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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 -
Research and Practice in Thrombosis and... May 2022Many cardiac arrest cases are encountered annually worldwide, with poor survival. The use of systemic thrombolysis during cardiopulmonary resuscitation for the treatment...
BACKGROUND
Many cardiac arrest cases are encountered annually worldwide, with poor survival. The use of systemic thrombolysis during cardiopulmonary resuscitation for the treatment of cardiac arrest remains controversial.
OBJECTIVES
Evaluate the safety and efficacy of systemic thrombolysis in patients with cardiac arrest due to presumed or confirmed pulmonary embolism or cardiac etiology.
METHODS
We searched the PubMed and Cochrane databases from inception through April 2021 to identify relevant randomized controlled trials and observational studies. The primary efficacy and safety outcomes were survival to hospital discharge and reported bleeding, respectively. Sensitivity analysis was performed on the basis of study design and etiology of cardiac arrest.
RESULTS
Eleven studies were included, with 4696 patients (1178 patients received systemic thrombolysis, and 3518 patients received traditional therapy). There was a higher rate of survival to hospital discharge in patients who received systemic thrombolysis versus no systemic thrombolysis (risk ratio [RR], 1.35; 95% confidence interval [CI], 0.95-1.91). There were also higher rates of survival at 24 hours (RR, 1.24; 95% CI, 0.97-1.59) and hospital admission (RR, 1.53; 95% CI, 1.04-2.24), and return of spontaneous circulation (ROSC) (RR, 1.34; 95% CI, 1.05-1.71) with the use of systemic thrombolysis. Impacts on survival to discharge and survival at 24 hours were not statistically significant. Patients receiving systemic thrombolysis had a 65% increase in bleeding events compared with no systemic thrombolysis (RR, 1.65; 95% CI, 1.20-2.27).
CONCLUSION
Systemic thrombolysis in cardiac arrest did not improve survival to hospital discharge and led to more bleeding events. However, it increased the rates of hospital admission and ROSC achievement.
PubMed: 35755853
DOI: 10.1002/rth2.12745 -
Pulmonary Circulation 2020Pulmonary Hypertension due to left heart disease is the most common type of Pulmonary Hypertension. Morbidity and mortality significantly increase once Pulmonary...
Targeted therapy with phosphodiesterase 5 inhibitors in patients with pulmonary hypertension due to heart failure and elevated pulmonary vascular resistance: a systematic review.
Pulmonary Hypertension due to left heart disease is the most common type of Pulmonary Hypertension. Morbidity and mortality significantly increase once Pulmonary Hypertension is present. Treatment is aimed toward optimizing the underlying condition. Targeted therapy has been evaluated in small studies with mixed results. The goal of this systematic review is to identify the possible benefit and safety of Phosphodiesterase 5 inhibitors in Pulmonary Hypertension due to left heart disease with elevated pulmonary vascular resistance, diagnosed by right heart catheterization. Electronic searches using MEDLINE/PREMEDLINE, EMBASE, and The Cochrane Library were searched on 21 October 2018. Randomized clinical trials comparing Phosphodiesterase 5 inhibitors versus placebo in patients with proven Pulmonary Hypertension by right heart catheterization secondary to left heart disease (both heart failure with reduced ejection fraction and with preserved ejection fraction) and reported pulmonary vascular resistance were included. We identified 436 potentially relevant studies. After reviewing the titles and abstracts to exclude irrelevant articles, five randomized clinical trials were considered for the study. Sildenafil was well tolerated among all studies. Sildenafil was found to improve hemodynamics, exercise capacity, and quality of life in patients with elevated pulmonary vascular resistance. Phosphodiesterase 5 inhibitors therapy in patients with proven Pulmonary Hypertension due to left heart disease and elevated pulmonary vascular resistance by right heart catheterization may improve the quality of life, exercise capacity, and pulmonary hemodynamics. Further prospective randomized controlled studies are needed to confirm.
