Abstract 2668: Critical Role of Granzyme B in Left Ventricular Remodeling after Acute Myocardial Infarction

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hideyuki Kondo ◽  
Yukihiro Hojo ◽  
Yoshioki Nishimura ◽  
Nozomu Takahashi ◽  
Tomokazu Ikemoto ◽  
...  

Background: Granzyme B is a member of the serine esterase family produced by cytotoxic T lymphocytes (CTLs), and has an important role in cellular apoptosis and extracellular matrix degradation. We hypothesized that granzyme B is involved in left ventricular (LV) remodeling after acute myocardial infarction (AMI). Objectives: To elucidate the role of granzyme B in LV remodeling after AMI. Subjects and methods: We employed 41 patients with the first AMI (mean age: 61.9±8.9 years old). We obtained peripheral blood on day 1, day 7 and day 14 after onset. Plasma levels of apoptosis-related molecules, including tumor necrosis factor α (TNFα), a soluble form of the Fas ligand (sFasL) and granzyme B were measured. We checked the activation of CTLs by flow cytometry. Patients were treated by percutaneous coronary intervention within 12 hours after onset. Successful myocardial reperfusion (TIMI flow grade 2 or 3) was accomplished in all patients. LV end-diastolic volume index (LVEDVI) was calculated on day 1 and 6 months after onset. Results: Plasma levels of TNFα, sFasL and granzyme B increased significantly after the onset of AMI (TNFα; day 1: 1.6±0.47, day 7: 3.3±0.65, day14: 4.0±1.2 pg/ml, p<0.05, sFasL; day 1: 72±5.2, day 7: 86±6.7, day14: 95±7.3 pg/ml, p<0.05, granzyme B; day 1: 63±18.4, day 7: 283±57.8, day14: 210.9±46.3 pg/ml, p<0.001). The percentage of CD69± to CD3+ CD8+ lymphocytes was significantly increased (CD69+/CD3+ CD8+; day 1: 14.5±1.7, day 7: 15.8±1.2, day 14: 19.1±1.4%, p<0.05), suggesting that CTLs were activated after onset. Univariate regression analysis showed a significant positive correlation between plasma granzyme B level on day 14 and fold-increase in LVEDVI (r=+0.45, p<0.01). No significant correlation was observed between TNFα and changes in LVEDVI, or sFasL and changes in LVEDVI. Stepwise multivariate regression analysis showed that the plasma granzyme B level on day 14 is a significant explanatory variable for changes in LVEDVI (β = +0.53, p<0.001). Conclusions: These results first indicate that among proapoptic molecules, granzyme B has a critical role in the progression of LV remodeling after AMI.

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hideyuki Kondo ◽  
Yukihiro Hojo ◽  
Yoshioki Nishimura ◽  
Nozomu Takahashi ◽  
Tomokazu Ikemoto ◽  
...  

Background: Ghrelin is a novel growth hormone (GH)-releasing peptide, originally isolated from the stomach, which has been identified as an endogenous ligand for the GH secretagogues receptor (GHS-R). Previous studies revealed that chronic administration of ghrelin suppresses cardiac sympathetic activity and prevents left ventricular (LV) remodeling after acute myocardial infarction (AMI). However clinical role of ghrelin after AMI is still not clear. We examined the role of ghrelin in LV remodeling after AMI. Objectives: To elucidate the role of ghrelin in LV remodeling after AMI. Subjects and methods: We employed patients with the first AMI (n=41, mean age 61.9±8.9 years old). We obtained peripheral blood on 1, 7, 14 days and 6 months after the onset. Plasma total ghrelin levels were measured by enzyme-linked immunosorbent assay. Patients were treated by percutaneous coronary intervention within 12 hours after onset. Successful myocardial reperfusion (TIMI flow grade 2 or 3) was accomplished in all patients. To analyze LV remodeling, all patients submitted to two serial left ventriculographies carried out on the day of admission and 6 months after the onset (mean 199±13 days). LV volume index (LVEDVI) was calculated by QCA-CMS software. Results: Plasma total ghrelin levels increased after the onset of AMI (day 0: 28.4±6.4, day 7: 75.1±12.2, day 14: 89.9±14.8 pg/ml, 6months: 46.5±6.6 fmol/ml, p<0.001). There was a significant positive correlation between plasma ghrelin levels on day 14 after the onset and changes in LVEDVI (r=+0.53, p<0.001). The stepwise multivariate regression analysis showed that the plasma ghrelin level on day 14 is a significant explanatory variable for the changes in LVEDVI (F=8.77, p<0.01, β=+0.40). Conclusions: The elevation of Ghrelin levels might be a compensatory mechanism to prevent LV remodeling. These results first indicate that ghrelin has a critical role in the progression of left ventricular remodeling after AMI.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Sopova ◽  
C Park ◽  
A Al-Atta ◽  
K Bennaceur ◽  
A Mohammad ◽  
...  

