Impact of pulmonary hypertension on outcomes after TEER in patients suffering from mitral regurgitation.

AIM: Data on associations of invasively determined hemodynamic parameters with procedural success and outcomes in patients suffering from mitral regurgitation (MR) undergoing transcatheter edge-to-edge repair of the mitral valve (M-TEER) is limited. METHODS AND RESULTS: We enrolled 239 patients with symptomatic MR of grade 2 + , who received M-TEER. All patients underwent extensive pre-interventional invasive hemodynamic measurements via right heart catheterization (mean pulmonary arterial pressure (mPAP), systolic- (PAPsys) and diastolic pulmonary arterial pressure (PAPdia), pulmonary arterial wedge pressure (PAWP), a-wave, v-wave, pulmonary vascular resistance (PVR), transpulmonary pressure gradient (TPG), cardiac index (CI), stroke volume index (SVI)). mPAP and PAWP at baseline were neither associated with procedural success, immediate reduction of MR, nor residual MR after 6 months of follow-up. The composite outcome (All-cause mortality (ACM) and/or heart failure induced rehospitalization (HFH)) and HFH differed significantly after M-TEER when stratified according to mPAP, PAWP, PAPdia, a-wave and v-wave. ACM was not associated with the afore mentioned parameters. Neither PVR, TPG, CI nor SVI were associated with the composite outcome and HFH, respectively. In multivariable analyses, PAWP was independently associated with the composite outcome and HFH. PVR and SVI were not associated with outcomes. CONCLUSION: PAWP at baseline was significantly and independently associated with HFH and might serve as a valuable parameter for identifying patients at high risk for HFH after M-TEER. ACM and procedural success were not affected by pulmonary arterial pressure before M-TEER. We suggest that the post-capillary component of PH serves as the driving force behind the risk of HFH.

Machine learning insights into thrombo-ischemic risks and bleeding events through platelet lysophospholipids and acylcarnitine species.

Coronary artery disease (CAD) often leads to adverse events resulting in significant disease burdens. Underlying risk factors often remain inapparent prior to disease incidence and the cardiovascular (CV) risk is not exclusively explained by traditional risk factors. Platelets inherently promote atheroprogression and enhanced platelet functions and distinct platelet lipid species are associated with disease severity in patients with CAD. Lipidomics data were acquired using mass spectrometry and processed alongside clinical data applying machine learning to model estimates of an increased CV risk in a consecutive CAD cohort (n = 595). By training machine learning models on CV risk measurements, stratification of CAD patients resulted in a phenotyping of risk groups. We found that distinct platelet lipids are associated with an increased CV or bleeding risk and independently predict adverse events. Notably, the addition of platelet lipids to conventional risk factors resulted in an increased diagnostic accuracy of patients with adverse CV events. Thus, patients with aberrant platelet lipid signatures and platelet functions are at elevated risk to develop adverse CV events. Machine learning combining platelet lipidome data and common clinical parameters demonstrated an increased diagnostic value in patients with CAD and might improve early risk discrimination and classification for CV events.

Thrombus architecture is influenced by the antiplatelet loading treatment in patients with acute myocardial infarction.

BACKGROUND: Intracoronary thrombus formation is a main cause of acute myocardial infarction triggered by platelet activation. However, there are no data on the impact of different treatment strategies with antiplatelet agents before percutaneous coronary intervention (PCI) on histological characteristics of thrombus formation. OBJECTIVE: In this study, we investigate the impact of preinterventional administration of the P2Y12-inhibitors clopidogrel and prasugrel on thrombus composition, highlighting significant changes associated with the antiplatelet pre-treatment. METHODS: We prospectively enrolled 104 consecutive patients with ST-segment elevation myocardial infarction (STEMI) undergoing immediate PCI and thrombus aspiration by immunohistochemical staining along with RNA-sequencing employing Nanostring analysis. Fifty-two patients were treated with either prasugrel loading (60 mg) or clopidogrel loading (600 mg) prior to PCI, respectively. RESULTS: In Patients with STEMI, intracoronary thrombus architecture was significantly altered between patients pre-treated with prasugrel when compared to clopidogrel. Fibrin content of thrombi was significantly decreased (41.8 % versus 66.7 %, p = 0.009) after pre-treatment with prasugrel compared to clopidogrel. Furthermore, levels of MPO positive cells in intracoronary thrombi were significantly decreased in patients with prasugrel pre-treatment (90.5 versus 201.1, p = 0.014) indicating an association of antiplatelet pre-treatment and the inflammatory responses during thrombus formation. Most strikingly, we observed significant differences among both pre-treatment groups regarding altered RNA expression and signaling pathways of thrombo-inflammatory processes within the thrombotic material, which were independently associated with antiplatelet strategies. CONCLUSIONS: Our study elucidates the impact of antiplatelet pre-treatment on thrombus remodeling and architecture, thereby lowering the risk of recurrent adverse cardiovascular events in prasugrel-treated patients.

