scholarly journals Role of CMV-serostatus and CX3CR1 on lymphocyte kinetics and left ventricular remodelling in patients with acute myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Spray ◽  
C Park ◽  
S Cormack ◽  
A Mohammad ◽  
P Panahi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
T Cells ◽  
Lymphocyte Count ◽  
Microvascular Obstruction ◽  
Left Ventricular ◽  
Effector T Cells ◽  
T Cell Subsets ◽  
Cmv Status ◽  
Cx3cr1 Expression

Abstract Background Patients with latent cytomegalovirus (CMV) infection have higher rates of adverse cardiovascular outcomes, but the reasons for this remain elusive. CMV-induced changes to T-lymphocyte populations, with a proliferation of CMV-specific, CX3CR1+ effector memory cells, may contribute. Effector T-cells are associated with cardiovascular mortality in CMV positive patients, and ischaemia-reperfusion injury after ST-elevation myocardial infarction (STEMI) and primary percutaneous coronary intervention (pPCI). Purpose To investigate the effect of CMV status on lymphocyte kinetics and cardiac MRI (cMRI) parameters in 52 STEMI patients receiving pPCI, and examine the prognostic relevance of pre-reperfusion lymphocyte count in a large cohort. Methods We retrospectively analysed the association between pre-reperfusion lymphocyte count, troponin, and long-term survival in 4874 consecutive STEMI patients. Using flow cytometry, we analysed lymphocyte kinetics in 52 STEMI patients, of known CMV status, during and after pPCI. We assessed the impact of CMV status on infarct size, left-ventricular (LV) function and microvascular obstruction with cMRI in the first week after reperfusion in 101 patients. Repeat cMRI at 12 weeks, to assess LV remodelling, was obtained in 48 patients. Results Pre-reperfusion lymphopenia is an independent predictor of mortality over 7.5 years (hazard ratio for lowest vs highest quartile: 2.0; 95% CI 1.7–2.4; p<0.001), and is associated with higher admission troponins (p<0.001 for lowest vs second-lowest quartile), suggesting lymphocyte count falls prior to reperfusion in response to myocardial injury. CMV positive patients had more cytotoxic T-cells, strongly expressing the fractalkine receptor, CX3CR1. In CMV positive patients these cells fell dramatically by 90 minutes post-reperfusion, and dropped more sharply in patients with extensive microvascular obstruction on cMRI (p≤0.05 in all effector subsets). CX3CR1 expression was lower at 90 minutes post-reperfusion than at 24 hours (return to physiological expression) in all effector T-cell subsets. All subsets lost a similar proportion of their 24-hour value, but consistently lost a larger proportion in CMV positive patients (−27% in CMV+, −18% in CMV−; p=0.007). CX3CR1 expression falls in the presence of fractalkine, and we hypothesise that membrane-bound fractalkine is induced more strongly in CMV positive patients, as soluble fractalkine levels were similar. At 12 weeks, LV remodeling was worse in CMV positive patients (change in end-diastolic volume: +10.7ml vs −6.1ml; p=0.02). Conclusions Lymphopenia occurs prior to reperfusion in STEMI, and predicts long-term mortality. Effector T-cells drop substantially after reperfusion only in CMV positive patients, likely mediated by CX3CR1-fractalkine interaction, and this is associated with adverse cMRI findings. Remodeling is worse in CMV positive patients at 12 weeks post-STEMI. Lymphocytes, troponin and survival Funding Acknowledgement Type of funding source: Public Institution(s)

scholarly journals Electrical storm reveals worse prognosis compared to myocardial infarction complicated by ventricular tachyarrhythmias in ICD recipients

2021 ◽  
Author(s):  
Julian Müller ◽  
Michael Behnes ◽  
Tobias Schupp ◽  
Dominik Ellguth ◽  
Gabriel Taton ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Electrical Storm ◽  
Ventricular Tachyarrhythmias ◽  
Ventricular Ejection Fraction ◽  
St Segment ◽  
All Cause Mortality ◽  
Worse Prognosis

