Association Between Acute Inflammatory Response and Infarct Size in Stemi Patients Undergoing Primary PCI

ABSTRACT Background: The inflammatory response of the immune system plays a major role in the period following an acute myocardial infarction (MI), as it coordinates the formation of the fibrous scar tissue that replaces the infarcted myocardial cells and ultimately leads to healing and remodeling of the affected zone. Along with other pro- and anti-inflammatory cytokines and acute phase proteins, interleukin-6 (IL-6) and C-reactive protein (CRP) are associated with the extent of the infarct size (IS) and may serve as predictors for remodeling and adverse left ventricular (LV) function. Material and methods: A single-center, non-randomized, observational prospective study was conducted, which included 75 patients with primary revascularized ST-elevation myocardial infarction (STEMI). High-sensitivity CRP (hs-CRP) serum levels were determined on day 1 and day 5 following the acute event. IL-6 was also determined on day 1. All patients underwent cardiac magnetic resonance imaging (CMR) at 1-month follow-up with determination of LV function and quantification of the scar tissue using late gadolinium enhancement imaging. The patients were divided into 2 groups based on baseline hs-CRP values. Results: Patients with higher baseline hs-CRP levels presented significantly higher infarct size (p = 0.0003), higher transmural extent (p <0.0001), lower LV ejection fraction (p = 0.0024), end-systolic (p = 0.0021) and end-diastolic (p = 0.0065) volumes. Small IS (<10%) recorded the lowest levels of hs-CRP, while IS >20% presented the highest levels of hs-CRP, at baseline and day 5 (p = 0.4 and 0.001). IL-6 levels were also associated with the magnitude of infarct scar: 2.17 pg/mL for IS <10%, 15.52 pg/mL for IS between 10% and 20%, and 24.52 pg/mL for IS >20%, p = 0.002. Conclusion: hs-CRP and IL-6 serum levels following an MI are correlated with IS, transmurality extent of the scar tissue, as well as with altered systolic and diastolic LV function determined by CMR at 1-month follow-up.

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Effect of cardiosphere-derived cells on segmental myocardial function after myocardial infarction: ALLSTAR randomised clinical trial

Open Heart ◽

10.1136/openhrt-2021-001614 ◽

2021 ◽

Vol 8 (2) ◽

pp. e001614

Author(s):

Mohammad R Ostovaneh ◽

Raj R Makkar ◽

Bharath Ambale-Venkatesh ◽

Deborah Ascheim ◽

Tarun Chakravarty ◽

...

Keyword(s):

Myocardial Infarction ◽

Clinical Trial ◽

Myocardial Function ◽

Randomised Clinical Trial ◽

Scar Tissue ◽

Left Ventricular ◽

Lv Function ◽

Cardiac Events ◽

Lv Dysfunction ◽

Registration Number

BackgroundMost cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function indices are not able to detect the small treatment effects on segmental myocardial function which may have prognostic implications for cardiac events. We aimed to test the efficacy of allogeneic cardiosphere-derived cells (CDCs) for improving regional myocardial function and contractility.MethodsIn this exploratory analysis of a randomised clinical trial, 142 patients with post-MI with LVEF <45% and 15% or greater LV scar size were randomised in 2:1 ratio to receive intracoronary infusion of allogenic CDCs or placebo, respectively. Change in segmental myocardial circumferential strain (Ecc) by MRI from baseline to 6 months was compared between CDCs and placebo groups.ResultsIn total, 124 patients completed the 6-month follow-up (mean (SD) age 54.3 (10.8) and 108 (87.1%) men). Segmental Ecc improvement was significantly greater in patients receiving CDC (−0.5% (4.0)) compared with placebo (0.2% (3.7), p=0.05). The greatest benefit for improvement in segmental Ecc was observed in segments containing scar tissue (change in segmental Ecc of −0.7% (3.5) in patients receiving CDC vs 0.04% (3.7) in the placebo group, p=0.04).ConclusionsIn patients with post-MI LV dysfunction, CDC administration resulted in improved segmental myocardial function. Our findings highlight the importance of segmental myocardial function indices as an endpoint in future clinical trials of patients with post-MI.Trial registration numberNCT01458405.

