A year in heart failure: updates of clinical and preclinical findings.

We witnessed major advances in the management of heart failure (HF) in 2022. Results of recent clinical and preclinical investigations aid preventive strategies, diagnostic efforts, and therapeutic interventions, and collectively, they hold promises for a more effective HF care for the near future. Accordingly, currently available information extends the 2021 European Society of Cardiology guidelines and provides a solid background for the introduction of improved clinical approaches in the number of HF-related cases. Elaboration on the relationships between epidemiological data and risk factors lead to better understanding of the pathophysiology of HF with reduced ejection fraction and HF with preserved ejection fraction. The clinical consequences of valvular dysfunctions are increasingly interpreted not only in their haemodynamic consequences but also in association with their pathogenetic factors and modern corrective treatment possibilities. The influence of coronavirus disease 2019 pandemic on the clinical care of HF appeared to be less intense in 2022 than before; hence, this period allowed to refine coronavirus disease 2019 management options for HF patients. Moreover, cardio-oncology emerges as a new subdiscipline providing significant improvements in clinical outcomes for oncology patients. Furthermore, the introduction of state-of-the-art molecular biologic methods, multi-omic approaches forecast improved phenotyping and precision medicine for HF. All above aspects are addressed in this article that highlights a selection of papers published in ESC Heart Failure in 2022.

Decreased oxidative stress and altered urinary oxylipidome by intravenous omega-3 fatty acid emulsion in a randomized controlled trial of older subjects hospitalized for COVID-19.

Proinflammatory bioactive lipid mediators and oxidative stress are increased in coronavirus disease 2019 (COVID-19). The randomized controlled single-blind trial COVID-Omega-F showed that intravenous omega-3 polyunsaturated fatty acids (n-3 PUFA) shifted the plasma lipid signature of COVID-19 towards increased proresolving precursor levels and decreased leukotoxin diols, associated with a beneficial immunodulatory response. The present study aimed to determine the effects of n-3 PUFA on the urinary oxylipidome and oxidative stress in COVID-19. From the COVID-Omega-F trial, 20 patients hospitalized for COVID-19 had available serial urinary samples collected at baseline, after 24-48 h, and after completing 5 days treatment with one daily intravenous infusion (2 mL/kg) of either placebo (NaCl; n = 10) or a lipid emulsion containing 10 g of n-3 PUFA per 100 mL (n = 10). Urinary eicosanoids and isoprostanes were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Erythrocytes obtained at the different time-points from n = 10 patients (n = 5 placebo and n = 5 n-3 PUFA) were used for determination of reactive oxygen species. Intravenous n-3 PUFA emulsion administration altered eicosanoid metabolites towards decreased levels for mediators of inflammation and thrombosis, and increased levels of the endothelial function mediator prostacyclin. Furthermore, non-enzymatic metabolism was skewed towards n-3 PUFA-derived metabolites with potential anti-inflammatory and pro-resolving effects. The oxidative stress marker 15-F2t-isoprostane was significantly lower in patients receiving n-3 PUFA treatment, who also exhibited significantly decreased erythrocyte oxidative stress compared with placebo-treated patients. These findings point to additional beneficial effects of intravenous n-3 PUFA emulsion treatment through a beneficial oxylipin profile and decreased oxidative stress in COVID-19.

From novel discovery tools and biomarkers to precision medicine-basic cardiovascular science highlights of 2021/22.

Here, we review the highlights of cardiovascular basic science published in 2021 and early 2022 on behalf of the European Society of Cardiology Council for Basic Cardiovascular Science. We begin with non-coding RNAs which have emerged as central regulators cardiovascular biology, and then discuss how technological developments in single-cell 'omics are providing new insights into cardiovascular development, inflammation, and disease. We also review recent discoveries on the biology of extracellular vesicles in driving either protective or pathogenic responses. The Nobel Prize in Physiology or Medicine 2021 recognized the importance of the molecular basis of mechanosensing and here we review breakthroughs in cardiovascular sensing of mechanical force. We also summarize discoveries in the field of atherosclerosis including the role of clonal haematopoiesis of indeterminate potential, and new mechanisms of crosstalk between hyperglycaemia, lipid mediators, and inflammation. The past 12 months also witnessed major advances in the field of cardiac arrhythmia including new mechanisms of fibrillation. We also focus on inducible pluripotent stem cell technology which has demonstrated disease causality for several genetic polymorphisms in long-QT syndrome and aortic valve disease, paving the way for personalized medicine approaches. Finally, the cardiovascular community has continued to better understand COVID-19 with significant advancement in our knowledge of cardiovascular tropism, molecular markers, the mechanism of vaccine-induced thrombotic complications and new anti-viral therapies that protect the cardiovascular system.

Stimulating the Resolution of Inflammation Through Omega-3 Polyunsaturated Fatty Acids in COVID-19: Rationale for the COVID-Omega-F Trial.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 triggers an immune response with local inflammation in the lung, which may extend to a systemic hyperinflammatory reaction. Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications. In addition to the release of cytokines, referred to as cytokine release syndrome or "cytokine storm," increased pro-inflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an "eicosanoid storm," which contributes to the uncontrolled systemic inflammation. Specialized pro-resolving mediators, which are derived from omega-3 PUFA, limit inflammatory reactions by an active process called resolution of inflammation. Here, the rationale for omega-3 PUFA supplementation in COVID-19 patients is presented along with a brief overview of the study protocol for the trial "Resolving Inflammatory Storm in COVID-19 Patients by Omega-3 Polyunsaturated Fatty Acids - A single-blind, randomized, placebo-controlled feasibility study" (COVID-Omega-F). EudraCT: 2020-002293-28; clinicaltrials.gov: NCT04647604.

Endothelial dysfunction in COVID-19: a position paper of the ESC Working Group for Atherosclerosis and Vascular Biology, and the ESC Council of Basic Cardiovascular Science.

The COVID-19 pandemic is an unprecedented healthcare emergency causing mortality and illness across the world. Although primarily affecting the lungs, the SARS-CoV-2 virus also affects the cardiovascular system. In addition to cardiac effects, e.g. myocarditis, arrhythmias, and myocardial damage, the vasculature is affected in COVID-19, both directly by the SARS-CoV-2 virus, and indirectly as a result of a systemic inflammatory cytokine storm. This includes the role of the vascular endothelium in the recruitment of inflammatory leucocytes where they contribute to tissue damage and cytokine release, which are key drivers of acute respiratory distress syndrome (ARDS), in disseminated intravascular coagulation, and cardiovascular complications in COVID-19. There is also evidence linking endothelial cells (ECs) to SARS-CoV-2 infection including: (i) the expression and function of its receptor angiotensin-converting enzyme 2 (ACE2) in the vasculature; (ii) the prevalence of a Kawasaki disease-like syndrome (vasculitis) in COVID-19; and (iii) evidence of EC infection with SARS-CoV-2 in patients with fatal COVID-19. Here, the Working Group on Atherosclerosis and Vascular Biology together with the Council of Basic Cardiovascular Science of the European Society of Cardiology provide a Position Statement on the importance of the endothelium in the underlying pathophysiology behind the clinical presentation in COVID-19 and identify key questions for future research to address. We propose that endothelial biomarkers and tests of function (e.g. flow-mediated dilatation) should be evaluated for their usefulness in the risk stratification of COVID-19 patients. A better understanding of the effects of SARS-CoV-2 on endothelial biology in both the micro- and macrovasculature is required, and endothelial function testing should be considered in the follow-up of convalescent COVID-19 patients for early detection of long-term cardiovascular complications.