Study of Cellular Aging in a Cohort of Patients with Heart Failure.

INTRODUCTION: Cellular senescence and fibrosis are important phenomena in the development of heart failure (HF). These processes are closely related to telomeric length (TL). AIM: To assess cellular senescence in HF through the study of TL in peripheral blood mononuclear cells (PBMCs). METHODS: Using real-time PCR, TL was measured in PBMCs from 20 patients diagnosed with HF, aged between 51 and 77 years (50% males). Ten patients had HF with reduced ejection fraction (HFrEF) and ten had preserved EF (HFpEF). TL was measured in 20 healthy controls matched by age and gender. Obtained values were compared with an internal control, the 36B4 gene, which never modifies its expression, and correlated with the clinical parameters. RESULTS: TL mean was 1327 in patients with HF (95% CI 1309-1344) compared to 1286 (95% CI 1264-1308) in controls (p = 0.005). No differences were found when studying the correlation of telomere size with subgroups by gender, left ventricle ejection fraction (LVEF), presence of ischemic heart disease, smoking, Chronic Obstructive Pulmonary Disease (COPD), NYHA stage, degree of renal function or number of hospital admissions in the previous year. A significant and negative correlation was found between age and renal function (r = - 0.544, p < 0.05), as well as LVEF and NT-proBNP values (ρ = - 0.475, p < 0.05). CONCLUSIONS: TL is shorter in patients with HF when compared with age and gender balanced controls. The shortening of TL is independent of age, gender and degree of kidney function, and does not correlate with LVEF decrease or functional status.

Convalescent Plasma for COVID-19: A multicenter, randomized clinical trial

BackgroundPassive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is lacking. MethodsWe conducted a multi-center, randomized clinical trial in patients hospitalized for COVID-19. All patients received standard of care treatment, including off-label use of marketed medicines, and were randomized 1:1 to receive one dose (250-300 mL) of CP from donors with IgG anti-SARS-CoV-2. The primary endpoint was the proportion of patients in categories 5, 6 or 7 of the COVID-19 ordinal scale at day 15. ResultsThe trial was stopped after first interim analysis due to the fall in recruitment related to pandemic control. With 81 patients randomized, there were no patients progressing to mechanical ventilation or death among the 38 patients assigned to receive plasma (0%) versus 6 out of 43 patients (14%) progressing in control arm. Mortality rates were 0% vs 9.3% at days 15 and 29 for the active and control groups, respectively. No significant differences were found in secondary endpoints. At inclusion, patients had a median time of 8 days (IQR, 6-9) of symptoms and 49,4% of them were positive for anti-SARS-CoV-2 IgG antibodies. ConclusionsConvalescent plasma could be superior to standard of care in avoiding progression to mechanical ventilation or death in hospitalized patients with COVID-19. The strong dependence of results on a limited number of events in the control group prevents drawing firm conclusions about CP efficacy from this trial. (Funded by Instituto de Salud Carlos III; NCT04345523).