scholarly journals Cytotoxic CD8+ T cells promote granzyme B-dependent adverse post-ischemic cardiac remodeling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Icia Santos-Zas ◽  
Jeremie Lemarié ◽  
Ivana Zlatanova ◽  
Marine Cachanado ◽  
Jean-Christophe Seghezzi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
T Cells ◽  
T Lymphocytes ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Granzyme B ◽  
Acute Ischemia ◽  
Risk Of Death ◽  
Increased Risk

AbstractAcute myocardial infarction is a common condition responsible for heart failure and sudden death. Here, we show that following acute myocardial infarction in mice, CD8+ T lymphocytes are recruited and activated in the ischemic heart tissue and release Granzyme B, leading to cardiomyocyte apoptosis, adverse ventricular remodeling and deterioration of myocardial function. Depletion of CD8+ T lymphocytes decreases apoptosis within the ischemic myocardium, hampers inflammatory response, limits myocardial injury and improves heart function. These effects are recapitulated in mice with Granzyme B-deficient CD8+ T cells. The protective effect of CD8 depletion on heart function is confirmed by using a model of ischemia/reperfusion in pigs. Finally, we reveal that elevated circulating levels of GRANZYME B in patients with acute myocardial infarction predict increased risk of death at 1-year follow-up. Our work unravels a deleterious role of CD8+ T lymphocytes following acute ischemia, and suggests potential therapeutic strategies targeting pathogenic CD8+ T lymphocytes in the setting of acute myocardial infarction.

scholarly journals Cytotoxic CD8+ T Cells Promote Granzyme B-Dependent Adverse Post-Ischemic Cardiac Remodeling

2020 ◽  
Author(s):  
Icia Santos Zas ◽  
Jeremie Lemarie ◽  
Ivana Zlatanova ◽  
Marine Cachanado ◽  
Jean-Christophe Seghezzi ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Ventricular Remodeling ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Granzyme B ◽  
Acute Ischemia ◽  
Risk Of Death ◽  
Increased Risk ◽  
Acute Mi

Abstract Acute myocardial infarction (MI) is a common condition responsible for heart failure and sudden death. Here, we show that following acute MI in mice, CD8+ T lymphocytes are recruited and activated in the ischemic heart tissue, and release Granzyme B leading to cardiomyocyte apoptosis, adverse ventricular remodeling and deterioration of myocardial function. Depletion of CD8+ T lymphocytes decreases apoptosis within the ischemic myocardium, hampers inflammatory response, limits myocardial injury and improves heart function. These effects are recapitulated in mice with Granzyme B-deficient CD8+ T cells. The protective effect of CD8 depletion on heart function was confirmed by using a model of ischemia/reperfusion in pigs. Finally, we reveal that elevated circulating levels of Granzyme B in patients with acute MI predict increased risk of death at 1-year follow-up. Our work unravels an unsuspected deleterious role of CD8+ T lymphocytes following acute ischemia, and identifies novel therapeutic strategy targeting pathogenic CD8+ T lymphocytes in the setting of acute MI.

D-dimer and the incidence of heart failure and mortality after acute myocardial infarction

Heart ◽  
2020 ◽  
pp. heartjnl-2020-316880 ◽  
Author(s):  
Xiaoyuan Zhang ◽  
Shanjie Wang ◽  
Jinxin Liu ◽  
Yini Wang ◽  
Hengxuan Cai ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Plaque Rupture ◽  
Risk Of Death ◽  
Increased Risk ◽  
Clinical Covariates ◽  
All Cause Mortality ◽  
D Dimer

ObjectiveD-dimer might serve as a marker of thrombogenesis and a hypercoagulable state following plaque rupture. Few studies explore the association between baseline D-dimer levels and the incidence of heart failure (HF), all-cause mortality in an acute myocardial infarction (AMI) population. We aimed to explore this association.MethodsWe enrolled 4504 consecutive patients with AMI with complete data in a prospective cohort study and explored the association of plasma D-dimer levels on admission and the incidence of HF, all-cause mortality.ResultsOver a median follow-up of 1 year, 1112 (24.7%) patients developed in-hospital HF, 542 (16.7%) patients developed HF after hospitalisation and 233 (7.1%) patients died. After full adjustments for other relevant clinical covariates, patients with D-dimer values in quartile 3 (Q3) had 1.51 times (95% CI 1.12 to 2.04) and in Q4 had 1.49 times (95% CI 1.09 to 2.04) as high as the risk of HF after hospitalisation compared with patients in Q1. Patients with D-dimer values in Q4 had more than a twofold (HR 2.34; 95% CI 1.33 to 4.13) increased risk of death compared with patients in Q1 (p<0.001). But there was no association between D-dimer levels and in-hospital HF in the adjusted models.ConclusionsD-dimer was found to be associated with the incidence of HF after hospitalisation and all-cause mortality in patients with AMI.

