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Coronavirus disease 2019 (COVID-19) is a viral infection with the novel severe acute respiratory distress syndrome corona virus 2 (SARS-CoV-2). Until now, more than 670 million people have suffered from COVID-19 worldwide, and roughly 7 million death cases were attributed to COVID-19. Recent evidence suggests an interplay between COVID-19 and cardiovascular disease (CVD). COVID-19 may serve as a yet underappreciated CVD risk modifier, including risk factors such as diabetes mellitus or arterial hypertension. In addition, recent data suggest that previous COVID-19 may increase the risk for many entities of CVD to an extent similarly observed for traditional cardiovascular (CV) risk factors. Furthermore, increased CVD incidence and worse clinical outcomes in individuals with preexisting CVD have been observed for myocarditis, acute coronary syndrome, heart failure (HF), thromboembolic complications, and arrhythmias. Direct and indirect mechanisms have been proposed by which COVID-19 may impact CVD and CV risk, including viral entry into CV tissue or by the induction of a massive systemic inflammatory response. In the current review, we provide an overview of the literature reporting an interaction between COVID-19 and CVD, review potential mechanisms underlying this interaction, and discuss preventive and treatment strategies and their interference with CVD that were evaluated since the onset of the COVID-19 pandemic.

Mitochondrial medicine is increasingly discussed as a promising therapeutic approach, given that mitochondrial defects are thought to contribute to many prevalent diseases and their complications. In individuals with diabetes mellitus (DM), defects in mitochondrial structure and function occur in many organs throughout the body, contributing both to the pathogenesis of DM and complications of DM. Diabetic cardiomyopathy (DbCM) is increasingly recognized as an underlying cause of increased heart failure in DM, and several mitochondrial mechanisms have been proposed to contribute to the development of DbCM. Well established mechanisms include myocardial energy depletion due to impaired adenosine triphosphate (ATP) synthesis and mitochondrial uncoupling, and increased mitochondrial oxidative stress. A variety of upstream mechanisms of impaired ATP regeneration and increased mitochondrial reactive oxygen species have been proposed, and recent studies now also suggest alterations in mitochondrial dynamics and autophagy, impaired mitochondrial Ca²⁺ uptake, decreased cardiac adiponectin action, increased O-GlcNAcylation, and impaired activity of sirtuins to contribute to mitochondrial defects in DbCM, among others. In the current review, we present and discuss the evidence that underlies both established and recently proposed mechanisms that are thought to contribute to mitochondrial dysfunction in DbCM.

Astaxanthin (ASX) has demonstrated various cardioprotective effects, including reductions in body weight, adipose tissue mass, hypertension, myocardial infarct size, and oxidative stress markers. Despite these findings, the underlying mechanisms remain unclear. This study examines the role of ASX in murine atherosclerosis and metabolic derangements induced by atherogenic diet, aiming to gain a deeper understanding of its biological effects and potential therapeutic applications. Ldlr-/- mice were fed a high-fat, high-cholesterol diet (HCD) for 16 weeks, receiving 70 mg/kg ASX or vehicle every other day. A week before the study ended, glucose and insulin tolerance tests were performed. Plaque size in the aorta was analyzed via histology (Oil-red-O and Masson's trichrome). Flow cytometry assessed immune cells from blood, aorta, adipose tissue, and cytokines in plasma. Additional mice underwent intravital microscopy for further investigation. The overall body weight of animals treated with ASX or vehicle did not differ. ASX-treated mice showed a reduced abundance of peripheral monocytes by 34%, lower numbers of leukocytes in adipose tissue depots, and improved glucose metabolism and insulin sensitivity compared with animals receiving vehicle. White adipose mass decreased while brown adipose and muscle mass increased in mice treated with ASX. Atherosclerotic lesions of Ldlr-/- mice receiving ASX were significantly smaller and contained fewer lipids (3.3 vs 2.6 x 105 µm2) and M1 macrophages (0.97 vs 0.42x103) but increased collagen, in line with a more stable plaque phenotype. Mechanistic experiments revealed that ASX attenuated leukocyte recruitment (43% ± 1.87) to the vessel wall in intravital microscopy and dampened inflammatory signaling through Mitogen-activated protein kinases. ASX treatment reduces experimental atherosclerosis and blunts metabolic syndrome features in mice. This effect is linked to reduced leukocyte recruitment and systemic/local inflammation. The findings support ASX's potential in treating atherosclerosis and metabolic diseases, offering new mechanistic insights and ultimately warrant the rigorous clinical evaluation of such putative effects.

