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Heart & Lung : the Journal of Critical... Jun 2024Progressive exercise intolerance is a hallmark of pulmonary hypertension (pH), severely impacting patients' independence and quality of life (QoL). Accumulating evidence... (Review)
Review
Respiratory, cardiovascular and musculoskeletal mechanisms involved in the pathophysiology of pulmonary hypertension: An updated systematic review of preclinical and clinical studies.
BACKGROUND
Progressive exercise intolerance is a hallmark of pulmonary hypertension (pH), severely impacting patients' independence and quality of life (QoL). Accumulating evidence over the last decade shows that combined abnormalities in peripheral reflexes and target organs contribute to disease progression and exercise intolerance.
OBJECTIVE
The aim of this study was to review the literature of the last decade on the contribution of the cardiovascular, respiratory, and musculoskeletal systems to pathophysiology and exercise intolerance in pH.
METHODS
A systematic literature search was conducted using specific terms in PubMed, SciELO, and the Cochrane Library databases for original pre-clinical or clinical studies published between 2013 and 2023. Studies followed randomized controlled/non-randomized controlled and pre-post designs.
RESULTS
The systematic review identified 25 articles reporting functional or structural changes in the respiratory, cardiovascular, and musculoskeletal systems in pH. Moreover, altered biomarkers in these systems, lower cardiac baroreflex, and heightened peripheral chemoreflex activity seemed to contribute to functional changes associated with poor prognosis and exercise intolerance in pH. Potential therapeutic strategies acutely explored involved manipulating the baroreflex and peripheral chemoreflex, improving cardiovascular autonomic control via cardiac vagal control, and targeting specific pathways such as GPER1, GDF-15, miR-126, and the JMJD1C gene.
CONCLUSION
Information published in the last 10 years advances the notion that pH pathophysiology involves functional and structural changes in the respiratory, cardiovascular, and musculoskeletal systems and their integration with peripheral reflexes. These findings suggest potential therapeutic targets, yet unexplored in clinical trials, that could assist in improving exercise tolerance and QoL in patients with pH.
PubMed: 38941771
DOI: 10.1016/j.hrtlng.2024.06.001 -
Renal Failure Dec 2024To estimate the predictors, prevalence and prognostic role of pulmonary hypertension (PH) in patients with chronic kidney disease (CKD) using meta-analysis. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To estimate the predictors, prevalence and prognostic role of pulmonary hypertension (PH) in patients with chronic kidney disease (CKD) using meta-analysis.
METHODS
The PubMed, EmBase, and the Cochrane library were systematically searched for eligible studies from inception till May 2024. All of pooled analyses were performed using the random-effects model.
RESULTS
Fifty observational studies involving 17,558 CKD patients were selected. The prevalence of PH in CKD patients was 38% (95% confidence interval [CI]: 33%-43%), and the prevalence according to CKD status were 31% (95% CI: 20%-42%) for CKD (I-V), 39% (95% CI: 25%-54%) for end stage kidney disease (ESKD) (predialysis), 42% (95% CI: 35%-50%) for ESKD (hemodialysis), and 26% (95% CI: 19%-34%) for renal transplant. We noted the risk factors for PH in CKD included Black individuals (relative risk [RR]: 1.39; 95% CI: 1.18-1.63; < 0.001), chronic obstructive pulmonary disease (RR: 1.48; 95% CI: 1.21-1.82; < 0.001), cardiovascular disease history (RR: 1.62; 95% CI: 1.05-2.51; = 0.030), longer dialysis (RR: 1.70; 95% CI: 1.18-2.46; = 0.005), diastolic dysfunction (RR: 1.88; 95% CI: 1.38-2.55; < 0.001), systolic dysfunction (RR: 3.75; 95% CI: 2.88-4.87; < 0.001), and grade 5 CKD (RR: 5.64; 95% CI: 3.18-9.98; < 0.001). Moreover, PH in CKD patients is also associated with poor prognosis, including all-cause mortality, major cardiovascular events, and cardiac death.
CONCLUSION
This study systematically identified risk factors for PH in CKD patients, and PH were associated with poor prognosis. Therefore, patients with high prevalence of PH should be identified for treatment.