Platelet miRNAs: differential expression in coronary artery disease and associations with course of left ventricular systolic function.

BACKGROUND: MicroRNAs are paramount in post transcriptional gene regulation. We investigated platelet miRNAs in patients with CAD and examined potential associations with course of left ventricular ejection fraction (LVEF%). MATERIALS AND METHODS: In a first cohort, 62 MiRNAs were measured in platelets of 100 patients suffering from CAD. Expression profiles of individuals with chronic coronary syndrome (CCS) and MI were compared (CCS n = 67, MI n = 33). Also, associations between miRNA profiles and change in left ventricular ejection fraction (LVEF%) were investigated. In a second cohort of patients suffering from CCS (n = 10), MI (n = 11) or no CAD (n = 13), we measured miRNA expression in platelets, platelet supernatant and serum. This was carried out before and after in vitro platelet activation with CRP. RESULTS: Platelet miRNAs 103a-3p and 155-5p demonstrated higher expression in patients with CCS then in individuals with MI. Furthermore, multiple miRNAs were significantly higher expressed in matched controls compared to MI patients. 8 miRNAs showed higher expression in patients with improving LVEF% after a 1-year follow-up. In our second cohort, we found higher concentrations of 6 miRNAs in the platelet supernatant of patients with CCS, MI and no CAD after in vitro platelet activation. Most of these miRNAs showed a higher abundance in serum of MI patients as compared to CCS. CONCLUSION: Several miRNAs show higher expression in platelets of CCS compared to MI. After in vitro platelet activation, a release of multiple miRNAs out of the thrombocyte was observed. Furthermore, upregulation of serum miRNAs was found in MI patients when compared to CCS patients and individuals without CAD. Hence, platelets could present a source of upregulated circulating miRNAs in MI and additionally affect course of LVEF%.

Large-scale lipidomics profiling reveals characteristic lipid signatures associated with an increased cardiovascular risk.

BACKGROUND AND AIMS: Patients with cardiovascular disease (CVD) are at high risk to develop adverse events. The distinct risk of developing adverse cardiovascular (CV) events is not solely explained by traditional risk factors. Platelets are essentially involved in progression of CVD including coronary artery disease (CAD) and platelet hyperreactivity leads to development of adverse CV events. Alterations in the platelet lipidome lead to platelet hyperresponsiveness and thus might alter the individual risk profile. In this study, we investigate the platelet lipidome of CAD patients by untargeted lipidomics and elucidate alterations in the lipid composition of patients with adverse CV events. METHODS: We characterized the platelet lipidome in a large consecutive CAD cohort (n = 1057) by an untargeted lipidomics approach using liquid chromatography coupled to mass spectrometry. RESULTS: The platelet lipidome in this study identified 767 lipids and characteristic changes occurred in patients with adverse CV events. The most prominent upregulated lipids in patients with cardiovascular events primarily belong to the class of phospholipids and fatty acyls. Further, upregulated platelet lipids are associated with an increased cardiovascular or bleeding risk and independently associated with adverse events. In addition, alterations of the platelet lipidome are associated with modulation of in vitro platelet functions. CONCLUSIONS: Our results reveal that the composition of the platelet lipidome is altered in CVD patients with an increased cardiovascular risk and distinct platelet lipids may indicate adverse events. Results of this study may contribute to improved risk discrimination and classification for cardiovascular events in patients with CVD. Main findings of this study and hypothetical impact of altered platelet lipid signatures in patients with adverse cardiovascular events on platelet function and clinical outcome. LPE lysophosphatidylethanolamines, CAR acylcarnitines, FA fatty acids.

Platelet versus plasma CXCL14, coronary artery disease, and clinical outcomes.

