Larger Infarct Size Research Articles

Functional outcome of ischemic stroke in diabetics

Objective: Objective was to determine whether the outcome of ischemic stroke is different or not in diabetics than nondiabetics. Study Design: Prospective observational. analytical study Study place and Duration; It was conducted in medical unit-2 Bahawal Victoria Hospital, affiliated with Quaid-e-Azam Medical College Bahawalpur from October I, 2004 to September 30. 2005. Patients and methods: 132 patients of ischemic stroke, confirmed by CT scan, were enrolled during one year study period. The patients of hemorrhagic stroke, TlA, focal deficits of non-vascular origin and infratentorial lesions were excluded. Patients were devided into two groups; diabetics and nondiabetics and were studied regarding their in hospital outcome according to the modified Rankin Scale. The variables applied were age, sex, hypertension and type of infarct (lacunar/cerebral). Results: Out of 132 ischemic stroke patients 36 (27%) were diabetics and 96 were nondiabetics. Hjipertension was present in 83 (62%). Overall mortality wa s 11.3%. Mortality was significantly more frequent in diabetics than nondiabetics (16.6% Vs 9.3% p<0.05). Disability was also more frequent in diabetics (25% Vs 13.5% p<0.05). In diabetic group good recovery (8.8% Vs 12.5%) as well as partial recovery (50% Vs 64.5%) was less frequent. Patients <40 years were few in number with good recovery in both diabetics as well as nondiabetics. Diabetics of 40-60 years were found to have significantly high number of deaths (15.3% Vs 7% p<0.05) and disability (15.3% Vs 10.7% p<0.05) than non-diabetics. Similar pattern was seen in patients >60 years. Increasing age was found to be associated with poor outcome in both the groups but poorer in diabetics. Sex did not discriminate the poor outcome in diabetics. The presence of hypertension worsened the out come in both the groups but more in the diabetic group both in term of mortality (20.8% Vs 11.8% p<0.05) as well as disability (33.3% Vs 15.2% p<0.05). Lacunar infarct was found in few patient with good prognosis while cere bral infarct was associated with poor prognosis and put the diabetics at higher risk in term of mortality (17.6% Vs 9.8% p<0.05) as well as disability (26.4% Vs 14.2% p<0.05). Conclusion: Diabetes Mellitus is associated with poor outcome of ischemic stroke patients both in terms of mortality and morbidity during acute hospitalization. Hypertension. increasing age and large infarct size further worsens the outcome.

(1055) - Role of ECMO in Acute Myocardial Infarction Complicating Cardiogenic Shock

Background: There are increasing role of extracorporeal membrane oxygenation (ECMO) in refractory cardiogenic shock. Among them, temporary support for myocardial stunning during peri-myocardial infarction (MI) period is utmost importance. We aimed to evaluate the role of ECMO in such patients. Methods: Of 11,974 patients of acute myocardial infarction from March 2006 through December 2014 from Korea Acute Myocardial Infarction Registry, 1,022 patients (8.5%) were complicated with cardiogenic shock during index hospitalization. Of 766 cardiogenic shock patients with available data, 115 (15%) patients were in ECMO group and 651 (85%) patients were in No-ECMO group. Clinical outcomes were in-hospital and long-term mortality, and complications during hospitalization. We evaluated in both crude and propensity matched cohort. Cox regression analysis was performed to evaluate the factors associated with long-term mortality. Results: Patients in ECMO group were younger, and had low initial mean BP, large infarct size, and more left sided coronary artery disease as target vessel. Crude in-hospital and long-term mortality rate were significantly higher in ECMO group compared to the NO-ECMO group as well as major and minor bleeding complications. However, there were no statistical difference in in-hospital and long-term mortality between ECMO and NO-ECMO groups. After matching, hemoglobin decrease ≥ 3g/dL and minor bleedings were higher in ECMO group. Cox regression analysis revealed that ECMO application was not a significant predictor for mortality (HR 1.505, 95% CI 0.907-2.498, p＝0.11). Conclusions: ECMO application did not affect survival in this study population. Once ECMO was applied, early application was associated with increased survival.