Topics: Humans; Hypertension, Pulmonary; Renal Insufficiency, Chronic; Prevalence; Prognosis; Risk Factors; Renal Dialysis; Observational Studies as Topic
PubMed: 38938193
DOI: 10.1080/0886022X.2024.2368082 -
Medicina Clinica Jun 2024Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism and a major cause of chronic pulmonary hypertension leading to right heart...
BACKGROUND AND OBJECTIVES
Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism and a major cause of chronic pulmonary hypertension leading to right heart failure and death. While pulmonary endarterectomy is the treatment of choice, some patients might benefit from medical therapy or balloon pulmonary angioplasty. Sex differences in outcomes of these therapies are not well characterized.
MATERIAL AND METHODS
We conducted a systematic review and meta-analysis to investigate sex differences in outcomes of various therapies for CTEPH. We searched MEDLINE, PubMed, Embase, CINAHL and the Cochrane Library databases between January 1, 2010 and April 30, 2021, published in English. We pooled incidence estimates using random-effects meta-analyses. We evaluated heterogeneity using the I statistic. We assessed publication bias using Begg's and Egger's tests. This study is registered in PROSPERO, CRD42021268504.
RESULTS
A total of 19 studies met the eligibility criteria, but only 3 trials provided separate outcomes for women and men. Two studies evaluated the efficacy of BPA, and one study evaluated the efficacy of riociguat (129 patients). Overall, 57.3% of patients were women and 62.6% were in functional class III. Mean time of follow-up was 55.5 (SD 26.1) weeks. Women showed a significantly better response in cardiac index (mean difference [MD], 0.10L/min/m; 95% confidence interval [CI], 0.04-0.16; I=0%; P=0.001). Alternatively, the reduction of pulmonary vascular resistances was significantly higher for men than for women (MD, 161.17dynscm; 95% CI, 67.99-254.35; I=0%; P=0.0007).
CONCLUSIONS
Women and men might show different hemodynamic responses to riociguat or BPA for CTEPH.
PubMed: 38908993
DOI: 10.1016/j.medcli.2024.03.014 -
Journal of the American Heart... Jul 2024In pulmonary arterial hypertension, it is recommended to base therapeutic decisions on risk stratification. This systematic review aims to report the prognostic value of...
BACKGROUND
In pulmonary arterial hypertension, it is recommended to base therapeutic decisions on risk stratification. This systematic review aims to report the prognostic value of serial risk stratification in adult and pediatric pulmonary arterial hypertension and to explore the usability of serial risk stratification as treatment target.
METHODS AND RESULTS
Electronic databases PubMed, Embase, and Web of Science were searched up to January 30, 2023, using terms associated with pulmonary arterial hypertension, pediatric pulmonary hypertension, and risk stratification. Observational studies and clinical trials describing risk stratification at both baseline and follow-up were included. Sixty five studies were eligible for inclusion, including only 2 studies in a pediatric population. C-statistic range at baseline was 0.31 to 0.77 and improved to 0.30 to 0.91 at follow-up. In 53% of patients, risk status changed (42% improved, 12% worsened) over 168 days (interquartile range, 137-327 days; n=22 studies). The average proportion of low-risk patients increased from 18% at baseline to 36% at a median follow-up of 244 days (interquartile range, 140-365 days; n=40 studies). In placebo-controlled drug studies, risk statuses of the intervention groups improved more and worsened less compared with the placebo groups. Furthermore, a low-risk status, but also an improved risk status, at follow-up was associated with a better outcome. Similar results were found in the 2 pediatric studies.
CONCLUSIONS
Follow-up risk stratification has improved prognostic value compared with baseline risk stratification, and change in risk status between baseline and follow-up corresponded to a change in survival. These data support the use of serial risk stratification as treatment target in pulmonary arterial hypertension.
Topics: Humans; Risk Assessment; Prognosis; Child; Pulmonary Arterial Hypertension; Adult; Risk Factors; Antihypertensive Agents
PubMed: 38904230
DOI: 10.1161/JAHA.123.034151 -
World Journal of Critical Care Medicine Jun 2024Pulmonary hypertension (PH) is a serious progressive disorder of the modern world, characterized by endothelial dysfunction and impaired vasoreactivity. Patients with PH...