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Evolution of left ventricular function after Wharton's jelly mesenchymal stem cells transcoronary administration: 5-year follow up in a pilot cohort of CIRCULATE-AMI Randomized Trial

European Heart Journal ◽

10.1093/ehjci/ehaa946.1719 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

E Kwiecien ◽

L Drabik ◽

A Mazurek ◽

M Sikorska ◽

L Czyz ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Infarct Size ◽

Troponin T ◽

Left Ventricular ◽

Lv Function ◽

Funding Source ◽

Double Blind ◽

Wharton's Jelly

Abstract Introduction CIRCULATE-Acute Myocardial Infarction is a double-blind controlled trial randomizing (RCT) in 105 consecutive patients with their first, large AMI (cMRI-LVEF ≤45% and/or cMRI-infarct size ≥10% of LV) with successful infarct-related artery (IRA) primary percutaneous coronary intervention (pPCI) to transcoronary administration of Wharton's Jelly Mesenchymal Stem Cells (WJMSCs) vs. placebo (2:1). The pilot study cohort (PSC) preceded the RCT. Aim To evaluate WJMSCs long-term safety, and evolution of left-ventricular (LV) function in CIRCULATE-AMI PSC. Material and methods 30 000 000 WJMSCs (50% labelled with 99mTc-exametazime) were administered via IRA in a ten-patient PCS (age 32–65 years, peak hs-Troponin T 17.3±9.1ng/mL and peak CK-MB 533±89U/L, cMRI-LVEF 40.3±2.7% and infarct size 20.1±2.8%) at ≈5–7 days after AMI using a cell delivery-dedicated, coronary-non-occlusive method. Other treatments were per guidelines. WJMSCs showed an unprecedented high myocardial uptake (30.2±5.3%; 95% CI 26.9–33.5%), corresponding to ≈9×10 000 000 cells retention in the infarct zone – in absence of epicardial flow or myocardial perfusion impairment (TIMI-3 in all; cTFC 45±8 vs. 44±9, p=0.51) or any hs-Troponin T elevation. Five-year follow up included cardiac Magnetic Resonance Imaging (cMRI) (at baseline, 1 year and 3 years) and detailed echocardiography (echo) at baseline, 1 year, 3 years and 5 years. Results By 5 years, one patient died from a new, non-index territory AMI. There were no other cardiovascular events and MACCE that might be related to WJMSCs transplantation. On echo (Fig), there was an increase in left ventricular ejection fraction (LVEF) between WJMSCs administration point and 1 year (37.7±2.9% vs. 48.3±2.5%, p=0.002) that was sustained at 3 years (47.2±2.6%, p=0.005 vs. baseline) and at 5 years: (44.7±3.2%, p=0.039 vs. baseline). LVEF reached a peak at 1 year after the AMI and WJMSCs transfer (Fig). cMRI data (obtained up to 3 years; 1 year 41.9±2.6% vs. 51.0±3.3%, p<0.01; 3 years 52.2±4.0%, p<0.01 vs. baseline) were consistent with the echo LVEF assessment. Conclusions 5-year follow up in CIRCULATE-AMI PSC indicates that WJMSC transcoronary application is safe and may be associated with an LVEF improvement. The magnitude of LV increase appears to peak at 1 year, suggesting a potential role for repeated WJMSCs administration(s). Currently running double-blind RCT will provide placebo-controlled insights into the WJMSCs effect(s) on changes in LV function, remodelling, scar reduction and clinical outcomes. Echo-LVEF evolution Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): STRATEGMED 265761 “CIRCULATE” National Centre for Research and Development/Poland/ZDS/00564 Jagiellonian University Medical College

