Treating Pulmonary Arterial Hypertension With Sotatercept: A Meta-Analysis.

Pulmonary arterial hypertension (PAH) results from proliferative remodeling and narrowing of the pulmonary vasculature. Sotatercept is a first-in-class fusion protein that has recently garnered attention for showing improvements in patients with PAH. This meta-analysis of randomized controlled trials (RCTs) assesses the overall efficacy of Sotatercept in treating PAH. PubMed, Google Scholar, and Clinicaltrials.gov were searched using relevant keywords and MeSH terms. Studies were included if RCTs compared Sotatercept with placebo in patients with PAH. Our comprehensive literature search yielded 3,127 results, of which two RCTs with 429 patients were included in this meta-analysis. The patients were on background therapy for PAH. Results of the meta-analysis show that when compared with placebo, Sotatercept improved the six-minute walk distance (mean difference [MD] 34.99; 95% confidence interval [CI] 19.02-50.95; P < 0.0001), the World Health Organization (WHO) functional class (odds ratio [OR] 2.50; 95% CI 1.50-4.15; P = 0.0004), and pulmonary vascular resistance (PVR, MD -253.90; 95% CI -356.05 to -151.75; P < 0.00001). However, reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP, MD -1563.14; 95% CI -3271.93 to 145.65; P = 0.07) was not statistically significant in the Sotatercept group versus placebo. In conclusion, Sotatercept improves the six-minute walk distance, WHO functional class, and PVR in patients with PAH receiving background therapy. However, the effect on NT-proBNP levels was not statistically significant. More research is needed to assess the clinical relevance of these findings.

Safety and efficacy of clot-dissolving therapies for submassive pulmonary embolism: A network meta-analysis of randomized controlled trials.

BACKGROUND: Acute pulmonary embolism (PE) is a serious condition that needs quick and effective treatment. Anticoagulation therapy is the usual care for most PE patients but may not work well for higher-risk ones. Thrombolysis breaks the clot and improves blood flow. It can be given systemically or locally. Ultrasound-assisted catheter-directed thrombolysis (USAT) is a new technique that boosts clot-busting drugs. This network meta-analysis compares death, bleeding, and benefits of four treatments in acute submassive PE. METHODS: We comprehensively searched relevant databases up to July 2023 for RCTs. The outcomes encompassed all-cause mortality, major and minor bleeding, PE recurrence, and hospital stay duration. Bayesian network meta-analysis computed odds ratios (OR) and 95 % CI estimates. RESULTS: In this network meta-analysis of 23 RCTs involving 2521 PE patients, we found that SCDT had the most favorable performance for mortality, as it had the lowest odds ratio (OR) among the four interventions (OR 5.41e-42; 95 % CI, 5.68e-97, 1.37e-07). USAT had the worst performance for major bleeding, as it had the highest OR among the four interventions (OR 4.73e+04; 95 % CI, 1.65, 9.16e+13). SCDT also had the best performance for minor bleeding, as it had the lowest OR among the four interventions (OR 5.68e-11; 95 % CI, 4.97e-25, 0.386). CONCLUSION: Our meta-analysis suggests that SCDT is the most effective treatment intervention in improving the risks of All-cause mortality and bleeding. Thrombolytic therapy helps in improving endpoints including the risk of PE recurrence and the duration of hospital stay.

Beyond biventricular pacing: Exploring the advantages of his-bundle pacing and left bundle branch pacing in heart failure-A systematic review and meta-analysis.

BACKGROUND: This meta-analysis compares His-Purkinje system pacing (HPSP), a novel cardiac resynchronization therapy (CRT) technique that targets the intrinsic conduction system of the heart, with conventional biventricular pacing (BiVP) in heart failure (HF) patients with left ventricular (LV) dysfunction and dyssynchrony. METHODS: We searched multiple databases up to May 2023 and identified 18 studies (five randomized controlled trials and 13 observational studies) involving 1291 patients. The outcome measures were QRS duration, left ventricular ejection fraction (LVEF) improvement, left ventricular end-diastolic diameter (LVEDD) change, HF hospitalization, and New York Heart Association (NYHA) functional class improvement. We used a random-effects model to calculate odds ratios (OR), and mean differences (MD) with 95% confidence intervals (CI). We also assessed the methodological quality of the studies. RESULTS: The mean LVEF was 30.7% and the mean follow-up duration was 8.1 months. Among LBBP, HBP, and BiVP, HBP provided the shortest QRS duration [MD: -18.84 ms, 95% CI: -28.74 to -8.94; p = 0.0002], while LBBP showed the greatest improvement in LVEF [MD: 5.74, 95% CI: 2.74 to 7.46; p < 0.0001], LVEDD [MD: -5.55 mm, 95% CI: -7.51 to -3.59; p < 0.00001], and NYHA functional class [MD: -0.58, 95% CI: -0.80 to --0.35; p < 0.00001]. However, there was no significant difference in HF hospitalization between HPSP and BiVP. CONCLUSION: LBBP as modality of HPSP demonstrated superior outcomes in achieving electrical ventricular synchrony and systolic function, as well as alleviating HF symptoms, compared to other pacing techniques.