Abstract Background Adverse left ventricular (LV) remodelling is associated with development of heart failure and poor outcomes in patients with acute myocardial infarction (AMI). Understanding the immunomodulatory mechanisms of LV remodelling is an essential step for the development of novel therapies. Interferon-γ-inducible protein-10 (IP-10)/CXCL10 is a chemokine involved in the recruitment of activated T cells into sites of tissue inflammation. Although IP-10 was reported to reduce adverse LV remodeling in a preclinical myocardial infarction model, its role in LV remodeling in humans with AMI remains unknown. Purpose To determine the clinical predictive value of serum IP-10 in LV remodeling in patients with ST-segment elevation myocardial infarction (STEMI). Methods This is a substudy of the double-blind, randomised controlled trial “Evaluating the effectiveness of intravenous ciclosporin on reducing reperfusion injury in patients undergoing primary percutaneous coronary intervention” (CAPRI; ClinicalTrials.gov registry number NCT02390674), which enrolled 52 acute STEMI patients. LV remodeling was assessed by cardiovascular magnetic resonance (CMR) imaging and was defined as the 12-week vs. the 3-day post-myocardial infarction change of the left ventricular ejection fraction (ΔLVEF), LV end-diastolic volume (ΔEDV) or LV end-systolic volume (ΔESV). Serum IP-10 was measured before and 5min, 15min, 30min, 90min and 24h after reperfusion by ELISA. Linear regression analysis was used to determine the independent association of IP-10 with the endpoints of the study. Results Serum IP-10 concentration peaked at 30min after reperfusion followed by a 2-fold decrease at the 24h post reperfusion compared to pre-reperfusion levels (P&lt;0.001 for all). Comparison of the 12-week CMR to the baseline CMR imaging revealed that baseline pre-reperfusion as well as 5min, 15min, 30min and 90min, but not 24h, post-reperfusion IP-10 serum levels associated with increased LVEF and decreased ESV at 12-weeks (range correlation coefficient r=[0.35–0.41], P&lt;0.05 with ΔLVEF and r=[−0.33 to −0.44], P&lt;0.05 with ΔESV) indicating that the increase of IP-10 at the acute phase of myocardial infarction confers a cardioprotective role. Multivariable linear regression analysis for ΔLVEF showed that in a model including baseline pre-reperfusion or 5min or 15min or 30min or 90min post-reperfusion IP-10 and age, gender, traditional risk factors (arterial hypertension, body-mass index, hyperlipoproteinemia, diabetes mellitus, smoking, family history of CAD), infarct location, admission high-sensitivity troponin T, door-to-balloon time and ciclosporin treatment, only IP-10 was the independent determinant of ΔLVEF. Conclusions Increased serum IP-10 levels early after reperfusion are associated with reverse LV remodeling in patients with STEMI undergoing primary PCI. The clinical application of IP-10 as a novel biomarker of LV remodeling post-AMI should be further explored and validated. Funding Acknowledgement Type of funding source: None