scholarly journals Does sacubitril/valsartan work in acute myocardial infarction? The PARADISE-AMI study

2021 ◽  
Vol 23 (Supplement_E) ◽  
pp. E87-E90
Author(s):  
Laura Gatto
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Left Ventricular Dysfunction ◽  
Clinical Studies ◽  
Ventricular Dysfunction ◽  
Left Ventricular ◽  
Laboratory Animals ◽  
Risk Of Death ◽  
Increased Risk

Abstract Patients with acute myocardial infarction (AMI) complicated by left ventricular dysfunction have an increased risk of death and heart failure. Numerous clinical studies have demonstrated the ability of ACE inhibitors in optimizing the outcome in this particular clinical setting. In recent years, the sacubitril/valsartan association has drastically improved the prognosis of patients with heart failure with reduced ejection fraction with a significant decrease in mortality from cardiovascular causes and hospitalizations due to acute heart failure. However, it has not yet been fully clarified whether this pharmacological association may play a role in patients with AMI. Pre-clinical studies have suggested the possibility that sacubitril/valsartan can reduce the size of the infarct scar and prevent the onset of ventricular arrhythmias in laboratory animals in which myocardial infarction was induced. On the other hand, small clinical experiences with patients after myocardial infarction have provided conflicting data. The results of the PARADISE-MI study were recently presented, which enrolled 5661 patients with AMI complicated by pulmonary congestion and left ventricular dysfunction randomized to therapy with ramipril or sacubitril/valsartan and followed up for ∼2 years. Although combination therapy was associated with an ∼10% reduction in the risk of death from cardiovascular causes or an episode of heart failure, this was not enough to achieve statistical significance. However, treatment with sacubitril/valsartan was shown to be more effective than ramipril in preventing recurrence of heart failure after the first one.

scholarly journals Long-term outcome of patients with invasive electrophysiology procedure-related cardiac tamponade

EP Europace ◽  
2020 ◽  
Vol 22 (10) ◽  
pp. 1547-1557
Author(s):  
Gesa von Olshausen ◽  
Tara Bourke ◽  
Jonas Schwieler ◽  
Nikola Drca ◽  
Hamid Bastani ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Cardiac Tamponade ◽  
Cardiovascular Events ◽  
Control Group ◽  
Risk Of Death ◽  
Increased Risk

Abstract Aims Iatrogenic cardiac tamponades are a rare but dreaded complication of invasive electrophysiology procedures (EPs). Their long-term impact on clinical outcomes is unknown. This study analysed the risk of death or serious cardiovascular events in patients suffering from EP-related cardiac tamponade requiring pericardiocentesis during long-term follow-up. Methods and results Out of 19 997 invasive EPs at the Karolinska University Hospital between January 1998 and September 2018, all patients with EP-related periprocedural cardiac tamponade were identified (n = 60) and matched (1:3 ratio) to a control group (n = 180). After a follow-up of 5 years, the composite primary endpoint — death from any cause, acute myocardial infarction, transitory ischaemic attack (TIA)/stroke, and hospitalization for heart failure — occurred in significantly more patients in the tamponade than in the control group [12 patients (20.0%) vs. 19 patients (10.6%); hazard ratio (HR) 2.53 (95% confidence interval, CI 1.15–5.58); P = 0.021]. This was mainly driven by a higher incidence of TIA/stroke in the tamponade than in the control group [HR 3.75 (95% CI 1.01–13.97); P = 0.049]. Death from any cause, acute myocardial infarction, and hospitalization for heart failure did not show a significant difference between the groups. Hospitalization for pericarditis occurred in significantly more patients in the tamponade than in the control group [HR 36.0 (95% CI 4.68–276.86); P = 0.001]. Conclusion Patients with EP-related cardiac tamponade are at higher risk for cerebrovascular events during the first 2 weeks and hospitalization for pericarditis during the first months after index procedure. Despite the increased risk for early complications tamponade patients have a good long-term prognosis without increased risk for mortality or other serious cardiovascular events.

scholarly journals Risk of ischemic stroke in patients with acute myocardial infarction and new atrial fibrillation: a nationwide analysis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Fauchier ◽  
A Bisson ◽  
A Bodin ◽  
J Herbert ◽  
T Genet ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Acute Myocardial Infarction ◽  
Ischemic Stroke ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Risk Of Death ◽  
Increased Risk ◽  
History Of

