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Annals of Palliative Medicine Oct 2021Riociguat therapy has been recommended for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), and it might have therapeutic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Riociguat therapy has been recommended for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), and it might have therapeutic significance for other types of pulmonary hypertension (PH). Our purpose was to evaluate the specific impact of riociguat on all types of PH.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the safety and efficacy of riociguat treatment for PH through databases of the Cochrane Library, PubMed, Embase, and Web of Science from inception to the present. Duplicate publications, studies with no full text, incomplete information or inability to extract data, animal experiments and reviews, and systematic reviews were excluded. The software RevMan 5.4 was used for data synthesis.
RESULTS
There were 8 RCTs included in our study, involving 1,606 participants. For PAH and CTEPH patients, riociguat treatment extended 6-minute walk distance (6MWD) by 39.84 meters, decreased mean pulmonary arterial pressure (PAP) by 4.20 mmHg, lowered pulmonary vascular resistance (PVR) by 218.76 dynes/sec/cm-5, cut down right atrial pressure (RAP) by 0.9 mmHg, increased cardiac index (CI) by 0.49 L/min/m2, improved cardiac output (CO) by 0.89 L/min, reduced N-terminal pro-type B natriuretic peptide (NT-proBNP) by 436.21 pg/mL, and decreased adverse events and clinical worsening as compared with placebo. For other types of PH including PH due to left heart disease and PH due to lung disease, riociguat was reported as having improved CI by 0.42 L/min/m2 and CO was increased by 0.92 L/min compared with placebo. Other efficacy outcomes and safety outcomes did not attain statistical difference in other types of PH.
CONCLUSIONS
For PAH and CTEPH, riociguat treatment is safe and effective, but for other types of PH, it can only improve some hemodynamic parameters.
Topics: Chronic Disease; Humans; Hypertension, Pulmonary; Pyrazoles; Pyrimidines
PubMed: 34763472
DOI: 10.21037/apm-21-2656 -
Journal of Clinical Medicine Nov 2022Pulmonary endarterectomy (PEA) is the treatment of choice in case of chronic thromboembolic pulmonary hypertension (CTEPH). PEA is performed by an increasing number of... (Review)
Review
Pulmonary endarterectomy (PEA) is the treatment of choice in case of chronic thromboembolic pulmonary hypertension (CTEPH). PEA is performed by an increasing number of surgeons; however, the reported outcomes are limited to a few registries or to individual centers' experiences. This systematic review focuses on pre-operative evaluation, intra-operative procedure and post-operative results in patients submitted to PEA for CTEPH. The literature included was searched using a formal strategy, combining the terms "pulmonary endarterectomy" AND "chronic pulmonary hypertension" and focusing on studies published in the last 5 years (2017-2022) to give a comprehensive overview on the most updated literature. The selection of the adequate surgical candidate is a crucial point, and the decision should always be performed by expert multidisciplinary teams composed of surgeons, pulmonologists and radiologists. In all the included studies, the surgical procedure was performed through a median sternotomy with intermittent deep hypothermic circulatory arrest under cardiopulmonary bypass. In case of residual pulmonary hypertension, alternative combined treatments should be considered (balloon angioplasty and/or medical therapy until lung transplantation in highly selected cases). Short- and long-term outcomes, although not homogenous across the different studies, are acceptable in highly experienced CTEPH centers.
PubMed: 36498551
DOI: 10.3390/jcm11236976 -
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 -
Frontiers in Medicine 2023Pulmonary hypertension due to chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) is classified as group 3 pulmonary hypertension. Inhaled... (Review)
Review
BACKGROUND
Pulmonary hypertension due to chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) is classified as group 3 pulmonary hypertension. Inhaled treprostinil, a prostaglandin I analogue also known as prostacyclin, has recently been approved as a first drug for patients with pulmonary hypertension secondary to ILD. However, due to a lack of evidence, no therapies are currently approved for those with COPD-associated pulmonary hypertension. Thus, this systematic review aims to summarise the current evidence to assess the impact of inhaled prostaglandin I analogue use on the pulmonary hemodynamics, exercise function, lung function, and gas exchange in patients with pulmonary hypertension due to COPD.
METHODS
We systematically searched the electronic databases of Medline, Embase, Scopus and Cochrane from inception to 1 February 2023. Studies of adult patients with a confirmed diagnosis of COPD-associated pulmonary hypertension who received inhaled drugs targeting the prostacyclin pathway were included in the systematic review. Case reports, systematic reviews, conference abstracts with no full text, non-full-text articles, non-English manuscripts and book chapters were excluded from this systematic review. A risk-of-bias assessment was carried out for the studies included in this review, using two different Cochrane risk-of-bias tools for randomised and non-randomised clinical trials.
RESULTS
A total of four studies met our inclusion criteria and were included in this systematic review. The results of one prospective clinical trial showed an improvement in the pulmonary hemodynamics (e.g., cardiac index, cardiac output and mean pulmonary artery pressure) in response to inhaled prostacyclin use in patients with pulmonary hypertension secondary to COPD. However, the severity of dyspnoea, lung function, exercise capacity and gas exchange were not affected when inhaled prostacyclin was used for patients with COPD-related pulmonary hypertension.
