Infarct Mass Research Articles

Role of B lymphocytes in the infarcted mass in patients with acute myocardial infarction.

Despite early reperfusion, patients with ST segment elevation myocardial infarction (STEMI) may present large myocardial necrosis and significant impairment of ventricular function. The present study aimed to evaluate the role of subtypes of B lymphocytes and related cytokines in the infarcted mass and left ventricular ejection fraction obtained by cardiac magnetic resonance imaging performed after 30 days of STEMI. This prospective study included 120 subjects with STEMI submitted to pharmacoinvasive strategy. Blood samples were collected in subjects in the first (D1) and 30th (D30) days post STEMI. The amount of CD11b+ B1 lymphocytes (cells/ml) at D1 were related to the infarcted mass (rho = 0.43; P=0.033), measured by cardiac MRI at D30. These B1 cells were associated with CD4+ T lymphocytes at D1 and D30, while B2 classic lymphocytes at day 30 were related to left ventricular ejection fraction (LVEF). Higher titers of circulating IL-4 and IL-10 were observed at D30 versus D1 (P=0.013 and P<0.001, respectively). Titers of IL-6 at D1 were associated with infarcted mass (rho = 0.41, P<0.001) and inversely related to LVEF (rho = −0.38, P<0.001). After multiple linear regression analysis, high-sensitivity troponin T and IL-6 collected at day 1 were independent predictors of infarcted mass and, at day 30, only HDL-C. Regarding LVEF, high-sensitivity troponin T and high-sensitivity C-reactive protein were independent predictors at day 1, and B2 classic lymphocytes, at day 30. In subjects with STEMI, despite early reperfusion, the amount of infarcted mass and ventricular performance were related to inflammatory responses triggered by circulating B lymphocytes.

Omega-3 intake is associated with attenuated inflammatory response and cardiac remodeling after myocardial infarction

BackgroundMyocardial infarction (MI) elicits an intense acute inflammatory response that is essential for cardiac repair. However, an excessive inflammatory response also favors myocardial apoptosis, cardiac remodeling, and cardiovascular mortality. Omega-3 polyunsaturated fatty acids (ω-3) bear anti-inflammatory effects, which may mitigate the inflammatory response during MI. This study investigated whether ω-3 intake is associated with attenuation of the MI-related inflammatory response and cardiac remodeling.MethodsST-elevation MI (STEMI) patients (n = 421) underwent clinical, biochemical, nutritional, 3D echocardiogram, Cardiac Magnetic Resonance imaging (CMRi) at 30 days and 3D echocardiogram imaging at six months after the MI. Blood tests were performed at day one (D1) and day five (D5) of hospitalization. Changes in inflammatory markers (ΔD5-D1) were calculated. A validated food frequency questionnaire estimated the nutritional consumption and ω-3 intake in the last 3 months before admission.ResultsThe intake of ω-3 below the median (< 1.7 g/day) was associated with a short-term increase in hs-C-reactive protein [OR:1.96(1.24–3.10); p = 0.004], Interleukin-2 [OR:2.46(1.20–5.04); p = 0.014], brain-type natriuretic peptide [OR:2.66(1.30–5.44); p = 0.007], left-ventricle end-diastolic volume [OR:5.12(1.11–23.52)]; p = 0.036] and decreases in left-ventricle ejection fraction [OR:2.86(1.47–6.88); p = 0.017] after adjustment for covariates. No differences were observed in the extension of infarcted mass obtained by CMRi.ConclusionThese findings suggest that a reduced daily intake of ω-3 may intensify outcome-determining mechanisms after STEMI, such as acute inflammatory response and late left ventricular remodeling.Trial registrationClinical Trial Registry number and website: NCT02062554.

Pulsatile antagonism on bradykinin 2-receptor (BK2R) by icatibant triggers the most effective kinin-dependent post-conditioning on rat hearts.