PubMed: 33088478
DOI: 10.1177/2045894020948780 -
Danish Medical Journal Mar 2018During conventional cardiopulmonary bypass (CPB) there is no active perfusion of the pulmonary circulation and the mechanical ventilation is ceased leaving the lungs... (Review)
Review
During conventional cardiopulmonary bypass (CPB) there is no active perfusion of the pulmonary circulation and the mechanical ventilation is ceased leaving the lungs exposed to warm ischemia. Pulmonary dysfunction is seen in varying degrees after major surgery, but more severe in cardiac surgery patients probably due to the effects of CPB. The evidence for effect and safety are limited, but active pulmonary artery perfusion during CPB could be beneficial for the patients' postoperative oxygenation. Our aim was in a randomised clinical trial to assess primarily the effect of pulmonary artery perfusion during CPB on postoperative oxygenation in patients diagnosed with chronic obstructive pulmonary disease (COPD), secondarily to assess other possible benefits and harms. Furthermore, we wanted in a systematic review with meta-analyses of all randomised clinical trials to investigate the pooled effects of pulmonary artery perfusion during CPB. We planned and conducted a randomised, partly blinded, clinical trial assigning cardiac surgery patients diagnosed with COPD to receive pulmonary artery perfusion with oxygenated blood or histidine-tryptophan-ketoglutarate (HTK) solution compared to no pulmonary perfusion during CPB. The primary outcome was the oxygenation index measured during and after surgery. Secondary outcomes were intubation time, serious adverse events, days alive outside the intensive care unit and outside the hospital, 30- and 90-days mortality. Secondly, we conducted a systematic review of randomised clinical trials comparing benefits and harms of using pulmonary artery perfusion versus no pulmonary perfusion during CPB pooling results in meta-analyses and trial sequential analyses (TSA). Of the 90 randomised patients 89 were included in analysis of the primary outcome, the inverse oxygenation index, measured at a single time point 21 hours after CPB start and longitudinally 1, 3, 5, 7, and 21 hours after CPB start. At 21 hours, patients randomised to pulmonary artery perfusion with oxygenated blood had a higher inverse oxygenation index compared to patients randomised to no pulmonary perfusion during CPB (mean difference (MD) 0.94; 95% confidence interval (CI), 0.05 to 1.83; P=0.04). The inverse oxygenation index was also significantly higher at 21 hours after CPB start (MD 0.99; CI, 0.29 to 1.69; P=0.007), and longitudinally (P=0.009), for patients receiving pulmonary artery perfusion with oxygenated blood compared to pulmonary artery perfusion with HTK solution. This corresponds to a PaO difference of 23 mmHg with a median FiO of 0.32. We found no additional significant differences for the remaining comparisons of the inverse oxygenation index neither for any of the secondary outcomes. The systematic review identified 4 trials with a total of 210 patients. In meta-analyses pulmonary artery perfusion with blood versus no pulmonary perfusion during CPB was not associated with relative risk of death (1.7; 95% CI, 0.4 to 6.9; 210 patients in three trials with high and one trial with low risk of bias), serious adverse events (1.2; 95% CI, 0.8 to 1.8; 180 patients in two trials with high and one trial with low risk of bias) or intubation time (-0.4 hours; 95% CI, -1.1 to 0.4; 176 patients in three trials with high and one trial with low risk of bias). TSA on mortality, serious adverse events, and PaO/FiO ratio showed that required information sizes have not been reached, but pulmonary artery perfusion with blood was associated with a higher PaO/FiO ratio (27.8 mmHg; 95% CI, 5.7 to 50.0 mmHg; 119 patients in two trials with high and one trial with low risk of bias). TSA on intubation time showed that the boundary for lack of superiority (futility) was crossed refuting a shorten intubation time of 1.5 hours or more. Our trial provided additional knowledge about the use of pulmonary artery perfusion during CPB in cardiac surgery patients with COPD, and improved oxygenation for patients receiving pulmonary artery perfusion with oxygenated blood. Pulmonary artery perfusion with HTK solution did not result in an improved oxygenation. In line with this, the systematic review including data from additional trials showed a possible association between pulmonary artery perfusion with blood and improved oxygenation, but no significant associations with mortality, serious adverse events or intubation time. However, all data are too sparse to be conclusive.
