COVID19-associated cardiomyocyte dysfunction, arrhythmias and the effect of Canakinumab

BACKGROUND: Cardiac injury associated with cytokine release frequently occurs in SARS-CoV-2 mediated coronavirus disease (COVID19) and mortality is particularly high in these patients. The mechanistic role of the COVID19 associated cytokine-storm for the concomitant cardiac dysfunction and associated arrhythmias is unclear. Moreover, the role of anti-inflammatory therapy to mitigate cardiac dysfunction remains elusive. AIMS AND METHODS: We investigated the effects of COVID19-associated inflammatory response on cardiac cellular function as well as its cardiac arrhythmogenic potential in rat and induced pluripotent stem cell derived cardiomyocytes (iPS-CM). In addition, we evaluated the therapeutic potential of the IL-1β antagonist Canakinumab using state of the art in-vitro confocal and ratiometric high-throughput microscopy. RESULTS: Isolated rat ventricular cardiomyocytes were exposed to control or COVID19 serum from intensive care unit (ICU) patients with severe ARDS and impaired cardiac function (LVEF 41±5%; 1/3 of patients on veno-venous extracorporeal membrane oxygenation; CK 154±43 U/l). Rat cardiomyocytes showed an early increase of myofilament sensitivity, a decrease of Ca(2+) transient amplitudes and altered baseline [Ca(2+)] upon exposure to patient serum. In addition, we used iPS-CM to explore the long-term effect of patient serum on cardiac electrical and mechanical function. In iPS-CM, spontaneous Ca(2+) release events were more likely to occur upon incubation with COVID19 serum and nuclear as well as cytosolic Ca(2+) release were altered. Co-incubation with Canakinumab had no effect on pro-arrhythmogenic Ca(2+) release or Ca(2+) signaling during excitation-contraction coupling, nor significantly influenced cellular automaticity. CONCLUSION: Serum derived from COVID19 patients exerts acute cardio-depressant and chronic pro-arrhythmogenic effects in rat and iPS-derived cardiomyocytes. Canakinumab had no beneficial effect on cellular Ca(2+) signaling during excitation-contraction coupling. The presented method utilizing iPS-CM and in-vitro Ca(2+) imaging might serve as a novel tool for precision medicine. It allows to investigate cytokine related cardiac dysfunction and pharmacological approaches useful therein

Magnetic field-induced interactions between phones containing magnets and cardiovascular implantable electronic devices: Flip it to be safe?

BACKGROUND: Recent case reports and small studies have reported activation of the magnet-sensitive switches in cardiovascular implantable electronic devices (CIED) by the new iPhone 12 series, initiating asynchronous pacing in pacemakers and suspension of anti-tachycardia therapies in ICDs. OBJECTIVE AND METHODS: We performed a prospective single-center observational study to quantify the risk of magnetic field interactions of the iPhone 12 with CIEDs. A representative model of each CIED series from all manufacturers was tested ex vivo. Incidence and minimum distance necessary for magnet mode triggering were analyzed in 164 CIED patients with either the front or the back of the phone facing the device. The magnetic field of the iPhone 12 was analyzed using a 3-axis hall probe. RESULTS: Ex vivo, magnetic interferences occurred in 84.6% with the back compared to 46.2% with the front of the iPhone 12 facing the CIED. In vivo, activation of the magnet-sensitive switch occurred in 30 CIED patients (18.3%; 21 pacemaker, 9 ICDs) when the iPhone 12 was placed in close proximity over the CIED pocket and the back of the phone was facing the skin. Multiple binary logistic regression analysis identified the implantation depth (95% confidence interval [CI], 0.02 to 0.24) as independent predictor of magnet-sensitive switch activation. CONCLUSION: Magnetic field interactions occur only in close proximity, and with precise alignment of the iPhone 12 and CIEDs. It is important to advise CIED patients to not put the iPhone 12 directly on the skin above the CIED. Further recommendations are not necessary