Pharmacological post-conditioning (PC) by intermittent but not continuous administration of exogenous bradykinin (BK) reduces ischemia/reperfusion (I/R) injury via the Reperfusion Injury Salvage Kinase (RISK) pathway activation. We evaluated whether intermittent administration with icatibant (HOE140), a BK2R antagonist, may represent an effective PC strategy, with the advantage of limiting the potential risks of supra-physiologic BK activity. Hearts from male Sprague-Dawley (SD) rats on a Langendorff system were exposed to I/R injury (30/120 min). BK (100 nM) and HOE140 (1 µM) were administered post-ischemically during the first 3 min of reperfusion, under continuous or intermittent infusion (10 s/each). Hearts were randomly assigned to 5 groups: 1) I/R alone (n=5); 2) continuous HOE140 (cHOE n=6); 3) intermittent HOE140 (iHOE n=6); 4) continuous BK (cBK n=6); 5) intermittent BK (iBK n=6). End-diastolic left ventricular pressure (LVEDP), developed left ventricular pressure (dLVP) and coronary flow (CF) were monitored throughout reperfusion. Left ventricular infarct mass (IM) was quantified together with the phosphorylated levels of Akt and GSK3β (RISK pathway kinases) at the end of reperfusion. IM was not significantly changed in cBK or cHOE groups (vs. I/R). Conversely, both iBK and iHOE groups showed a significant limitation in IM (vs. I/R, p<0.05, p<0.01, respectively). Akt and GSK3β phosphorylation levels were higher in iBK and iHOE groups (vs. I/R, p<0.05). When compared to I/R group, both LVEDP values (p<0.05, first 60-min reperfusion), as well as dLVP values (p<0.01) were improved only in iHOE group. CF values did not vary among all groups. In isolated rat hearts, intermittent modulation of the endogenous kallikrein-kinin system by a selective BK2R antagonist mediates PC cardioprotection via RISK signaling.

HDL-Targeted Therapies During Myocardial Infarction.

It is now apparent that a variety of deleterious mechanisms intrinsic to myocardial infarction (MI) exists and underlies its high residual lethality. Indeed, despite effective coronary patency therapies, ischemia and reperfusion (I/R) injury accounts for about 50% of the infarcted mass. In this context, recent studies in animal models have demonstrated that coronary reperfusion with high-density lipoproteins (HDL) may reduce MI size in up to 30%. A spectrum of mechanisms mediated by either HDL-related apolipoproteins or phospholipids attenuates myocardial cell death. Hence, promising therapeutic approaches such as infusion of reconstituted HDL particles, new HDL by genomic therapy, or the infusion of apoA-I mimetic peptides have been sought as a way of ensuring protection against I/R injury. In this review, we will explore the limitations and potential therapeutic effects of HDL therapies during the acute phase of MI.

Activation of AMPK/SIRT1 axis is required for adiponectin-mediated preconditioning on myocardial ischemia-reperfusion (I/R) injury in rats.

BackgroundAdiponectin (AD) cardioprotective activities are mediated by AMPK, a fuel-sensing molecule sharing common targets and cellular activities with SIRT-1. Whether AD preconditioning may involve SIRT-1 activity is not known; however, the protective role of SIRT-1 during ischemia and the potential interplay between AMPK and SIRT-1 suggest this possibility.MethodsIsolated hearts from male Sprague-Dawley rats (n = 85) underwent ischemia/reperfusion (I/R, 30/180 min). Preconditioning with resveratrol (RSV, SIRT-1 activator) was compared to preconditioning with AD alone, or in combination with compound C (CC, AMPK inhibitor) or sirtinol (STN, SIRT-1 inhibitor). For each heart, left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (dLVP), coronary flow (CF) and left ventricular infarct mass (IM) were measured, together with the phosphorylation/activation status of AMPK, LKB1, eNOS and SIRT-1, at the beginning (15 min) and at the end (180 min) of reperfusion.Results and conclusionsWhen compared to I/R, both RSV and AD improved cardiac function and reduced IM (p < 0.01, p < 0.05, respectively). Cardioprotective effects of AD were completely reversed in the AD+CC group, and significantly attenuated in the AD+STN group. Both RSV and AD increased eNOS, AMPK and LKB1 phosphorylation (for each parameter: p < 0.05 vs. I/R, in both RSV and AD treatment groups) at 15 min of reperfusion, and SIRT-1 activity at the end of reperfusion (p < 0.01, p < 0.05 vs. I/R, respectively). Interestingly, AD-mediated phosphorylation of AMPK and LKB1, and SIRT-1 deacetylation activity was markedly reduced in both the AD+CC and AD+STN groups (p < 0.05 vs. AD). Thus, AD-mediated cardioprotection requires both AMPK and SIRT-1 signaling pathways, that act as a component of a cycle and regulate each other’s activities.

ROUTINE USE OF SUPPLEMENTAL OXYGEN IN PATIENTS WITH MYOCARDIAL INFARCTION WITHOUT HYPOXIA IS ASSOCIATED WITH HIGHER RATES OF RE-INFARCTION: A META-ANALYSIS