Association between e-cigarette use and myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: The popularity of e-cigarettes has risen dramatically over the last few years, particularly among the younger population. Although the use of combustible cigarettes has established evidence to be associated with the development of several adverse cardiopulmonary diseases, the investigations regarding the prospective long-term effects of e-cigarette use on the cardiovascular system have just begun. We set to investigate if there is an association between the history of MI and e-cigarette use among smokers and non-smokers? METHODS: The current review aims to assess the association of myocardial infarction with e-cigarette consumption. PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials (CENTRAL) were queried up to October 2022 to identify articles assessing the incidence of myocardial infarction among e-cigarette users. Data were meta-analyzed using a random-effects model to derive odds ratios (OR) and 95% confidence intervals. RESULTS: Nine studies involving 984,764 patients were included. The mean age of e-cigarette smokers was less than the controls, and female participants dominated the sample size. E-cigarette users were associated with increased odds of MI than non-users [OR = 1.44; 95% CI (1.22, 1.74); P < 0.0001]. Dual users were also associated with increased odds of MI with large effect when compared to non-users [OR = 4.04; 95% CI (3.40, 4.81); P < 0.00001]. CONCLUSIONS: Dual use is associated with an increased risk of MI than e-cigarette use only. Similarly, dual and solely e-cigarette consumption patterns of nicotine delivery are at a higher risk of MI than non-smokers.

Efficacy of anti-CD3 monoclonal antibodies in delaying the progression of recent-onset type 1 diabetes mellitus: A systematic review, meta-analyses and meta-regression.

AIM: Type 1 diabetes mellitus is widely recognized as a chronic autoimmune disease characterized by the pathogenic destruction of beta cells, resulting in the loss of endogenous insulin production. Insulin administration remains the primary therapy for symptomatic treatment. Recent studies showed that disease-modifying agents, such as anti-CD3 monoclonal antibodies, have shown promising outcomes in improving the management of the disease. In late 2022, teplizumab received approval from the US Food and Drug Administration (FDA) as the first disease-modifying agent for the treatment of type 1 diabetes. This review aims to evaluate the clinical evidence regarding the efficacy of anti-CD3 monoclonal antibodies in the prevention and treatment of type 1 diabetes. METHODS: A comprehensive search of PubMed, Google Scholar, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) was conducted up to December 2022 to identify relevant randomized controlled trials. Meta-analysis was performed using a random-effects model, and odds ratios with 95% confidence intervals (CIs) were calculated to quantify the effects. The Cochrane risk of bias tool was employed for quality assessment. RESULTS: In total, 11 randomized controlled trials involving 1397 participants (908 participants in the intervention arm, 489 participants in the control arm) were included in this review. The mean age of participants was 15 years, and the mean follow-up time was 2.04 years. Teplizumab was the most commonly studied intervention. Compared with placebo, anti-CD3 monoclonal antibody treatment significantly increased the C-peptide concentration in the area under the curve at shorter timeframes (mean difference = 0.114, 95% CI: 0.069 to 0.159, p = .000). Furthermore, anti-CD3 monoclonal antibodies significantly reduced the patients' insulin intake across all timeframes (mean difference = -0.123, 95% CI: -0.151 to -0.094, p < .001). However, no significant effect on glycated haemoglobin concentration was observed. CONCLUSION: The findings of this review suggest that anti-CD3 monoclonal antibody treatment increases endogenous insulin production and improves the lifestyle of patients by reducing insulin dosage. Future studies should consider the limitations, including sample size, heterogeneity and duration of follow-up, to validate the generalizability of these findings further.

Left Bundle Branch Pacing: A Paradigm Shift in Physiological Pacing for Patients With Atrioventricular Block and Preserved Left Ventricular Systolic Function, A Systematic Review and Meta-analysis.

His-Purkinje conduction system pacing (HPCSP) via His bundle pacing (HBP) and Left Bundle Branch Pacing (LBBP) offer a physiological approach to pacing by restoring normal ventricular activation. This meta-analysis compares the feasibility, outcomes, and success rates of HBP and LBBP in patients with atrioventricular block (AVB) and preserved left ventricular function. A systematic search identified studies comparing LBBP with HBP in AVB patients with preserved systolic function. Primary outcomes included QRS duration, success rates, pacing threshold, and improvement in R-wave amplitudes. Secondary outcomes were procedure time and fluoroscopy time. Random-effects models calculated odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI). Methodological quality was assessed using the Newcastle-Ottawa scale. Among 382 screened articles, seven observational studies involving 1035 patients were analyzed. The mean age was 69.9 years, the mean LVEF was 59.3%, and the average follow-up duration was 8.7 months. LBBP showed higher R-wave amplitudes (MD 7.88, 95% CI 7.26 to 8.50, P < 0.0001) and lower pacing thresholds (MD -0.64, 95% CI -0.81 to -0.47, P < 0.0001) compared to HBP. LBBP had shorter procedure time (MD -17.81, 95% CI -30.44 to -5.18, P = 0.006) and reduced fluoroscopy time (MD -5.39, 95% CI -8.81 to -1.97, P = 0.002). No significant differences were observed in QRS duration or success rates. LBBP offers advantages over HBP, including improved electrical activation, lower pacing thresholds, and shorter procedure and fluoroscopy times. Success rates and QRS duration reductions were comparable between LBBP and HBP. These findings support LBBP as a feasible and effective alternative to HBP in AVB patients with preserved systolic function.