Background: Platelets express CXCL14, while platelet-derived CXCL14 induces monocyte chemotaxis and exerts an angiostatic effect on endothelial cells. Objectives: This study investigated both platelet surface-associated and circulating levels of CXCL14 in patients with heart disease and associations of this chemokine with myocardial function and outcomes in patients with coronary artery disease (CAD). Methods: This prospective study enrolled 450 patients with symptomatic heart disease. Platelet surface-associated and plasma CXCL14 levels were analyzed. All patients were followed up for 360 days for a primary composite outcome consisting of all-cause mortality, myocardial infarction, and/or ischemic stroke. Secondary outcomes consisted of the single events of all-cause mortality or myocardial infarction. Results: Baseline platelet-associated but not circulating CXCL14 levels were significantly lower in patients with chronic coronary syndrome (mean fluorescence intensity logarithmized, 1.35 ± 0.35) when compared to those with acute coronary syndrome (1.47 ± 0.38) and without CAD (1.51 ± 0.40). Platelet CXCL14 levels were significantly lower (1.37 ± 0.37 vs 1.48 ± 0.39) and circulating CXCL14 levels were significantly higher (lg, 2.88 ± 0.20 pg/mL vs 2.82 ± 0.26 pg/mL) in patients with normal baseline left ventricular ejection fraction (LVEF) when compared to those with impaired LVEF. Low baseline circulating CXCL14 (hazard ratio, 2.33; 1.00-5.46) but not platelet CXCL14 was associated with worse outcome in patients with CAD. Conclusion: Platelet-associated and circulating CXCL14 levels show differential regulation in patients with and without CAD. Although platelet-associated CXCL14 increased and circulating CXCL14 decreased with impairment of LVEF, only lower circulating CXCL14 upon admission was associated with worse prognosis in patients with CAD.

Leaving Your Buddy in Jail: A Simplified Approach to the Jailed Buddy Wire Technique.

Stent delivery into highly tortuous and/or calcified coronary lesions represents a challenging problem during PCI. In this case series of 7 patients with complex coronary lesions, we had a hard time delivering larger and thus bulkier stents. We used a buddy wire and delivered a stent into the most distal lesion and jailed the buddy wire. We left the wire jailed during the whole procedure and were easily able to deliver large and long stents to the more proximal lesions. Retrieval of the buddy wire was possible without problems in all cases. The "leaving your buddy in jail" technique provides an excellent support and allows facilitated delivery and deployment of multiple stents, if necessary overlapping stents, into challenging coronary lesions.

Deceleration capacity of heart rate predicts 1-year mortality in patients undergoing transcatheter edge-to-edge mitral valve repair.

BACKGROUND: Risk stratification for transcatheter procedures in patients with severe mitral regurgitation is challenging. Deceleration capacity (DC) has already proven to be a reliable risk predictor in patients undergoing transcatheter aortic valve implantation. We hypothesized, that DC provides prognostic value in patients undergoing transcatheter edge-to-edge mitral valve repair (TEER). METHODS: We retrospectively analyzed electrocardiogram signals from 106 patients undergoing TEER at the University Hospital of Tübingen. All patients received continuous heart-rate monitoring to assess DC following the procedure. One-year all-cause mortality was defined as the primary end point. RESULTS: Sixteen patients (15.1%) died within 1 year. The DC in nonsurvivors was significantly reduced compared to survivors (5.1 ± 3.0 vs. 3.0 ± 1.6 ms, p = 0.002). A higher EuroSCORE II and impaired left ventricular function were furthermore associated with poor outcome. In Cox regression analyses, a DC < 4.5 ms was found a strong predictor of 1-year mortality (hazard ratio: 0.10, 95% confidence interval: 0.13-0.79, p = 0.029). Finally, a significant negative correlation was found between DC and residual mitral regurgitation after TEER (r = -0.41, p < 0.001). CONCLUSION: In patients with severe mitral regurgitation undergoing TEER, DC may serve as a new predictor of follow-up mortality.

Statin Treatment Is Associated with Alterations in the Platelet Lipidome.

BACKGROUND: Platelets are key players in the pathophysiology of coronary artery disease (CAD) and platelet hyperreactivity leads to increased risk of developing adverse cardiovascular events. Further, significant changes in the platelet lipidome occur in patients with acute coronary syndrome (ACS) and critically regulated lipids lead to platelet hyperresponsiveness. Statin treatment is crucial in the treatment and prevention of patients with CAD by remodeling lipid metabolism. OBJECTIVE: In this study, we investigate the platelet lipidome of CAD patients by untargeted lipidomics, highlighting significant changes between statin-treated and naïve patients. METHODS: We characterized the platelet lipidome in a CAD cohort (n = 105) by an untargeted lipidomics approach using liquid chromatography coupled to mass spectrometry. RESULTS: Among the annotated lipids, 41 lipids were significantly upregulated in statin-treated patients, whereas 6 lipids were downregulated compared to naïve patients. The most prominent upregulated lipids in statin-treated patients belong to the class of triglycerides, cholesteryl esters, palmitic acid, and oxidized phospholipids, whereas mainly glycerophospholipids were downregulated compared to untreated patients. A more pronounced effect of statin treatment on the platelet lipidome was observed in ACS patients. We further highlight a dose-dependent influence on the platelet lipidome. CONCLUSION: Our results reveal that the platelet lipidome is altered in CAD patients with statin treatment and upregulated lipids embody mainly characteristic triglycerides, whereas downregulated lipids mostly compromise glycerophospholipids, which may play a role in the pathophysiology of CAD. Results of this study may contribute to the understanding of statin treatment softening the lipid phenotype.