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The Association Between S100A8/A9 and the Development of Very Late Stent Thrombosis in Patients With Acute Myocardial Infarction

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029620943295 ◽

2020 ◽

Vol 26 ◽

pp. 107602962094329

Author(s):

Xiang Wang ◽

Meng Guan ◽

Xiuhang Zhang ◽

Taiyuan Ma ◽

Muli Wu ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Stent Thrombosis ◽

High Sensitivity ◽

Coronary Intervention ◽

Serum Levels ◽

Late Stent Thrombosis ◽

Very Late Stent Thrombosis ◽

Hs Crp

Very late stent thrombosis (VLST) is a rare but serious complication following percutaneous coronary intervention (PCI). S100A8/A9 plays an important role in thrombosis through modulating the inflammatory response. This observational study aimed to reveal the association between S100A8/A9 and VLST. Continuous blood samples were collected from patients at both the time of index PCI for acute myocardial infarction (AMI) and the time of PCI for VLST (VLST group) or follow-up coronary angiography (AMI group). In all, 56 patients were selected in each group from a cohort of 8476 patients and other 112 individuals who underwent health checkups (normal control [NC] group) were selected as controls. Serum levels of S100A8/A9 and high sensitivity C-reactive protein (hs-CRP) were tested and compared. The mean level of S100A8/A9 was 3754.4 ± 1688.9 ng/mL during index PCI and increased to 5517.8 ± 2650.9 ng/mL at the time of VLST; in the AMI group, S100A8/A9 level was 2434.9 ± 1243.4 ng/mL during index PCI and decreased to 1568.2 ± 772.1 ng/mL during follow-up, similar to that detected in the NC group (1618.2 ± 641.4 ng/mL). Of note, S100A8/A9 levels showed significant increases during VLST when compared to its own levels during index PCI, which was different from the changes of hs-CRP. Higher serum levels of S100A8/A9 are associated with the development of VLST.

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Late preconditioning enhances recovery of myocardial function after infarction in conscious rabbits

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2000.279.5.h2372 ◽

2000 ◽

Vol 279 (5) ◽

pp. H2372-H2381 ◽

Cited By ~ 6

Author(s):

Hitoshi Takano ◽

Xian-Liang Tang ◽

Eitaro Kodani ◽

Roberto Bolli

Keyword(s):

Myocardial Infarction ◽

Infarct Size ◽

Left Ventricular ◽

Nitric Oxide Donor ◽

Lv Function ◽

Wall Thickening ◽

Triphenyltetrazolium Chloride ◽

Independent Evidence ◽

Late Preconditioning ◽

Conscious Rabbits

It is unknown whether late preconditioning (PC) enhances the recovery of left ventricular (LV) function after a myocardial infarction. Thus 25 conscious rabbits were subjected to a 30-min coronary occlusion followed by 28 days of reperfusion after PC 24 h earlier with either ischemia or nitric oxide donor administration [ S-nitroso- N-acetylpenicillamine (SNAP)]. The recovery of wall thickening (WTh) after reperfusion was significantly improved in the ischemic PC and SNAP PC groups compared with controls, both at rest and during dobutamine stress. Interestingly, neither ischemia- nor SNAP-induced late PC attenuated myocardial stunning from day 1 through day 14. Infarct size was smaller in the ischemic PC and SNAP PC groups compared with controls. In all groups, WTh at 28 days was positively and linearly related to the percentage of viable tissue in the region underlying the ultrasonic crystal ( r = 0.90), indicating that the improvement in LV function after both ischemia-induced and NO donor-induced late PC can be fully explained by the reduction in infarct size; a separate effect of late PC on LV remodeling or LV contractility need not be invoked. In conclusion, in conscious rabbits late PC, induced either by ischemia or pharmacologically, not only limits infarct size but also enhances the recovery of LV function after myocardial infarction. This finding has important clinical implications and provides triphenyltetrazolium chloride-independent evidence that late PC limits myocellular death after sustained ischemia.

