Abstract 16525: Left Ventricular Unloading Before, Not After, Reperfusion Limits Infarct Size and Improves Survival in Acute Myocardial Infarction: A Bench to Bedside Study

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Navin K Kapur ◽  
Vikram Paruchuri ◽  
Xiaoying Qiao ◽  
Kevin Morine ◽  
Lyanne Buiten ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Infarct Size ◽  
Clinical Utility ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Coronary Reperfusion ◽  
Infarct Zone ◽  
Mitochondrial Integrity ◽  
Phosphorylated Akt

Ischemia-reperfusion injury (IRI) is a major determinant of myocardial damage in acute myocardial infarction (AMI). We explored the hypothesis that reducing left ventricular wall stress (LV unloading) with an axial flow catheter (Impella) before, not after, coronary reperfusion reduces infarct size and improves survival. Methods: We first employed a model of AMI. After 90 minutes of LAD occlusion, adult, male swine (n=4/group) were randomized to: 1) 120 minutes of reperfusion alone (IRI), 2) 30 minutes of LV unloading before 120 minutes of reperfusion (Impella to Balloon Group; ITB) or 3) 30 minutes of reperfusion followed by LV unloading and an additional 120 minutes of reperfusion (Balloon to Impella Group; BTI). Infarct size, myocardial kinase activity, and mitochondrial integrity were quantified. To explore the clinical utility of LV unloading before reperfusion we retrospectively studied all patients in the USPella registry presenting with ST-segmentc elevation AMI and cardiogenic shock who received an Impella within 120 minutes before (n=41; STEMI-ITB) or within 120 minutes after (n=76; STEMI-BTI) percutaneous reperfusion between 2009 and 2014. Results: Compared to IRI alone, infarct size was reduced in the ITB group, not the BTI group (62±2% vs 33±6% vs 58±15%, IRI vs ITB vs BTI, p<0.01 for IRI vs ITB; p<0.05 for ITB vs BTI). Levels of phosphorylated Akt, Erk-1/2, and GSK3b were increased within the infarct zone in the ITB, not BTI group. Mitochondrial numbers and markers of integrity were higher within the infarct zone in the ITB, compared to IRI or BTI. In the registry, in-hospital (51% vs 28%, p=0.02) and 30-day survival (42% vs 20%, p=0.03) were higher in the STEMI-ITB than the STEMI-BTI group. A STEMI-ITB time of less than 60 minutes (n=38) was associated with higher in-hospital survival than a STEMI-BTI time of less than 60 minutes (n=40) (50% vs 25%, p=0.02). Conclusion: Primary LV unloading before, not after, coronary reperfusion reduces infarct size, increases cardioprotective signaling, and improves mitochondrial integrity. These findings are supported by improved survival among patients treated with an Impella before, not after reperfusion in AMI. Future studies are required to explore the clinical utility of primary LV unloading in AMI.

Abstract 3379: Feasibility Of Adrenomedullin Infusion In Patients With Acute Myocardial Infarction -a Possible Cardioprotective Therapy Against Ischemic Injury-

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Satoshi Yasuda ◽  
Shunichi Miyazaki ◽  
Noritoshi Nagaya ◽  
Yu Kataoka ◽  
Teruo Noguchi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Infarct Size ◽  
Intravenous Administration ◽  
Ischemia Reperfusion ◽  
Coronary Intervention ◽  
Reperfusion Therapy ◽  
Left Ventricular ◽  
Stress Generation

Background : Adrenomedullin (ADM) is a 52-amino-acid vasodilator peptide that was originally isolated from human pheochromocytoma. In the previous experimental study with rat ischemia/reperfusion model, ADM reduced infarct size and inhibited myocyte apoptosis. ADM also suppressed the production of oxygen-free-radicals. The present study was designed to evaluate the feasibility of intravenous administration of ADM in patients with acute myocardial infarction (AMI). Methods : We studied 10 patients with first AMI (M/F;9/1, mean age;65 years, peak CPK level; 4090 U/L[median]), who were hospitalized within 12 hours of symptom onset. ADM infusion preceded percutaneous coronary intervention (PCI) and was continued at concentration of 0.0125 − 0.025μg/kg/minute for 12 hours. We also studied 10 control AMI patients matched for age, sex and infarct size, who did not receive ADM. Results : During ADM infusion, hemodynamics kept stable except one patient with right ventricular infarction. Urinary levels of 8-iso-prostaglandine F2α, which was measured after the reperfusion therapy with ADM infusion as a marker of oxidative stress, was significantly lower in patients who received ADM than those who did not (76 ± 40 vs 174±21 pmol/mol of creatinine, P<0.01). Infarct area (IA) evaluated by magnetic resonance imaging and brain natriuretic peptide (BNP) levels were also different between the two groups (Table ). Conclusions : Intravenous administration of ADM, which possesses a variety of cardiovascular protective actions, is feasible and can be adjunctive to PCI. Suppression of oxidative stress generation may be beneficial for attenuation of left ventricular dysfunction and remodeling following AMI.