Free-breathing Arterial Spin Labeling MRI for the Detection of Pulmonary Embolism.

Background Arterial spin labeling (ASL) MRI can be used to assess organ perfusion but has yet to be implemented for perfusion evaluation of the lung. Purpose To evaluate pseudo-continuous ASL (PCASL) MRI for the detection of acute pulmonary embolism (PE) and its potential as an alternative to CT pulmonary angiography (CTPA). Materials and Methods Between November 2020 and November 2021, 97 patients (median age, 61 years; 48 women) with suspected PE were enrolled in this prospective study. PCASL MRI was performed within a 72-hour period following CTPA under free-breathing conditions and included three orthogonal planes. The pulmonary trunk was labeled during systole, and the image was acquired during diastole of the subsequent cardiac cycle. Additionally, multisection, coronal, balanced, steady-state free-precession imaging was carried out. Two radiologists blindly assessed overall image quality, artifacts, and diagnostic confidence (five-point Likert scale, 5 = best). Patients were categorized as positive or negative for PE, and a lobe-wise assessment in PCASL MRI and CTPA was conducted. Sensitivity and specificity were calculated on a patient level with the final clinical diagnosis serving as the reference standard. Interchangeability between MRI and CTPA was also tested with use of an individual equivalence index (IEI). Results PCASL MRI was performed successfully in all patients with high scores for image quality, artifact, and diagnostic confidence (κ ≥ .74). Of the 97 patients, 38 were positive for PE. PCASL MRI depicted PE correctly in 35 of 38 patients with three false-positive and three false-negative findings, resulting in a sensitivity of 35 of 38 patients (92% [95% CI: 79, 98]) and a specificity of 56 of 59 patients (95% [95% CI: 86, 99]). Interchangeability analysis revealed an IEI of 2.6% (95% CI: 1.2, 3.8). Conclusion Free-breathing pseudo-continuous arterial spin labeling MRI depicted abnormal lung perfusion caused by acute pulmonary embolism and may be useful as a contrast material-free alternative to CT pulmonary angiography for selected patients. German Clinical Trials Register no. DRKS00023599 © RSNA, 2023.

Resumption of Antiplatelet Therapy after Major Bleeding.

Major bleeding is a common threat in patients requiring antiplatelet therapy. Timing and intensity with regard to resumption of antiplatelet therapy represent a major challenge in clinical practice. Knowledge of the patient's bleeding risk, defining transient/treatable and permanent/untreatable risk factors for bleeding, and weighing these against thrombotic risk are key to successful prevention of major adverse events. Shared decision-making involving various disciplines is essential to determine the optimal strategy. The present article addresses clinically relevant questions focusing on the most life-threatening or frequently occurring bleeding events, such as intracranial hemorrhage and gastrointestinal bleeding, and discusses the evidence for antiplatelet therapy resumption using individual risk assessment in high-risk cardiovascular disease patients.

Recovery of systemic hyperinflammation in patients with severe SARS-CoV-2 infection.

INTRODUCTION: Patients with cardiovascular disease (CVD) and acute SARS-CoV-2 infection might show an altered immune response during COVID-19. MATERIAL AND METHODS: Twenty-three patients with CVD and SARS-CoV-2 infection were prospectively enrolled and received a cardiological assessment at study entry and during follow-up visit. Inclusion criteria of our study were age older than 18 years, presence of CVD, and acute SARS-CoV-2 infection. The median age of the patient cohort was 69 (IQR 55-79) years. 12 (52.2%) patients were men. Peripheral monocytes and chemokine/cytokine profiles were analysed. RESULTS: Numbers of classical and non-classical monocytes were significantly decreased during acute SARS-CoV-2 infection compared to 3-month recovery. While classical monocytes reached the expected level in peripheral blood after 3 months, the number of non-classical monocytes remained significantly reduced. DISCUSSION: All three monocyte subsets exhibited changes of established adhesion and activation markers. Interestingly, they also expressed higher levels of pro-inflammatory cytokines like macrophage migration inhibitory factor (MIF) at the time of recovery, although MIF was only slightly increased during the acute phase. CONCLUSION: Changes of monocyte phenotypes and increased MIF expression after 3-month recovery from acute SARS-CoV-2 infection may indicate persistent, possibly long-lasting, pro-inflammatory monocyte function in CVD patients.

