Rationale and design of BERLIN VT study: a multicenter randomised trial comparing preventive versus deferred ablation of ventricular tachycardia

Introduction Catheter ablation ( CA) has shown to effectively reduce the burden of ventricular tachycardia in patients with implanted cardioverter-defibrillator (ICD). However, in patients with ICD implantation for secondary prevention of ventricular tachycardia (VT), the appropriate time point of CA and its effect on mortality and heart failure progression remains a matter of debate. Methods and analysis We present the design of the ongoing preventive aBlation of vEntriculartachycaRdia in patients with myocardiaLINfarction (BERLIN VT) study that aims to prospectively enrol 208 patients with a stable ischaemic cardiomyopathy, a left ventricular ejection fraction of 30% to 50% and documented ventricular tachycardia. Patients will be 1: 1 randomised to undergo CA at the time of ICD implantation or CA after the third appropriate ICD shock for ventricular tachycardia. ICD implantation will be performed in all patients. The primary endpoint is defined as the time to first event comprising all-cause mortality and unplanned hospital admission for congestive heart failure or for symptomatic VT/ventricular fibrillation. The patients will be followed until study termination according to the event driven design. Completion of enrolment is expected for mid of 2019. Ethics and dissemination The study had been approved by the "Ethik-kommission der Landesarztekammer Hamburg" as well as the local institutional review boards for each of the participation sites. The results of the trial will be published in peer-reviewed journal

Immunothrombotic Dysregulation in COVID-19 Pneumonia is Associated with Respiratory Failure and Coagulopathy

Background: SARS-CoV-2 infection causes severe pneumonia (COVID-19), but the mechanisms of subsequent respiratory failure and complicating renal and myocardial involvement are poorly understood. In addition, a systemic prothrombotic phenotype has been reported in COVID-19 patients. Methods: A total of 62 subjects were included in our study (n=38 patients with RT-PCR confirmed COVID-19 and n=24 non-COVID-19 controls). We performed histopathological assessment of autopsy cases, surface-marker based phenotyping of neutrophils and platelets, and functional assays for platelet, neutrophil functions as well as coagulation tests. Results: We provide evidence that organ involvement and prothrombotic features in COVID-19 are linked by immunothrombosis. We show that in COVID-19 inflammatory microvascular thrombi are present in the lung, kidney, and heart, containing neutrophil extracellular traps associated with platelets and fibrin. COVID-19 patients also present with neutrophil-platelet aggregates and a distinct neutrophil and platelet activation pattern in blood, which changes with disease severity. Whereas cases of intermediate severity show an exhausted platelet and hyporeactive neutrophil phenotype, severely affected COVID-19 patients are characterized by excessive platelet and neutrophil activation compared to healthy controls and non-COVID-19 pneumonia. Dysregulated immunothrombosis in SARS-CoV-2 pneumonia is linked to both ARDS and systemic hypercoagulability. Conclusions: Taken together, our data point to immunothrombotic dysregulation as a key marker of disease severity in COVID-19. Further work is necessary to determine the role of immunothrombosis in COVID-19

Influence of different digital terrain models (DTMs)on alpine permafrost modeling

The thawing of alpine permafrost due to changes in atmospheric conditions can have a severe impact, e.g., on the stability of rock walls. The energy balance model, PERMEBAL, was developed in order to simulate the changes and distribution of ground surface temperature (GST) in complex high-mountain topography. In such environments, the occurrence of permafrost depends greatly on the topography, and thus, the digital terrain model (DTM) is an important input of PERMEBAL. This study investigates the influence of the DTM on the modeling of the GST. For this purpose, PERMEBAL was run with six different DTMs. Five of the six DTMs are based on the same base data, but were generated using different interpolators. To ensure that only the topographic effect on the GST is calculated, the snow module was turned off and uniform conditions were assumed for the whole test area. The analyses showed that the majority of the deviations between the different model outputs related to a reference DTM had only small differences of up to 1 K, and only a few pixels deviated more than 1 K. However, we also observed that the use of different interpolators for the generation of a DTM can result in large deviations of the model output. These deviations were mainly found at topographically complex locations such as ridges and foot of slopes

