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High Altitude Medicine & Biology Mar 2024Poudel, Sangeeta, Sandesh Gautam, Purushottam Adhikari, and Ken Zafren. Physiological effects of sildenafil versus placebo at high altitude: a systematic review. .... (Review)
Review
Poudel, Sangeeta, Sandesh Gautam, Purushottam Adhikari, and Ken Zafren. Physiological effects of sildenafil versus placebo at high altitude: a systematic review. . 25:16-25, 2024. High altitude pulmonary edema (HAPE), a life-threatening condition that affects individuals ascending to high altitude, requires the development of pulmonary hypertension. Sildenafil can be used to prevent and treat HAPE, presumably by decreasing pulmonary artery pressure (PaP). We compared the physiological effects of sildenafil versus placebo at high altitude (above 2,500 m), including the effects on PaP. We performed a systematic search of PubMed, EMBASE, and Cochrane CENTRAL for randomized controlled studies of the physiological effects of sildenafil in hypoxia in healthy individuals. We conducted a systematic review of all studies meeting our criteria. Of the 14 studies that met the inclusion criteria, 8 were hypobaric hypoxia studies. Six studies reported data at rest at altitudes from 3,650 to 5,245 m. Two were simulations reporting exercise data at equivalent altitudes of 2,750-5,000 m. Nine studies used normobaric hypoxia corresponding to altitudes between 2,500 and 6,400 m. One reported only rest data, two reported rest and exercise data, and the others reported only exercise data. Sildenafil significantly reduced PaP at rest and exercise in hypobaric or normobaric hypoxia. There were no significant differences between arterial oxygen saturation (SpO) with sildenafil in hypobaric or normobaric hypoxia at rest or exercise. There were no significant differences in heart rate or mean arterial pressure (MAP) at rest or exercise and cardiac output during exercise in hypobaric or normobaric hypoxia. Sildenafil significantly reduces PaP at rest and exercise in normobaric or hypobaric hypoxia. Sildenafil has no significant effects on SpO, heart rate, cardiac output (during exercise), or MAP at rest or exercise in hypobaric or normobaric hypoxia.
Topics: Humans; Sildenafil Citrate; Altitude; Altitude Sickness; Hypoxia; Hypertension, Pulmonary
PubMed: 37751174
DOI: 10.1089/ham.2022.0043 -
European Journal of Preventive... Apr 2024Lipoprotein(a) [Lp(a)] is an atherogenic lipid particle associated with increased risk for coronary heart disease (CHD) events. Coronary artery calcium (CAC) score is a... (Meta-Analysis)
Meta-Analysis
AIMS
Lipoprotein(a) [Lp(a)] is an atherogenic lipid particle associated with increased risk for coronary heart disease (CHD) events. Coronary artery calcium (CAC) score is a tool to diagnose subclinical atherosclerosis and guide clinical decision-making for primary prevention of CHD. Studies show conflicting results concerning the relationship between Lp(a) and CAC in asymptomatic populations. We conducted a meta-analysis to evaluate the association of Lp(a) and CAC in asymptomatic patients.
METHODS AND RESULTS
We systematically searched PubMed, Embase, and Cochrane until April 2023 for studies evaluating the association between Lp(a) and CAC in asymptomatic patients. We evaluated CAC > 0 Agatston units, and CAC ≥ 100. Lp(a) was analysed as a continuous or dichotomous variable. We assessed the association between Lp(a) and CAC with pooled odds ratios (OR) adopting a random-effects model. A total of 23 105 patients from 18 studies were included in the meta-analysis with a mean age of 55.9 years, 46.4% female. Elevated Lp(a) increased the odds of CAC > 0 [OR 1.31; 95% confidence intervals (CI) 1.05-1.64; P = 0.02], CAC ≥100 (OR 1.29; 95% CI 1.01-1.65; P = 0.04; ), and CAC progression (OR 1.43; 95% CI 1.20-1.70; P < 0.01; ). For each increment of 1 mg/dL in Lp(a) there was a 1% in the odds of CAC > 0 (OR 1.01; 95% CI 1.01-1.01; P < 0.01).
CONCLUSION
Our findings of this meta-analysis suggest that Lp(a) is positively associated with a higher likelihood of CAC. Higher Lp(a) levels increased the odds of CAC >0. These data support the concept that Lp(a) is atherogenic, although with high heterogeneity and a low level of certainty.
PROTOCOL REGISTRATION
CRD42023422034.
KEY FINDINGS
Asymptomatic patients with elevated Lp(a) had 31% higher chances of having any coronary calcification (CAC > 0) and 29% higher chances of having more advanced calcification (CAC > 100). It increased the chances of having progression of coronary calcification over time by 43%. For each 1 mg/dL of Lp(a) there was an increment of 1% chance of having coronary calcification.
