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International Journal of Infectious... Apr 2021In this systematic review and meta-analysis, we assessed the association between tricuspid annular plane systolic excursion (TAPSE) measured by echocardiography and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In this systematic review and meta-analysis, we assessed the association between tricuspid annular plane systolic excursion (TAPSE) measured by echocardiography and mortality in coronavirus disease 2019 (COVID-19).
METHODS
We performed a systematic literature search using PubMed, Embase, and Scopus databases with the keywords "COVID-19" OR "SARS-CoV-2" OR "2019-nCoV" AND "Tricuspid annular plane systolic excursion" OR "TAPSE" until January 20, 2021. The main outcome was mortality. The effect estimate was reported as the hazard ratio (HR), which was pooled from the unadjusted and adjusted effect estimates retrieved from the studies included. Mean differences in TAPSE (in mm) between non-survivors and survivors were pooled.
RESULTS
In total, 641 patients from seven studies were included in this systematic review and meta-analysis. TAPSE was lower in non-survivors compared with survivors (mean difference = -3.74 [-5.22, -2.26], p < 0.001; I: 85.5%, p < 0.001). Each 1 mm decrease in TAPSE was associated with increased mortality (HR = 1.24 [1.18, 1.31], p < 0.001; I: 0.0%, p = 0.491). In the pooled adjusted model, each 1 mm decrease in TAPSE was associated with increased mortality (HR = 1.21 [1.11, 1.33], p < 0.001; I: 45.1%, p = 0.156). Meta-regression indicated that the difference in TAPSE between non-survivors and survivors was affected by chronic obstructive pulmonary disease (-0.183, p < 0.001) and pulmonary artery systolic pressure (-0.344, p = 0.039), but not by age (p = 0.668), male gender (p = 0.821), hypertension (p = 0.101), diabetes (p = 0.603), coronary artery disease (p = 0.564), smoking (p = 0.140), and left ventricular ejection fraction (p = 0.452).
CONCLUSION
Every 1 mm decrease in TAPSE was associated with an increase in mortality of approximately 20%.
PROSPERO ID
CRD42021232194.
Topics: Aged; Blood Pressure; COVID-19; Echocardiography; Female; Humans; Male; Middle Aged; Proportional Hazards Models; SARS-CoV-2; Stroke Volume; Tricuspid Valve; Ventricular Dysfunction, Right; Ventricular Function, Left; Ventricular Function, Right
PubMed: 33582370
DOI: 10.1016/j.ijid.2021.02.029 -
The Annals of Pharmacotherapy Aug 2021To evaluate clinical literature for direct oral anticoagulants (DOACs) therapy for non-Food and Drug Administration approved indications.
Off-label Use for Direct Oral Anticoagulants: Valvular Atrial Fibrillation, Heart Failure, Left Ventricular Thrombus, Superficial Vein Thrombosis, Pulmonary Hypertension-a Systematic Review.
OBJECTIVE
To evaluate clinical literature for direct oral anticoagulants (DOACs) therapy for non-Food and Drug Administration approved indications.
DATA SOURCES
Articles from MEDLINE, Cochrane Library, Google Scholar, and OVID databases were reviewed from 1946 through September 4, 2020.
STUDY SELECTION AND DATA EXTRACTION
Fully published studies assessing DOACs for atrial fibrillation (AF) with valvular heart disease (VHD), heart failure (HF), left ventricular thrombus (LVT), superficial vein thrombosis (SVT), or pulmonary hypertension (PH) were evaluated.
DATA SYNTHESIS
Our review showed that DOACs are safe to use in patients with AF and VHD except for mitral stenosis or mechanical heart valve. Rivaroxaban 2.5 mg twice daily should be used with caution in patients with HF with reduced ejection fraction until further evaluation is performed. Four retrospective studies for DOAC use in patients with LVT showed conflicting results. One phase 3 randomized controlled trial showed noninferiority of rivaroxaban to fondaparinux for SVT treatment. The use of DOACs for pulmonary arterial hypertension was not evaluated in any clinical study, but 2 retrospective studies for the use of DOACs in patients with chronic thromboembolic PH (CTEPH) showed similar efficacy between DOACs and warfarin.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
This review provides clinicians with a comprehensive literature review surrounding DOAC use in common off-label indications.