Safety and Efficacy of Intracoronary Vasodilators in the Treatment of No-Reflow after Primary Percutaneous Intervention in Patients with Acute ST-Elevation Myocardial Infarction: A Literature Review

Introduction: The investigation of no-reflow phenomenon after Percutaneous Coronary Intervention (PCI) in patients with acute ST-segment Elevation Myocardial Infarction (STEMI) has therapeutic implications. Several vasodilators were administered through intracoronary injection to treat this phenomenon. We aimed to elucidate the risk factors, predictors, and long-term effects of no-reflow phenomenon, and to compare the effects of various vasodilators on re-opening the obstructed vessels. Materials and Methods: All the reviewed articles were retrieved from MEDLINE and Science Direct (up to October 2014). All no-reflow cases were determined through Thrombolysis in Myocardial Infarction grading (TIMI) system. Results: Four articles were included, two of which mainly focused on risk factors, predictors, and long-term prognosis of no-reflow phenomenon, and its association with patient mortality and morbidity. The other two articles evaluated therapeutic interventions and compared their efficacy in treating no-reflow. Conclusion: Development of no-reflow in patients with STEMI after primary PCI is associated with low myocardial salvage by primary PCI, large scintigraphic infarct size, deteriorated left ventricle ejection fraction at six months, and increased risk of first-year mortality. During primary PCI, intracoronary infusion of diltiazem and verapamil can reverse no-reflow more effectively than nitroglycerin.

Association between epicardial adipose tissue volume and myocardial salvage in patients with a first ST-segment elevation myocardial infarction: An epicardial adipose tissue paradox

BackgroundEpicardial adipose tissue (EAT), defined as the adipose tissue between the visceral pericardium and the outer margin of the myocardium, is associated with coronary artery disease in the general population. However, the clinical implications of EAT in patients with ST-segment elevation myocardial infarction (STEMI) remain unclear. MethodsA total of 142 patients with a first STEMI, who received reperfusion therapy within 12h from symptom onset, were enrolled. All patients underwent cardiac magnetic resonance imaging to evaluate infarct core (Core), area at risk (AAR), and EAT volume. Myocardial salvage index (MSI) was defined as AAR minus Core divided by AAR. Patients in the lower tertile of EAT volume were classified as the low EAT group (group L) and the other two-thirds as the high EAT group (group H). ResultsThe mean MSI was lower in group L than in group H (0.43±0.13 vs 0.49±0.13, p=0.01), and the mean extent of Core was higher in group L than in group H (25±10% vs 19±10%, p<0.01). Multivariate linear regression analysis including coronary risk factors and previously reported predictors of infarct size demonstrated that EAT volume was an independent predictor of MSI (β coefficient=0.002 per 1mL, p=0.002). ConclusionsA lower EAT volume is associated with less myocardial salvage and larger infarct size in patients with a first STEMI.

The relationship between terminal QRS distortion on initial ECG and final infarct size at 4 months in conventional ST- segment elevation myocardial infarct patients

BackgroundIn the Sclarovsky-Birnbaum Ischemia Severity Grading System for patients with ST-segment elevation myocardial infarction (STEMI), “Terminal QRS distortion” is considered as “Grade III”. This evidence for most severe ischemia is associated with cardiovascular magnetic resonance imaging (CMR) markers of myocardial damage in the subacute phase. Our aim was to assess whether terminal QRS distortions on the initial electrocardiogram (ECG) is predictive for infarct size (IS) and left ventricular ejection fraction (LVEF) at 4months in anterior versus infarct locations. MethodsPatient data of the HEBE, GIPS III and MAST, were pooled. ECGs of 411 STEMI patients were classified as absence (Grade II) or presence (Grade III) of terminal QRS distortion according to Sclarovsky-Birnbaum grading. CMR was performed at approximately 4months and included IS and LVEF. ResultsGrade III ischemia was present in 142 of 411 (35%) patients and was more frequently observed with inferior STEMI (P=0.01). In the total cohort and in anterior STEMI, no difference in LVEF or IS was observed between the two Grades. Whereas, in inferior STEMI Grade III was associated with a larger IS (P<0.01) and also, a trend towards a lower LVEF was observed (P=0.09). ConclusionIn inferior STEMI, terminal QRS distortion on the initial ECG is associated with a larger IS at approximately 4months, and can be used to identify a high-risk population in the acute phase. Also, a Grade III was associated with a trend towards a lower LVEF.

Myeloid-Epithelial-Reproductive Receptor Tyrosine Kinase and Milk Fat Globule Epidermal Growth Factor 8 Coordinately Improve Remodeling After Myocardial Infarction via Local Delivery of Vascular Endothelial Growth Factor.