Topics: Humans; Female; Middle Aged; Male; Calcium; Coronary Artery Disease; Risk Factors; Coronary Vessels; Lipoprotein(a); Atherosclerosis; Calcinosis; Vascular Calcification
PubMed: 38300625
DOI: 10.1093/eurjpc/zwae043 -
Journal of Human Hypertension Oct 2022The study aims to compare clinical outcomes following renal denervation (RDN) in hypertensive patients with atrial fibrillation (AF). Three online databases were... (Meta-Analysis)
Meta-Analysis Review
The study aims to compare clinical outcomes following renal denervation (RDN) in hypertensive patients with atrial fibrillation (AF). Three online databases were searched (MEDLINE, EMBASE and PubMed) for literature related to outcomes of RDN on hypertension and AF, between January 1, 2010, and June 1, 2021. Where possible, risk ratios (RR) and mean differences (MD) were combined using a random effects model. Significance was set at p ≤ 0.05. Seven trials were included that assessed the effect of adding RDN to pulmonary vein isolation (PVI) in patients with hypertension and AF. A total of 711 patients (329 undergoing PVI + RDN and 382 undergoing PVI alone), with an age range of 56 ± 6 to 68 ± 9 years, were included. Pooled analysis showed a significant lowering of AF recurrence in the PVI + RDN (31.3%) group compared to the PVI-only (52.9%) group (p < 0.00001). Pooled analysis of patients with resistant hypertension showed a significant mean reduction of systolic blood pressure (SBP) (-9.42 mm Hg, p = 0.05), but not diastolic blood pressure (DBP) (-4.11 mm Hg, p = 0.16) in favor of PVI + RDN. Additionally, the pooled analysis showed that PVI + RDN significantly improved estimated glomerular filtration rate (eGFR) (+10.2 mL/min per 1.73 m, p < 0.001) compared to PVI alone. RDN procedures in these trials have proven to be both safe and efficacious with an overall complication rate of 6.32%. Combined PVI and RDN is beneficial for patients with hypertension and AF. Combined therapy showed improvement in SBP and eGFR, reducing the risk of AF recurrence. RDN may serve as an innovative intervention in the treatment of AF.
Topics: Atrial Fibrillation; Catheter Ablation; Humans; Hypertension; Recurrence; Renal Artery; Sympathectomy; Treatment Outcome
PubMed: 35094013
DOI: 10.1038/s41371-022-00658-0 -
The Clinical Respiratory Journal Apr 2022We conducted a meta-analysis to systematic assess the diagnostic value of computed tomography (CT)-based pulmonary artery to aorta (PA:A) ratio measurement in COPD with... (Meta-Analysis)
Meta-Analysis Review
Diagnostic value of computed tomography-based pulmonary artery to aorta ratio measurement in chronic obstructive pulmonary disease with pulmonary hypertension: A systematic review and meta-analysis.
OBJECTIVE
We conducted a meta-analysis to systematic assess the diagnostic value of computed tomography (CT)-based pulmonary artery to aorta (PA:A) ratio measurement in COPD with pulmonary hypertension (COPD-PH).
METHODS
Published studies referring to diagnostic accuracy of PA:A ratio for COPD-PH were screened out from PubMed, Embase, Web of science, China National Knowledge databases (CNKI), Wan fang databases, and VIP databases. We used bivariate random-effects model to estimate pooled sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR, respectively), and diagnostic odds ratios (DOR). Summary receiver operating characteristic (SROC) curves and area under the curve (AUC) were also calculated to summarize the aggregate diagnostic performance.
RESULTS
Nine eligible studies were included and the pooled SEN was 69% (95% CI: 59 ~ 78), SPE was 85% (95% CI: 77 ~ 90), PLR was 4.5 (95% CI: 2.8 ~ 7.5), and NLR was 0.36 (95% CI: 0.26 ~ 0.51), respectively. DOR reached 13.00 (95% CI: 6.00 ~ 28.00), and value of AUC was 0.84 (95% CI: 0.81 ~ 0.87). Subgroup analysis indicated that when the value of PA:A ratio was equal or greater than one (PA/A ≥ 1), the combined SEN, SPE, AUC, and DOR was 69%, 89%, 0.90, and 19.65, respectively.
CONCLUSIONS
PA:A ratio is helpful for appraisal of COPD-PH, and PA/A ≥ 1 possessed prominent diagnostic accuracy.