Topics: Cardiac Surgical Procedures; Cardiopulmonary Bypass; Glucose; Hospital Mortality; Humans; Lung; Mannitol; Perfusion; Potassium Chloride; Procaine; Pulmonary Artery; Pulmonary Circulation; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Randomized Controlled Trials as Topic
PubMed: 29510817
DOI: No ID Found -
Frontiers in Pharmacology 2021This systematic review and meta-analysis is aimed at assessing the risks of cardiovascular adverse events in patients with rheumatoid arthritis (RA) who have been... (Review)
Review
This systematic review and meta-analysis is aimed at assessing the risks of cardiovascular adverse events in patients with rheumatoid arthritis (RA) who have been treated with fostamatinib. The electronic databases of OVID Medline, OVID EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science were searched to identify studies that reported cardiovascular events or hypertension in RA patients treated with fostamatinib. Two reviewers separately and simultaneously screened the retrieved studies based on study selection criteria, collected data and performed methodological quality assessments. The effect size of meta-analysis was estimated by the Peto odds ratio (OR) or relative risk (RR) with 95% confidence intervals (95%CI). Funnel plot was used to estimate publication bias and sensitivity analysis was performed to test the robustness of the results. A total of 12 trials composed of 5,618 participants with low to moderate risk of bias were included. In comparison to the placebo, the use of fostamatinib was found to elevate the risk of hypertension (RR=3.82, 95%CI 2.88-5.05) but was not associated with the risks of all-cause death (Peto OR=0.16, 95%CI 0.02-1.24), major adverse cardiovascular events (Peto OR=1.24, 95%CI 0.26-5.97), pulmonary heart disease and disease of pulmonary circulation (Peto OR=1.23, 95%CI 0.13-11.87), in addition to other forms of heart disease (Peto OR=1.96, 95%CI 0.72-5.38). Furthermore, sensitivity analysis showed no significant change in effective trends and no publication bias was found. Fostamatinib is associated with increased risk of hypertension; however, no increased risks of cardiovascular events were observed. Further well-planned cohort studies with large study populations and longer follow-up times are needed to elucidate the outcomes. : [PROSPERO], identifier [CRD42020198217].
PubMed: 34349639
DOI: 10.3389/fphar.2021.632551 -
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 -
The Western Journal of Emergency... Mar 2024Intra-arrest transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) have been introduced in adult patients with cardiac arrest (CA). Whether the...
INTRODUCTION
Intra-arrest transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) have been introduced in adult patients with cardiac arrest (CA). Whether the diagnostic performance of TTE or TEE is superior during resuscitation is unclear. We conducted a systematic review following PRISMA guidelines.
METHODS
We searched databases from PubMed, Embase, and Google Scholar and evaluated articles with intra-arrest TTE and TEE in adult patients with non-traumatic CA. Two authors independently screened and selected articles for inclusion; they then dual-extracted study characteristics and target conditions (pericardial effusion, aortic dissection, pulmonary embolism, myocardial infarction, hypovolemia, left ventricular dysfunction, and sonographic cardiac activity). We performed quality assessment using the Quality Assessment of Diagnostic Accuracy Studies Version 2 criteria.
RESULTS
A total of 27 studies were included: 14 studies with 2,145 patients assessed TTE; and 16 with 556 patients assessed TEE. A high risk of bias or applicability concerns in at least one domain was present in 20 studies (74%). Both TTE and TEE found positive findings in nearly one-half of the patients. The etiology of CA was identified in 13% (271/2,145), and intervention was performed in 38% (102/271) of patients in the TTE group. In patients who received TEE, the etiology was identified in 43% (239/556), and intervention was performed in 28% (68/239). In the TEE group, a higher incidence regarding the etiology of CA was observed, particularly for those with aortic dissection. However, the outcome of those with aortic dissection in the TEE group was poor.