scholarly journals Veno-occlusive unloading of the heart reduces infarct size in experimental ischemia–reperfusion

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Esben Søvsø Szocska Hansen ◽  
Tobias Lynge Madsen ◽  
Gregory Wood ◽  
Asger Granfeldt ◽  
Nikolaj Bøgh ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Ejection Fraction ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Cardiac Work ◽  
Area At Risk ◽  
Lv Ejection Fraction

AbstractMechanical unloading of the left ventricle reduces infarct size after acute myocardial infarction by reducing cardiac work. Left ventricular veno-occlusive unloading reduces cardiac work and may reduce ischemia and reperfusion injury. In a porcine model of myocardial ischemia–reperfusion injury we randomized 18 pigs to either control or veno-occlusive unloading using a balloon engaged from the femoral vein into the inferior caval vein and inflated at onset of ischemia. Evans blue and 2,3,5-triphenyltetrazolium chloride were used to determine the myocardial area at risk and infarct size, respectively. Pressure–volume loops were recorded to calculate cardiac work, left ventricular (LV) volumes and ejection fraction. Veno-occlusive unloading reduced infarct size compared with controls (Unloading 13.9 ± 8.2% versus Control 22.4 ± 6.6%; p = 0.04). Unloading increased myocardial salvage (54.8 ± 23.4% vs 28.5 ± 14.0%; p = 0.02), while the area at risk was similar (28.4 ± 6.7% vs 27.4 ± 5.8%; p = 0.74). LV ejection fraction was preserved in the unloaded group, while the control group showed a reduced LV ejection fraction. Veno-occlusive unloading reduced myocardial infarct size and preserved LV ejection fraction in an experimental acute ischemia–reperfusion model. This proof-of-concept study demonstrated the potential of veno-occlusive unloading as an adjunctive cardioprotective therapy in patients undergoing revascularization for acute myocardial infarction.

Implication of anti-angiogenic VEGF-A165b in angiogenesis and systolic function after reperfused myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Marcos Garces ◽  
C Rios-Navarro ◽  
L Hueso ◽  
A Diaz ◽  
C Bonanad ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Adjuvant Therapy ◽  
Ejection Fraction ◽  
Infarct Size ◽  
Systolic Function ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Coronary Reperfusion ◽  
Ventricular Ejection Fraction

Abstract Background Angiogenesis participates in re-establishing microcirculation after myocardial infarction (MI). Purpose In this study, we aim to further understand the role of the anti-angiogenic isoform vascular endothelial growth factor (VEGF)-A165b after MI and explore its potential as a co-adjuvant therapy to coronary reperfusion. Methods Two mice MI models were formed: 1) permanent coronary ligation (non-reperfused MI), 2) transient 45-min coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. Serum and myocardial VEGF-A165b levels were determined. In both experimental MI models, functional and structural implication of VEGF-A165b blockade was assessed. In a cohort of 104 ST-segment elevation MI patients, circulating VEGF-A165b levels were correlated with cardiovascular magnetic resonance-derived left ventricular ejection fraction at 6-months and with the occurrence of adverse events (death, heart failure and/or re-infarction). Results In both models, circulating and myocardial VEGF-A165b presence was increased 21 days after MI induction. Serum VEGF-A165b levels inversely correlated with systolic function evaluated by echocardiography. VEGF-A165b blockage increased capillary density, reduced infarct size, and enhanced left ventricular function in reperfused, but not in non-reperfused MI experiments. In patients, higher VEGF-A165b levels correlated with depressed ejection fraction and worse outcomes. Conclusions In experimental and clinical studies, higher serum VEGF-A165b levels associates with a worse systolic function. Its blockage enhances neoangiogenesis, reduces infarct size, and increases ejection fraction in reperfused, but not in non-reperfused MI experiments. Therefore, VEGF-A165b neutralization represents a potential co-adjuvant therapy to coronary reperfusion. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (Exp. PIE15/00013, PI17/01836, PI18/00209 and CIBERCV16/11/00486).

Abstract 2832: Which Cardiac Marker is Most Useful to Predict Final Infarct Size and Cardiac Function Following Primary Percutaneous Coronary Intervention For Acute Myocardial Infarction?