In infarcted heart, improper clearance of dying cells by activated neighboring phagocytes may precipitate the transition to heart failure. We analyzed the coordinated role of 2 major mediators of efferocytosis, the myeloid-epithelial-reproductive protein tyrosine kinase (Mertk) and the milk fat globule epidermal growth factor (Mfge8), in directing cardiac remodeling by skewing the inflammatory response after myocardial infarction. We generated double-deficient mice for Mertk and Mfge8 (Mertk(-/-)/Mfge8(-/-)) and challenged them with acute coronary ligature. Compared with wild-type, Mertk-deficient (Mertk(-/-)), or Mfge8-deficient (Mfge8(-/-)) animals, Mertk(-/-)/Mfge8(-/-) mice displayed greater alteration in cardiac function and remodeling. Mertk and Mfge8 were expressed mainly by cardiac Ly6C(High and Low) monocytes and macrophages. In parallel, Mertk(-/-)/Mfge8(-/-) bone marrow chimeras manifested increased accumulation of apoptotic cells, enhanced fibrotic area, and larger infarct size, as well as reduced angiogenesis. We found that the abrogation of efferocytosis affected neither the ability of circulating monocytes to infiltrate cardiac tissue nor the number of resident Ly6C(High) and Ly6C(How) monocytes/macrophages populating the infarcted milieu. In contrast, combined Mertk and Mfge8 deficiency in Ly6C(High)/Ly6C(Low) monocytes/macrophages either obtained from in vitro differentiation of bone marrow cells or isolated from infarcted hearts altered their capacity of efferocytosis and subsequently blunted vascular endothelial growth factor A (VEGFA) release. Using LysMCre(+)/VEGFA(fl/fl) mice, we further identified an important role for myeloid-derived VEGFA in improving cardiac function and angiogenesis. After myocardial infarction, Mertk- and Mfge8-expressing monocyte/macrophages synergistically engage the clearance of injured cardiomyocytes, favoring the secretion of VEGFA to locally repair the dysfunctional heart.

Brain Atrophy Correlates with Severe Enlarged Perivascular Spaces in Basal Ganglia among Lacunar Stroke Patients.

BackgroundEnlarged perivascular spaces (EPVS) correlate with cognitive impairment and incident dementia. However, etiologies for severe basal ganglia EPVS (BG-EPVS) are still unclear. Our aim was to investigate the independent risk factors for severe BG-EPVS in patients with acute lacunar stroke.MethodsWe prospectively identified patients with lacunar stroke (diameter on DWI ≤ 20mm) from Jan 2011 to May 2015. Patients with severe BG-EPVS were identified on T2 weighted MRI. Age (± 1 year) and sex matched controls were also recruited in the same population (two controls for one case). Vascular risk factors, clinical data, EPVS in centrum semiovale (rated 0 to 4), white matter hyperintensities (WMH) (by Fazekas scale), brain atrophy (rated 0 to 6) were compared between two groups. Logistic regression was performed to determine independent risk factors for severe BG-EPVS.ResultsDuring study period, 89 patients with severe BG-EPVS and 178 matched controls were included. Vascular risk factors did not differ between two groups. Patients with severe BG-EPVS had lower level of HbA1c and diastolic BP at admission, but presented with larger infarct size, more severe WMH (including total WMH, periventricular WMH and deep WMH) and brain atrophy. In logistic regression, brain atrophy (OR = 1.40; 95%CI 1.13, 1.73) and deep WMH (OR = 1.88; 95%CI 1.24, 2.83) were independent risk factors for severe BG-EPVS.ConclusionsBrain atrophy and deep WMH are independent risk factors for severe BG-EPVS, supporting the hypothesis that brain atrophy may be associated with the development of EPVS in basal ganglia.

Abstract 141: Endothelial TRPA1 Channel is Protective Against Ischemia and Hemorrhagic Strokes in Mice

