Biologically derived epicardial patch induces macrophage mediated pathophysiologic repair in chronically infarcted swine hearts

There are nearly 65 million people with chronic heart failure (CHF) globally, with no treatment directed at the pathologic cause of the disease, the loss of functioning cardiomyocytes. We have an allogeneic cardiac patch comprised of cardiomyocytes and human fibroblasts on a bioresorbable matrix. This patch increases blood flow to the damaged heart and improves left ventricular (LV) function in an immune competent rat model of ischemic CHF. After 6 months of treatment in an immune competent Yucatan mini swine ischemic CHF model, this patch restores LV contractility without constrictive physiology, partially reversing maladaptive LV and right ventricular remodeling, increases exercise tolerance, without inducing any cardiac arrhythmias or a change in myocardial oxygen consumption. Digital spatial profiling in mice with patch placement 3 weeks after a myocardial infarction shows that the patch induces a CD45pos immune cell response that results in an infiltration of dendritic cells and macrophages with high expression of macrophages polarization to the anti-inflammatory reparative M2 phenotype. Leveraging the host native immune system allows for the potential use of immunomodulatory therapies for treatment of chronic inflammatory diseases not limited to ischemic CHF. © 2023, The Author(s).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Regional collaboration to improve atrial fibrillation care: Preliminary data from the Netherlands heart network

Background: Guideline non-adherence and variations in therapeutic and diagnostic trajectories result in suboptimal atrial fibrillation (AF) treatments. Large academic and referral hospitals demonstrated positive effects of dedicated outpatient AF clinics. Although similar results have not been indicated in (small) non-academic hospitals yet, ample opportunities are present when collaboration is initiated on a regional level. Therefore, this study assesses the effectiveness of outpatient AF clinics in a collaborative region in the Netherlands. Methods: For this study baseline and 6 months follow-up data of a prospective cohort including newly or recently diagnosed AF-patients of 4 hospitals involved in the Netherlands Heart Network are used. From January’15 to March’16 patient relevant outcome measures (ie EHRA score, stroke, major bleedings, hospitalizations, serious adverse effects of medication, and mortality) are gathered. Descriptive and regression analyses are performed to assess the effectiveness of outpatient AF clinics. Results: In the analyses 448 AF-patients were included. After 6 months, significant improvements regarding EHRA score (P < 0.01), hypertension (P < 0.01), and type of AF (P < 0.01) were indicated. Results of the patient relevant outcomes showed that AF-patients were hospitalized 23 times, no major bleedings and 2 strokes occurred. Furthermore, 0 AF-patients reported serious adverse effects of medication and no AF-patients deceased. Conclusions: Collaboration between cardiologists in a regional setting permits further improvement of AF care. Therefore, such quality targets are not exclusively reserved to large academic or referral hospitals. Although promising, future research should put effort in measuring the effectiveness of the outpatient AF clinics also on the long run

Sex Differences in Long COVID.

IMPORTANCE: A substantial number of individuals worldwide experience long COVID, or post-COVID condition. Other postviral and autoimmune conditions have a female predominance, but whether the same is true for long COVID, especially within different subgroups, is uncertain. OBJECTIVE: To evaluate sex differences in the risk of developing long COVID among adults with SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER)-Adult cohort, which consists of individuals enrolled in and prospectively followed up at 83 sites in 33 US states plus Washington, DC, and Puerto Rico. Data were examined from all participants enrolled between October 29, 2021, and July 5, 2024, who had a qualifying study visit 6 months or more after their initial SARS-CoV-2 infection. EXPOSURE: Self-reported sex (male, female) assigned at birth. MAIN OUTCOMES AND MEASURES: Development of long COVID, measured using a self-reported symptom-based questionnaire and scoring guideline at the first study visit that occurred at least 6 months after infection. Propensity score matching was used to estimate risk ratios (RRs) and risk differences (95% CIs). The full model included demographic and clinical characteristics and social determinants of health, and the reduced model included only age, race, and ethnicity. RESULTS: Among 12 276 participants who had experienced SARS-CoV-2 infection (8969 [73%] female; mean [SD] age at infection, 46 [15] years), female sex was associated with higher risk of long COVID in the primary full (RR, 1.31; 95% CI, 1.06-1.62) and reduced (RR, 1.44; 95% CI, 1.17-1.77) models. This finding was observed across all age groups except 18 to 39 years (RR, 1.04; 95% CI, 0.72-1.49). Female sex was associated with significantly higher overall long COVID risk when the analysis was restricted to nonpregnant participants (RR, 1.50; 95%: CI, 1.27-1.77). Among participants aged 40 to 54 years, the risk ratio was 1.42 (95% CI, 0.99-2.03) in menopausal female participants and 1.45 (95% CI, 1.15-1.83) in nonmenopausal female participants compared with male participants. CONCLUSIONS AND RELEVANCE: In this prospective cohort study of the NIH RECOVER-Adult cohort, female sex was associated with an increased risk of long COVID compared with male sex, and this association was age, pregnancy, and menopausal status dependent. These findings highlight the need to identify biological mechanisms contributing to sex specificity to facilitate risk stratification, targeted drug development, and improved management of long COVID