CONCLUSION
This systematic review demonstrated that although inhaled prostacyclin does not seem to improve COPD-related outcomes (e.g., lung function and exercise capacity), short-term use of inhaled prostacyclin has the potential to reduce mean pulmonary artery pressure and pulmonary vascular resistance without impairing ventilation-perfusion mismatch. Further studies with larger sample sizes are warranted.
SYSTEMATIC REVIEW REGISTRATION
CRD42022372803, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=372803.
PubMed: 37706024
DOI: 10.3389/fmed.2023.1217156 -
Journal of Cardiothoracic Surgery Aug 2022Pulmonary arterial hypertension (PAH) is a progressive disease. Although great progress has been made in its diagnosis and treatment in recent years, its mortality rate... (Review)
Review
Pulmonary arterial hypertension (PAH) is a progressive disease. Although great progress has been made in its diagnosis and treatment in recent years, its mortality rate is still very significant. The pathophysiology and pathogenesis of PAH are complex and involve endothelial dysfunction, chronic inflammation, smooth muscle cell proliferation, pulmonary arteriole occlusion, antiapoptosis and pulmonary vascular remodeling. These factors will accelerate the progression of the disease, leading to poor prognosis. Therefore, accurate etiological diagnosis, treatment and prognosis judgment are particularly important. Here, we systematically review the pathophysiology, diagnosis, genetics, prognosis and treatment of PAH.
Topics: Animals; Cell Proliferation; Disease Models, Animal; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Muscle, Smooth, Vascular; Pulmonary Arterial Hypertension; Pulmonary Artery
PubMed: 36038916
DOI: 10.1186/s13019-022-01947-y -
ERJ Open Research Jan 2022Chronic obstructive pulmonary disease-associated pulmonary hypertension (COPD-PH) is an increasingly recognised condition which contributes to worsening dyspnoea and...
Chronic obstructive pulmonary disease-associated pulmonary hypertension (COPD-PH) is an increasingly recognised condition which contributes to worsening dyspnoea and poor survival in COPD. It is uncertain whether specific treatment of COPD-PH, including use of medications approved for pulmonary arterial hypertension (PAH), improves clinical outcomes. This systematic review and meta-analysis assesses potential benefits and risks of therapeutic options for COPD-PH. We searched Medline and Embase for relevant publications until September 2020. Articles were screened for studies on treatment of COPD-PH for at least 4 weeks in 10 or more patients. Screening, data extraction, and risk of bias assessment were performed independently in duplicate. When possible, relevant results were pooled using the random effects model. Supplemental long-term oxygen therapy (LTOT) mildly reduced mean pulmonary artery pressure (PAP), slowed progression of PH, and reduced mortality, but other clinical or functional benefits were not assessed. Phosphodiesterase type 5 inhibitors significantly improved systolic PAP (pooled treatment effect -5.9 mmHg; 95% CI -10.3, -1.6), but had inconsistent clinical benefits. Calcium channel blockers and endothelin receptor antagonists had limited haemodynamic, clinical, or survival benefits. Statins had limited clinical benefits despite significantly lowering systolic PAP (pooled treatment effect -4.6 mmHg; 95% CI -6.3, -2.9). This review supports guideline recommendations for LTOT in hypoxaemic COPD-PH patients as well as recommendations against treatment with PAH-targeted medications. Effective treatment of COPD-PH depends upon research into the pathobiology and future high-quality studies comprehensively assessing clinically relevant outcomes are needed.
PubMed: 35198628
DOI: 10.1183/23120541.00348-2021 -
Pulmonary Circulation 2021Pregnancy is hazardous with pulmonary arterial hypertension, but maternal mortality may have fallen in recent years. We sought to systematically evaluate pulmonary... (Review)
Review
Pregnancy is hazardous with pulmonary arterial hypertension, but maternal mortality may have fallen in recent years. We sought to systematically evaluate pulmonary arterial hypertension and pregnancy-related outcomes in the last decade. We searched for articles describing outcomes in pregnancy cohorts published between 2008 and 2018. A total of 3658 titles were screened and 13 studies included for analysis. Pooled incidences and percentages of maternal and perinatal outcomes were calculated. Results showed that out of 272 pregnancies, 214 pregnancies advanced beyond 20 gestational weeks. The mean maternal age was 28 ± 2 years, mean pulmonary artery systolic pressure on echocardiogram was 76 ± 19 mmHg. Etiologies include idiopathic pulmonary arterial hypertension (22%), congenital heart disease (64%), and others (15%). Majority (74%) had good functional class I/II. Only 48% of women received pulmonary arterial hypertension-specific therapy. Premature deliveries occur in 58% of pregnancies at mean of 34 ± 1 weeks, most (76%) had Cesarean section. Maternal mortality rate was 12% overall ( = 26); even higher for idiopathic pulmonary arterial hypertension etiology alone (20%). Reported causes of death included right heart failure, cardiac arrest, pulmonary arterial hypertension crises, pre-eclampsia, and sepsis; 61% of maternal deaths occur at 0-4 days postpartum. Stillbirth rate was 3% and neonatal mortality rate was 1%. In conclusion, pulmonary arterial hypertension in pregnancy continues to be perilous with high maternal mortality rate. Continued prospective studies are needed.