The transient receptor potential ankyrin 1 (TRPA1) cation channel is more selective for Ca 2+ versus Na + ions (∼8:1). We showed that TRPA1 is located in the endothelium of cerebral arteries (eTRPA1) and that reactive oxygen species (ROS)-induced channel activity generates localized Ca 2+ signals (TRPA1 sparklets) that initiate endothelium-dependent hyperpolarization and vasorelaxation. Cerebrovascular disease is associated with increased ROS generation and oxidative stress. Thus, we hypothesized that eTRPA1 activity is protective against stroke. Tissue-specific deletion of eTRPA1 in mice was achieved using the Cre -recombinase (Tie2 promoter) / loxP system. Ischemic strokes were induced by permanent middle cerebral artery occlusion (pMCAO). Neurological function after pMCAO was assessed by a modified neurological severity scale, ranging from 0 to 4 (0: normal behavior; 1: failure to extend contralateral paw; 2: circling; 3: rolling to one side; 4: stupor). Deletion of eTRPA1 increased post-stroke (24 hours) neurological damage in eTRPA1 -/- versus WT mice, as shown by a higher severity score (2.6±0.4 vs 3.8±0.2, p&lt;0.05), and larger infarct size (%hemisphere infarcted: 45±7 vs 62±4%, p0.05, N=8), eTRPA1 -/- mice were significantly more susceptible to hemorrhagic strokes compared to WT. Kaplan-Meyer survival plots showed a higher survival rate for WT vs eTRPA1 -/- at day 10 (61 vs 54%), day 15 (44 vs 21%) and day 20 (22 vs 8%) (p&lt;0.05, N=25). All of the eTRPA1 -/- mice suffered hemorrhagic strokes by day 22, whereas some of the WT mice survived until day 52. Further, eTRPA1 -/- mice showed a higher number of hemorrhagic lesions in the cerebral cortex when compared to WT (12±4 vs 23±4 lesions per animal, p&lt;0.05, N=25 mice per group). These data suggest that eTRPA1 protects against major cerebrovascular accidents and may be considered as a therapeutic target for reducing cerebral infarct after ischemia and as a preventive agent against hemorrhagic strokes.

Abstract WMP16: Eloquence-Weighted Imaging Improves Clinical Outcomes Prediction in Endovascular Stroke Therapy

Background: Larger infarct size at presentation as determined by ASPECTS is associated with reduced likelihood of good outcome in acute ischemic stroke. However, infarct volume alone explains only a modest fraction (∼30%) of the variation in stroke outcome. Incorporating the relative eloquence of each ASPECTS region may improve the predictive power. Methods: In the combined database of the SWIFT and STAR trials, we identified patients treated with the Solitaire stent retriever. Using the 24hr CT scan, a multivariate linear regression was used to determine the relative contribution of each ASPECTS region, separately in each hemisphere, to freedom from disability (mRS 0-2) at 90 days. The coefficients from the regression were used to create an Eloquence-weighted ASPECTS score (EL-ASPECTS), which was compared against the original in predicting outcome based on the presentation CT scan. Results: Among 254 patients treated with ET, average age was 68, 64% were female, and NIHSS was mean 16 (SD +/- 5). Mean ASPECTS at presentation was 8.2 and 6.4 at 24 hrs. The most commonly involved ASPECTS regions were the lentiform nuclei (70%), insula (55%), and caudate (52%). In multivariate analysis, for the right hemisphere on 24hr CT, preservation of M1 (OR 1.6) and M4 (OR 1.2) regions were most strongly predictive of good outcome. For the left hemisphere on 24 hr CT, preservation of M3 (OR 2.6), and M5 (OR 2.5) and involvement of M2 (OR -1.9) were most predictive. Eloquence weights were assigned to all 20 R/L ASPECTS regions to create EL-ASPECTS. EL-ASPECTS, compared with original ASPECTS, demonstrated improved discrimination for independent functional outcome for right hemisphere (C-statistic 0.78 vs. 0.69), left hemisphere (0.78 vs. 0.72), and all stroke patients (0.76 vs. 0.70). On presentation CTs, multivariate analyses including age and presentation NIHSS demonstrated EL-ASPECTS but not original ASPECTS was predictive of good clinical outcome (OR 1.65, p&lt;.01). Higher C-statistic values were seen with EL-ASPECTS in analysis of presentation CT scans. Conclusions: Incorporation of regional weighting into ASPECTS improves the ability to predict who will achieve independent functional outcomes with endovascular therapy in acute ischemic stroke.

Relationship Between White Matter Hyperintensities Penumbra and Cavity Formation.