A wearable cardioverter-defibrillator (WCD) is a temporary treatment option for patients at high risk for sudden cardiac death (SCD) and for patients who are temporarily not candidates for an implantable cardioverter defibrillator (ICD). In addition, the need for telemedical concepts in the detection and treatment of heart failure (HF) and its arrhythmias is growing. The WCD has evolved from a shock device detecting malignant ventricular arrhythmias (VA) and treating them with shocks to a heart-failure-monitoring device that captures physical activity and cardioacoustic biomarkers as surrogate parameters for HF to help the treating physician surveil and guide the HF therapy of each individual patient. In addition to its important role in preventing SCD, the WCD could become an important tool in heart failure treatment by helping prevent HF events by detecting imminent decompensation via remote monitoring and monitoring therapy success.

CD40L (CD154), a member of the tumor necrosis factor superfamily, is a co-stimulatory molecule that was first discovered on activated T cells. Beyond its fundamental role in adaptive immunity-ligation of CD40L to its receptor CD40 is a prerequisite for B cell activation and antibody production-evidence from more than two decades has expanded our understanding of CD40L as a powerful modulator of inflammatory pathways. Although inhibition of CD40L with neutralizing antibodies has induced life-threatening side effects in clinical trials, the discovery of cell-specific effects and novel receptors with distinct functional consequences has opened a new path for therapies that specifically target detrimental properties of CD40L. Here, we carefully evaluate the signaling network of CD40L by gene enrichment analysis and its cell-specific expression, and thoroughly discuss its role in cardiovascular pathologies with a specific emphasis on atherosclerotic and thrombotic disease.

While hospital admissions for myocardial infarction (MI) and pulmonary embolism (PE) are decreased during the COVID-19 pandemic, controversy remains about respective complication and mortality rates. This study evaluated admission rates, complications, and intrahospital mortality for selected life-threatening cardiovascular emergencies (MI, PE, and acute aortic dissection (AAD)) during COVID-19-associated restrictive social measures (RM) in Styria, Austria. By screening a patient information system for International Statistical Classification of Diseases and Related Health Problems (ICD) diagnosis codes covering more than 85% of acute hospital admissions in the state of Styria (~1.24 million inhabitants), we retrospectively identified patients with admission diagnoses for MI (I21, I22), PE (I26), and AAD (I71). Rates of complications such as cardiogenic shock and cardiopulmonary resuscitation, treatment escalations (thrombolysis for PE), and mortality were analyzed by patient chart review during 6 weeks following onset of COVID-19 associated RM, and during respective time frames in the years 2016 to 2019. 1,668 patients were included. Cumulative admissions for MI, PE and AAD decreased (RR 0.77; p<0.001) during RM compared to previous years. In contrast, intrahospital mortality increased by 65% (RR 1.65; p = 0.041), mainly driven by mortality following MI (RR 1.80; p = 0.042). PE patients received more frequently thrombolysis treatment (RR 3.63; p = 0.006), while rates of cardiogenic shock and cardiopulmonary resuscitation remained unchanged. Of 226 patients hospitalized during RM, 81 patients with suspected COVID-19 disease were screened for SARS-CoV-2 infection with only 5 testing positive. Thus, cumulative hospital admissions for cardiovascular emergencies decreased during COVID-19 associated RM while intrahospital mortality increased.

Diabetes worsens atherosclerosis progression and leads to a defect in repair of arteries after cholesterol reduction, a process termed regression. Empagliflozin reduces blood glucose levels via inhibition of the sodium glucose cotransporter 2 (SGLT-2) in the kidney and has been shown to lead to a marked reduction in cardiovascular events in humans. To determine whether glucose lowering by empagliflozin accelerates atherosclerosis regression in a mouse model, male C57BL/6J mice were treated intraperitoneally with LDLR- and SRB1- antisense oligonucleotides and fed a high cholesterol diet for 16 weeks to induce severe hypercholesterolemia and atherosclerosis progression . At week 14 all mice were rendered diabetic by streptozotocin (STZ) injections. At week 16 a baseline group was sacrificed and displayed substantial atherosclerosis of the aortic root. In the remaining mice, plasma cholesterol was lowered by switching to chow diet and treatment with LDLR sense oligonucleotides to induce atherosclerosis regression . These mice then received either empagliflozin or vehicle for three weeks. Atherosclerotic plaques in the empagliflozin treated mice were significantly smaller, showed decreased lipid and CD68 + macrophage content, as well as greater collagen content. Proliferation of plaque resident macrophages and leukocyte adhesion to the vascular wall were significantly decreased in empagliflozin-treated mice. In summary, plasma glucose lowering by empagliflozin improves plaque regression in diabetic mice.