CONCLUSION
DOACs can be considered for AF complicated by VHD except for mitral stenosis or mechanical valve replacement. DOACs (especially rivaroxaban) are considered as an alternative therapy for SVT and CTEPH. Further prospective studies for DOAC uses are needed for HF or LVT.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Heart Failure; Humans; Hypertension, Pulmonary; Off-Label Use; Prospective Studies; Retrospective Studies; Stroke; Thrombosis
PubMed: 33148014
DOI: 10.1177/1060028020970618 -
Reviews in Cardiovascular Medicine Sep 2020The clinical status and prognosis of patients with human immunodeficiency virus (HIV) infection has dramatically changed in the recent years. Cardiovascular diseases can...
The clinical status and prognosis of patients with human immunodeficiency virus (HIV) infection has dramatically changed in the recent years. Cardiovascular diseases can be related to combined antiretroviral therapy and to the aging of HIV-positive population, resulting in significant mortality and morbidity in those patients. It is crucial to understand whether the HIV-status affects the indications and outcomes of cardiac surgery. A literature search was conducted through electronic databases up to 15 May 2020 following PRISMA guidelines. Variables (i.e. patients characteristics) and endpoints (i.e. postoperative complications) were considered as defined in the original publications. All paper describing post-operative outcomes after cardiac surgery were included. Methodological quality of all included studies was assessed using the Newcastle-Ottawa Scale, the Cochrane Risk of Bias tool and the US Preventive Services Task Force grade. A total of eight studies were included in this systematic review; five studies discussed the outcomes of patients with HIV infection, while three studies compared results based on HIV status. All evidences derived from retrospective observational studies with high variability and poor-to-fair quality. Most patients underwent surgical myocardial revascularization. HIV status is not associated with differences in operative mortality ( = 0.32), postoperative mediastinitis ( = 0.30) or pulmonary infective complications ( = 0.67). Cardiac surgery can be considered safe in HIV-positive patients, and HIV status alone should not be considered as a contraindication for cardiac surgery and should not be considered a risk factor for postoperative mortality or perioperative complications. Further studies are required for patients with AIDS.
Topics: Anti-HIV Agents; Cardiac Surgical Procedures; Clinical Decision-Making; HIV Infections; HIV Long-Term Survivors; Heart Diseases; Humans; Patient Selection; Postoperative Complications; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 33070545
DOI: 10.31083/j.rcm.2020.03.104 -
Journal of Cardiothoracic Surgery Sep 2020Valve replacement surgery is the definitive management strategy for patients with severe valvular disease. However, valvular conduits currently in clinical use are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Valve replacement surgery is the definitive management strategy for patients with severe valvular disease. However, valvular conduits currently in clinical use are associated with significant limitations. Tissue-engineered (decellularized) heart valves are alternative prostheses that have demonstrated promising early results. The purpose of this systematic review and meta-analysis is to perform robust evaluation of the clinical performance of decellularized heart valves implanted in either outflow tract position, in comparison with standard tissue conduits.
METHODS
Systematic searches were conducted in the PubMed, Scopus, and Web of Science databases for articles in which outcomes between decellularized heart valves surgically implanted within either outflow tract position of human subjects and standard tissue conduits were compared. Primary endpoints included postoperative mortality and reoperation rates. Meta-analysis was performed using a random-effects model via the Mantel-Haenszel method.
RESULTS
Seventeen articles were identified, of which 16 were included in the meta-analysis. In total, 1418 patients underwent outflow tract reconstructions with decellularized heart valves and 2725 patients received standard tissue conduits. Decellularized heart valves were produced from human pulmonary valves and implanted within the right ventricular outflow tract in all cases. Lower postoperative mortality (4.7% vs. 6.1%; RR 0.94, 95% CI: 0.60-1.47; P = 0.77) and reoperation rates (4.8% vs. 7.4%; RR 0.55, 95% CI: 0.36-0.84; P = 0.0057) were observed in patients with decellularized heart valves, although only reoperation rates were statistically significant. There was no statistically significant heterogeneity between the analyzed articles (I = 31%, P = 0.13 and I = 33%, P = 0.10 respectively).