PubMed: 34104423
DOI: 10.1177/20458940211013671 -
Frontiers in Cardiovascular Medicine 2021Cardiomyopathies (CMPs) due to myocytes involvement are among the leading causes of sudden adolescent death and heart failure. During the COVID-19 pandemic, there are...
Cardiomyopathies (CMPs) due to myocytes involvement are among the leading causes of sudden adolescent death and heart failure. During the COVID-19 pandemic, there are limited data available on cardiac complications in patients with COVID-19, leading to severe outcomes. We conducted a systematic search in Pubmed/Medline, Web of Science, and Embase databases up to August 2020, for all relevant studies about COVID-19 and CMPs. A total of 29 articles with a total number of 1460 patients were included. Hypertension, diabetes, obesity, hyperlipidemia, and ischemic heart disease were the most reported comorbidities among patients with COVID-19 and cardiomyopathy. In the laboratory findings, 21.47% of patients had increased levels of troponin. Raised D-dimer levels were also reported in all of the patients. Echocardiographic results revealed mild, moderate, and severe Left Ventricular (LV) dysfunction present in 17.13, 11.87, and 10% of patients, respectively. Cardiac injury and CMPs were common conditions in patients with COVID-19. Therefore, it is suggested that cardiac damage be considered in managing patients with COVID-19.
PubMed: 34222385
DOI: 10.3389/fcvm.2021.695206 -
Journal of Personalized Medicine May 2022Pulmonary hypertension (PH) treatment decisions are driven by the results of randomized controlled trials (RCTs). Subgroup analyses are often performed to assess whether... (Review)
Review
Pulmonary hypertension (PH) treatment decisions are driven by the results of randomized controlled trials (RCTs). Subgroup analyses are often performed to assess whether the intervention effect will change due to the patient's characteristics, thus allowing for individualized decisions. This review aimed to evaluate the appropriateness and interpretation of subgroup analyses performed in PH-specific therapy RCTs published between 2000 and 2020. Claims of subgroup effects were evaluated with prespecified criteria. Overall, 30 RCTs were included. Subgroup analyses presented: a high number of subgroup analyses reported, lack of prespecification, and lack of interaction tests. The trial protocol was not available for most RCTs; significant differences were found in those articles that published the protocol. Authors reported 13 claims of subgroup effect, with 12 claims meeting four or fewer of Sun's criteria. Even when most RCTs were generally at low risk of bias and were published in high-impact journals, the credibility and general quality of subgroup analyses and subgroup claims were low due to methodological flaws. Clinicians should be skeptical of claims of subgroup effects and interpret subgroup analyses with caution, as due to their poor quality, these analyses may not serve as guidance for personalized care.
PubMed: 35743648
DOI: 10.3390/jpm12060863 -
Frontiers in Cardiovascular Medicine 2022Currently, risk stratification is the cornerstone of determining treatment strategy for patients with pulmonary arterial hypertension (PAH). Since the 2015 European...
INTRODUCTION
Currently, risk stratification is the cornerstone of determining treatment strategy for patients with pulmonary arterial hypertension (PAH). Since the 2015 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines for the diagnosis and treatment of pulmonary hypertension recommended risk assessment, the number of studies reporting risk stratification has considerably increased. This systematic review aims to report and compare the variables and prognostic value of the various risk stratification models for outcome prediction in adult and pediatric PAH.
METHODS
A systematic search with terms related to PAH, pediatric pulmonary hypertension, and risk stratification was performed through databases PubMed, EMBASE, and Web of Science up to June 8, 2022. Observational studies and clinical trials on risk stratification in adult and pediatric PAH were included, excluding case reports/series, guidelines, and reviews. Risk of bias was assessed using the Prediction model Risk Of Bias Assessment Tool. Data on the variables used in the models and the predictive strength of the models given by c-statistic were extracted from eligible studies.
RESULTS
A total of 74 studies were eligible for inclusion, with this review focusing on model development ( = 21), model validation ( = 13), and model enhancement ( = 9). The variables used most often in current risk stratification models were the non-invasive WHO functional class, 6-minute walk distance and BNP/NT-proBNP, and the invasive mean right atrial pressure, cardiac index and mixed venous oxygen saturation. C-statistics of current risk stratification models range from 0.56 to 0.83 in adults and from 0.69 to 0.78 in children (only two studies available). Risk stratification models focusing solely on echocardiographic parameters or biomarkers have also been reported.
CONCLUSION
Studies reporting risk stratification in pediatric PAH are scarce. This systematic review provides an overview of current data on risk stratification models and its value for guiding treatment strategies in PAH.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022316885], identifier [CRD42022316885].
PubMed: 36440049
DOI: 10.3389/fcvm.2022.1035453