Topics: Aorta; Humans; Hypertension, Pulmonary; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Sensitivity and Specificity; Tomography, X-Ray Computed
PubMed: 35289083
DOI: 10.1111/crj.13485 -
International Journal of Obstetric... Apr 2024Women with pulmonary hypertension (PH) have increased mortality during pregnancy and the peripartum period. An increasing number of publications suggest improvements in... (Review)
Review
Women with pulmonary hypertension (PH) have increased mortality during pregnancy and the peripartum period. An increasing number of publications suggest improvements in maternal outcomes, so we conducted a systematic review focusing on disease severity and maternal survival. After screening 9097 potential studies from 1967 to 2021, we identified 66 relevant publications. Outcomes improved continuously over time and mortality fell from 11.6% in studies published before 2015 to 8.2% in studies published after 2015. Mortality was lower in patients with mild disease (0.8%) than in those with Eisenmenger syndrome (26.2%) or idiopathic pulmonary arterial hypertension (7.4-24.0%). One major drawback of the published studies is that they define severity using echocardiographic-estimated pulmonary artery pressures, without considering more contemporary parameters. This systematic review provides new insights for preconception counseling on pregnancy risks related to PH and suggests that PH classification and severity should be carefully considered in determining an individual's pregnancy-associated risk.
PubMed: 38781778
DOI: 10.1016/j.ijoa.2024.104210 -
Annals of Palliative Medicine Jan 2022The prognosis of patients with untreated pulmonary arterial hypertension (PAH) has historically been poor. Previous studies have recommended that sildenafil was... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prognosis of patients with untreated pulmonary arterial hypertension (PAH) has historically been poor. Previous studies have recommended that sildenafil was beneficial, but the dose varies greatly. In this study, we aimed to evaluate the safety and effectiveness of sildenafil [dose: 20 mg/three times a day (TID)] for adult Asian PAH patients.
METHODS
Electronic databases (MEDLINE, Embase, Web of Science, the Cochrane Library, CBM, CNKI, and Wanfang Data) were searched from their inception to January 2022. We recruited all randomized controlled trials and non-randomized studies of interventions that compared sildenafil (20 mg/TID) versus placebo or symptomatic treatment for adult Asian PAH patients.
RESULTS
A total of 10 studies involving 480 participants were included. Compared to symptomatic treatment, sildenafil-treated patients were more likely to walk 57.68 meters further in six-minute walk distance [mean difference (MD) =57.68 m, 95% confidence interval (CI): 41.55 to 73.81], achieve an improvement in systemic arterial oxygen saturation (MD =2.48%, 95% CI: 1.26 to 3.71), and increase the score of the Borg scale for dyspnea (MD =-0.99 points, 95% CI: -1.45 to -0.53). The total number of patients with World Health Organization class III and IV also exhibited a downtrend. Compared to the placebo, sildenafil was associated with a reduction in the mean pulmonary artery pressure (MD =-4.13 mmHg, 95% CI: -6.52 to -1.74) and the level of brain natriuretic peptide (MD =-86.16 pg/mL, 95% CI: -103.39 to -68.93). The most common adverse events were headache, flushing, dyspepsia, and diarrhea, which were relatively mild.
DISCUSSION
Sildenafil at a dose of 20 mg/TID is well tolerated in adult Asian PAH patients, and is associated with statistically significant improvements in exercise capacity, cardio-pulmonary function, and haemodynamic indices. The long-term prognosis still needs to be evaluated and confirmed by further trials.
Topics: Adult; Dyspnea; Humans; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Quality of Life; Sildenafil Citrate; Treatment Outcome
PubMed: 35144425
DOI: 10.21037/apm-21-3979 -
Frontiers in Cardiovascular Medicine 2023Pulmonary complications occur in a substantial proportion of patients who undergo coronary artery bypass grafting. Inspiratory muscle training (IMT), a simple,... (Review)
Review
BACKGROUND
Pulmonary complications occur in a substantial proportion of patients who undergo coronary artery bypass grafting. Inspiratory muscle training (IMT), a simple, well-tolerated physical therapy, has been proposed to reduce the risk of complications, but its efficacy remains controversial.
METHOD
Randomized controlled trials (RCTs) examining the influence of IMT on the risk of pulmonary complications after coronary artery bypass grafting were identified from PubMed, Embase, CENTRAL, CINAL, and Web of Science through March 2023. Data were meta-analyzed for the primary outcomes of pulmonary complications, defined as pneumonia, pleural effusion, and atelectasis; and in terms of the secondary outcomes of maximum inspiratory pressure, maximum expiratory pressure, length of hospitalization, 6 min walk test, and peak expiratory flow and other outcomes. Risk of bias and quality of evidence assessments were carried out using the RoB 2.0 and Grading of Recommendations Assessment, Development and Evaluation (GRADE) applied to primary outcomes of pulmonary complications.