CONCLUSIONS
Decellularized heart valves implanted within the right ventricular outflow tract have demonstrated significantly lower reoperation rates when compared to standard tissue conduits. However, in order to allow for more accurate conclusions about the clinical performance of decellularized heart valves to be made, there need to be more high-quality studies with greater consistency in the reporting of clinical outcomes.
Topics: Bioprosthesis; Heart Valve Prosthesis; Humans; Prosthesis Design; Pulmonary Valve; Pulmonary Valve Stenosis; Reference Standards; Tissue Engineering
PubMed: 32948234
DOI: 10.1186/s13019-020-01292-y -
The Cochrane Database of Systematic... Apr 2020Escalating awareness of the magnitude of the challenge posed by low levels of physical activity in people with chronic obstructive pulmonary disease (COPD) highlights... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Escalating awareness of the magnitude of the challenge posed by low levels of physical activity in people with chronic obstructive pulmonary disease (COPD) highlights the need for interventions to increase physical activity participation. The widely-accepted benefits of physical activity, coupled with the increasing availability of wearable monitoring devices to objectively measure participation, has led to a dramatic rise in the number and variety of studies that aimed to improve the physical activity of people with COPD. However, little was known about the relative efficacy of interventions tested so far.
OBJECTIVES
In people with COPD, which interventions are effective at improving objectively-assessed physical activity?
SEARCH METHODS
We identified trials from the Cochrane Airways Trials Register Register, which contains records identified from bibliographic databases including the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, AMED, and PsycINFO. We also searched PEDro, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform portal and the Australian New Zealand Clinical Trials Registry (from inception to June 2019). We checked reference lists of all primary studies and review articles for additional references, as well as respiratory journals and respiratory meeting abstracts, to identify relevant studies.
SELECTION CRITERIA
We included randomised controlled trials of interventions that used objective measures for the assessment of physical activity in people with COPD. Trials compared an intervention with no intervention or a sham/placebo intervention, an intervention in addition to another standard intervention common to both groups, or two different interventions.
DATA COLLECTION AND ANALYSIS
We used standard methods recommended by Cochrane. Subgroup analyses were possible for supervised compared to unsupervised pulmonary rehabilitation programmes in clinically-stable COPD for a range of physical activity outcomes. Secondary outcomes were health-related quality of life, exercise capacity, adverse events and adherence. Insufficient data were available to perform prespecified subgroup analyses by duration of intervention or disease severity. We undertook sensitivity analyses by removing studies that were at high or unclear risk of bias for the domains of blinding and incomplete outcome data.
MAIN RESULTS
We included 76 studies with 8018 participants. Most studies were funded by government bodies, although some were sponsored by equipment or drug manufacturers. Only 38 studies had physical activity as a primary outcome. A diverse range of interventions have been assessed, primarily in single studies, but improvements have not been systematically demonstrated following any particular interventions. Where improvements were demonstrated, results were confined to single studies, or data for maintained improvement were not provided. Step count was the most frequently reported outcome, but it was commonly assessed using devices with documented inaccuracy for this variable. Compared to no intervention, the mean difference (MD) in time in moderate- to vigorous-intensity physical activity (MVPA) following pulmonary rehabilitation was four minutes per day (95% confidence interval (CI) -2 to 9; 3 studies, 190 participants; low-certainty evidence). An improvement was demonstrated following high-intensity interval exercise training (6 minutes per day, 95% CI 4 to 8; 2 studies, 275 participants; moderate-certainty evidence). One study demonstrated an improvement following six months of physical activity counselling (MD 11 minutes per day, 95% CI 7 to 15; 1 study, 280 participants; moderate-certainty evidence), but we found mixed results for the addition of physical activity counselling to pulmonary rehabilitation. There was an improvement following three to four weeks of pharmacological treatment with long-acting muscarinic antagonist and long-acting beta-agonist (LAMA/LABA) compared to placebo (MD 10 minutes per day, 95% CI 4 to 15; 2 studies, 423 participants; high-certainty evidence). These interventions also demonstrated improvements in other measures of physical activity. Other interventions included self-management strategies, nutritional supplementation, supplemental oxygen, endobronchial valve surgery, non-invasive ventilation, neuromuscular electrical stimulation and inspiratory muscle training.