BackgroundPenumbra has been detected on the edge of white matter hyperintensities (WMH). The aim of our study was to investigate whether cavity formation is different between acute infarcts on the edge of WMH and those away from the edge.Material/MethodsNinety-six subjects with acute lacunar infarct ≤25 mm in diameter were recruited. Subjects with infarct contacting or overlapping with WMH (on axial T2 or coronal FLAIR) were defined as the Edge Group (on the edge of the WMH). Those outside the edge of the WMH were the Non-edge Group. Vascular risk factors, clinical data, baseline infarct size, infarct sites, and severity of WMH (by Fazekas scale) were recorded. Cavity formation was identified by MR follow-up imaging. Risk factors for cavity formation were also investigated.ResultsThere were 37 (38.5%) subjects in the Edge Group and 59 (61.5%) in the Non-edge Group; 55 (57.3%) subjects had cavity formation in follow-up imaging. Subjects in the Edge Group had higher risk of developing cavities than those in the Non-edge Group (78.4% vs. 44.1%, p<0.05). In univariate analysis, subjects with cavity formation had larger infarct size and their infarcts were more often located in subcortical white matter. Vascular risk factors, clinical data, and WMH did not differ between subjects with cavity formation and those without. In logistic regression analysis, DWI infarct size and being in the Edge Group were independent risk factors for cavity formation.ConclusionsLacunar infarcts on the edge of WMH are more likely to develop cavities, suggesting that WMH penumbra affects cavity formation.

Infarct size following complete revascularization in patients presenting with STEMI: a comparison of immediate and staged in-hospital non-infarct related artery PCI subgroups in the CvLPRIT study

BackgroundThe CvLPRIT study showed a trend for improved clinical outcomes in the complete revascularisation (CR) group in those treated with an immediate, as opposed to staged in-hospital approach in patients with multivessel coronary disease undergoing primary percutaneous intervention (PPCI). We aimed to assess infarct size and left ventricular function in patients undergoing immediate compared with staged CR for multivessel disease at PPCI.MethodsThe Cardiovascular Magnetic Resonance (CMR) substudy of CvLPRIT was a multicentre, prospective, randomized, open label, blinded endpoint trial in PPCI patients with multivessel disease. These data refer to a post-hoc analysis in 93 patients randomized to the CR arm (63 immediate, 30 staged) who completed a pre-discharge CMR scan (median 2 and 4 days respectively) after PPCI. The decision to stage non-IRA revascularization was at the discretion of the treating interventional cardiologist.ResultsPatients treated with a staged approach had more visible thrombus (26/30 vs. 31/62, p = 0.001), higher SYNTAX score in the IRA (9.5, 8–16 vs. 8.0, 5.5–11, p = 0.04) and a greater incidence of no-reflow (23.3 % vs. 1.6 % p < 0.001) than those treated with immediate CR. After adjustment for confounders, staged patients had larger infarct size (19.7 % [11.7–37.6] vs. 11.6 % [6.8–18.2] of LV Mass, p = 0.012) and lower ejection fraction (42.2 ± 10 % vs. 47.4 ± 9 %, p = 0.019) compared with immediate CR.ConclusionsOf patients randomized to CR in the CMR substudy of CvLPRIT, those in whom the operator chose to stage revascularization had larger infarct size and lower ejection fraction, which persisted after adjusting for important covariates than those who underwent immediate CR. Prospective randomized trials are needed to assess whether immediate CR results in better clinical outcomes than staged CR.Trial registrationISRCTN70913605, Registered 24th February 2011.

Shock Index as a Predictor of Myocardial Damage and Clinical Outcome in ST-Elevation Myocardial Infarction.

Data on the prognostic value of the shock index in patients with ST-elevation myocardial infarction (STEMI) are scarce. Furthermore, the relationship of the shock index with myocardial damage is unknown. The aim of this study was to evaluate the association of the shock index with markers of myocardial damage and clinical outcome in patients with STEMI. This multicenter study analyzed 791 patients. Patients were categorized in 2 groups according to the admission shock index (optimized cut-off=0.62). Infarct severity was determined by cardiac magnetic resonance (CMR) imaging. Patients with cardiogenic shock that were unable to undergo CMR acquisition were excluded. Major adverse cardiac events (MACE) were defined as a composite of death, reinfarction and congestive heart failure within 12 months. Patients with elevated admission shock index (n=321 [40.6%]) had a significantly larger area-at-risk (37.6 [27.8-50.4] % of left ventricular volume [LV] vs. 34.3 [24.5-46.0] % LV, P=0.02), larger infarct size (19.5 [10.7-28.0] % LV vs. 14.9 [7.7-22.3] % LV, P<0.001), lower myocardial salvage index (46.2 [27.9-64.5] vs. 53.5 [36.5-75.2], P<0.001), and a larger extent of microvascular obstruction (0.3 [0.0-2.2] % LV vs. 0.0 [0.0-1.4] % LV, P=0.01). An elevated shock index was associated with reduced MACE-free survival (P<0.001). Furthermore, the admission shock index was identified as an independent predictor of MACE (hazard ratio=2.92 [1.24-4.22], P<0.01). STEMI patients with an elevated admission shock index had more pronounced myocardial and microvascular damage. Moreover, the shock index was independently associated with MACE at 12 months.