RESULTS
Data from eight RCTs involving 755 patients were meta-analyzed. IMT was associated with a significantly lower risk of postoperative pneumonia [relative risk (RR) 0.39, 95% confidence interval (CI) 0.25-0.62, < 0.0001] and atelectasis (RR 0.43, 95% CI 0.27-0.67, = 0.0002), but not pleural effusion (RR 1.09, 95% CI 0.62-1.93, = 0.76). IMT was associated with significantly better maximum inspiratory pressure (preoperative: mean difference (MD) 16.55 cmHO, 95% CI 13.86-19.24, < 0.00001; postoperative: mean difference (MD) 8.99 cmHO, 95% CI 2.39-15.60, = 0.008) and maximum expiratory pressure (MD 7.15 cmHO, 95% CI: 1.52-12.79, = 0.01), and with significantly shorter hospitalization (MD -1.71 days, 95% CI -2.56 to -0.87, < 0.001). IMT did not significantly affect peak expiratory flow or distance traveled during the 6 min walk test.
CONCLUSIONS
The available evidence from medium and high quality trials suggests that IMT can significantly decrease the risk of pneumonia and atelectasis after coronary artery bypass grafting while shortening hospitalization and improving the strength of respiratory muscles.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42023415817.
PubMed: 37560113
DOI: 10.3389/fcvm.2023.1223619 -
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 Jul 2024Pulmonary thromboendarterectomy (PTE) is the current gold standard treatment for chronic thromboembolic pulmonary hypertension (CTEPH) and is a viable treatment option...
Pulmonary thromboendarterectomy (PTE) is the current gold standard treatment for chronic thromboembolic pulmonary hypertension (CTEPH) and is a viable treatment option for chronic thromboembolic pulmonary disease (CTEPD). The progressive nature of both diseases severely impacts health-related quality of life (HRQoL) across a variety of domains. This systematic review was performed to evaluate the impact of PTE on short- and long-term HRQoL. A literature search was conducted on PubMed for studies matching the eligibility criteria between January 2000 and September 2022. OVID (MEDLINE), Google Scholar, EBSCOhost (EMBASE), and bibliographies of included studies were reviewed. Inclusion of studies was based on predetermined eligibility criteria. Quality appraisal and data tabulation were performed using predetermined forms. Results were synthesized by narrative review. The structure of this systematic review follows the PRISMA guidelines. This systematic review was prospectively registered in the PROSPERO register (CRD42022342144). Thirteen studies (2184 patients) were included. Within 3 months post-PTE, HRQoL improved in both CTEPD and CTEPH as measured by disease-specific and generic questionnaires. HRQoL improvements were sustained up to 5 years postoperatively in patients with CTEPH post-PTE. PTE remains the gold standard for treating CTEPH and improving HRQoL. Residual pulmonary hypertension and comorbidities such as COPD and coronary artery disease decrement HRQoL over time. The impact of mPAP and PVR on HRQoL outcomes postoperatively remain ambiguous. Pulmonary thromboendarterectomy remains the gold standard for treating CTEPH and has shown to improve HRQoL outcomes at 3-month sustaining improvements up to 5-year postoperatively. Residual pulmonary hypertension and comorbidities hinder HRQoL outcomes post-PTE.
PubMed: 38962182
DOI: 10.1002/pul2.12407 -
Medical Journal of the Islamic Republic... 2023Heart Failure (HF) imposes a relevant burden and a considerable health concern, with high prevalence and mortality rates. This study was conducted to assess the... (Review)
Review
BACKGROUND
Heart Failure (HF) imposes a relevant burden and a considerable health concern, with high prevalence and mortality rates. This study was conducted to assess the cost-effectiveness of remote cardiac monitoring with the CardioMEMS Heart Failure System.
METHODS
In the present systematic review, several scholarly databases were searched and updated from inception up to September 20, 2022. The objective of the present review was formulated according to the patient/population, intervention, comparison and outcomes format. Mortality rate, hospitalization rate, quality-adjusted life year (QALY), total costs, and the incremental cost-effectiveness ratio regarding the use of the CardioMEMS System were the key outcomes of the present study. The quality of included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS) checklist.
RESULTS
Finally, 5 articles were retained and analyzed in the present systematic review. All studies employed the Markov and decision tree models. Results show that the CardioMEMS system reduced mortality and hospitalization rate and created a higher QALY. In all selected countries the CardioMEMS method is a more expensive method than the standard of care (SoC), with the highest cost in the United States (US) ($201,437) and the lowest cost in the United Kingdom ($25,963), respectively. the highest willingness to pay in the US and the lowest in Italy ($100,000 and $33,000 per QALY), respectively. Results showed that the most cost per QALY for the CardioMEMS system was in the US and the lowest was in the Netherlands ($46,622 and $26,615 per QALY), respectively.
CONCLUSION
In all selected countries, CardioMEMS is a cost-effective method for monitoring and managing pulmonary artery pressures in HF patients. Strategies such as CardioMEMS, which decrease the rate of hospitalization, are likely to be only more cost-effective in the future.
PubMed: 37123330
DOI: 10.47176/mjiri.37.16