Influenza virus replication in cardiomyocytes drives heart dysfunction and fibrosis.

Cardiac dysfunction is a common complication of severe influenza virus infection, but whether this occurs due to direct infection of cardiac tissue or indirectly through systemic lung inflammation remains unclear. To test the etiology of this aspect of influenza disease, we generated a novel recombinant heart-attenuated influenza virus via genome incorporation of target sequences for miRNAs expressed in cardiomyocytes. Compared with control virus, mice infected with miR-targeted virus had significantly reduced heart viral titers, confirming cardiac attenuation of viral replication. However, this virus was fully replicative in the lungs and induced similar systemic inflammation and weight loss compared to control virus. The miR-targeted virus induced fewer cardiac conduction irregularities and significantly less fibrosis in mice lacking interferon-induced transmembrane protein 3 (IFITM3), which serve as a model for influenza-associated cardiac pathology. We conclude that robust virus replication in the heart is required for pathology, even when lung inflammation is severe.

Selective arterial temporary flow arrest with balloons during transvenous embolization for the treatment of brain arteriovenous malformations: a feasibility study with MRI-monitored adverse events.

BACKGROUND: The technique of endovascular transvenous embolization for brain arteriovenous malformations (AVMs) has emerged in the last 8 years as a very promising therapeutic alternative for otherwise incurable cases. Selective temporary flow arrest during transvenous endovascular embolization (TFATVE) is a novel adaptation of our previously described transvenous approach, which employs hyper-compliant balloons intra-arterially for the selective occlusion of arterial feeders during ethylene vinyl copolymer (EVOH) injection, in order to reduce intra-nidal pressure and increase nidi occlusion rates. METHODS: We performed a feasibility study of the TFATVE technique between January 2016 and April 2020. Consecutive patients were included. All patients had at least one axial brain MRI or CT in the first 48 hours following intervention, and at least one brain MRI scan within the first postoperative month, in order to detect both silent and clinically evident adverse events. Patients' demographics, angio-architectural characteristics, total injection and procedure times, angiographic and clinical outcomes were analyzed. RESULTS: 22 patients underwent TFATVE during transvenous endovascular treatment of brain AVMs. Among them, 86.4% were high Spetzler-Martin's grade. Good clinical outcome (modified Rankin Scale <2) was achieved in 95.5% of the cases, with 0% of procedure-related mortality and 4.5% of clinically significant, procedure-related morbidity. Total occlusion of the nidus was achieved in >90% of the cases at the end of the procedure and angiographic stability was achieved in all cases; 100% of the cases had angiographic cure at follow-up. CONCLUSIONS: TFATVE seems a safe and effective technique when conducted in carefully selected patients in highly specialized centers.