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Stanley Chia ◽  
O. Christopher Raffel ◽  
Faisal Merchant ◽  
Frans J Wackers ◽  
Fred Senatore ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Infarct Size ◽  
Troponin I ◽  
Troponin T ◽  
Coronary Intervention ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Primary Pci ◽  
Percutaneous Coronary

Background: Assessment of cardiac biomarker release has been traditionally used to estimate the size of myocardial damage after acute myocardial infarction (AMI). However, the significance of cardiac biomarkers in the setting of primary percutaneous coronary intervention (PCI) has not been systematically studied in a large patient cohort. We evaluated the usefulness of serial and single time-point measures of various cardiac biomarkers (creatine kinase (CK), CK-MB, troponin T and I) in predicting infarct size and left ventricular ejection fraction (LVEF) after primary PCI. Methods: EVOLVE (Evaluation of MCC-135 for Left Ventricular Salvage in AMI) was a randomized double-blind, placebo-controlled trial comparing the efficacy of intracellular calcium modulator as an adjunct to primary PCI in patients with first large AMI. Levels of cardiac biomarkers (CK, CK-MB mass, troponin T and I) were determined in 375 patients at baseline before PCI and 2, 4, 12, 24, 48 and 72 hours thereafter. Single photon emission computed tomography imaging was performed to measure infarct size and LVEF on day 5. Results: Area under curve and peak concentrations of all cardiac markers: CK, CK-MB mass, troponin T and troponin I were significantly correlated with myocardial infarct size and LVEF determined on day 5 (Spearman correlation, all P< 0.001; Table ). Troponin I, however provided the best predictor and a single measure at 72 hr was a strong indicator of both infarct size and LVEF. Using receiver operator characteristics curve, troponin I cutoff value of >55 pg/mL at 72 hr has 90% sensitivity and 70% specificity for detection of large infarct size≥10% ( c =0.88; P< 0.001). Conclusions: Plasma levels of CK, CK-MB, troponin T and troponin I remain useful predictors of infarct size and cardiac function in the era of primary PCI for AMI. A single measurement of circulating troponin I at 72 hours can provide an effective and convenient indicator of infarct size and LVEF in clinical practice. Correlation of cardiac biomarkers with Day 5 SPECT determined infarct size and LVEF

Abstract 18996: Impact of Infarct Size on Left Ventricular Diastolic Function Following Acute Myocardial Infarction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Andrew Lin ◽  
Christopher Kwan ◽  
Kristyan Guppy-Coles ◽  
Joanne Sippel ◽  
John Atherton ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Infarct Size ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Troponin I ◽  
Left Ventricular Diastolic Function ◽  
Left Ventricular ◽  
Ventricular Diastolic Function ◽  
St Elevation

Introduction: Severe left ventricular diastolic dysfunction is associated with worse prognosis after acute myocardial infarction (MI). Twenty percent of patients have a restrictive filling pattern (RFP) following MI, and this is associated with a fourfold increase in mortality. The determinants of diastolic function in this setting are not well defined. Aim: We sought to determine the correlation between enzymatic infarct size and RFP in patients with a first ever MI. We hypothesized that a larger infarct size would result in greater impairment of left ventricular diastolic function. Methods: Data analysis was performed on consecutive patients admitted with first ever non-ST elevation MI (NSTEMI) or ST-elevation MI (STEMI) to a single large tertiary referral hospital from January 2013 to December 2014. All patients underwent coronary angiography during the index admission. Infarct size was determined by peak troponin I. Doppler transmitral flow pattern was obtained from the initial transthoracic echocardiogram performed within 48 hours of admission. RFP was defined as: E/A ratio >2.0 and/or E-wave deceleration time <160ms (American Society of Echocardiography Guidelines 2009). Results: Data were available on 645 consecutive patients who underwent coronary angiography for MI. We excluded 160 patients with a previous MI. Of the remaining 485 patients (mean age 62±13 years; mean left ventricular ejection fraction (LVEF) 53±12%), there were 338 NSTEMIs (70%) and 147 STEMIs (30%). PCI was performed in 360 (74%) patients (single vessel (82%), ≥2 vessels (18%)); coronary artery bypass surgery in 58 (13%); and medical management in 67 (13%). Sixty-nine patients (14.4%) had RFP; 52% of these had a LVEF ≥45%. Peak troponin I levels were higher in the RFP group (31.8±30.9μg/L vs 16.8±25.2μg/L, p=<0.001). On multivariate analysis, infarct size by peak troponin I (OR 1.02, 95%CI 1.00-1.03, p=0.026) and low LVEF (OR 0.95, 95%CI 0.91-0.99, p=0.015) were the only independent predictors of RFP. Conclusion: Infarct size was a major determinant of diastolic dysfunction following first ever MI. Whilst LV systolic dysfunction was strongly associated with impaired diastolic function, 52% of patients with severe diastolic dysfunction had relatively preserved LVEF.

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