AbstractBoth acute myocardial infarction complicated by ventricular tachyarrhythmias (AMI–VTA) and electrical storm (ES) represent life-threatening clinical conditions. However, a direct comparison of both sub-groups regarding prognostic endpoints has never been investigated. All consecutive implantable cardioverter-defibrillator (ICD) recipients were included retrospectively from 2002 to 2016. Patients with ES apart from AMI (ES) were compared to patients with AMI accompanied by ventricular tachyarrhythmias (AMI–VTA). The primary endpoint was all-cause mortality at 3 years, secondary endpoints were in-hospital mortality, rehospitalization rates and major adverse cardiac event (MACE) at 3 years. A total of 198 consecutive ICD recipients were included (AMI–VTA: 56%; ST-segment elevation myocardial infarction (STEMI): 22%; non-ST-segment myocardial infarction (NSTEMI) 78%; ES: 44%). ES patients were older and had higher rates of severely reduced left ventricular ejection fraction (LVEF) < 35%. ES was associated with increased all-cause mortality at 3 years (37% vs. 19%; p = 0.001; hazard ratio [HR] = 2.242; 95% CI 2.291–3.894; p = 0.004) and with increased risk of first cardiac rehospitalization (44% vs. 12%; p = 0.001; HR = 4.694; 95% CI 2.498–8.823; p = 0.001). This worse prognosis of ES compared to AMI–VTA was still evident after multivariable adjustment (long-term all-cause mortality: HR = 2.504; 95% CI 1.093–5.739; p = 0.030; first cardiac rehospitalization: HR = 2.887; 95% CI 1.240–6.720; p = 0.014). In contrast, the rates of MACE (40% vs. 32%; p = 0.326) were comparable in both groups. At long-term follow-up of 3 years, ES was associated with higher rates of all-cause mortality and rehospitalization compared to patients with AMI–VTA.

scholarly journals Long-Term Depletion of Naive T Cells in Patients Treated for Hodgkin's Disease

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3662-3672 ◽  
Author(s):  
Nobukazu Watanabe ◽  
Stephen C. De Rosa ◽  
Anthony Cmelak ◽  
Richard Hoppe ◽  
Leonore A. Herzenberg ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Cell Counts

Abstract We investigated the representation of T cells in patients who had been treated for Hodgkin's disease (HD). We found a marked depletion in both CD4 and CD8 naive T-cell counts that persists up to 30 years after completion of treatment. In contrast, CD4 and CD8 memory T-cell subsets recovered to normal or above normal levels by 5 years posttreatment. Thus, the previously-reported long-term deficit in total CD4 T-cell counts after treatment for HD is due to specific depletion of naive T cells. Similarly, total CD8 T-cell counts return to normal by 5 years only because CD8 memory T cells expand to higher than normal levels. These findings suggest that the treatment (mediastinal irradiation) results in a longterm dysregulation of T-cell subset homeostasis. The profound depletion of naive T cells may explain the altered T-cell function in treated patients, including the poor response to immunization after treatment for HD. Further, in some individuals, we identified expansions of unusual subsets expressing low levels of CD8. Eight-color fluorescence-activated cell sorting analyses showed that these cells largely express CD8αα homodimers and CD57, consistent with the phenotype of potentially extrathymically derived T cells. In addition, these cells, both CD4+ and CD4−, are probably cytotoxic lymphocytes, as they express high levels of intracellular perforin. In adults treated for HD, an increased activity of extrathymic T-cell differentiation may partially compensate for the loss of thymic-derived T cells.