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Bone marrow mesenchymal stem cells transfer in patients with ST-segment elevation myocardial infarction: single-blind, randomized controlled muticentre trial

10.21203/rs.3.rs-54127/v1 ◽

2020 ◽

Author(s):

Runfeng Zhang ◽

Jiang Yu ◽

Ningkun Zhang ◽

Wensong Li ◽

Jisheng Wang ◽

...

Keyword(s):

Myocardial Infarction ◽

Ejection Fraction ◽

General Hospital ◽

Myocardial Viability ◽

Left Ventricular ◽

Control Group ◽

Lv Function ◽

St Segment Elevation ◽

Lv Ejection Fraction

Abstract Objective: Our aimed to evaluate efficacy and safety of intracoronary autologous bone morrow mesenchymal stem cells (BM-MSCs) transplantation in patients with ST-segment elevation myocardial infarction（STEMI）. Methods: In this randomised, single-blind, controlled trial, patients with STEMI (aged 39-76 years) were enrolled at 6 centers in Beijing (the People's Liberation Army Navy General Hospital, Beijing Armed Police General Hospital, Chinese People's Liberation Army General Hospital, Beijing Huaxin Hospital, Beijing Tongren Hospital, Beijing Chaoyang Hospital West Hospital). Patients underwent optimum medical treatment and percutaneous coronary intervention,and were randomly assigned in a 1:1 ratio to BM-MSCs group or control group. The primary endpoint was change of myocardial viability at 6 months' follow-up and left-ventricular (LV) function at 12 months' follow-up.The secondary endpoints were incidence of cardiovascular event, total mortality and adverse event at 12 months' follow-up. The myocardial viability assessed by single- photon emission tomography (SPECT). The left ventricular ejection fraction was used to assess LV function. All patients underwent dynamic ECG and laboratory evaluations. This trial is registered with ClinicalTrails.gov, number NCT04421274. Results: Between March , 2008, and July , 2010, 43 patients were randomly assigned to BM-MSCs group (n=21)or control group(n=22) and followed up for 12 months. LV ejection fraction increased from baseline to 12 months in the BM-MSCs group and control group ( mean baseline-adjusted BM-MSCs treatment differences in LV ejection fraction 4.8% (SD 9.0) and mean baseline-adjusted control group treatment differences in LV ejection fraction 5.8% (SD 6.04) ). After 6 months of follow-up, there was no significant improvement in myocardial metabolic activity in the BM-MSCs group before and after transplantation. however,there was no statistically significant difference between the two groups in the change of LV ejection fraction (p=0.30) and myocardial metabolic activity(p>0.05). We noticed that ,after 12 months of follow-up, except for 1 death and 1 coronary microvascular embolism in the BM-MSCs group, no other events occurred and Alanine transaminase(ALT) and C-reactive protein(CRP) in BM-MSCs group were significantly lower than that in control group. Conclusions: It is unreasonable to speculate that intracoronary transfer of autologous bone marrow MSCs could augment recovery of LV function and myocardial viability after acute myocardial infarction.Trial registration: clinicaltrials,NCT04421274. Registered 06,08,2020- Retrospectively registered, https://register.clinicaltrials.gov/NCT04421274.

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Tolerogenic dendritic cells induced by atorvastatin via inhibition of the TLR-4/NF-κB pathway improve cardiac remodeling after myocardial infarction

10.21203/rs.3.rs-118076/v1 ◽

2020 ◽

Author(s):

Jianbing Zhu ◽

Hang Chen ◽

Yuanji Ma ◽

Haibo Liu ◽

Zhaoyang Chen

Keyword(s):

