Citations

Background: Persistent atrial fibrillation (AF) presents a significant management challenge, particularly in patients with concurrent heart failure. The effectiveness of catheter ablation compared to medical therapy for these patients remains under debate. Aim: This meta-analysis aims to evaluate the outcomes of catheter ablation versus medical therapy for managing persistent AF. Research Question: How does catheter ablation compare to medical therapy in managing persistent AF considering outcomes like arrhythmia recurrence, hospitalizations, cardiac function, exercise capacity, and mortality? Methods: We performed a meta-analysis of randomized controlled trials (RCTs) comparing catheter ablation with medical therapy in patients with persistent AF. Data sources included PubMed, Embase, Cochrane Library, Clinicaltrial.gov, Google Scholar, and CINAHL/EBSCOHOST, with studies selected based on predefined inclusion criteria. Primary outcomes assessed were recurrence of atrial arrhythmias, hospitalizations, changes in left ventricular ejection fraction (LVEF), changes in 6-minute walk test (6MWT) distance, and all-cause mortality. The data extraction was done using a spreadsheet, and the data analysis was done using RevMan 5.4.1: for meta-analysis Results: A total of 10 RCTs involving 1812 patients were included in the analysis. Compared to medical therapy, catheter ablation significantly reduced the recurrence of atrial arrhythmias (risk ratio [RR] = 0.43, 95% confidence interval [CI]: 0.29-0.63, P < 0.0001). Hospitalization rates due to heart failure were also lower in the ablation group (RR = 0.57, 95% CI: 0.44-0.73, P < 0.001). Improvements in LVEF were observed with a mean difference (MD) of 5.98% (95% CI: 3.81% to 8.15%, P < 0.00001). The performance on the 6MWT was better in the catheter ablation group, with an MD of 28.83 meters (95% CI: 8.61 to 49.05 meters, P = 0.005). Additionally, catheter ablation was associated with a reduction in all-cause mortality (RR = 0.60, 95% CI: 0.45-0.80, P = 0.00006). Conclusion: This meta-analysis demonstrates that catheter ablation is superior to medical therapy in managing persistent atrial fibrillation. Catheter ablation offers significant benefits in reducing atrial arrhythmia recurrence, lowering hospitalization rates, improving cardiac function and exercise capacity, and reducing mortality. These findings support the consideration of catheter ablation as a preferred treatment strategy for patients with persistent AF.

Background: The new Global definition of ARDS recently introduced a subgroup known as non-intubated ARDS. This study aimed to assess the risk of progression from noninvasive oxygen support to intubation and ARDS severity based on the S pO 2 /F IO 2 among non-intubated subjects with ARDS. Methods: This retrospective study included subjects with COVID-19 admitted to 7 hospitals (5 in the United States and 2 in Argentina) from January 2020–January 2023. Subjects meeting the new non-intubated ARDS definition (high-flow nasal cannula [HFNC] with an S pO 2 /F IO 2 ≤315 [with S pO 2 ≤97%] or a P aO 2 /F IO 2 ≤300 mm Hg while receiving ≥30 L/min O 2 via HFNC) were included. The study evaluated the proportion of subjects who progressed to intubation, severity levels using the S pO 2 /F IO 2 cutoff proposed in the new ARDS definition, and mortality. Results: Nine hundred sixty-five non-intubated subjects with ARDS were included, of whom 27% ( n = 262) progressed to meet the Berlin criteria within a median of 3 d (interquartile range 2–6). The overall mortality was 23% (95% CI 20–26) ( n = 225), and among subjects who progressed to the Berlin criteria, it was 37% (95% CI 31–43) ( n = 98). Additionally, the worst S pO 2 /F IO 2 within 1 d of ARDS diagnosis was correlated with mortality, with mortality rates of 26% (95% CI 23–30) ( n = 177) for subjects with S pO 2 /F IO 2 ≤148, 17% (95% CI 12–23) ( n = 38) for those with S pO 2 /F IO 2 between 149–234, and 16% (95% CI 8–28) ( n = 10) for subjects maintaining an S pO 2 /F IO 2 higher than 235 ( P < .001). Conclusions: The non-intubated ARDS criteria encompassed a broader spectrum of subjects with lower in-hospital mortality compared to the Berlin criteria. The S pO 2 /F IO 2 and ARDS severity cutoff proposed in the new Global ARDS definition were valuable predictors of in-hospital mortality in these subjects.

Extracorporeal membrane oxygenation (ECMO) is often used in acute respiratory distress syndrome (ARDS) with refractory hypoxemia. There is limited literature highlighting the development of right ventricular (RV) failure while on ECMO. We conducted a retrospective multicenter observational study including 70 patients who were placed on veno-venous (VV)-ECMO for respiratory failure at Mayo Clinic, Jacksonville, and Mayo Clinic, Rochester, between January 2018 and June 2022 and had at least two post-ECMO transthoracic echoes. The primary outcomes were the incidence and progression of RV dysfunction and dilatation. The secondary outcome was in-patient mortality. Among 70 patients in our cohort, 60.6% had a normal RV function at the time of ECMO placement, whereas only 42% had a normal RV function at the second post-ECMO echo. On multinomial regression, a moderate decrease in RV function was associated with ECMO flow (odds ratio [OR] = 2.32, p = 0.001) and ECMO duration (OR = 1.01, p = 0.01). A moderately dilated RV size was also associated with ECMO flow (OR = 2.62, p < 0.001) and ECMO duration (OR = 1.02, p = 0.02). An increasing degree of RV dysfunction was associated with worse outcomes. Our study showed that the increasing duration and flow of VV-ECMO correlated with progressive RV dilatation and dysfunction, which were associated with poor survival.

