonary risk in patients with perioperative ECMO in PEA, and its insertion rate was 8.7%. Further studies that compare the use of ECMO in high-risk patients who undergo PEA are anticipated.

Pulse Methylprednisolone Versus Dexamethasone in COVID-19: A Multicenter Cohort Study.

Although pulse (high-dose) methylprednisolone therapy can hypothetically control immune system flare-ups effectively, the clinical benefit of pulse methylprednisolone compared with dexamethasone in COVID-19 remains inconclusive. OBJECTIVES: To compare pulse methylprednisolone to dexamethasone as a COVID-19 treatment. DESIGN SETTING AND PARTICIPANTS: Using a Japanese multicenter database, we identified adult patients admitted for COVID-19 and discharged between January 2020 and December 2021 treated with pulse methylprednisolone (250, 500, or 1,000 mg/d) or IV dexamethasone (≥ 6 mg/d) at admission day 0 or 1. Main Outcomes and Measures: The primary outcome was in-hospital mortality. Secondary outcomes were 30-day mortality, new ICU admission, insulin initiation, fungal infection, and readmission. Multivariable logistic regression was conducted to differentiate the dose of pulse methylprednisolone (250, 500, or 1,000 mg/d). Additionally, subgroup analyses by characteristics such as the need for invasive mechanical ventilation (IMV) were also conducted. RESULTS: A total of 7,519, 197, 399, and 1,046 patients received dexamethasone, 250, 500, and 1,000 mg/d of methylprednisolone, respectively. The crude in-hospital mortality was 9.3% (702/7,519), 8.6% (17/197), 17.0% (68/399), and 16.2% (169/1,046) for the different doses, respectively. The adjusted odds ratio (95% CI) was 1.26 (0.69-2.29), 1.48 (1.07-2.04), and 1.75 (1.40-2.19) in patients starting 250, 500, and 1,000 mg/d of methylprednisolone, respectively, compared with those starting dexamethasone. In subgroup analyses, the adjusted odds ratio of in-hospital mortality was 0.78 (0.25-2.47), 1.12 (0.55-2.27), and 1.04 (0.68-1.57) in 250, 500, and 1,000 mg/d of methylprednisolone, respectively, among patients with IMV, whereas the adjusted odds ratio was 1.54 (0.77-3.08), 1.62 (1.13-2.34), and 2.14 (1.64-2.80) among patients without IMV. CONCLUSIONS AND RELEVANCE: Higher doses of pulse methylprednisolone (500 or 1,000 mg/d) may be associated with worse COVID-19 outcomes when compared with dexamethasone, especially in patients not on IMV.

Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis.

BACKGROUND: The relationship between coronavirus disease 2019 (COVID-19) vaccination and long COVID has not been firmly established. We conducted a systematic review and meta-analysis to evaluate the association between COVID-19 vaccination and long COVID. METHODS: PubMed and EMBASE databases were searched on September 2022 without language restrictions (CRD42022360399) to identify prospective trials and observational studies comparing patients with and without vaccination before severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We also included studies reporting symptomatic changes of ongoing long COVID following vaccination among those with a history of SARS-CoV-2 infection. Odds ratios (ORs) for each outcome were synthesized using a random-effects model. Symptomatic changes after vaccination were synthesized by a one-group meta-analysis. RESULTS: Six observational studies involving 536,291 unvaccinated and 84,603 vaccinated (before SARS-CoV-2 infection) patients (mean age, 41.2-66.6; female, 9.0-67.3%) and six observational studies involving 8,199 long COVID patients (mean age, 40.0 to 53.5; female, 22.2-85.9%) who received vaccination after SARS-CoV-2 infection were included. Two-dose vaccination was associated with a lower risk of long COVID compared to no vaccination (OR, 0.64; 95% confidence interval [CI], 0.45-0.92) and one-dose vaccination (OR, 0.60; 95% CI, 0.43-0.83). Two-dose vaccination compared to no vaccination was associated with a lower risk of persistent fatigue (OR, 0.62; 95% CI, 0.41-0.93) and pulmonary disorder (OR, 0.50; 95% CI, 0.47-0.52). Among those with ongoing long COVID symptoms, 54.4% (95% CI, 34.3-73.1%) did not report symptomatic changes following vaccination, while 20.3% (95% CI, 8.1-42.4%) experienced symptomatic improvement after two weeks to six months of COVID-19 vaccination. CONCLUSIONS: COVID-19 vaccination before SARS-CoV-2 infection was associated with a lower risk of long COVID, while most of those with ongoing long COVID did not experience symptomatic changes following vaccination.

Pulmonary vasodilator therapies in pulmonary arterial hypertension associated with CHD: a systematic review and network meta-analysis.

The optimal treatment strategy using pulmonary vasodilators in pulmonary arterial hypertension associated with CHD (PAH-CHD) remains controversial. We aimed to compare the efficacy and safety of pulmonary vasodilators in PAH-CHD. PubMed and EMBASE databases were searched through May 2022 and a network meta-analysis was conducted. The primary outcomes were mean difference of changes in 6-minute walk distance, NYHA functional class, and N-terminal pro-brain natriuretic peptide. The secondary outcomes included pulmonary vascular resistance, mean pulmonary arterial pressure, and resting oxygen saturation. We identified 14 studies, yielding 807 patients with PAH-CHD. Bosentan and sildenafil were associated with a significant increase in 6-minute walk distance from baseline compared with placebo (MD 48.92 m, 95% CI 0.32 to 97.55 and MD 59.70 m, 95% CI 0.88 to 118.53, respectively). Bosentan, sildenafil, and combination of bosentan and sildenafil were associated with significant improvement in NYHA functional class compared with placebo (MD -0.33, 95% CI -0.51 to -0.14, MD -0.58, 95% CI -0.75 to -0.22 and MD -0.62, 95% CI -0.92 to -0.31, respectively). Bosentan and sildenafil were also associated with significant improvements in secondary outcomes. These findings were largely confirmed in the subgroup analysis. Various adverse events were reported; however, serious adverse event rates were relatively low (4.8-8.7%), including right heart failure, acute kidney injury, respiratory failure, hypotension, and discontinuation of pulmonary vasodilators. In conclusion, bosentan and sildenafil were the most effective in improving prognostic risk factor such as 6-minute walk distance and NYHA class. Overall, pulmonary vasodilators were well tolerated in PAH-CHD.