BACKGROUND
Pulmonary hypertension (PH) is a serious progressive disorder of the modern world, characterized by endothelial dysfunction and impaired vasoreactivity. Patients with PH usually present exercise intolerance from the very early stages and reduced exercise capacity. Exercise training has been shown to have beneficial effects in patients with cardiovascular comorbidities. However, data regarding the effects of combined exercise training programs in patients with PH still remains limited.
AIM
To investigate the effects of combined exercise training programs on exercise capacity and quality of life in patients with PH.
METHODS
Our search included all available randomized controlled trials (RCTs) regarding combined aerobic, resistance and inspiratory training programs in patients with PH in 4 databases (Pubmed, PEDro, Embase, CINAHL) from 2012 to 2022. Five RCTs were included in the final analysis. Functional capacity, assessed by peak VO or 6-min walking test (6MWT), as well as quality of life, assessed by the SF-36 questionnaire, were set as the primary outcomes in our study.
RESULTS
Peak VO was measured in 4 out of the 5 RCTs while 6MWT was measured in all RCTs. Both indices of functional capacity were significantly increased in patients with PH who underwent combined exercise training compared to the controls in all of the included RCTs ( < 0.05). Quality of life was measured in 4 out of 5 RCTs. Although patients improved their quality of life in each group, however, only 2 RCTs demonstrated further improvement in patients performing combined training compared to controls.
CONCLUSION
By this systematic review, we have demonstrated that combined aerobic, resistance and inspiratory exercise training is safe and has beneficial effects on aerobic capacity and quality of life in patients with PH. Such exercise training regimen may be part of the therapeutic strategy of the syndrome.
PubMed: 38855278
DOI: 10.5492/wjccm.v13.i2.92585 -
Scientific Reports Jun 2024Heart failure (HF) poses a significant challenge, often leading to frequent hospitalizations and compromised quality of life. Continuous pulmonary artery pressure (PAP)... (Meta-Analysis)
Meta-Analysis
Heart failure (HF) poses a significant challenge, often leading to frequent hospitalizations and compromised quality of life. Continuous pulmonary artery pressure (PAP) monitoring offers a surrogate for congestion status in ambulatory HF care. This meta-analysis examines the efficacy of PAP monitoring devices (CardioMEMS and Chronicle) in preventing adverse outcomes in HF patients, addressing gaps in prior randomized controlled trials (RCTs). Five RCTs (2572 participants) were systematically reviewed. PAP monitoring significantly reduced HF-related hospitalizations (RR 0.72 [95% CI 0.6-0.87], p = 0.0006) and HF events (RR 0.86 [95% CI 0.75-0.99], p = 0.03), with no impact on all-cause or cardiovascular mortality. Subgroup analyses highlighted the significance of CardioMEMS and blinded studies. Meta-regression indicated a correlation between prolonged follow-up and increased reduction in HF hospitalizations. The risk of bias was generally high, with evidence certainty ranging from low to moderate. PAP monitoring devices exhibit promise in diminishing HF hospitalizations and events, especially in CardioMEMS and blinded studies. However, their influence on mortality remains inconclusive. Further research, considering diverse patient populations and intervention strategies with extended follow-up, is crucial for elucidating the optimal role of PAP monitoring in HF management.
Topics: Humans; Heart Failure; Pulmonary Artery; Hospitalization; Randomized Controlled Trials as Topic; Quality of Life
PubMed: 38839890
DOI: 10.1038/s41598-024-63742-0 -
Cardiology in Review Jun 2024Chronic thromboembolic pulmonary hypertension (CTEPH) is a subtype of pulmonary hypertension characterized by organized thrombi inside the pulmonary vasculature, leading...