AUTHORS' CONCLUSIONS
A diverse range of interventions have been assessed, primarily in single studies. Improvements in physical activity have not been systematically demonstrated following any particular intervention. There was limited evidence for improvement in physical activity with strategies including exercise training, physical activity counselling and pharmacological management. The optimal timing, components, duration and models for interventions are still unclear. Assessment of quality was limited by a lack of methodological detail. There was scant evidence for a continued effect over time following completion of interventions, a likely requirement for meaningful health benefits for people with COPD.
Topics: Exercise; Humans; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Telerehabilitation
PubMed: 32297320
DOI: 10.1002/14651858.CD012626.pub2 -
Journal of Thoracic Disease Mar 2020Patients with achondroplasia and other causes of dwarfism suffer from increased rates of cardiovascular disease relative to the remainder of the population. Few studies... (Review)
Review
Patients with achondroplasia and other causes of dwarfism suffer from increased rates of cardiovascular disease relative to the remainder of the population. Few studies have examined these patients when undergoing cardiac surgery or percutaneous intervention. This systematic review examines the literature to determine outcomes following cardiac intervention in this unique population. An electronic search was performed in the English literature to identify all reports of achondroplasia, dwarfism, and cardiac intervention. Of the 5,274 articles identified, 14 articles with 14 cases met inclusion criteria. Patient-level data was extracted and analyzed. Median patient age was 55.5 [interquartile ranges (IQR), 43.8, 59.8] years, median height 102.0 [98.8, 112.5] cm, median BMI 32.1 [27.0, 45.9], and 57.1% (8/14) were male. Of these 14 patients, nine had the following documented skeletal abnormalities: 66.7% (6/9) had scoliosis, 66.7% (6/9) had kyphosis, 11.1% (1/9) had lordosis, 11.1% (1/9) pectus carinatum and 11.1% (1/9) spinal stenosis. Coronary artery disease was present in 53.8% (7/13), and 30.8% (4/13) patients previously suffered a myocardial infarction. Of the eight patients who underwent cardiac surgery, 37.5% (3/8) underwent multivessel coronary artery bypass grafting, 37.5% (3/8) underwent aortic valve replacement, 25.0% (2/8) underwent type A aortic dissection repair, and the remaining 12.5% (1/8) underwent pulmonary thromboendarterectomy. Six patients underwent percutaneous intervention. Median cardiopulmonary bypass time was 136.5 [110.0, 178.8] minutes. Median arterial cannula size was 20.0 [20.0, 24.0] Fr. Bicaval cannulation was performed in all cases describing cannulation strategy (5/5). Median superior vena cava cannula size was 28.0 [28.0, 28.0] Fr, and inferior vena cava cannula size was 28.0 [28.0, 28.0] Fr. No mortality was reported with a median follow up time of 6.0 [6.0, 10.5] months. In conclusion, Common cardiac procedures can be performed with reasonable safety in this patient population. Operative adjustments may need to be made with respect to equipment to accommodate patient-specific needs.
PubMed: 32274169
DOI: 10.21037/jtd.2020.02.05 -
Journal of Atrial Fibrillation 2019Endocardial LAAO has been increasingly utilized in atrial fibrillation (AF) patients who are not suitable for long term oral anticoagulation. While overall procedural...
Endocardial LAAO has been increasingly utilized in atrial fibrillation (AF) patients who are not suitable for long term oral anticoagulation. While overall procedural complications have decreased, rare complications like contiguous vessel and valve injury may be more frequently seen in the future with increase in the procedure volume. We performed a systematic search using predefined terms which reviewed all cases published in literature of contiguous vessel (pulmonary artery, pulmonary vein and left circumflex artery) and mitral valve injury caused by LAAO devices. Our results showed that Amplatzer Cardiac Plug (ACP) and Amplatzer Amulet devices were the most commonly used devices. Pulmonary artery perforation was the most commonly seen collateral vessel injury associated with LAAO. Close proximity of left atrial appendage to pulmonary artery was noted in all cases of pulmonary artery injury. Pulmonary artery injury commonly manifests as pericardial tamponade with hemodynamic collapse and is often fatal. Most common denominator of all the reviewed cases was the presence of an oversized LAAO device. In conclusion, collateral vessels and valve injury can be seen after LAAO mostly with double lobe devices such as ACP or Amulet. Increased awareness by the operators along with proper imaging and investigations could potentially mitigate such rare complications associated with LAAO.