Oxidative Stress ◽

Myocardial Infarction ◽

Dendritic Cells ◽

Inflammatory Response ◽

Infarct Size ◽

Inflammatory Reaction ◽

Ventricular Remodeling ◽

Inflammatory Responses ◽

Systolic Function ◽

Left Ventricular

Abstract BackgroundNecrosis of ischemic cardiomyocytes after myocardial infarction (MI) activates an intense inflammatory reaction. Dendritic cells (DCs) play a crucial role in the repair process after MI. Tolerogenic DCs (tDCs) can inhibit inflammatory responses. Methods and resultsWe investigated the role of atorvastatin and supernatants of necrotic cardiomyocytes (SNC) on DCs. We found that SNC induced DCs maturation, activated TLR-4/NF-κB pathway, promoted inflammatory cytokines secretion and oxidative stress. Co-treatment with SNC and atorvastatin suppressed DC maturation and inflammatory response, which meant that atorvastatin induced DCs tolerate to SNC. Then, we investigated the effect of mDCs induced by SNC and tDCs induced by atorvastatin on ventricular remodeling after MI. tDCs treatment significantly improved the left ventricular systolic function, reduced the infiltration of MPO+ neutrophil, Mac3+ macrophages and CD3+ T cells, inhibited myocardial apoptosis and fibrosis, and decreased infarct size. Compared with PBS, treatment with mDCs did not showed beneficial effect on ventricular remodeling and inflammatory reaction after MI in mice.ConclusionAtorvastatin inactivated the TLR-4/NF-κB pathway, repressed the oxidative stress, inflammatory response, and immune maturity induced by SNC. Treatment with tDCs, induced by co-treated with atorvastatin, preserved left ventricular function, limited infarct size, suppressed the infiltration of inflammatory cells, and attenuated the severity of fibrosis, and reduced the number of apoptotic cardiomyocytes.

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Serum Levels of Bone Morphogenetic Proteins 2 and 4 in Patients with Acute Myocardial Infarction

Cells ◽

10.3390/cells9102179 ◽

2020 ◽

Vol 9 (10) ◽

pp. 2179

Author(s):

Maria Kercheva ◽

Anna M. Gusakova ◽

Tamara R. Ryabova ◽

Tatiana E. Suslova ◽

Julia Kzhyshkowska ◽

...

Keyword(s):

Myocardial Infarction ◽

Serum Level ◽

Bone Morphogenetic Proteins ◽

Elevated Level ◽

Elevated Serum ◽

Serum Levels ◽

Left Ventricular ◽

High Serum ◽

High Serum Level

Background: Bone morphogenetic proteins-2 and -4 (BMPs) have been implicated in left ventricular remodeling (LVR) processes such as an inflammation and fibrogenesis. We hypothesized that this knowledge could be translated into clinics. Methods: We studied the dynamics of serum levels of BMPs, its correlation with markers of LVR and with parameters of echocardiography in patients (n = 31) during the six-month follow-up period after myocardial infarction (MI). Results: Elevated serum levels of BMPs decreased by the six-month follow-up period. BMP-2 decreased from the first day after MI, and BMP-4 decreased from the Day 14. The elevated level of BMP-2 at Day 1 was associated with a lower level of troponin I, reperfusion time and better left ventricular ejection fraction (LV EF) at the six-month follow-up. Elevated serum level of BMP-4 at Day 1 was associated with a lower level of a soluble isoform of suppression of tumorigenicity 2 (sST2), age and reperfusion time. An elevated level of BMP-2 at the six-month follow-up was associated with higher levels of BMP-4, high-sensitivity C-reactive protein (hCRP) and sST2. High serum level of BMP-2 correlated with high levels of hCRP and matrix metalloproteinase (MMP)-9 on Day 7. High serum level of BMP-4 correlated with low levels of hCRP, MMP-9 at Day 3, sST2 at Day 1 and with decreased LV EF on Day 7. The findings of multivariate analysis support the involvement of BMP-2 in the development of post-infarction LVR. Conclusions: Our research translates experimental data about the BMPs in the development of adverse LVR into the clinic. Elevated serum levels of BMPs decreased by the end of the six-month period after MI. BMP-2 decreased from the first day and BMP-4 decreased from Day 14. BMP-2 and BMP-4 were associated with the development of LVR. Their correlations with markers of inflammation, degradation of the extracellular matrix, hemodynamic stress and markers of myocardial damage further support our hypothesis. Diagnostic and predictive values of these BMPs at the development of post-infarction LVR in vivo should be investigated further.