Abstract Background In patients with acute myocardial infarction (AMI), history of atrial fibrillation (AF) and new onset AF during the early phase may be associated with a worse prognosis. Whether both conditions are associated with a similar risk of stroke and should be similarly managed is a matter of debate. Methods Based on the administrative hospital-discharge database, we collected information for all patients treated with AMI between 2010 and 2019 in France. The adverse outcomes were investigated during follow-up. Results Among 797,212 patients with STEMI or NSTEMI, 146,922 (18.4%) had history of AF, and 11,824 (1.5%) had new AF diagnosed between day 1 and day 30 after AMI. Patients with new AF were older and had more comorbidities than those with no AF but were younger and had less comorbidities than those with history of AF. Both groups with history of AF or new AF had less frequent STEMI and anterior MI, less frequent use of percutaneous coronary intervention but more frequent HF at the acute phase than patients with no AF. During follow-up (mean [SD] 1.8 [2.4] years, median [interquartile range] 0.7 [0.1–3.1] years), 163,845 deaths and 20,168 ischemic strokes were recorded. Using Cox multivariable analysis, compared to patients with no AF, history of AF was associated with a higher risk of death during follow-up (adjusted hazard ratio HR 1.06 95% CI 1.05–1.08) while this was not the case for patients with new AF (adjusted HR 0.98 95% CI 0.95–1.02). By contrast, both history of AF and new AF were associated with a higher risk of ischemic stroke during follow-up compared to patients with no AF: adjusted hazard ratio HR 1.29 95% CI 1.25–1.34 for history of AF, adjusted HR 1.72 95% CI 1.59–1.85 for new AF. New AF was associated with a higher risk of ischemic stroke than history of AF (adjusted HR 1.38 95% CI 1.27–1.49). Conclusion In a large and systematic nationwide analysis, AF first recorded in the first 30 days after AMI was associated with an increased risk of ischemic stroke. Specific management should be considered in order to improve outcomes in these patients after AMI. Funding Acknowledgement Type of funding source: None

scholarly journals Characterization of Circulating IL-10-Producing Cells in Septic Shock Patients: A Proof of Concept Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Astrid Fabri ◽  
Khalil Kandara ◽  
Rémy Coudereau ◽  
Morgane Gossez ◽  
Paul Abraham ◽  
...  
Keyword(s):  
Septic Shock ◽  
T Cells ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Whole Blood ◽  
Cd4 T Cells ◽  
Interleukin 10 ◽  
Risk Of Death ◽  
Hla Dr ◽  
Increased Risk

Sepsis is a worldwide health priority characterized by the occurrence of severe immunosuppression associated with increased risk of death and secondary infections. Interleukin 10 (IL-10) is a potent immunosuppressive cytokine which plasma concentration is increased in septic patients in association with deleterious outcomes. Despite studies evaluating IL-10 production in specific subpopulations of purified cells, the concomitant description of IL-10 production in monocytes and lymphocytes in septic patients’ whole blood has never been performed. In this pilot study, we characterized IL-10 producing leukocytes in septic shock patients through whole blood intracellular staining by flow cytometry. Twelve adult septic shock patients and 9 healthy volunteers were included. Intracellular tumor necrosis factor-α (TNFα) and IL-10 productions after lipopolysaccharide stimulation by monocytes and IL-10 production after PMA/Ionomycine stimulation by lymphocytes were evaluated. Standard immunomonitoring (HLA-DR expression on monocytes, CD4+ T lymphocyte count) of patients was also performed. TNFα expression by stimulated monocytes was reduced in patients compared with controls while IL-10 production was increased. This was correlated with a reduced monocyte HLA-DR expression. B cells, CD4+, and CD4- T lymphocytes were the three circulating IL-10 producing lymphocyte subsets in both patients and controls. No difference in IL-10 production between patients and controls was observed for B and CD4- T cells. However, IL-10 production by CD4+ T lymphocytes significantly increased in patients in parallel with reduced CD4+ T cells number. Parameters reflecting altered monocyte (increased IL-10 production, decreased HLA-DR expression and decreased TNFα synthesis) and CD4+ T lymphocyte (increased IL-10 production, decreased circulating number) responses were correlated. Using a novel technique for intracellular cytokine measurement in whole blood, our results identify monocytes and CD4+ T cells as the main IL-10 producers in septic patients’ whole blood and illustrate the development of a global immunosuppressive profile in septic shock. Overall, these preliminary results add to our understanding of the global increase in IL-10 production induced by septic shock. Further research is mandatory to determine the pathophysiological mechanisms leading to such increased IL-10 production in monocytes and CD4+ T cells.