Platelet SR-PSOX/CXCL16-CXCR6 Axis Influences Thrombotic Propensity and Prognosis in Coronary Artery Disease.

Platelets express the transmembrane chemokine SR-PSOX/CXCL16, proteolytic cleavage of which generates the sCXCL16 soluble-(s) chemokine. The sCXCL16 engages CXCR6 on platelets to synergistically propagate degranulation, aggregation and thrombotic response. Currently, we have investigated the pro-thrombotic and prognostic association of platelet CXCL16−CXCR6 axis in CAD-(n = 240; CCS n = 62; ACS n = 178) patients. Platelet surface-associated-CXCL16 and CXCR6 surface expression ascertained by flow cytometry correlated significantly with platelet activation markers (CD62P denoting degranulation and PAC-1 binding denoting α2bß3-integrin activation). Higher platelet CXCL16 surface association (1st quartile vs. 2nd−4th quartiles) corresponded to significantly elevated collagen-induced platelet aggregation assessed by whole blood impedance aggregometry. Platelet-CXCL16 and CXCR6 expression did not alter with dyslipidemia, triglyceride, total cholesterol, or LDL levels, but higher (>median) plasma HDL levels corresponded with decreased platelet-CXCL16 and CXCR6. Although platelet-CXCL16 and CXCR6 expression did not change significantly with or correlate with troponin I levels, they corresponded with higher Creatine Kinase-(CK) activity and progressively deteriorating left ventricular ejection fraction (LVEF) at admission. Elevated-(4th quartile) platelet-CXCL16 (p = 0.023) and CXCR6 (p = 0.030) measured at admission were significantly associated with a worse prognosis. However, after Cox-PH regression analysis, only platelet-CXCL16 was ascertained as an independent predictor for all-cause of mortality. Therefore, the platelet CXCL16−CXCR6 axis may influence thrombotic propensity and prognosis in CAD patients.

Risk assessment in COVID-19: Prognostic importance of cardiovascular parameters.

BACKGROUND: Cardiovascular risk factors and comorbidities are highly prevalent among COVID-19 patients and are associated with worse outcomes. HYPOTHESIS: We therefore investigated if established cardiovascular risk assessment models could efficiently predict adverse outcomes in COVID-19. Furthermore, we aimed to generate novel risk scores including various cardiovascular parameters for prediction of short- and midterm outcomes in COVID-19. METHODS: We included 441 consecutive patients diagnosed with SARS-CoV-2 infection. Patients were followed-up for 30 days after the hospital admission for all-cause mortality (ACM), venous/arterial thromboembolism, and mechanical ventilation. We further followed up the patients for post-COVID-19 syndrome for 6 months and occurrence of myocarditis, heart failure, acute coronary syndrome (ACS), and rhythm events in a 12-month follow-up. Discrimination performance of DAPT, GRACE 2.0, PARIS-CTE, PREDICT-STABLE, CHA2-DS2-VASc, HAS-BLED, PARIS-MB, PRECISE-DAPT scores for selected endpoints was evaluated by ROC-analysis. RESULTS: Out of established risk assessment models, GRACE 2.0 score performed best in predicting combined endpoint and ACM. Risk assessment models including age, cardiovascular risk factors, echocardiographic parameters, and biomarkers, were generated and could successfully predict the combined endpoint, ACM, venous/arterial thromboembolism, need for mechanical ventilation, myocarditis, ACS, heart failure, and rhythm events. Prediction of post-COVID-19 syndrome was poor. CONCLUSION: Risk assessment models including age, laboratory parameters, cardiovascular risk factors, and echocardiographic parameters showed good discrimination performance for adverse short- and midterm outcomes in COVID-19 and outweighed discrimination performance of established cardiovascular risk assessment models.

Homophilic Interaction Between Transmembrane-JAM-A and Soluble JAM-A Regulates Thrombo-Inflammation: Implications for Coronary Artery Disease.