Prediction of long-term major events soon after a first ST-segment elevation myocardial infarction by cardiovascular magnetic resonance

BackgroundCardiovascular magnetic resonance (CMR) predicts combined clinical events in post-ST-segment elevation myocardial infarction (STEMI) patients. However, its contribution to predicting long-term major events (ME: cardiac death and non-fatal myocardial infarction [MI]) is unknown. We aimed to assess whether CMR predicts long-term MEs when performed soon after STEMI. Methods and resultsWe prospectively recruited 546 STEMI patients between 2004 and 2012. The Left ventricular (LV) ejection fraction (LVEF,%), infarct size (IS), edema, hemorrhage, microvascular obstruction, and myocardial salvage were quantified by CMR at pre-discharge. During a mean follow-up of 840 days, 57 ME events (10%; 23 cardiac deaths, 34 non-fatal MIs) were documented. Patients with MEs has more depressed LVEFs (p<0.001), larger ISs (p<0.001), more extensive edema, hemorrhage, and microvascular obstruction, and lower myocardial salvage (p<0.05). CMR indexes were dichotomized according to the best cutoff values for predicting ME. In a comprehensive multivariate model, a LVEF<40% (HR: 2.3; 95% CI [12, 43]; p= 0.009) and an IS>30% of LV mass (HR: 2.4; 95% CI [13, 44]; p= 0.007) independently doubled the ME risk. The ME risk rates were 6%, 14%, and 30%, respectively (p<0.001) in patients with both the LVEF≥40% and an IS≤30% of LV mass (n=393), those with only one altered value (n=84), and in cases with both the LVEF<40% and an IS>30% of LV mass (n=69). Similar tendencies were observed regarding cardiac deaths (2%, 6%, 14%; p<0.001) and MI (4%, 8%, 16%; p < 0.001). ConclusionsCMR performed soon after STEMI predicts long-term MEs. Combined analysis of CMR-derived LVEF and IS allows robust stratification of patient outcomes.

Spatial Relationship between Acute Lacunar Infarction and White Matter Hyperintensities

Background: White matter hyperintensities (WMH) predict incident strokes and new lacunes; moreover, WMH may also affect infarct locations. Our aim in this study was to examine the spatial relationship between WMH and acute lacunar infarction. Methods: Five hundred and ninety patients with acute lacunar infarction in supratentorial region were included. Four situations between infarction and WMH were assessed by axial and coronal MRI: no contact (Grade 0), contact without overlap (Grade Ia), partial overlap (Grade Ib), and complete overlap (Grade II) with preexisting WMH. Furthermore, we defined infarctions in Grades Ia and Ib as edge-localized infarctions and investigated their predictors and short-term outcome. Results: 47.9% (283) of the infarctions were edge-localized infarctions (Grade Ia = 27.6% and Grade Ib = 20.3%), 51.5% (304) were Grade 0, only 0.5% (3) were Grade II. Patients with edge-localized infarction had larger infarct size, more severe WMH, higher National Institutes of Health Stroke Scale (NIHSS) and lower Barthel index (BI) score at admission than those with non-edge-localized infarction. They also had lower BI score at discharge. Infarction in subcortical white matter, diffusion-weighted imaging infarct size, periventricular WMH and deep WMH were predictors for edge-localized infarction. Conclusions: Half of lacunar infarctions were located at the edge of WMH. Both periventricular WMH and deep WMH were predictors for edge-localized infarction.

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

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 &gt;2.0 and/or E-wave deceleration time &lt;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=&lt;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.

Abstract 12444: Toll-like Receptor 3 is Required for Neonatal Heart Repair and Regeneration Following Myocardial Infarction via Glycolysis Dependent Yap/taz Activation