CONCLUSION
While TEE could identify more causes of CA than TTE, sonographic cardiac activity was reported much more in the TTE group. The impact of TTE and TEE on the return of spontaneous circulation and further survival was still inconclusive in the current dataset.
Topics: Adult; Humans; Echocardiography; Echocardiography, Transesophageal; Ventricular Dysfunction, Left; Resuscitation; Aortic Dissection
PubMed: 38596913
DOI: 10.5811/westjem.18440 -
Journal of Clinical Medicine Apr 2023Outcomes following in-hospital cardiac arrest (IHCA) in patients with COVID-19 have been reported by several small single-institutional studies; however, there are no... (Review)
Review
BACKGROUND
Outcomes following in-hospital cardiac arrest (IHCA) in patients with COVID-19 have been reported by several small single-institutional studies; however, there are no large studies contrasting COVID-19 IHCA with non-COVID-19 IHCA. The objective of this study was to compare the outcomes following IHCA between COVID-19 and non-COVID-19 patients.
METHODS
We searched databases using predefined search terms and appropriate Boolean operators. All the relevant articles published till August 2022 were included in the analyses. The systematic review and meta-analysis were conducted as per Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. An odds ratio with a 95% confidence interval (CI) was used to measure effects.
RESULTS
Among 855 studies screened, 6 studies with 27,453 IHCA patients (63.84% male) with COVID-19 and 20,766 (59.7% male) without COVID-19 were included in the analysis. IHCA among patients with COVID-19 has lower odds of achieving return of spontaneous circulation (ROSC) (OR: 0.66, 95% CI: 0.62-0.70). Similarly, patients with COVID-19 have higher odds of 30-day mortality following IHCA (OR: 2.26, 95% CI: 2.08-2.45) and have 45% lower odds of cardiac arrest because of a shockable rhythm (OR: 0.55, 95% CI: 0.50-0.60) (9.59% vs. 16.39%). COVID-19 patients less commonly underwent targeted temperature management (TTM) or coronary angiography; however, they were more commonly intubated and on vasopressor therapy as compared to patients who did not have a COVID-19 infection.
CONCLUSIONS
This meta-analysis showed that IHCA with COVID-19 has a higher mortality and lower rates of ROSC compared with non-COVID-19 IHCA. COVID-19 is an independent risk factor for poor outcomes in IHCA patients.
PubMed: 37109134
DOI: 10.3390/jcm12082796 -
The Cochrane Database of Systematic... Aug 2016Pulmonary embolism (PE) can occur when a thrombus (blood clot) travels through the veins and lodges in the arteries of the lungs, producing an obstruction. People who... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pulmonary embolism (PE) can occur when a thrombus (blood clot) travels through the veins and lodges in the arteries of the lungs, producing an obstruction. People who are thought to be at risk include those with cancer, people who have had a recent surgical procedure or have experienced long periods of immobilisation and women who are pregnant. The clinical presentation can vary, but unexplained respiratory symptoms such as difficulty breathing, chest pain and an increased respiratory rate are common.D-dimers are fragments of protein released into the circulation when a blood clot breaks down as a result of normal body processes or with use of prescribed fibrinolytic medication. The D-dimer test is a laboratory assay currently used to rule out the presence of high D-dimer plasma levels and, by association, venous thromboembolism (VTE). D-dimer tests are rapid, simple and inexpensive and can prevent the high costs associated with expensive diagnostic tests.
OBJECTIVES
To investigate the ability of the D-dimer test to rule out a diagnosis of acute PE in patients treated in hospital outpatient and accident and emergency (A&E) settings who have had a pre-test probability (PTP) of PE determined according to a clinical prediction rule (CPR), by estimating the accuracy of the test according to estimates of sensitivity and specificity. The review focuses on those patients who are not already established on anticoagulation at the time of study recruitment.
SEARCH METHODS
We searched 13 databases from conception until December 2013. We cross-checked the reference lists of relevant studies.