Protocol of the Berlin Long-term Observation of Vascular Events (BeLOVE): a prospective cohort study with deep phenotyping and long-term follow up of cardiovascular high-risk patients

INTRODUCTION: The Berlin Long-term Observation of Vascular Events is a prospective cohort study that aims to improve prediction and disease-overarching mechanistic understanding of cardiovascular (CV) disease progression by comprehensively investigating a high-risk patient population with different organ manifestations. METHODS AND ANALYSIS: A total of 8000 adult patients will be recruited who have either suffered an acute CV event (CVE) requiring hospitalisation or who have not experienced a recent acute CVE but are at high CV risk. An initial study examination is performed during the acute treatment phase of the index CVE or after inclusion into the chronic high risk arm. Deep phenotyping is then performed after ~90 days and includes assessments of the patient's medical history, health status and behaviour, cardiovascular, nutritional, metabolic, and anthropometric parameters, and patient-related outcome measures. Biospecimens are collected for analyses including 'OMICs' technologies (e.g., genomics, metabolomics, proteomics). Subcohorts undergo MRI of the brain, heart, lung and kidney, as well as more comprehensive metabolic, neurological and CV examinations. All participants are followed up for up to 10 years to assess clinical outcomes, primarily major adverse CVEs and patient-reported (value-based) outcomes. State-of-the-art clinical research methods, as well as emerging techniques from systems medicine and artificial intelligence, will be used to identify associations between patient characteristics, longitudinal changes and outcomes. ETHICS AND DISSEMINATION: The study was approved by the Charité-Universitätsmedizin Berlin ethics committee (EA1/066/17). The results of the study will be disseminated through international peer-reviewed publications and congress presentations. STUDY REGISTRATION: First study phase: Approved WHO primary register: German Clinical Trials Register: https://drks.de/search/de/trial/DRKS00016852; WHO International Clinical Registry Platform: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00016852. Recruitment started on July 18, 2017.Second study phase: Approved WHO primary register: German Clinical Trials Register DRKS00023323, date of registration: November 4, 2020, URL: http://www.drks.de/ DRKS00023323. Recruitment started on January 1, 2021

The DZHK research platform: maximisation of scientific value by enabling access to health data and biological samples collected in cardiovascular clinical studies

The German Centre for Cardiovascular Research (DZHK) is one of the German Centres for Health Research and aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics that impact the lives of people with cardiovascular disease. Therefore, DZHK members designed a collaboratively organised and integrated research platform connecting all sites and partners. The overarching objectives of the research platform are the standardisation of prospective data and biological sample collections among all studies and the development of a sustainable centrally standardised storage in compliance with general legal regulations and the FAIR principles. The main elements of the DZHK infrastructure are web-based and central units for data management, LIMS, IDMS, and transfer office, embedded in a framework consisting of the DZHK Use and Access Policy, and the Ethics and Data Protection Concept. This framework is characterised by a modular design allowing a high standardisation across all studies. For studies that require even tighter criteria additional quality levels are defined. In addition, the Public Open Data strategy is an important focus of DZHK. The DZHK operates as one legal entity holding all rights of data and biological sample usage, according to the DZHK Use and Access Policy. All DZHK studies collect a basic set of data and biosamples, accompanied by specific clinical and imaging data and biobanking. The DZHK infrastructure was constructed by scientists with the focus on the needs of scientists conducting clinical studies. Through this, the DZHK enables the interdisciplinary and multiple use of data and biological samples by scientists inside and outside the DZHK. So far, 27 DZHK studies recruited well over 11,200 participants suffering from major cardiovascular disorders such as myocardial infarction or heart failure. Currently, data and samples of five DZHK studies of the DZHK Heart Bank can be applied for

Myocardial systolic and diastolic performance derived by 2-dimensional speckle tracking echocardiography in heart failure with normal left ventricular ejection fraction