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Yukio Arita

Left ventricular (LV) remodeling after acute myocardial infarction (AMI) is a precursor of the development of overt heart failure and is an important predictor of mortality. Adiponectin (AN) is an adipose-derived plasma protein that has the cardio-protective role against ischemia-reperfusion injury. Altered activity of matrix metalloproteinase (MMP) family has been implicated in the development of LV remodeling after myocardial infarction. Serum AN levels affect MMPs and tissue inhibitor of MMP (TIMP) levels, and attenuate adverse LV remodeling after AMI. In 88 consecutive patients with AMI successfully treated with primary percutaneous coronary intervention (PCI), serum levels of AN, MMP-2, MMP-9, and TIMP-1 were measured on admission, at day 7, and at 6 months after the onset. LV end-diastolic volume index (EDVI) and ejection fraction (EF) were assessed with 99m− Tc-tetrofosmin quantitative gated single-photon emission computed tomography within 10 days (early) and six months (chronic) after the onset. Serum AN and MMP-2 levels were decreased and serum MMP-9 and TIMP-1 levels were increased at day 7 compared to those at the onset and 6 months. Chronic/early EDVI ratio was negatively correlated with log AN at day 7 (r= −0.265, p=0.013), log AN at 6 months (r= −0.335, p=0.008), log MMP-2 at day 7 (r= −0.229, p=0.042), and positively correlated with log MMP-9 at day 7 (r= 0.237, p=0.037), log TIMP-1 on admission (r=0.277, p=0.0408). Chronic EF was positively correlated with log AN at day 7 (r=0.225, p=0.0374) and negatively correlated with log TIMP-1 at day 7 (r= −0.281, p=0.0133). Multiple logistic regression analyses revealed that chronic/early EDVI ratio independently correlated with log AN (r= −0.249, p=0.034) at day 7, although Log AN correlated positively log MMP-2, and negatively with log MMP-9 both at day 7 and 6 months. Measurement of AN at subacute phase can predict adverse cardiac remodeling in patients with AMI successfully treated with PCI.


2020 ◽  
Vol 16 (6) ◽  
pp. 876-880
Author(s):  
Sh. I. Farag ◽  
Kh. E. El-Rabbat ◽  
M. A. El-Awadi ◽  
A. M. Sabry

Background. Left ventricular (LV) remodeling is an adverse consequence after acute myocardial infarction.Aim. To assess the role of speckle tracking in the evaluation of LV remodeling after streptokinase infusion in patients with acute anterior ST-segment elevation myocardial infarction (STEMI).Material and methods. A total of 200 patients with first acute anterior STEMI received streptokinase as a reperfusion therapy were included. Conventional echocardiography and speckle tracking were performed within 3 days of admission and 3 months later. According to the development of LV remodeling, patients were classified into two groups. Group (I) patients with LV remodeling (60 patients) and group (II) patients without remodeling (140 patients).Results. Patients with LV remodeling had lower global longitudinal (GLS) and circumferential (GCS) strain values (-13.19±4.57 vs. -18.90±4.23 % and -13.16±4.27 vs. -17.16±3.3 %, respectively, p<0.001). GLS cutoff value of >-13.5 was shown to have the best diagnostic accuracy (sensitivity =60.0% & specificity =87.1%) in predicting LV remodeling (AUC 0.816, 95% confidence interval [CI] 0.754-0.877, p<0.001). GCS cutoff value of >-16.21 was shown to have the best diagnostic accuracy (sensitivity =75.0% & specificity =71.4%) in predicting LV remodeling (AUC 0.785, 95%CI 0.719-0.85, p<0.001).Conclusion. Speckle tracking echocardiography either longitudinal or circumferential strain has good sensitivity and specificity in predicting LV remodeling after acute myocardial infarction.


1993 ◽  
Vol 34 (2) ◽  
pp. 145-157 ◽  
Author(s):  
Ahmet ALPMAN ◽  
Muharrem GÜLDAL ◽  
Çetin EROL ◽  
Günes AKGÜN ◽  
Celal KERVANCIOGLU ◽  
...  

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Garlichs ◽  
J Torzewski ◽  
A Sheriff ◽  
C Pfluecke ◽  
H Darius ◽  
...  