Assessment of Efficacy and Safety of mRNA COVID-19 Vaccines in Children Aged 5 to 11 Years: A Systematic Review and Meta-analysis.

Importance: Evidence of the efficacy and safety of messenger RNA (mRNA) COVID-19 vaccines in children aged 5 to 11 years has been emerging. Collecting these data will inform clinicians, families, and policy makers. Objective: To evaluate the efficacy and safety of mRNA COVID-19 vaccines in children aged 5 to 11 years in a systematic review and meta-analysis. Data Sources: PubMed and Embase databases were searched on September 29, 2022, without language restrictions. Study Selection: Randomized clinical trials and observational studies comparing vaccinated vs unvaccinated children aged 5 to 11 years and reporting efficacy or safety outcomes were included. Studies reporting safety outcomes in vaccinated children only (ie, no control group) were also included. Data Extraction and Synthesis: Two investigators independently extracted relevant data from each study. Odds ratios (ORs) for efficacy and safety outcomes and incidences of adverse events (AEs) following vaccination were synthesized using a random-effects model. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology reporting guidelines. Main Outcomes and Measures: The primary outcome was SARS-CoV-2 infections with or without symptoms. The secondary outcomes included symptomatic SARS-CoV-2 infections, hospitalizations, and multisystem inflammatory syndrome in children. The incidences of each AE following vaccination were also evaluated. Results: Two randomized clinical trials and 15 observational studies involving 10 935 541 vaccinated children (median or mean age range, 8.0-9.5 years) and 2 635 251 unvaccinated children (median or mean age range, 7.0-9.5 years) were included. Two-dose mRNA COVID-19 vaccination compared with no vaccination was associated with lower risks of SARS-CoV-2 infections with or without symptoms (OR, 0.47; 95% CI, 0.35-0.64), symptomatic SARS-CoV-2 infections (OR, 0.53; 95% CI, 0.41-0.70), hospitalizations (OR, 0.32; 95% CI, 0.15-0.68), and multisystem inflammatory syndrome in children (OR, 0.05; 95% CI, 0.02-0.10). Two randomized clinical trials and 5 observational studies investigated AEs among vaccinated children. Most vaccinated children experienced at least 1 local AE following the first injection (32 494 of 55 959 [86.3%]) and second injection (28 135 of 46 447 [86.3%]). Vaccination was associated with a higher risk of any AEs compared with placebo (OR, 1.92; 95% CI, 1.26-2.91). The incidence of AEs that prevented normal daily activities was 8.8% (95% CI, 5.4%-14.2%) and that of myocarditis was estimated to be 1.8 per million (95% CI, 0.000%-0.001%) following the second injection. Conclusions and Relevance: In this systematic review and meta-analysis, COVID-19 mRNA vaccines among children aged 5 to 11 years were associated with measures of efficacy in preventing SARS-CoV-2 infection and severe COVID-19-related illnesses. While most children developed local AEs, severe AEs were rare, and most of AEs resolved within several days. These data provide evidence for future recommendations.

Extracorporeal Membrane Oxygenation in Children With COVID-19: A Systematic Review and Meta-Analysis.

OBJECTIVES: The indication, complications, and outcomes of extracorporeal membrane oxygenation (ECMO) in children with COVID-19-related illnesses remain unelucidated. Our study aimed to investigate the characteristics and outcomes of ECMO in children with COVID-19-related illnesses. DATA SOURCES: We searched PubMed and EMBASE databases in March 2022. STUDY SELECTION: We retrieved all studies involving children (age ≤ 18 yr) with COVID-19-related illnesses who received ECMO. DATA EXTRACTION: Two authors independently extracted data and assessed the risk of bias. Mortality, successful weaning rate, and complications while on ECMO were synthesized by a one-group meta-analysis using a random-effect model. Meta-regression was performed to explore the risk factors for mortality. DATA SYNTHESIS: We included 18 observational studies, four case series, and 22 case reports involving 110 children with COVID-19-related illnesses receiving ECMO. The median age was 8 years (range, 10 d to 18 yr), and the median body mass index was 21.4 kg/m 2 (range, 12.3-56.0 kg/m 2 ). The most common comorbidities were obesity (11% [7/63]) and congenital heart disease (11% [7/63]), whereas 48% (30/63) were previously healthy. The most common indications for ECMO were multisystem inflammatory syndrome in children (52% [47/90]) and severe acute respiratory distress syndrome (40% [36/90]). Seventy-one percent (56/79) received venoarterial-ECMO. The median ECMO runtime was 6 days (range, 3-51 d) for venoarterial ECMO and 11 days (range, 3-71 d) for venovenous ECMO. The mortality was 26.6% (95% CI, 15.9-40.9), and the successful weaning rate was 77.0% (95% CI, 55.4-90.1). Complications were seen in 37.0% (95% CI, 23.1-53.5) while on ECMO, including stroke, acute kidney injury, pulmonary edema, and thromboembolism. Corticosteroids and IV immunoglobulin therapies were associated with lower mortality. CONCLUSIONS: The mortality of children on ECMO for COVID-19 was relatively low. This invasive treatment can be considered as a treatment option for critically ill children with COVID-19.