AbstractBackgroundPrecursor plasma cell disorders such as monoclonal gammopathy of undetermined significance (MGUS) always precede the development of active malignancies such as multiple myeloma (MM). There is a need for novel biomarkers to identify those patients with such precursor plasma cell disorders who rapidly progress to MM. Plasma‐derived extracellular vesicles (EVs) may serve as a reservoir of potential biomarkers that can shed light on the pathogenesis and disease biology of MM.MethodsThis study isolated small EVs (SEVs) and large EVs (LEVs) from the platelet‐poor peripheral blood plasma of MGUS (n = 9) and MM (n = 12) patients using the size exclusion chromatography‐based method and evaluated their proteome using a label‐free proteomics workflow.ResultsIn total, 2055 proteins were identified in SEVs, while 2794 proteins were identified in LEVs. The transferrin receptor (or CD71) protein was upregulated in both populations of EVs derived from MM patients compared to MGUS patients and was of prognostic significance. Similarly, three isoforms of serum amyloid A (SAA) protein, SAA1, SAA2, and SAA4, were also highly upregulated in SEVs within MM patients relative to MGUS patients. Finally, CD40 expression was also higher in the LEVs derived from MM patients than in MGUS patients.ConclusionsThis study demonstrates the feasibility of successfully isolating both SEVs and LEVs from the peripheral blood of patients with plasma cell disorders and quantifying protein biomarkers within these EVs that could be of prognostic and diagnostic interest.

Abstract Background Myocarditis is an inflammation of the heart muscle most often caused by an immune response to viral infections. Sex differences in the immune response during myocarditis have been well described but upstream mechanisms in the heart that might influence sex differences in disease are not completely understood. Methods Male and female BALB/c wild type mice received an intraperitoneal injection of heart-passaged coxsackievirus B3 (CVB3) or vehicle control. Bulk-tissue RNA-sequencing was conducted to better understand sex differences in CVB3 myocarditis. We performed enrichment analysis to understand sex differences in the transcriptional landscape of myocarditis and identify candidate transcription factors that might drive sex differences in myocarditis. Results The hearts of male and female mice with myocarditis were significantly enriched for pathways related to an innate and adaptive immune response compared to uninfected controls. When comparing females to males with myocarditis, males were enriched for inflammatory pathways and gene changes that suggested worse mitochondrial transcriptional support (e.g., mitochondrial electron transport genes). In contrast, females were enriched for pathways related to mitochondrial respiration and bioenergetics, which were confirmed by higher transcript levels of master regulators of mitochondrial function including peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1α), nuclear respiratory factor 1 (NRF1) and estrogen-related receptor alpha (ERRα). TRANSFAC analysis identified ERRa as a transcription factor that may mediate sex differences in mitochondrial function during myocarditis. Conclusions Master regulators of mitochondrial function were elevated in females with myocarditis compared to males and may promote sex differences in mitochondrial respiratory transcript expression during viral myocarditis resulting in less severe myocarditis in females following viral infection.

Introduction: Sepsis and its associated systemic inflammatory response syndrome in the heart can lead to septic cardiomyopathy. We aim to explore new onset cardiac dysfunction in septic shock patients and its association of right heart dysfunction with hospital outcomes. Hypothesis: Early development of correct ventricular abnormalities due to septic shock may lead to worse hospital outcomes. Methods: We conducted a retrospective study of 102 patients who were hospitalized at the Mayo Clinic between August 2018 and September 2022 with septic shock and had at least one pre-sepsis echo (within one year before admission) and one post-sepsis echo (within seven days of access). Information on patient demographics, comorbidities, echo parameters, and outcomes was collected from our sepsis database and retrospective chart review. Categorical variables were described as percentages and compared by Chi-square test, and continuous variables as medians and compared using an independent sample t-test. Statistical analysis was performed using BlueSky Statistics v10.3.1. Results: Our study included 102 patients with a median age of 68 (55, 78) years, the majority being men (68%) and Caucasians (80%). Between pre- and post-sepsis echos, there was a noticeable decrease in LVEF (60% vs 50.5 %; p=0.002). Moreover, there was an increase in reduced RV function (31.6% vs. 62.6%, p<0.001), reduced LV function (56.5% vs. 85.2%, p=0.048), and RV dilatation (35.8% vs. 51.5%, p=0.03). There was also a noticeable decrease in IVC collapsibility of more than 50% (65.9% vs 22.9%, p<0.001). There was no significance in terms of demographics, comorbidities, and baseline vitals and labs among patients with RV dysfunction and without RV dysfunction except for a lower LVEF (49% vs 62 %, p= 0.004) and decreased >50 % IVC collapsibility (14.5% vs 48%, p=0.005) in RV dysfunction group. We found no differences in hospital mortality, ICU and hospital LOS, or mechanical ventilation requirements amongst patients with RV abnormalities in function and size. Conclusions: Our retrospective study shows that abnormalities in RV function and RV size are commonly observed in the initial week of septic shock. However, such RV abnormalities did not translate into worse hospital outcomes.