Abstract Background Inflammation is increasingly recognized as an important pathogenic feature in cardiovascular disease. In patients with STEMI, C-reactive protein (CRP), the prototype human acute phase protein, is a marker of poor prognosis and independently predicts 30-day mortality. In STEMI, CRP may indeed be intimately involved in myocardial damage by activating the complement system in the ischemic tissue. In animal experiments, CRP removal after STEMI reduces infarct size and results in a significantly better left ventricular ejection fraction (LVEF). Recently, in the multi-center matched-control pilot study on CRP apheresis in Acute Myocardial Infarction (CAMI1), a newly designed CRP adsorber has been demonstrated to efficiently and selectively lower CRP plasma levels in humans. Here, we present preliminary data of the ongoing trial. Methods Up to the present day, 67 STEMI patients were enrolled in the study following complete coronary revascularization. 32 patients received CRP apheresis, whereas 35 patients treated by standard protocols served as controls. CRP apheresis started 24±12 h and 48±12 h after onset of symptoms. In case of a rapid increase in CRP plasma levels following the 2nd session, a 3rd session was carried out another 24 h later. In each apheresis session, 6000 ml plasma was treated via peripheral venous access. Primary study endpoint was myocardial infarction size as determined by Cardiac Magnetic Resonance Imaging (MRI) 5±3 days after STEMI. Results Apheresis sessions were well tolerated with no relevant side effects. Peak CRP plasma levels after STEMI ranged from 12 mg/l to 279 mg/l. The peak CRP level after AMI can be calculated precisely with at 2–3 CRP quantifications during the first 24 h after the onset of symptoms. The regression coefficient for this analysis is 0.95. This mathematical step allows for the comparison of the CRP-apheresis group and the controls on the basis of their individual CRP peak levels. The statistical evaluation shows that the apheresis patients no longer correlate with the control with regard to the endpoints infarct size, LVEF, longitudinal strain and circumferential strain. They perform significantly better at all endpoints. The CRP apheresis reduced the development of myocardial damage. Conclusions Here, an unequivocal association between infarct size and CRP is demonstrated for the first time. CRP apheresis following STEMI is feasible and safe. Our preliminary results in a small cohort show a significant beneficial effect of CRP apheresis on myocardial infarction size and wall motion. Selective CRP apheresis may emerge as a new therapeutic approach in the treatment of acute myocardial infarction.


2014 ◽  
Vol 1 (2) ◽  
pp. 51
Author(s):  
Jitendra Kodilkar ◽  
Mrunal Suresh Patil ◽  
Neelima Chafekar ◽  
Ashwinkumar More

<strong>Introduction:</strong> Echocardiography is noninvasive, most frequently used usually the initial imaging test to evaluate all cardiovascular disease related to structural, functional, or hemodynamic abnormality of the heart or great vessels. The major advantage of echocardiography is the ability to obtain instantaneous real time image even in emergency units. The present study was undertaken to evaluate left ventricular function, extent of myocardium involved and complications of acute myocardial infarction by 2D ECHO, to correlate these findings with ECG and clinical presentation, and to assess the role of 2D ECHO in management and prognosis of patients with acute myocardial infarction. <strong>Materials and Methods:</strong> The present study was conducted on patients visiting our tertiary health centre, Nasik over a period of 2 years. 55 patients were included in the study. Patients with prior history of acute myocardial infarction, valvular heart disease, cardiomyopathy, cardiac surgery, congenital heart disease and non ST elevation MI were not included in the study. Patients were classified as per Killip classification and 2D ECHO was performed on the patients within 24 hours of admission. The findings of which were correlated with clinical and ECG findings. <strong>Results:</strong> Of 55 patients studied it was found that MI had male preponderance with hypertension as major risk factor. Also, the severity of the infarction increased with the increase in the Killip class. Mean ejection fraction was also observed to be decreasing in patients with increase in severity of the infarction. <strong>Conclusion:</strong> 2D ECHO performed within 24 hours of admission helps the clinician to predict and diagnose complications in patients with acute MI and take proper steps in the management of the patient.


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