Kostantinos Vlachos

As discussed in the Journal recently 1 the SARS-CoV-2, a new -Coronavirus, uses the Angiotensin Converting Enzyme-2 Receptor to enter airway cells. Viral endocytosis is mediated by several factors, including clathrin, the adaptor protein-2 complex (AP2) and the adaptor-associated kinase-1 (AAK1). 2 According to a recent report, 3 COVID-19, the disease caused by SARS-CoV-2, is characterized by three clinical patterns: no symptoms, mild to moderate disease, severe pneumonia requiring admission to Intensive Care Unit (ICU) in up to 31% of the patients. 3 Thus far, there is no specific therapy for COVID-19 infection. No benefit of lopinavir-ritonavir treatment resulted in a recent trial. 4 Hydroxychloroquine, currently used in view of its "in vitro" observed effect of reduction of viral replication, seems unsatisfactory. 5 Elevated proinflammatory cytokine/chemokine responses seem associated with respiratory failure. 3 Recently, tocilizumab, an interleukin-6 inhibitor, was reported as effective in patients with severe COVID-19 pneumonia. 6 Baricitinib, another inhibitor of cytokine-release, seems an interesting anti-inflammatory drug. It is a Janus kinase inhibitor (anti-JAK) licensed for the treatment of rheumatoid arthritis (RA) with good efficacy and safety records. 7 Moreover it seems to have anti-viral effects by its affinity for AP2-associated protein AAK1, reducing SARS-CoV-2 endocytosis. 8 On this basis, we assessed the safety of baricitinib therapy combined with lopinavir-ritonavir in moderate COVID-19 pneumonia patients and we evaluated its clinical impact.

Abstract Background Little is known regarding the characterization of electrical substrate in both atria in patients with atrial fibrillation (AF). Methods Eight consecutive patients undergoing AF ablation (five paroxysmal, three persistent) underwent electrical substrate characterization during sinus rhythm. Mapping of the left (LA) and right atrium (RA) was performed with the use of the HD Grid catheter (Abbott). Bipolar voltage maps were analyzed to search for low voltage areas (LVA), the following electrophysiological phenomena were assessed: (1) slow conduction corridors, and (2) lines of block. EGMs were characterized to search for fractionation. Electrical characteristics were compared between atria and between paroxysmal versus persistent AF patients. Results In the RA, LVAs were present in 60% of patients with paroxysmal AF and 100% of patients with persistent AF. In the LA, LVAs were present in 40% of patients with paroxysmal AF and 66% of patients with persistent AF. The areas of LVA in the RA and LA were 4.8±7.3 cm 2 and 7.8±13.6 cm 2 in patients with paroxysmal AF versus 11.7±3.0 cm 2 and 2.1±1.8 cm 2 in patients with persistent AF. In the RA, slow conduction corridors were present in 40.0% (paroxysmal AF) versus 66.7% (persistent AF) whereas in the LA, slow conduction corridors occurred in 20.0% versus 33.3% respectively (p = ns). EGM analysis showed more fractionation in persistent AF patients than paroxysmal (RA: persistent AF 10.8 vs. paroxysmal AF 4.7%, p = .036, LA: 10.3 vs. 4.1%, p = .108). Conclusion Bi‐atrial involvement is present in patients with paroxysmal and persistent AF. This is expressed by low voltage areas and slow conduction corridors whose extension progresses as the arrhythmia becomes persistent. This electrophysiological substrate demonstrates the important interplay with the pulmonary vein triggers to constitute the substrate for persistent arrhythmia.

INTRODUCTION: Electrogram (EGM) fractionation is often associated with diseased atrial tissue; however, mechanisms for fractionation occurring above an established threshold of 0.5 mV have never been characterized. We sought to investigate during sinus rhythm (SR) the mechanisms underlying bipolar EGM fractionation with high-density mapping in patients with atrial fibrillation (AF). METHODS: Forty-five patients undergoing AF ablation (73% paroxysmal, 27% persistent) were mapped at high density (18562 ± 2551 points) during SR (Rhythmia). Only bipolar EGMs with voltages above 0.5 mV were considered for analysis. When fractionation (> 40 ms and >4 deflections) was detected, we classified the mechanisms as slow conduction, wave-front collision, or a pivot point. The relationship between EGM duration and amplitude, and tissue anisotropy and slow conduction, was then studied using a computational model. RESULTS: Of the 45 left atria analyzed, 133 sites of EGM fragmentation were identified with voltages above 0.5 mV. The most frequent mechanism (64%) was slow conduction (velocity 0.45 m/s ± 0.2) with mean EGM voltage of 1.1 ± 0.5 mV and duration of 54.9 ± 9.4 ms. Wavefront collision was the second most frequent (19%), characterized by higher voltage (1.6 ± 0.9 mV) and shorter duration (51.3 ± 11.3 ms). Pivot points (9%) were associated with the highest degree of fractionation with 70.7 ± 6.6 ms and 1.8 ± 1 mV. In 10 sites (8%) fractionation was unexplained. The EGM duration was significantly different among the 3 mechanisms (p = .0351). CONCLUSION: In patients with a history of AF, EGM fractionation can occur at amplitudes > 0.5 mV when in SR in areas often considered not to be diseased tissue. The main mechanism of EGM fractionation is slow conduction, followed by wavefront collision and pivot sites.

Abstract Introduction Atrial fibrillation (AF) represents the most common arrhythmia in the postoperative setting. We aimed to investigate the incidence of postoperative AF (POAF) and determine its predictors, with a specific focus on inflammation markers. Methods We performed a retrospective single tertiary center cohort study including consecutive adult patients who underwent a major surgical procedure between January 2016 and January 2020. Patients were divided into four subgroups according to the type of surgery. Results Among 53,387 included patients (79.4% male, age 64.5 ± 9.5 years), POAF occurred in 570 (1.1%) with a mean latency after surgery of 3.4 ± 2.6 days. Ninety patients died (0.17%) after a mean of 13.7 ± 8.4 days. The 28‐day arrhythmia‐free survival was lower in patients undergoing lung and cardiovascular surgery ( p < .001). Patients who developed POAF had higher levels of C‐reactive protein (CRP) (0.70 ± 0.03 vs. 0.40 ± 0.01 log10 mg/dl; p < .001). In the multivariable Cox regression analysis, adjusting for confounding factors, CRP was an independent predictor of POAF [HR per 1 mg/dL increase in log‐scale = 1.81 (95% CI 1.18–2.79); p = .007]. Moreover, independent predictors of POAF were also age (HR/1 year increase = 1.06 (95% CI 1.04–1.08); I < .001), lung and cardiovascular surgery (HR 23.62; (95% CI 5.65–98.73); p < .001), and abdominal and esophageal surgery (HR 6.26; 95% CI 1.48–26.49; p = .013). Conclusions Lung and cardiovascular surgery had the highest risk of POAF in the presented cohort. CRP was an independent predictor of POAF and postsurgery inflammation may represent a major driver in the pathophysiology of the arrhythmia.