Claire Martin

INTRODUCTION: Radiofrequency (RF) lesion metrics are influenced by underlying parameters like RF power, duration, and contact force (CF), and utilization of lesion metric indices (ablation index [AI]) is a proposed strategy to predict lesion quality. The aim of this study was to analyze the influence of underlying parameters on lesion metrics of high-power short-duration (HPSD) and standard RF applications using an in silico and ex vivo model. METHODS AND RESULTS: An in silico simulation study was designed to simulate HPSD and standard ablations, in which ablation parameters could systematically be varied. For each simulated ablation process (n = 5732), the corresponding AI value was calculated. HPSD and standard RF settings were then applied in a porcine ex vivo model ( n = 120 lesions). The resulting lesion metrics were compared and analyzed regarding underlying parameters. RF applications of 50 W/13 seconds, 60 W/10 seconds, 70 W/7 seconds, and 80 W/6 seconds resulted in lesion volumes not significantly different from standard RF applications (30 W/30 seconds, P > 0.05). HPSD lesion diameters were significantly larger and lesion depths were significantly smaller ( P < 0.01) when compared with standard settings. Prolonging RF duration from 5 to 10 seconds resulted in a +27.5% increase, whereas a prolongation of RF duration from 35 to 40 seconds resulted in a +4.8% increase of AI value only. An increase of CF from 1 to 10 g resulted in a +73.0%, an increase of CF from 20 to 30 g resulted in a +10.1% increase of AI value. CONCLUSION: HPSD RF applications resulted in similar lesion volumes but significantly different lesion geometries when compared with standard setting RF applications.

We have investigated the potential for the p16-cyclin D-CDK4/6-retinoblastoma protein pathway to be exploited as a therapeutic target in melanoma. In a cohort of 143 patients with primary invasive melanoma, we used fluorescence in situ hybridization to detect gene copy number variations (CNVs) in CDK4, CCND1, and CDKN2A and immunohistochemistry to determine protein expression. CNVs were common in melanoma, with gain of CDK4 or CCND1 in 37 and 18% of cases, respectively, and hemizygous or homozygous loss of CDKN2A in 56%. Three-quarters of all patients demonstrated a CNV in at least one of the three genes. The combination of CCND1 gain with either a gain of CDK4 and/or loss of CDKN2A was associated with poorer melanoma-specific survival. In 47 melanoma cell lines homozygous loss, methylation or mutation of CDKN2A gene or loss of protein (p16(INK) (4A) ) predicted sensitivity to the CDK4/6 inhibitor PD0332991, while RB1 loss predicted resistance.

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.

AIMS: Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management, and outcome are sparse. METHODS AND RESULTS: This international multicentre registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation. A total of 553 729 catheter ablation procedures (radiofrequency: 62.9%, cryoballoon: 36.2%, other modalities: 0.9%) were performed, at 214 centres in 35 countries. In 78 centres 138 patients [0.025%, radiofrequency: 0.038%, cryoballoon: 0.0015% (P < 0.0001)] were diagnosed with an oesophageal fistula. Peri-procedural data were available for 118 patients (85.5%). Following catheter ablation, the median time to symptoms and the median time to diagnosis were 18 (7.75, 25; range: 0-60) days and 21 (15, 29.5; range: 2-63) days, respectively. The median time from symptom onset to oesophageal fistula diagnosis was 3 (1, 9; range: 0-42) days. The most common initial symptom was fever (59.3%). The diagnosis was established by chest computed tomography in 80.2% of patients. Oesophageal surgery was performed in 47.4% and direct endoscopic treatment in 19.8% and conservative treatment in 32.8% of patients. The overall mortality was 65.8%. Mortality following surgical (51.9%) or endoscopic treatment (56.5%) was significantly lower as compared to conservative management (89.5%) [odds ratio 7.463 (2.414, 23.072) P < 0.001]. CONCLUSION: Oesophageal fistula after catheter ablation of atrial fibrillation is rare and occurs mostly with the use of radiofrequency energy rather than cryoenergy. Mortality without surgical or endoscopic intervention is exceedingly high.

Tachycardiomyopathies (TCMP) are an important cause of left ventricular (LV) dysfunction that should be recognised by physicians as they are potentially reversible and have a significant impact on morbidity and prognosis. They are classically defined as the reversible impairment of ventricular function induced by persistent arrhythmia. However, it is becoming increasingly evident that they can be induced by atrial and ventricular ectopy promoting dyssynchrony and indeed the term ‘arrhythmia-induced cardiomyopathy’ is emerging to describe the phenomenon.1 2 A more current proposed definition highlights aetiology: ‘Atrial and/or ventricular dysfunction—secondary to rapid and/or asynchronous/irregular myocardial contraction, partially or completely reversed after treatment of the causative arrhythmia’ 3 (figure 1). Two categories of the condition exist: the arrhythmia is the only reason for ventricular dysfunction (arrhythmia-induced), and another where the arrhythmia exacerbates ventricular dysfunction and/or worsens heart failure (HF) in a patient with concomitant heart disease (arrhythmia-mediated).4 The exclusion of underlying structural heart disease can be challenging as current imaging techniques, for example, MRI cannot easily identify diffuse fibrosis which may itself be primary or secondary to the effects of arrhythmia promoting ventricular wall dyskinesis and stretch or valvular regurgitation.