PubMed: 32002118
DOI: 10.4022/jafib.2256 -
Medicine Jan 2020Bronchoscopic lung volume reduction (BLVR) offers alternative novel treatments for patients with emphysema. Comprehensive evidence for comparing different BLVR remains... (Meta-Analysis)
Meta-Analysis
Bronchoscopic lung volume reduction (BLVR) offers alternative novel treatments for patients with emphysema. Comprehensive evidence for comparing different BLVR remains unclear. To estimate the effects of different BLVR on patients with emphysema. PubMed, EMBASE, Cochrane Library, and Web of Science databases from January 2001 to August 2017 were searched. Randomized clinical trials evaluated effects of BLVR on patients with emphysema. The relevant information was extracted from the published reports with a predefined data extraction sheet, and the risk of bias was assessed with the Cochrane risk of bias tools. Pair-wise metaanalyses were made using the random-effects model. A random-effects network meta-analysis was applied within a Bayesian framework. The quality of evidence contributing to primary outcomes was assessed using the GRADE framework. 13 trials were deemed eligible, including 1993 participants. The quality of evidence was rated as moderate in most comparisons. Medical care (MC)was associated with the lowest adverse events compared with intrabronchial valve (IBV)(-2.5,[-4.70 to -0.29]), endobronchial valve (EBV) (-1.73, [-2.37 to -1.09]), lung volume reduction coils (LVRC) (-0.76, [-1.24 to -0.28]), emphysematous lung sealant (ELS) (-1.53, [-2.66 to -0.39]), and airway bypass(-1.57, [-3.74 to 0.61]). Adverse events in LVRC were lower compared with ELS (-0.77,[-2.00 to 0.47]). Bronchoscopic thermal vapor ablation (BTVA) showed significant improvement in FEV1 compared with MC (0.99, [0.37 to 1.62]), IBV (1.25, [0.25 to 2.25]), and LVRC (0.72, [0.03 to 1.40] ). Six minute walking distance (6 MWD) in ELS was significantly improved compared with other four BLVR, sham control, and MC (-1.96 to 1.99). Interestingly, MC showed less improvement in FEV1 and 6MWDcompared with EBV (-0.45, [-0.69 to -0.20] and -0.39, [-0.71 to -0.07], respectively). The mortality in MC and EBV was lower compared with LVRC alone (-0.38, [-1.16 to 0.41] and -0.50, [-1.68 to 0.68], respectively). BTVA and EBV led to significant changes in St George's respiratory questionnaire (SGRQ) compared with MC alone (-0.74, [-1.43 to -0.05] and 0.44, [0.11 to 0.78], respectively). BLVR offered a clear advantage for patients with emphysema. EBV had noticeable beneficial effects on the improvement of forced expiratory volume 1, 6MWD and SGRQ, and was associated with lower mortality compared with MC in different strategies of BLVR.
Topics: Bronchoscopy; Humans; Network Meta-Analysis; Pulmonary Emphysema
PubMed: 32000409
DOI: 10.1097/MD.0000000000018936 -
Annals of Cardiothoracic Surgery Nov 2019Optimal surgical treatment of infective tricuspid valve endocarditis in patients with intravenous drug use (IVDU) remains controversial. Tricuspid valvectomy has been...
BACKGROUND
Optimal surgical treatment of infective tricuspid valve endocarditis in patients with intravenous drug use (IVDU) remains controversial. Tricuspid valvectomy has been proposed for infective tricuspid valve endocarditis in this patient population given the inherent social concerns. The aim of this systematic review and meta-analysis was to compare outcomes of valvectomy versus replacement for the surgical treatment of isolated infective tricuspid valve endocarditis.
METHODS
An electronic search was performed to identify all relevant studies published. After assessment for inclusion and exclusion criteria, 16 original studies were pooled for systematic review and meta-analysis.