Abstract 424: Effector T Cells Induce Cardiac Fibroblasts Transition to Myofibroblasts & Contribute to Pressure Overload Induced Cardiac Fibrosis

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Tania A Nevers ◽  
Ane Salvador ◽  
Francisco Velazquez ◽  
Mark Aronovitz ◽  
Robert Blanton
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Pressure Overload ◽  
Effector T Cells ◽  
T Cell Subsets ◽  
Naive T Cells ◽  
Effector T Cell ◽  
Naïve T Cells

Background: Cardiac fibrogenesis is a major pathogenic factor that occurs in heart failure (HF) and results in contractile dysfunction and ventricular dilation. Recently, we showed that T cell deficient mice (TCRα -/- ) do not develop cardiac fibrosis (CF) and have preserved cardiac function in the thoracic aortic constriction (TAC) mouse model of pressure overload (PO). Specifically, CD4 + T cells are activated in the cardiac draining lymph nodes and infiltrate the LV, where the Th1 and Th17 effector T cell signature transcription factors are significantly upregulated as compared with control mice. However, the T cell subsets involved and the mechanisms by which they contribute to CF and pathogenesis of non-ischemic HF remains to be determined. Thus, we hypothesize that heart infiltrated effector T cells perpetuate the fibrotic response by regulating the differentiation and activation of extracellular matrix-producing cardiac myofibroblasts. Methods and Results: Naïve or effector T cells differentiated in vitro or isolated from mice undergoing TAC or Sham surgery were co-cultured with adult C57BL/6 cardiac fibroblasts (CFB). In contrast with naïve T cells, effector T cells and PO activated T cells strongly adhered to CFB and mediated fibroblast to myofibroblasts transition as depicted by immunofluorescence expression of SMAα. Effector T cell supernatants only slightly mediated this transition, indicating that effector T cells direct contact with CFB, rather than cytokine release is required to mediate CFB transformation. Adoptive transfer of effector, but not naïve T cells, into TCRα -/- recipient mice in the onset of TAC resulted in T cells infiltration into the left ventricle and increased CF. Conclusions: Our data indicate that CD4+ effector T cells directly interact with CFB to induce CF in response to PO induced CF. Future studies will determine the adhesion mechanisms regulating this crosstalk and evaluate the pro-fibrotic mechanisms induced and whether this is a T effector cell specific subset. These results will provide an attractive tool to counteract the inflammatory/fibrotic process as an alternative option for the treatment of CF in non- ischemic HF.

Abstract 12691: Long-term Optimal Medical Therapy for Patients With Mid-range Left Ventricular Ejection Fraction After Acute Myocardial Infarction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
YeeKyoung KO ◽  
Seungjae JOO ◽  
Jong Wook Beom ◽  
Jae-Geun Lee ◽  
Joon-Hyouk CHOI ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Left Ventricular Ejection Fraction ◽  
Medical Therapy ◽  
Beta Blockers ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Ras Inhibitors

Introduction: In the era of the initial optimal interventional and medical therapy for acute myocardial infarction (AMI), a number of patients with mid-range left ventricular ejection fraction (40% <EF<50%) becomes increasing. However, the long-term optimal medical therapy for these patients has been rarely studied. Aims: This observational study aimed to investigate the association between the medical therapy with beta-blockers or inhibitors of renin-angiotensin system (RAS) and clinical outcomes in patients with mid-range EF after AMI. Methods: Among 13,624 patients enrolled in the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH), propensity-score matched patients who survived the initial attack and had mid-range EF were selected according to beta-blocker or RAS inhibitor therapy at discharge. Results: Patients with beta-blockers showed significantly lower 1-year cardiac death (2.4 vs. 5.2/100 patient-year; hazard ratio [HR] 0.46; 95% confidence interval [CI] 0.22-0.98; P =0.045) and MI (1.7 vs. 4.0/100 patient-year; HR 0.41; 95% CI 0.18-0.95; P =0.037). On the other hand, RAS inhibitors were associated with lower 1-year re-hospitalization due to heart failure (2.8 vs. 5.5/100 patient-year; HR 0.54; 95% CI 0.31-0.92; P =0.024), and no significant interaction with classes of RAS inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) was observed ( P for interaction=0.332). Conclusions: Beta-blockers or RAS inhibitors at discharge were associated with better 1-year clinical outcomes in patients with mid-range EF after AMI.

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