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Single-Point Cardiac Troponin T at Coronary Care Unit Discharge after Myocardial Infarction Correlates with Infarct Size and Ejection Fraction

Clinical Chemistry ◽

10.1093/clinchem/48.9.1432 ◽

2002 ◽

Vol 48 (9) ◽

pp. 1432-1436 ◽

Cited By ~ 60

Author(s):

Mauro Panteghini ◽

Claudio Cuccia ◽

Graziella Bonetti ◽

Raffaele Giubbini ◽

Franca Pagani ◽

...

Keyword(s):

Myocardial Infarction ◽

Ejection Fraction ◽

Infarct Size ◽

Cardiac Troponin ◽

Coronary Care Unit ◽

Troponin T ◽

Left Ventricular ◽

Lv Function ◽

Cardiac Troponin T ◽

Coronary Care

Abstract Background: One of the major concerns in replacing creatine kinase MB (CK-MB) with cardiac troponins is the lack of evidence of the ability of troponins to estimate the size of acute myocardial infarction (AMI). We investigated the ability of a single measurement of cardiac troponin T (cTnT) at coronary care unit (CCU) discharge to estimate infarct size and assess left ventricular (LV) function in AMI patients. Methods: We studied 65 AMI patients in whom infarct size was estimated by CK-MB peak concentrations and gated single-photon emission computed tomography (SPECT) myocardial perfusion using technetium-99m sestamibi and LV function by SPECT imaging. Measurements of cTnT and SPECT were performed 72 h (median) after admission (range, 40–160 h). SPECT was also repeated 3 months later. Results: We found a significant correlation between cTnT and both the peak CK-MB concentrations (r = 0.76; P <0.001) and the perfusion defect size at SPECT (r = 0.62; P <0.001). cTnT was inversely related to LV ejection fraction (LVEF) assessed both early (r = −0.56; P <0.001) and 3 months after AMI (r = −0.70; P <0.001). cTnT >2.98 μg/L predicted a LVEF <40% at 3 months with a sensitivity of 86.7%, specificity of 81.4%, and a likelihood ratio for a positive test of 4.7 (95% confidence interval, 4.0–5.4). Conclusions: A single cTnT measurement at CCU discharge after AMI is useful as a noninvasive estimate of infarct size and for the assessment of LV function in routine clinical setting.

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P3126Immediate versus delayed revascularization in patients with transient ST-elevation myocardial infarction: 1-year follow-up of the randomized clinical TRANSIENT trial

European Heart Journal ◽

10.1093/eurheartj/ehz745.0201 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

G N Janssens ◽

N W Van Der Hoeven ◽

J S Lemkes ◽

H Everaars ◽

P Van De Ven ◽

...

Keyword(s):