Genetic predisposition through F11R-single-nucleotide variation (SNV) influences circulatory soluble junctional adhesion molecule-A (sJAM-A) levels in coronary artery disease (CAD) patients. Homozygous carriers of the minor alleles (F11R-SNVs rs2774276, rs790056) show enhanced levels of thrombo-inflammatory sJAM-A. Both F11R-SNVs and sJAM-A are associated with worse prognosis for recurrent myocardial infarction in CAD patients. Platelet surface-associated JAM-A correlate with platelet activation markers in CAD patients. Activated platelets shed transmembrane-JAM-A, generating proinflammatory sJAM-A and JAM-A-bearing microparticles. Platelet transmembrane-JAM-A and sJAM-A as homophilic interaction partners exaggerate thrombotic and thrombo-inflammatory platelet monocyte interactions. Therapeutic strategies interfering with this homophilic interface may regulate thrombotic and thrombo-inflammatory platelet response in cardiovascular pathologies where circulatory sJAM-A levels are elevated.

COVID-19 versus seasonal influenza: myocardial injury and prognostic importance.

BACKGROUND: Acute myocardial injury is associated with poor prognosis in respiratory tract infections. We aimed to highlight the differences in prevalence of myocardial injury and its impact on prognosis in patients with COVID-19 compared to those with seasonal influenza. METHODS: This was a single-center prospective cohort study with a historical control group. 300 age-/sex-matched SARS-CoV-2 and seasonal influenza positive patients were enrolled. Myocardial injury was assessed by electrocardiogram (ECG), transthoracic echocardiography and biomarkers including high-sensitivity troponin-I. All patients were followed-up for 30 days after enrollment for all-cause mortalitiy, admission to the intensive care unit (ICU) and mechanical ventilation. RESULTS: Right ventricular distress was more common in COVID-19 whereas pathological ECG findings and impaired left ventricular function were more prevalent among influenza patients. COVID-19 patients suffered from a higher percentage of hypertension and dyslipidaemia. Contrary to COVID-19, pericardial effusion at admission was associated with poor outcome in the influenza group. Severe course of disease and respiratory failure resulted in significantly higher rates of ICU treatment and mechanical ventilation in COVID-19 patients. Although distribution of myocardial injury was similar, significantly fewer cardiac catheterizations were performed in COVID-19 patients. However, number of cardiac catheterizations was low in both groups. Finally, 30-day mortality was significantly higher in COVID-19 compared to influenza patients. CONCLUSIONS: In adults requiring hospitalization due to COVID-19 or seasonal influenza, cardiovascular risk factors and signs of myocardial distress differ significantly. Furthermore, cardiovascular comorbidities may impair prognosis in COVID-19 patients to a higher degree than in their influenza counterparts.

ACKR3 regulates platelet activation and ischemia-reperfusion tissue injury.

Platelet activation plays a critical role in thrombosis. Inhibition of platelet activation is a cornerstone in treatment of acute organ ischemia. Platelet ACKR3 surface expression is independently associated with all-cause mortality in CAD patients. In a novel genetic mouse strain, we show that megakaryocyte/platelet-specific deletion of ACKR3 results in enhanced platelet activation and thrombosis in vitro and in vivo. Further, we performed ischemia/reperfusion experiments (transient LAD-ligation and tMCAO) in mice to assess the impact of genetic ACKR3 deficiency in platelets on tissue injury in ischemic myocardium and brain. Loss of platelet ACKR3 enhances tissue injury in ischemic myocardium and brain and aggravates tissue inflammation. Activation of platelet-ACKR3 via specific ACKR3 agonists inhibits platelet activation and thrombus formation and attenuates tissue injury in ischemic myocardium and brain. Here we demonstrate that ACKR3 is a critical regulator of platelet activation, thrombus formation and organ injury following ischemia/reperfusion.

Venous Thrombosis and SARS-CoV-2.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is associated with high risk of venous and arterial thrombosis. Thrombotic complications, especially pulmonary embolism, lead to increased all-cause mortality in both intensive care unit and noncritically ill patients. Damage and activation of vascular endothelium, platelet activation, followed by thrombotic and fibrinolytic imbalance as well as hypercoagulability are the key pathomechanisms in immunothrombosis leading to a significant increase in thromboembolism in coronavirus disease 2019 (COVID-19) compared with other acute illnesses. In this review article, we discuss the incidence and prognosis, diagnosis, prevention, and treatment of venous thromboembolism in patients with COVID-19 disease, based on clinical experience and research available to date.