Independent susceptibility markers for atrial fibrillation on chromosome 4q25

Background-: Genetic variants on chromosome 4q25 are associated with atrial fibrillation (AF). We sought to determine whether there is more than 1 susceptibility signal at this locus. Methods and results-: Thirty-four haplotype-tagging single-nucleotide polymorphisms (SNPs) at the 4q25 locus were genotyped in 790 case and 1177 control subjects from Massachusetts General Hospital and tested for association with AF. We replicated SNPs associated with AF after adjustment for the most significantly associated SNP in 5066 case and 30 661 referent subjects from the German Competence Network for Atrial Fibrillation, Atherosclerosis Risk In Communities Study, Cleveland Clinic Lone AF Study, Cardiovascular Health Study, and Rotterdam Study. All subjects were of European ancestry. A multimarker risk score composed of SNPs that tagged distinct AF susceptibility signals was constructed and tested for association with AF, and all results were subjected to meta-analysis. The previously reported SNP, rs2200733, was most significantly associated with AF (minor allele odds ratio 1.80, 95% confidence interval 1.50 to 2.15, P=1.2×10) in the discovery sample. Adjustment for rs2200733 genotype revealed 2 additional susceptibility signals marked by rs17570669 and rs3853445. A graded risk of AF was observed with an increasing number of AF risk alleles at SNPs that tagged these 3 susceptibility signals. Conclusions-: We identified 2 novel AF susceptibility signals on chromosome 4q25. Consideration of multiple susceptibility signals at chromosome 4q25 identifies individuals with an increased risk of AF and may localize regulatory elements at the locus with biological relevance in the pathogenesis of AF

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Rock glaciers and mountain hydrology: A review

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.In mountainous regions, climate change threatens cryospheric water resources, and understanding all components of the hydrological cycle is necessary for effective water resource management. Rockglaciers are climatically more resilient than glaciers and contain potentially hydrologically valuable ice volumes, and yet havereceived lessattention, even though rock glacier hydrologicalimportance may increase under future climate warming. In synthesising data from a range of global studies, we provide the first compre-hensive evaluation of the hydrological role played by rock glaciers. Weevaluate hydrological significanceover a range of temporal and spatial scales, alongsidethe complex multiple hydrological processes with which rock glaciers can interact diurnally, seasonally, annually, decadally and both at local and regional extents.We report that although no global-extent, complete inventory for rock glaciers exists currently, recent research efforts have greatly elaborated spatialcoverage.Using these research papers,we synthe-sise information on rock glacier spatial distribution, morphometric characteristics, surface and subsurface features, ice-storage and hydrological flow dynamics, water chemistry, and future resilience, from which we provide the first comprehensive evaluation of their hydrological contribution. We identify and discuss long-, intermediate-and short-term timescales for rock glacier storage, allowing a more balanced assess-ment of the contrasting perspectives regarding the relative significance of rock glacier-derived hydrological contributions compared to other water sources.We show that further empirical observations are required to gain a deeper hydrological understanding of rock glaciers, in terms of(i) their genesis and geomorpho-logical dynamics (ii) total ice/water volume; (iii) water discharge; and (iv) water quality. Lastly, we hypothesisethat at decadal and longer timescales, under future climate warming, degradation of ice within rock glaciers may represent an increasing hydrological contribution to downstream regions, and thus in-creased hydrological significance while rock glacier water stores persist.Royal Geographical SocietyNatural Environment Research Council (NERC

Longer and better lives for patients with atrial fibrillation:the 9th AFNET/EHRA consensus conference

Aims: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Methods and results: Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF. Conclusions: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF

A roadmap to improve the quality of atrial fibrillation management:proceedings from the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference

At least 30 million people worldwide carry a diagnosis of atrial fibrillation (AF), and many more suffer from undiagnosed, subclinical, or 'silent' AF. Atrial fibrillation-related cardiovascular mortality and morbidity, including cardiovascular deaths, heart failure, stroke, and hospitalizations, remain unacceptably high, even when evidence-based therapies such as anticoagulation and rate control are used. Furthermore, it is still necessary to define how best to prevent AF, largely due to a lack of clinical measures that would allow identification of treatable causes of AF in any given patient. Hence, there are important unmet clinical and research needs in the evaluation and management of AF patients. The ensuing needs and opportunities for improving the quality of AF care were discussed during the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference in Nice, France, on 22 and 23 January 2015. Here, we report the outcome of this conference, with a focus on (i) learning from our 'neighbours' to improve AF care, (ii) patient-centred approaches to AF management, (iii) structured care of AF patients, (iv) improving the quality of AF treatment, and (v) personalization of AF management. This report ends with a list of priorities for research in AF patients