BACKGROUND: The aim of this study was to investigate the myocardial systolic and diastolic performance of the left ventricle (LV) in patients with heart failure with normal LV ejection fraction (HFNEF) through novel LV myocardial indices, which assess the systolic and diastolic function of the whole myocardium of the LV. METHODS AND RESULTS: LV myocardial systolic and diastolic performance were assessed as the average value of peak systolic strain and peak early-diastolic strain rate, respectively, in longitudinal, circumferential, and radial directions from all LV segments using 2-dimensional speckle-tracking echocardiography. We studied patients with HFNEF and a control group consisting of asymptomatic subjects with LV diastolic dysfunction of similar age, sex, and LV ejection fraction. A total of 322 patients were included (92 with HFNEF and 230 with asymptomatic LV diastolic dysfunction). Myocardial systolic and diastolic LV performance were significantly lower in HFNEF (20.13+/-6.02% and 1.14+/-0.27 s(-1)) than in patients with asymptomatic LV diastolic dysfunction (25.33+/-6.06% and 1.37+/-0.33 s(-1), respectively; all P<0.0001). In addition, patients with HFNEF with low systolic and diastolic LV myocardial performance had significantly higher LV filling pressures (17.1+/-6.6 and 17.6+/-6.3 versus 12.0+/-5.1 and 11.7+/-4.7, respectively; all P<0.001) and lower cardiac output (4.8+/-1.0 L/min and 4.9+/-1.1 L/min versus 5.7+/-1.2 L/min and 5.8+/-1.1 L/min, respectively; all P<0.001) than patients with normal LV myocardial performance. In relation to these findings, the symptomatic status (ie, New York Heart Association functional class) was significantly altered in those patients with low systolic and diastolic LV myocardial performance. CONCLUSIONS: In patients with HFNEF, both systolic and diastolic LV myocardial performance are impaired, which is associated with increased LV filling pressures, decreased cardiac output, and worse New York Heart Association functional class. Therefore, the measurement of these myocardial parameters could be of great importance in HFNEF because these echocardiographic indices assess the multidirectional function of the whole myocardium of the LV, thereby allowing detection of an alteration of the global function of the LV which is associated with a worse symptomatic status in these patients

Absent proximal right coronary artery with a fistula into the pulmonary vein

A 32-year-old woman was admitted with a third-degree atrioventricular block. A permanent pacemaker was implanted and the patient was discharged. One week later, the patient presented again with a sustained ventricular tachycardia. Coronary angiography and computed tomography imaging with three-dimensional reconstructions revealed the absence of the proximal part of the right coronary artery (RCA) with a fistula into the pulmonary vein. This is the first case describing an absent proximal RCA combined with a pulmonary vein fistula

Optimal heart failure therapy and successful cardioversion in heart failure patients with atrial fibrillation

BACKGROUND: Effectiveness, safety, and other factors associated with success of cardioversion (CV) of atrial fibrillation (AF) have not yet been evaluated in patients with reduced left ventricular ejection fraction. We studied 148 consecutive patients with left ventricular dysfunction (ejection fraction < or = 45%), who underwent electrical CV for AF in our department. The patients had New York Heart Association heart failure ranging from class II to IV. The overall CV success rate was 71%. We relied on univariate and multivariate regression and sought variables influencing success rate. Conversion success did not correlate with New York Heart Association class. Instead, we found that the greatest predictor was the degree of heart failure treatment. Patients receiving beta-blockers, angiotensin-converting enzyme inhibitors or angiotension receptor blockers, plus mineralocorticoid receptor blockers had the greatest chance for conversion success. Success was more likely in patients with coronary artery disease (91%) than in patients with nonischemic cardiomyopathy. CONCLUSIONS: Cardioversion is a safe and effective method for the restoration of sinus rhythm in patients with AF and reduced left ventricular ejection fraction. Our findings underscore the value of aggressive heart failure treatment before CV in patients with AF