Background—
Atrial fibrillation is characterized by progressive atrial structural and electrical changes (atrial remodeling) that favor arrhythmia recurrence and maintenance. Reduction of L-type Ca
2+
current (
I
Ca,L
) density is a hallmark of the electrical remodeling. Alterations in atrial microRNAs could contribute to the protein changes underlying atrial fibrillation–induced atrial electrical remodeling. This study was undertaken to compare miR-21 levels in isolated myocytes from atrial appendages obtained from patients in sinus rhythm and with chronic atrial fibrillation (CAF) and to determine whether L-type Ca
2+
channel subunits are targets for miR-21.
Methods and Results—
Quantitative polymerase chain reaction analysis showed that miR-21 was expressed in human atrial myocytes from patients in sinus rhythm and that its expression was significantly greater in CAF myocytes. There was an inverse correlation between miR-21 and the mRNA of the α1c subunit of the calcium channel (CACNA1C) expression and
I
Ca,L
density. Computational analyses predicted that CACNA1C and the mRNA of the β2 subunit of the calcium channel (CACNB2) could be potential targets for miR-21. Luciferase reporter assays demonstrated that miR-21 produced a concentration-dependent decrease in the luciferase activity in Chinese Hamster Ovary cells transfected with CACNA1C and CACNB2 3′ untranslated region regions. miR-21 transfection in HL-1 cells produced changes in
I
Ca,L
properties qualitatively similar to those produced by CAF (ie, a marked reduction of
I
Ca,L
density and shift of the inactivation curves to more depolarized potentials).
Conclusions—
Our results demonstrated that CAF increases miR-21 expression in enzymatically isolated human atrial myocytes. Moreover, it decreases
I
Ca,L
density by downregulating Ca
2+
channel subunits expression. These results suggested that this microRNA could participate in the CAF-induced
I
Ca,L
downregulation and in the action potential duration shortening that maintains the arrhythmia.
At present, there is unclear evidence on the need for a negative SARS‐CoV‐2 RT‐PCR for donors with a history of COVID‐19 prior to transplantation
1,2
. We report two cases of heart and liver recipients from a donor with previous documented COVID‐19 and positive RT‐PCR at time of transplantation.
Objectives
(1) To describe the incidence, clinical characteristics, treatment and outcome of Aspergillus Endocarditis (AE) in a nationwide multicentric cohort (GAMES). (2) To compare the AE cases of the GAMES cohort, with the AE cases reported in the literature since 2010. (3) To identify variables related to mortality.
Methods
We recruited 10 AE cases included in the GAMES cohort (January 2008‐December 2018) and 51 cases from the literature published from January 2010 to July 2019.
Results
4528 patients with infectious endocarditis (IE) were included in the GAMES cohort, of them 10 (0.2%) were AE. After comparing our 10 cases with the 51 of the literature, no differences were found. Analysing the 61 AE cases together, 55.7% were male, median age 45 years. Their main underlying conditions were as follows: prosthetic valve surgery (34.4%) and solid organ transplant (SOT) (19.7%). Mainly affecting mitral (36.1%) and aortic valve (29.5%). Main isolated species were as follows: Aspergillus fumigatus (47.5%) and Aspergillus flavus (24.6%). Embolisms occurred in 54%. Patients were treated with antifungals (90.2%), heart surgery (85.2%) or both (78.7%).
Overall, 52.5% died. A greater mortality was observed in immunosuppressed patients (59.4% vs. 24.1%, OR = 4.09, 95%CI = 1.26–13.19, p = .02), and lower mortality was associated with undergoing cardiac surgery plus azole therapy (28.1% vs. 65.5%, OR = 0.22, 95%CI = 0.07–0.72, p = .01).
Conclusions
AE accounts for 0.2% of all IE episodes of a national multicentric cohort, mainly affecting patients with previous valvular surgery or SOT recipients. Mortality remains high especially in immunosuppressed hosts and azole‐based treatment combined with surgical resection are related to a better outcome.
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