Clinical Efficacy and Safety of Bempedoic Acid in High Cardiovascular Risk Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Bempedoic acid (BA) is the new addition to lipid-lowering medications. This systematic review and meta-analysis of randomized controlled trials (RCTs) assess the clinical efficacy and safety of BA in high cardiovascular (CV) risk patients along with its effects on low-density lipoprotein cholesterol (LDL-C) and total cholesterol. PubMed, Google Scholar, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials.gov were searched for RCTs comparing BA with placebo, reporting CV outcomes. Seven RCTs with a total of 17,816 patients were selected for the analysis. Results showed that BA significantly reduced the risk of MACE (RR 0.87, 95% CI 0.80-0.94; P = 0.007), nonfatal myocardial infarction (RR 0.73; 95% CI 0.62-0.85; P < 0.0001), hospitalization for unstable angina (RR 0.69; 95%CI 0.54-0.88; P = 0.003), coronary and noncoronary revascularization (RR 0.82; 95%CI 0.73-0.92; P = 0.0007) and (RR 0.41; 95%CI 0.18-0.96; P = 0.04), respectively. However, BA increased the risk of gout (RR 1.55; 95% CI 1.26-1.90; P < 0.0001), hyperuricemia (RR 1.94; 95% CI 1.73-2.18; P < 0.00001) and worsening renal function (RR 1.34; 95%CI 1.21-1.48; P < 0.00001). BA also reduced LDL-C (MD -22.38%; 95% CI -25.94 to - 18.82; P < 0.00001) and total cholesterol (MD -13.86%; 95% CI -15.82 to -11.91; P < 0.0000) compared with placebo. Bempedoic acid is an addition to the arsenal of lipid-lowering drugs used in patients that are statin intolerant or need additional lipid-lowering therapy.

Monkeypox Virus and Other Emerging Outbreaks: An Overview and Future Perspective.

Monkeypox (MPX) is a zoonotic disease caused by the MPX virus from the poxviridae family of orthopoxviruses. Typically, endemic in central and west Africa, it has now become a matter of concern since cases have been reported in non-endemic countries around mid-June 2022, especially in the European region, with the transmission not related to travel. The diagnosis is made by PCR testing of the skin lesions. Even though treatment is symptomatic, antiretrovirals, such as tecovirimat, are used in severe cases. Vaccination with second and third generation vaccines is approved for prophylaxis in high risk individuals. Unfortunately, these options of treatment and prevention are only available in high income countries at the moment. This review, through a thorough literature search of articles from 2017 onward, focuses on epidemiology, clinical manifestations, challenges, treatment, prevention and control of MPX virus and how they can be corelated with other viral outbreaks including COVID-19, Acute Hepatitis of unknown origin, Measles and Dengue, to better predict and therefore prevent its transmission. The previous COVID-19 pandemic increased the disease burden on healthcare infrastructure of low-middle income countries, therefore, this recent MPX outbreak calls for a joint effort from healthcare authorities, political figures, and NGOs to combat the disease and prevent its further spread not only in high income but also in middle- and low-income countries.

Polypill Therapy in Cardiovascular Disease: A Meta-Analysis of Randomized Controlled Trials.

The effectiveness of polypill therapy in the prevention and treatment of cardiovascular disorders is still unclear. This meta-analysis aimed to assess the efficacy of polypill therapy in reducing cardiovascular risk factors. We conducted a systematic search of PubMed, Cochrane CENTRAL, SCOPUS, and Google Scholar for randomized controlled trials (RCTs) that evaluated polypill therapy for cardiovascular diseases, hypertension, or dyslipidemia. We included 18 RCTs with a total of 20,463 participants in our analysis. Pooled effect estimates were reported as Odds ratios (ORs) with a 95% confidence interval (CI) using a random-effects model. Polypill therapy was associated with a statistically significant reduction in systolic blood pressure (SBP) (OR: -0.33, 95% CI [-0.64, -0.03]; P-value = 0.03), diastolic blood pressure (DBP) (OR: -0.70, 95% CI [-1.20, -0.21]; P-value = 0.005), and total cholesterol level (OR: -1.25, 95% CI [-1.82, -0.68]; P-value < 0.0001). Polypill therapy also showed improved adherence (OR 2.18, 95% CI [1.47, 3.24]; P-value = 0.0001). However, there was no statistically significant benefit in the reduction of all-cause mortality, major cardiovascular events, and LDL-c levels. The use of polypill therapy is associated with a statistically significant reduction in SBP, DBP, and total cholesterol levels, as well as improved adherence. Further research is needed to determine its impact on hard clinical outcomes such as mortality and major cardiovascular events.