Safety and Outcomes with Direct Oral Anticoagulants Versus Vitamin-K Antagonists in Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review, Meta-Analysis, and Meta-Regression.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a subtype of pulmonary hypertension characterized by organized thrombi inside the pulmonary vasculature, leading to an increase in pulmonary artery pressure. CTEPH is seen in about 3-4% of patients with acute pulmonary embolism and is associated with poor outcomes. Apart from surgical intervention, lifelong anticoagulation is the mainstay of CTEPH management. Traditionally, CTEPH is managed with vitamin-K antagonists (VKA); however, direct oral anticoagulants (DOACs) are recently gaining popularity. However, the current literature comparing DOACs versus VKAs in CTEPH has inconsistent results. An electronic search of the major bibliographic databases was performed to retrieve studies comparing DOACs versus VKAs in CTEPH patients. For dichotomous outcomes, the odds ratio (ORs) with 95% confidence intervals (CI) were pooled using the DerSimonian and Laird random-effects model to generate forest plots. Statistical significance was considered at P < 0.05. Ten studies were included with 3936 patients (1269 in the DOAC group and 2667 in the VKA group). Treatment with DOAC was associated with no statistically significant difference in the risk of all-cause mortality (OR, 0.78; 95% CI, 0.35-1.71; P < 0.53), venous thromboembolism (OR, 1.19; 95% CI, 0.59-2.40; P = 0.63), major bleeding (OR, 0.68; 95% CI, 0.38-1.22; P = 0.20), and clinically relevant nonmajor bleeding (OR, 1.22; 95% CI, 0.80-1.86; P = 0.37). Our analysis demonstrates that DOACs are noninferior to VKAs in terms of their safety and outcomes profile in CTEPH. Further trials are needed to evaluate more robust evidence and to compare additional outcomes.
PubMed: 38833432
DOI: 10.1097/CRD.0000000000000735 -
Clinical Nuclear Medicine Jul 2024This meta-analysis and systematic review assessed the diagnostic accuracy of lung SPECT compared with lung planar imaging in patients with suspected acute pulmonary... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis and systematic review assessed the diagnostic accuracy of lung SPECT compared with lung planar imaging in patients with suspected acute pulmonary embolism (PE) or chronic thromboembolic pulmonary hypertension.
PATIENTS AND METHODS
A search of Medline, Embase, and Cochrane databases identified suitable articles published before October 2023. Meta-analyses were performed to determine the diagnostic accuracy of SPECT imaging modalities, including perfusion (Q) SPECT, ventilation (V)/Q SPECT, Q SPECT/CT, and V/Q SPECT/CT. Network meta-analyses were performed to compare the diagnostic accuracy of SPECT and planar imaging in paired-design studies.
RESULTS
Twenty-four articles (total n = 6576) were included in the analysis. For suspected acute PE, the respective sensitivity and specificity of SPECT imaging modalities were as follows: Q SPECT, 0.93 (95% confidence interval [CI], 0.87-0.99; I2 = 49%) and 0.72 (95% CI, 0.54-0.95; I2 = 94%); V/Q SPECT, 0.96 (95% CI, 0.94-0.98; I2 = 51%) and 0.95 (95% CI, 0.92-0.98; I2 = 80%); Q SPECT/CT, 0.93 (95% CI, 0.87-0.98; I2 = 66%) and 0.82 (95% CI, 0.70-0.96; I2 = 87%); and V/Q SPECT/CT, 0.97 (95% CI, 0.93-1.00; I2 = 7%) and 0.98 (95% CI, 0.97-1.00; I2 = 31%). The relative sensitivity and specificity of SPECT compared with planar imaging were 1.17 (95% CI, 1.06-1.30; P < 0.001) and 1.14 (95% CI, 1.00-1.29; P = 0.05), respectively. For suspected chronic thromboembolic pulmonary hypertension, the pooled sensitivity and specificity of SPECT imaging were 0.97 (95% CI, 0.95-1.00; I2 = 0%) and 0.91 (95% CI, 0.87-0.94; I2 = 0%), respectively.
CONCLUSIONS
SPECT exhibited superior diagnostic performance for PE. V/Q SPECT/CT was the most accurate modality.