SELECTION CRITERIA
Two review authors independently applied exclusion criteria to full papers and resolved disagreements by discussion.We included cross-sectional studies of D-dimer in which ventilation/perfusion (V/Q) scintigraphy, computerised tomography pulmonary angiography (CTPA), selective pulmonary angiography and magnetic resonance pulmonary angiography (MRPA) were used as the reference standard.•
PARTICIPANTS
Adults who were managed in hospital outpatient and A&E settings and were suspected of acute PE were eligible for inclusion in the review if they had received a pre-test probability score based on a CPR.•
INDEX TESTS
quantitative, semi quantitative and qualitative D-dimer tests.• Target condition: acute symptomatic PE.• Reference standards: We included studies that used pulmonary angiography, V/Q scintigraphy, CTPA and MRPA as reference standard tests.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed quality using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). We resolved disagreements by discussion. Review authors extracted patient-level data when available to populate 2 × 2 contingency tables (true-positives (TPs), true-negatives (TNs), false-positives (FPs) and false-negatives (FNs)).
MAIN RESULTS
We included four studies in the review (n = 1585 patients). None of the studies were at high risk of bias in any of the QUADAS-2 domains, but some uncertainty surrounded the validity of studies in some domains for which the risk of bias was uncertain. D-dimer assays demonstrated high sensitivity in all four studies, but with high levels of false-positive results, especially among those over the age of 65 years. Estimates of sensitivity ranged from 80% to 100%, and estimates of specificity from 23% to 63%.
AUTHORS' CONCLUSIONS
A negative D-dimer test is valuable in ruling out PE in patients who present to the A&E setting with a low PTP. Evidence from one study suggests that this test may have less utility in older populations, but no empirical evidence was available to support an increase in the diagnostic threshold of interpretation of D-dimer results for those over the age of 65 years.
Topics: Acute Disease; Adult; Biomarkers; Cross-Sectional Studies; False Negative Reactions; False Positive Reactions; Fibrin Fibrinogen Degradation Products; Humans; Pulmonary Embolism; Reference Standards; Venous Thromboembolism
PubMed: 27494075
DOI: 10.1002/14651858.CD010864.pub2 -
Journal of Applied Physiology... Dec 2017Exercise performance is determined by oxygen supply to working muscles and vital organs. In healthy individuals, exercise performance is limited in the hypoxic...
Exercise performance is determined by oxygen supply to working muscles and vital organs. In healthy individuals, exercise performance is limited in the hypoxic environment at altitude, when oxygen delivery is diminished due to the reduced alveolar and arterial oxygen partial pressures. In patients with pulmonary hypertension (PH), exercise performance is already reduced near sea level due to impairments of the pulmonary circulation and gas exchange, and, presumably, these limitations are more pronounced at altitude. In studies performed near sea level in healthy subjects, as well as in patients with PH, maximal performance during progressive ramp exercise and endurance of submaximal constant-load exercise were substantially enhanced by breathing oxygen-enriched air. Both in healthy individuals and in PH patients, these improvements were mediated by a better arterial, muscular, and cerebral oxygenation, along with a reduced sympathetic excitation, as suggested by the reduced heart rate and alveolar ventilation at submaximal isoloads, and an improved pulmonary gas exchange efficiency, especially in patients with PH. In summary, in healthy individuals and in patients with PH, alterations in the inspiratory Po by exposure to hypobaric hypoxia or normobaric hyperoxia reduce or enhance exercise performance, respectively, by modifying oxygen delivery to the muscles and the brain, by effects on cardiovascular and respiratory control, and by alterations in pulmonary gas exchange. The understanding of these physiological mechanisms helps in counselling individuals planning altitude or air travel and prescribing oxygen therapy to patients with PH.
Topics: Altitude; Exercise; Humans; Hyperoxia; Hypertension, Pulmonary; Hypoxia; Oxygen Consumption; Pulmonary Gas Exchange
PubMed: 28775065
DOI: 10.1152/japplphysiol.00186.2017