Regenerative therapies for repair of the damaged heart could benefit millions of patients annually. The neonatal heart has the capability of repairing/regenerating damaged myocardium. However, this capability is lost when cardiomyocyte metabolism changes from glycolysis to oxidative phosphorylation, within 7 days after birth. Interestingly, Toll-like receptors (TLRs) are required for somatic cell nuclear reprogramming, which is important for tissue regeneration. The Hippo pathway effector YAP promotes cardiac regeneration. We have reported that TLR ligands can induce protection against myocardial ischemic injury. We hypothesized that TLRs are required for cardiac regeneration in neonatal heart via glycolysis dependent YAP/TAZ activation. To evaluate our hypothesis, myocardial infarction (MI) was induced in one day of wild type (WT) and TLR3 deficient (TLR3 -/- ) neonatal mice (n=5/group). Cardiac function was examined by echocardiography 3 weeks after MI. Cardiomyocyte regeneration and proliferation were examined by histone3 phosphorylation (p-histone3) and EdU incorporation into the cardiomyocytes. In WT neonatal MI mice, cardiac function completely recovered, infarct size was smaller, more p-histone3, EdU was incorporated into the cardiomyocytes, and YAP/TAZ activation was significantly increased following MI. In contrast, TLR3 -/- neonatal hearts showed impaired cardiac function, larger infarct size, less p-histone3 and EdU incorporation and inactivation of YAP/TAZ after MI. To examine whether stimulation of TLR3 will promote glycolysis, cardiomyocytes were isolated from one day old WT neonatal mice and treated with Poly I:C, the TLR3 ligand. Poly I:C treatment significantly increases lactate production, NAD + /NADH ratio, extracellular acidification (ECAR) and YAP/TAZ activation. However, inhibition of glycolysis with 2-Deoxyglucose (2DG) prevented Poly I:C-induced neonatal cardiomyocyte proliferation and regeneration as well as YAP/TAZ activation. In vivo treatment of WT neonatal mice with 2DG (n=6/group) abolished cardiac functional recovery 3 weeks after MI. We conclude that TLR3 is required for neonatal heart regeneration and repair after MI. The mechanisms involve glycolysis dependent activation of YAP/TAZ.

Galectin-3 and sST2 in prediction of left ventricular ejection fraction after myocardial infarction

BackgroundFibrosis is a pivotal event in infarct repair and progressive remodeling after myocardial infarction (MI). Biomarkers may be used to monitor fibrosis, and therefore we evaluated the predictive value of galectin-3 and sST2 for cardiac remodeling after MI. MethodsPlasma galectin-3 and sST2 were measured in patients admitted with primary percutaneous coronary intervention (PCI) for acute MI, at baseline and at 4months. Left ventricular ejection fraction (LVEF) and infarct size were measured after 4months with cardiac MRI (CMR). ResultsIn total, 247 patients had blood samples and CMR data available (mean age 57.7±11.6years; 79.8% male). Increased baseline galectin-3 (≥17.8ng/mL) identified patients with lower LVEF (50.3% (±9.1) vs. non-elevated galectin-3 55.0% (±8.0); P<0.001), and larger infarct size (13.8g. (±12.9) vs. 8.6g. (±8.7); P=0.002) after 4months. Elevated sST2 (≥35.0ng/mL) did not predict decreased LVEF or larger infarct size. Furthermore we showed that at baseline, galectin-3 was an independent predictor for LVEF (β=−0.18; P=0.005) and infarct size (β=0.18; P=0.004). We repeated the analyses using median values of galectin-3 (13.4ng/mL) and sST2 (30.3ng/mL) as a cut point, and this validated our results. ConclusionThe fibrosis biomarker galectin-3, but not sST2, taken immediately after MI, predicts LVEF and infarct size after 4months. We hypothesize that galectin-3 may play a role in the pathophysiology of cardiac remodeling after acute MI.

Frame counting improves the assessment of post-reperfusion microvascular patency by TIMI myocardial perfusion grade: Evidence from cardiac magnetic resonance imaging

BackgroundQuantitative modification of TIMI myocardial perfusion grade (TMPG) by the method of frame counting may improve its sensitivity and the false negative rate for post-reperfusion microvascular dysfunction (MVD) in ST segment-elevated myocardial infarction (STEMI) patients. MethodsThe durations of contrast-washout from infarction area of 139 patients were measured by counting the cine-frame numbers between the appearance and disappearance of myocardial blush. The achieved new index, TMP Frame Counting (TMP-FC) was referenced by cardiac magnetic resonance, by which MVD was defined as microvascular obstruction on gadolinium late-enhancement imaging. ResultsMedian TMP-FC differed significantly between patients with and without MVD (126 frames, IQR 105-160 vs. 86 frames, IQR 75-100, p<0.001). By receiver-operating characteristic analysis, the cutoff of TMP-FC at ≥95.5 frames represented an independent predictor of MVD (OR=11.61, p<0.001). TMP-FC had similar specificity (75%) and positive predictive value (88%), but significantly improved sensitivity (85.3%) and negative predictive value (70.2%) for MVD compared with TMPG (88.6%, 86.5%, 33.7% and 38.2%, respectively) and other traditional angiographic assessments, leading to a better overall accuracy (area under the curve: 0.801 compared with 0.612 from TMPG, p<0.001) for the evaluation of microvascular patency. TMP-FC was positively correlated with MVD extent (r=0.5, p<0.001). Abnormal TMP-FC was associated with larger infarction size (28.67±13.72% vs. 16.51±10.68% of left ventricular mass, p<0.001) and lower LVEF (49.37±11.06% vs. 56.84±9.72%, p<0.001). ConclusionFrame counting can improve the accuracy of TMPG for MVD. Moreover, TMP-FC is correlated with the degree of MVD and cardiac detriments, which is useful for risk stratification.