SESSION TITLE: Cardiovascular Disease SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 PM - 02:00 PM PURPOSE: Routine use of oxygen in patients with myocardial infarction (MI) used to be the standard of practice until recently. However, recent studies have not shown any benefits in this setting. In addition, recently published AVOID study showed that routine use of oxygen is associated with a larger 6-month myocardial infarct size. At the same time, several studies published recently failed to show any harmful effect of the routine use of oxygen. We did this meta-analysis to further explore this controversial issue. We are aiming to assess whether routine use of oxygen is associated with worsened clinical outcomes. METHODS: We used the PRISMA model for our analysis. We performed a systematic search of PubMed, Scopus, Cochrane library and clinicaltrial.gov since inception till January 2017. We used following terms for the search: “infarction”, “myocardial infarction”, “acute coronary syndrome”, “ACS”, “MI”, “oxygen therapy”, “oxygen effect”, “oxygen supplementation” and “oxygen treatment”. Total of 5 studies was included in our analysis. We used RevMan 5.3 for windows (Cochrane Collaboration, Oxford, United Kingdom) for all the analysis. We used random effect model for analysis of the continuous and dichotomous variables. We used Mental-Haenszel method for the analysis. In addition, we used a confidence interval of 95% as significant and along with p-value of less than 0.5 as significant. Heterogeneity was measured using I2. The heterogeneity of <30 % was considered low, 30%-60 % was considered moderate and >60% was considered substantial. We calculated the mean difference (MD) and odds ratio (OR) for the continuous and dichotomous variables respectively RESULTS: A total of 914 patients were included in our analysis (449 in oxygen group). Infarcted myocardial mass between two groups was not significantly different (MD, 2.76-gram, 95% CI [-1.94, 7.47], a p-value 0.25; I2=67%). Similarly, we did not find a significant difference in percent infarct mass (MD, 1.48 %, CI [-1.34, 4.29], p-value 0.30; I2= 55%). We did not find any significant difference in EF between two groups (MD, -0.71, 95% CI [-3.94, 2.53], a p-value 0.67; I2= 0%). However, we found a significant increase in the incidence of re-infarction in oxygen group(4.92% vs 0.73%) (OR, 5.70, 95%, CI [1.45, 22.35], p-value 0.01; I2= 0%). There was no significant difference between two groups in in-hospital mortality (OR,1.06, 95% CI [0.30, 3.70], p-value 0.93;I2= 49%). CONCLUSIONS: Regular use of supplemental oxygen in MI without hypoxia is associated with adverse clinical outcome secondary to increased rates of re-infarction. CLINICAL IMPLICATIONS: There is uncertainty regarding the use of supplemental oxygen in patients with MI without heart failure or dyspnea in the recent guidelines. In light of our evidence of increased adverse clinical outcome, we think the guidelines should actually now recommend against the regular supplemental use of oxygen. DISCLOSURES: No relevant relationships by Ghassan Bachuwa, source=Web Response No relevant relationships by Sai Pavan Kumar Chintalapati, source=Web Response No relevant relationships by Sunil Upadhaya, source=Web Response No relevant relationships by Ravi Kanth Velagapudi, source=Web Response

Smoking and Risk of Ischemic Stroke in Young Men.

There is a strong dose-response relationship between smoking and risk of ischemic stroke in young women, but there are few data examining this association in young men. We examined the dose-response relationship between the quantity of cigarettes smoked and the odds of developing an ischemic stroke in men under age 50 years. The Stroke Prevention in Young Men Study is a population-based case-control study of risk factors for ischemic stroke in men ages 15 to 49 years. The χ2 test was used to test categorical comparisons. Logistic regression models were used to calculate the odds ratio for ischemic stroke occurrence comparing current and former smokers to never smokers. In the first model, we adjusted solely for age. In the second model, we adjusted for potential confounding factors, including age, race, education, hypertension, myocardial infarction, angina, diabetes mellitus, and body mass index. The study population consisted of 615 cases and 530 controls. The odds ratio for the current smoking group compared with never smokers was 1.88. Furthermore, when the current smoking group was stratified by number of cigarettes smoked, there was a dose-response relationship for the odds ratio, ranging from 1.46 for those smoking <11 cigarettes per day to 5.66 for those smoking 40+ cigarettes per day. We found a strong dose-response relationship between the number of cigarettes smoked daily and ischemic stroke among young men. Although complete smoking cessation is the goal, even smoking fewer cigarettes may reduce the risk of ischemic stroke in young men.

Effect of T1-mapping technique and diminished image resolution on quantification of infarct mass and its ability in predicting appropriate ICD therapy.