Topics: Pulmonary Embolism; Humans; Tomography, Emission-Computed, Single-Photon; Network Meta-Analysis
PubMed: 38831512
DOI: 10.1097/RLU.0000000000005167 -
Chest May 2024Pulmonary hypertension (PH) is a key complication in interstitial lung disease (ILD), with recent therapeutic advances.
BACKGROUND
Pulmonary hypertension (PH) is a key complication in interstitial lung disease (ILD), with recent therapeutic advances.
RESEARCH QUESTION
What are the diagnostic evaluation, epidemiologic features, associated factors, prognostic significance, and outcome measures in interventional trials for PH in patients with ILD in the current literature?
STUDY DESIGN AND METHODS
Ovid MEDLINE, Embase, and CENTRAL databases were searched for original research evaluating PH in participants with ILD of any cause. The definition of PH was based on the investigators' criteria.
RESULTS
Three hundred two studies were included, with varying diagnostic evaluations used to define PH. Commonly used diagnostic tests were right heart catheterization (RHC; 56%) and transthoracic echocardiography (TTE; 50%). The pooled prevalence for PH in general populations with ILD was 36% (95% CI, 30%-42%) using RHC and 34% (95% CI, 29%-38%) using TTE. Lower diffusion capacity of the lungs for carbon monoxide, worse oxygenation status, reduced exercise capacity, increased pulmonary artery to aorta ratio and pulmonary artery diameter, and elevated serum brain natriuretic peptide consistently were associated with the presence of PH in at least 60% of reported studies. The presence of PH was associated with increased symptom burden and worse prognosis. Outcome measures in interventional trials of PH in ILD focused on changes in pulmonary vascular hemodynamics and 6-min walk distance.
INTERPRETATION
PH is a common complication in ILD with significant health impacts. A standardized definition with prospective evaluation of risk-stratified assessments for PH using identified associated risk factors is warranted. Our findings provide an evidence base for validation as surrogate end points in future PH interventional trials in ILD.
TRIAL REGISTRY
International Prospective Register of Systematic Reviews; No.: CRD42021255394; URL: https://www.crd.york.ac.uk/prospero/.
PubMed: 38821182
DOI: 10.1016/j.chest.2024.04.025 -
Annals of the American Thoracic Society May 2024There are no direct comparisons of sotatercept to add-on therapies approved for PAH.
RATIONALE
There are no direct comparisons of sotatercept to add-on therapies approved for PAH.
OBJECTIVE
This study aimed to compare the efficacy and safety of add-on sotatercept versus other add-on therapies using a network meta-analysis.
METHODS
We searched MEDLINE, Embase, the Cochrane CENTRAL, and Clinicaltrials.gov until April 15, 2023, for randomized trials involving PAH patients treated with add-on sotatercept or add-on other PAH therapies. Data extraction and risk of bias assessments were performed independently and in duplicate using the Cochrane RoB 2.0 tool. We performed frequentist random-effects network meta-analysis using the restricted maximum likelihood (REML) estimator and assessed the certainty of evidence using the GRADE approach.
RESULTS
Our search found 18 trials (5777 patients) eligible for analysis. Sotatercept reduces clinical worsening as compared to placebo (RR 0.21 [95% CI 0.11 to 0.41]; high certainty). Sotatercept probably reduces clinical worsening more compared to add-on ERA (RR 0.28 [95% CI 0.14 to 0.55]), prostanoid (Inh) (RR 0.21 [95% CI 0.07 to 0.67]), and prostanoid (PO) (RR 0.32 [95% CI 0.16 to 0.67]) (all moderate certainty). Sotatercept probably improves 6MWD as compared to placebo (MD 36.89m [95% CI 25.26 to 48.51]). Although sotatercept probably improves 6MWD more than add-on ERA (MD 18.38m [95% CI 5.92 to 30.84]) and prostanoid (PO) (MD 25.66m [95% CI 13.71 to 37.61]), it did not exceed the MCID of 33m (both moderate certainty).
CONCLUSION
Sotatercept is an effective add-on therapy for PAH, likely superior to many approved add-on PAH therapies in reducing clinical worsening.
PubMed: 38820258
DOI: 10.1513/AnnalsATS.202311-942OC