scholarly journals Outcome of Thrombolysis in Acute Myocardial Infarction in a Tertiary Care Hospital

2019 ◽  
Vol 13 (2) ◽  
pp. 42-44
Author(s):  
Md Wali Ur Rahman ◽  
Syed Asif Iqbal ◽  
Syeda Aleya Sultana ◽  
Md Abdul Malek ◽  
Abu Yusuf Md Shahidul Alam ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Chest Pain ◽  
Thrombolytic Therapy ◽  
Complete Resolution ◽  
Left Ventricular ◽  
Military Hospital ◽  
Care Hospital ◽  
Risk Of Death ◽  
Increased Risk

Introduction: The main purpose of thrombolysis in acute myocardial infarction is early and complete reperfusion. Incomplete or delayed thrombolysis is associated with an increased risk of death and left ventricular dysfunction. The time to reperfusion and complete reperfusion remain the key determinants for appropriate outcome of cardiovascular events. Objective: To find out the effect of thrombolytic therapy and its outcome in relation with timing of thrombolysis and associated risk factors in ST elevated myocardial infarction (STEMI) patients. Materials and Methods: This cross-sectional interventional study was carried out in combined military hospital, Dhaka from July 2017 to May 2018. Total 85 patients of acute STEMI having specified criteria were selected and treated with Streptokinase at a dose of 1.5 million units diluted in 100 mL normal saline. Twelve-lead ECG was recorded immediately before the start of thrombolytic therapy and 180 min afterwards. Results: Among 85 STEMI patients 65 were male and the age range was 40-80 years. Sixty nine patients (81.2%) underwent thrombolysis within 12 hours of onset of chest pain among them complete resolution of ST segment occurs in 45(65.2%) patients while 16 patients (18.8%) received thrombolysis after 12 hours among them complete resolution occurs only in 7(43.8%) patients.  Fully reperfused patients have no complications. Patients having diabetes mellitus, presented with atypical chest pain and received thrombolytic therapy after 12 hours had various types of complication. Conclusion: STEMI patients received thrombolysis therapy within 12 hours of onset of chest pain responded well to thrombolytic therapy. Journal of Armed Forces Medical College Bangladesh Vol.13(2) 2017: 42-44

scholarly journals Targeting TLR4 with ApTOLL Improves Heart Function in Response to Coronary Ischemia Reperfusion in Pigs Undergoing Acute Myocardial Infarction

Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1167 ◽  
Author(s):  
Rafael Ramirez-Carracedo ◽  
Laura Tesoro ◽  
Ignacio Hernandez ◽  
Javier Diez-Mata ◽  
David Piñeiro ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Inflammatory Cytokines ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Triphenyltetrazolium Chloride ◽  
Gm Csf ◽  
Tissue Integrity ◽  
Coronary Ischemia ◽  
Masson Trichrome Staining

Toll-like receptor 4 (TLR4) contributes to the pathogenesis of coronary ischemia/reperfusion (IR). To test whether the new TLR4 antagonist, ApTOLL, may prevent coronary IR damage, we administered 0.078 mg/kg ApTOLL or Placebo in pigs subjected to IR, analyzing the levels of cardiac troponins, matrix metalloproteinases, pro-, and anti-inflammatory cytokines, heart function, and tissue integrity over a period of 7 days after IR. Our results show that ApTOLL reduced cardiac troponin-1 24 h after administration, improving heart function, as detected by a significant recovery of the left ventricle ejection fraction (LVEF) and the shortening fraction (FS) cardiac parameters. The extension of necrotic and fibrotic areas was also reduced, as detected by Evans blue/2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxylin/Eosine, and Masson Trichrome staining of heart sections, together with a significant reduction in the expression of the extracellular matrix-degrading, matrix metalloproteinase 9. Finally, the expression of the following cytokines, CCL1, CCL2, MIP1-A-B, CCL5, CD40L, C5/C5A, CXCL1, CXCL10, CXCL11, CXCL12, G-CSF, GM-CSF, ICAM-1, INF-g, IL1-a, ILI-b, IL-1Ra, IL2, IL4, IL5, IL6, IL8, IL10, IL12, IL13, IL16, IL17-A, IL17- E, IL18, IL21, IL27, IL32, MIF, SERPIN-E1, TNF-a, and TREM-1, were also assayed, detecting a pronounced decrease of pro-inflammatory cytokines after 7 days of treatment with ApTOLL. Altogether, our results show that ApTOLL is a promising new tool for the treatment of acute myocardial infarction (AMI).

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