RESULTS
There were a total of 752 patients with infective tricuspid valve endocarditis, of which 14% underwent valvectomy and 86% underwent replacement (mean follow-up 4.2 years, 95% CI, 1.9-6.4 years). The most common indications for surgical intervention were septic pulmonary embolism in the valvectomy group (74%, 95% CI, 28-95%) and persistent sepsis in the replacement group (62%, 95% CI, 31-86%). There were no differences in rates of stroke [valvectomy 4% (95% CI, 1-11%) replacement 3% (95% CI, 1-16%), P=0.85] but there was increased likelihood of prolonged ventilation in those who underwent valvectomy [valvectomy 40% (95% CI, 30-51%) replacement 26% (95% CI, 23-30%), P<0.01]. There were no differences in 30-day post-operative mortality [valvectomy 13% (95% CI, 5-30%) replacement 7% (95% CI, 5-10%), P=0.21], post-operative right heart failure [valvectomy 27% (95% CI, 10-53%) replacement 11% (95% CI, 5-25%), P=0.17] and recurrent endocarditis [valvectomy 7% (95% CI, 2-23%) replacement 19% (95% CI, 12-28%), P=0.81]. Valvectomy had a higher rate of tricuspid valve reoperation [valvectomy 56% (95% CI, 15-90%) initial replacement 14% (95% CI, 7-27%), P=0.06].
CONCLUSIONS
Tricuspid valvectomy is an acceptable initial therapy for infective tricuspid valve endocarditis in patients with IVDU, providing a bridge to identify those who will self-select as candidates for staged valve replacement.
PubMed: 31832351
DOI: 10.21037/acs.2019.11.06 -
Cardiology Research Dec 2019Pulmonary hypertension is a usual complication of long-standing mitral valve disease. Perioperative pulmonary hypertension is a risk factor for right ventricular failure...
BACKGROUND
Pulmonary hypertension is a usual complication of long-standing mitral valve disease. Perioperative pulmonary hypertension is a risk factor for right ventricular failure and is an important cause of morbidity and mortality in patients with pulmonary hypertension undergoing mitral valve surgery. Phosphodiesterase-5 inhibitors particularly sildenafil citrate have proven clinical benefit for pulmonary arterial hypertension but have shown discordant results in group 2 pulmonary hypertension patients. We sought to determine the effect of pre-operative sildenafil on the intra-operative hemodynamic parameters of these patients.
METHODS
Studies were included if they satisfied the following criteria: 1) Randomized controlled trials; 2) Adult patients with pulmonary hypertension scheduled for elective mitral valve surgery; and 3) Reported data on changes in pre-, intra-, and post-operative hemodynamic parameters. Using PUBMED, Clinical Key, Science Direct, and Cochrane databases, a search for eligible studies was conducted from September 1 to December 31, 2018. The quality of each study was evaluated using the Cochrane Risk of Bias Tool. The primary outcome of interest is on the effect of pre-operative sildenafil on the improvement of intra-operative hemodynamic parameters such as systolic pulmonary artery pressure (sPAP), mean pulmonary arterial pressure, mean arterial pressure, pulmonary and systemic vascular resistances. We also investigated its effect on the post-operative mortality, length of cardiopulmonary bypass time, ventilation time, and inotrope support requirement. Review Manager 5.3 was utilized to perform analysis of random effects for continuous outcomes.
RESULTS
We identified three studies involving 153 patients with pulmonary hypertension undergoing mitral valve surgery, showing that among those who received pre-operative sildenafil there is a significant decrease in intra-operative systolic pulmonary arterial pressure (mean difference -11.19 (95% confidence interval (CI), -20.23 to -2.15), P < 0.05) and post-operative sPAP (mean difference -13.67 (95% CI, - 19.56 to - 7.78), P < 0.05) without significantly affecting the mean arterial pressure (mean difference 1.94 (95% CI, -5.49 to 9.37), P < 0.05). The systemic and pulmonary vascular resistances were not affected as well.
CONCLUSIONS
Administration of pre-operative sildenafil to patients with pulmonary hypertension undergoing mitral valve surgery decreases intra-operative and post-operative systolic pulmonary arterial pressure without significantly affecting other systemic hemodynamic parameters.
PubMed: 31803335
DOI: 10.14740/cr962