Myocardial Infarction ◽

Infarct Size ◽

Target Lesion ◽

Left Ventricular ◽

St Elevation Myocardial Infarction ◽

Cardiac Events ◽

Invasive Group ◽

St Elevation ◽

One Year

Abstract Background Up to 24% of acute coronary syndrome patients present with ST-elevation but show complete resolution of ST-elevation and symptoms before revascularization. The current guidelines do not clearly state whether these transient ST-elevation myocardial infarction (TSTEMI) patients should be treated with a ST-elevation myocardial infarction (STEMI)-like or a non-STEMI-like invasive approach. Purpose The aim of the present study is to determine the effect of an immediate versus a delayed invasive strategy on infarct size measured by 4-month cardiac magnetic resonance imaging (CMR) and clinical outcome up to one year. Methods In this multicenter trial, 142 TSTEMI patients were randomized 1:1 to either an immediate or a delayed intervention. CMR was performed at four days and at 4-month follow-up to assess infarct size and myocardial function. Clinical follow-up was performed at four months and one year. Results Both in the immediate (0.4 h) and the delayed invasive group (22.7 h) CMR-derived infarct size at four months was very small and left ventricular function was good. In addition, major adverse cardiac events and all-cause mortality at one year were low and not different between both groups (table 1). CMR and clinical outcomes up to one year Outcome Immediate invasive group (n=70) Delayed invasive group (n=72) p-value Myocardial infarct size (% of LV), median (IQR) 0.4 (0.0–3.5) 0.4 (0.0–2.5) 0.79 LVEF (%), mean ± SD 59.9±5.4 59.3±6.5 0.63 LVEF recovery (%), mean ± SD 2.2±5.4 1.7±5.3 0.66 MVO present, No. (%) 0 (0.0) 1 (1.9) 0.50 MACE (death, reinfarction, target lesion revascularization), No. (%) 3 (4.4) 4 (5.7) 1.00 Death from any cause, No. (%) 0 (0.0) 3 (4.3) 0.24 Reinfarction, No. (%) 2 (3.0) 1 (1.4) 0.62 Target lesion revascularization, No. (%) 2 (3.0) 1 (1.4) 0.62 Definite stent thrombosis, No. (%) 1 (1.5) 1 (1.4) 1.00 Abbreviations: IQR, interquartile range; LV, left ventricle; LVEF, left ventricle ejection fraction; MACE, major adverse cardiac events; MVO, microvascular obstruction; NA, not applicable; SD, standard deviation. Conclusions We demonstrated that patients with TSTEMI have limited infarct size and preserved left ventricular function and that an immediate or delayed approach has no effect on clinical outcome up to one year. Therefore, patients with TSTEMI can be treated with both an immediate or a delayed invasive strategy with similar outcome. These findings extend our current knowledge about the optimal timing of coronary intervention in patients with TSTEMI and complement the guidelines. Acknowledgement/Funding AstraZeneca, Biotronik

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Elastin Stabilizes an Infarct and Preserves Ventricular Function

Circulation ◽

10.1161/01.circulationaha.105.523795 ◽

2005 ◽

Vol 112 (9_supplement) ◽

Author(s):

Tomohiro Mizuno ◽

Terrence M. Yau ◽

Richard D. Weisel ◽

Chris G. Kiani ◽

Ren-Ke Li

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Infarct Size ◽

Left Ventricular ◽

Myocardial Scar ◽

Elastic Fibers ◽

Control Group ◽

Lv Function ◽

Infarct Region ◽

Lv Volume

Background— After a myocardial infarction, the injured region becomes fibrotic and the myocardial scar may expand if the ventricular wall lacks elasticity. Cardiac dilatation may precipitate the vicious cycle of progressive heart failure. The present study evaluated the functional benefits of increasing elastin within a myocardial scar using cell based gene therapy. Methods and Results— A myocardial infarction was generated by ligation of the left anterior descending artery in rats. Six days later, 2×10 6 syngeneic rat endothelial cells transfected with the rat elastin gene (elastin group, n=14) or an empty plasmid (control group, n=14) were transplanted into the infarct scar. Cardiac function, left ventricular (LV) volume, and infarct size were monitored over 3 months by echocardiography, Langendorff measurements, and planimetry. Elastin deposition was evaluated in the cells and in the infarct region by Western blot assay and by histological examination. Recombinant elastin was found in the scar in the elastin group but not the control group during the 3 months after cell transplantation. Histological assessment demonstrated organized elastic fibers within the infarct region. LV volume and infarct size were significantly smaller ( P <0.05) in the elastin group than in the control group. Cardiac function evaluated by echocardiography and during Langendorff perfusion was significantly better ( P <0.05) in the elastin group than in the control group. Conclusions— Expressing recombinant elastin within the myocardial scar reduced scar expansion and prevented LV enlargement after a myocardial infarction. Altering matrix remodeling after an infarct preserved the LV function for at least 3 months.

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