Background SGTL2-inhibitors are a cornerstone in the treatment of heart failure, but data on patients with acute myocardial infarction (AMI) is limited. The EMMY trial was the first to show a significant reduction in NTproBNP levels as well as improved cardiac structure and function in post-AMI patients treated with Empagliflozin compared to placebo. However, data on the potential impact of SGLT2-inhibitors on inflammatory biomarkers after AMI are scarce. Materials and methods The EMMY trial is an investigator-initiated, multicentre, double-blind, placebo-controlled trial, which enrolled patients after AMI, receiving either 10 mg Empagliflozin once daily or placebo over a period of 26 weeks on top of standard guideline-recommended therapy starting within 72 h after percutaneous coronary intervention. In this post-hoc subgroup analysis of the EMMY trial, we investigated inflammatory biomarkers of 374 patients. The endpoints investigated were the mean change in inflammatory biomarkers such as high-sensitive c-reactive protein (hsCRP), interleukin-6 (IL-6), neutrophils, leukocytes, neutrophile/lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) from baseline to 26 weeks. Results Baseline median (interquartile ranges) IL-6 was 17.9 pg/mL (9.0-38.7), hsCRP 18.9 mg/L (11.2–37.1), neutrophil count 7.9 x G/L (6.2–10.1), leukocyte count 10.8 x G/L (9.1–12.8) and neutrophile/lymphocyte ratio (NLR) of 0.74 (0.67–0.80). At week 26, a significant mean reduction in inflammatory biomarkers was observed, being 35.1 ± 3.2% (p < 0.001) for IL-6, 57.4 ± 0.7% (p < 0.001) for hsCRP, 26.1 ± 0.7% (p < 0.001) for neutrophils, 20.5 ± 0.6% (p < 0.001) for leukocytes, 10.22 ± 0.50% (p < 0.001) for NLR, and − 2.53 ± 0.92% for PLR (p = 0.006) with no significant difference between Empagliflozin and placebo treatment. Conclusion Trajectories of inflammatory biomarkers showed a pronounced decline after AMI, but Empagliflozin treatment did not impact this decline indicating no central role in blunted systemic inflammation mediating beneficial effects.

Mitral regurgitation (MR) and tricuspid regurgitation (TR) commonly coexist in patients with heart failure (HF). Their concomitant occurrence carries a much poorer prognosis than isolated valve disease. Transcatheter edge-to-edge repair (TEER) of MR and TR is safe and effective, but there is limited data on combined MR/TR TEER. The study evaluates the safety and efficacy of combined TEER for MR and TR in a real-world cohort. This retrospective safety and efficacy analysis included the first 40 patients treated with combined MR/TR TEER between 2019 and 2021 at our single tertiary care referral centre. Combined procedural success (MR reduction ≥2° and TR reduction ≥1°) was achieved in 80% of the cases. Simultaneous TEER was safe, with no intraprocedural death, myocardial infarction (MI), stroke, or major bleeding. At 1-year follow-up, the median New York Heart Association functional (NYHA) class improved by one grade; twelve patients (30%) died, and fourteen patients (35%) were hospitalized for HF. Procedural success and postprocedural residual MR ≤ 1° were associated with reduced 1-year mortality rates but not HF hospitalizations. Combined MR/TR TEER is safe and reduces MR and TR in most patients, conferring a potential benefit regarding symptoms and prognosis. Randomized controlled trials (RCTs) are needed to rigorously evaluate combination therapy in this setting.

Integrin-based therapeutics have garnered considerable interest in the medical treatment of inflammation. Integrins mediate the fast recruitment of monocytes and neutrophils to the site of inflammation, but are also required for host defense, limiting their therapeutic use. Here, we report a novel monoclonal antibody, anti-M7, that specifically blocks the interaction of the integrin Mac-1 with its pro-inflammatory ligand CD40L, while not interfering with alternative ligands. Anti-M7 selectively reduces leukocyte recruitment in vitro and in vivo. In contrast, conventional anti-Mac-1 therapy is not specific and blocks a broad repertoire of integrin functionality, inhibits phagocytosis, promotes apoptosis, and fuels a cytokine storm in vivo. Whereas conventional anti-integrin therapy potentiates bacterial sepsis, bacteremia, and mortality, a ligand-specific intervention with anti-M7 is protective. These findings deepen our understanding of ligand-specific integrin functions and open a path for a new field of ligand-targeted anti-integrin therapy to prevent inflammatory conditions. Integrin-based therapeutics could block inflammatory processes but they also impair host defence, limiting their usefulness. Here the authors report an anti-Mac1 antibody that blocks its interaction with pro-inflammatory ligand CD40L but not other ligands, and show that it can protect against sepsis in mice.