A protective role of early collateral blood flow in patients with ST-segment elevation myocardial infarction

Conflict persists regarding whether the presence of early collateral blood flow to the infarct-related artery has an effective role in reducing infarct size and improving myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI). We sought to investigate the impact of the collateral circulation on myocardial salvage and infarct size in STEMI patients. In 306 patients who were diagnosed with STEMI and underwent cardiac magnetic resonance within 1 week after revascularization, initial collateral flow to the infarct-related artery was assessed by coronary angiography. Using cardiac magnetic resonance imaging, myocardial infarct size and salvage were measured. Among 247 patients with preprocedural Thrombolysis in Myocardial Infarction flow 0/1, 54 (22%) patients had good collaterals (Rentrop grade ≥ 2, Collateral Connection Score ≥ 2). Infarct size and area at risk were significantly smaller in patients with good collaterals than those with poor collaterals (infarct size: 17.1 ± 10.1 %LV vs 21.8 ± 10.5 %LV, P = .003, area at risk: 33.8 ± 16.8 %LV vs 38.8 ± 15.5 %LV, P = .039). There was a significant difference of myocardial salvage index between 2 groups (50.9% ± 15.0% vs 43.8% ± 18.5%, P = .005). Poor collateralization was an independent predictor for large infarct size (odd ratio 2.48 [1.28-4.80], P = .007). In patients with STEMI, the presence of well-developed collaterals to occluded coronary artery from the noninfarct vessel and its extent were independently associated with reduced infarct burden and improved myocardial salvage. Our results help explain why MI patients with well-developed collateralization have reduced mortality and morbidity.

QRS distortion in pre-reperfusion electrocardiogram is a bedside predictor of large myocardium at risk and infarct size (a METOCARD-CNIC trial substudy)

BackgroundQRS distortion is an electrocardiographic (ECG) sign of severe ongoing ischemia in the setting of ST-segment elevation acute myocardial infarction (STEMI). We sought to evaluate the association between the degree of QRS distortion and myocardium at risk and final infarct size, measured by cardiac magnetic resonance (CMR). MethodsA total of 174 patients with a first anterior STEMI reperfused by primary angioplasty were prospectively recruited. Pre-reperfusion ECG was used to divide the study population into three groups according to the absence of QRS distortion (D0) or its presence in a single lead (D1) or in 2 or more contiguous leads (D2+). Myocardium at risk and infarct size were determined by CMR one week after STEMI. Multiple regression analysis was used to study the association of QRS distortion with myocardium at risk and infarct size, with adjustment for relevant clinical and ECG variables. Results101 patients (58%) were in group D0, 30 (17%) in group D1, and 43 (25%) in group D2+. Compared with group D0, presence of QRS distortion (groups D2+ and D1) was associated with a significantly adjusted larger extent of myocardium at risk (group D2+: absolute increase 10.4%, 95% CI 6.1–14.8%, p<0.001; group D1: absolute increase 3.3%, 95% CI 1.3–7.9%, p=0.157) and larger infarct size (group D2+: absolute increase 10.1%, 95% CI 5.5–14.7%, p<0.001; group D1: absolute increase 4.9%, 95% CI 0.08–9.8%, p=0.046). ConclusionsDistortion in the terminal portion of the QRS complex on pre-reperfusion ECG in two or more leads is independently associated with larger myocardium at risk and infarct size in the setting of primary angioplasty-reperfused anterior STEMI. QRS distortion in only one lead is independently associated with larger infarct size in this setting. Our findings suggest that QRS distortion analysis could be included in risk-stratification of patients presenting with anterior STEMI.