Myocardial infarct (MI) may consist of an infarct core (IC) and a heterogeneous, semi-viable border zone (BZ). Patients with chronic MI in the left ventricular (LV) myocardium are at increased risk of developing ventricular arrhythmias, and may therefore qualify for implantable cardioverter defibrillator (ICD) therapy. Indices based on MI mass, as determined by cardiac magnetic resonance (CMR) imaging, are shown to be sensitive in predicting adverse ventricular arrhythmic events. However, several factors, such as imaging technique and spatial resolution affect the accuracy of MI mass quantification. The aim of this study was to compare the MI masses determined by T1-mapping CMR techniques to those of conventional late Gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) using inversion recovery fast gradient echo (IR-FGRE). We additionally aimed to investigate the effect of diminishing image resolution on quantification of the MI mass and its ability to predict appropriate ICD therapy. Thirty-eight patients with known MI underwent acquisitions of three CMR imaging techniques: the multicontrast late enhancement (MCLE) and modified look-locker inversion recovery (MOLLI) T1-mapping techniques, and conventional inversion recovery fast gradient echo (IR-FGRE) about 20 min after double-dose injection of Gadolinium. We postprocessed images to quantify IC and BZ masses determined by each CMR technique using a full-width half-maximum (FWHM) approach in IR-FGRE images and a fuzzy c-means clustering algorithm for T1-mapping images. To determine the impact of spatial resolution in sensitivity of predicting ICD events, we artificially diminished resolution of MCLE images acquired from a separate group of 27 patients who had been followed up for ICD therapy and compared the MI masses estimated from the original and downsampled MCLE images. Twelve patients out of 27 (44%) received ICD therapy (i.e., one or more delivered shock) during the follow-up stage. Between each of the three imaging methods, IC masses were not significantly different. Conversely, BZ masses determined by MOLLI were larger compared to those determined by MCLE and IR-FGRE (P value = 0.0022 and 0.0003, respectively). The BZ masses determined by MCLE were not significantly different from those determined by IR-FGRE; however, BZ masses determined by the downsampled MCLE were significantly larger than those determined by IR-FGRE and original MCLE (P value = 0.0033 and 0.0003, respectively). The BZ mass estimated by original MCLE was larger in patients who had received ICD therapy compared to those who did not (P value = 0.044). However, when the spatial resolution of the MCLE images was diminished to that of MOLLI, BZ masses were not significantly different between patients with and without ICD therapy. While estimated IC masses were consistent among all three techniques, the estimated BZ masses were not consistent, especially when spatial resolution of images differed between the techniques. In particular, our study showed that diminished image resolution caused an increase in estimation of the BZ mass, likely due to partial volume effects, which led to a reduced sensitivity in the prediction of appropriate ICD therapy.

Abstract TMP50: Smoking Increases Risk of Ischemic Stroke in Young Men

Introduction: There is a strong dose-response relationship between smoking and risk of ischemic stroke (IS) in young women, but there are few data examining this association in young men. We examined the dose-response relationship between the quantity of cigarettes smoked and the odds of developing an IS in men under age 50. Methods: The Stroke Prevention in Young Men Study is a population-based case-control study of risk factors for IS in 1145 men ages 15-49. Controls were identified by random-digit dialing and were balanced to cases for geographic region of residence, age, and ethnicity. Logistic regression models were used to calculate the odds ratio for IS occurrence comparing smokers to never smokers. In the first model, we adjusted solely for age. In the second model, we adjusted for potential confounding factors, including age, race, education, hypertension, myocardial infarction, angina, diabetes mellitus and body mass index. Interaction terms were used to examine potential effect modification by other risk factors. Statistical tests were 2-tailed and P-values less than 0.05 were considered statistically significant. Results: The table shows that IS risk increased with amount of current smoking and that 2 packs per day current smokers had over a 5-fold increased risk of IS. There were no significant interactions with other risk factors. Conclusions: We found a strong dose-response relationship between the number of cigarettes smoked daily and IS among young men. While complete smoking cessation is the goal, even reducing the number of cigarettes smoked may reduce the risk of IS in young men.

Health-related quality of life in gout in primary care: Baseline findings from a cohort study.

ObjectivesTo examine gout-related, comorbid, and sociodemographic characteristics associated with generic and disease-specific health-related quality of life (HRQOL) in gout.MethodsAdults with gout from 20 general practices were mailed a questionnaire containing the Health Assessment Questionnaire-Disability Index (HAQ-DI), Short-Form-36 Physical Function subscale (PF-10), Gout Impact Scale (GIS), and questions about gout-specific, comorbid and sociodemographic characteristics. Variables associated with HRQOL were examined using multivariable linear regression models.ResultsA total of 1184 completed questionnaires were received (response 65.9%). Worse generic and gout-specific HRQOL was associated with frequent gout attacks (≥5 attacks PF-10 β = −4.90, HAQ-DI β = 0.14, GIS subscales β = 8.94, 33.26), current attack (HAQ-DI β = 0.15, GIS β = −1.94, 18.89), oligo/polyarticular attacks (HAQ-DI β = 0.11, GIS β = 0.78, 7.86), body pain (PF-10 β = −10.68, HAQ-DI β = 0.29, GIS β = 2.61, 11.89), anxiety (PF-10 β = −1.81, HAQ-DI β = 0.06, GIS β = 0.38, 1.70), depression (PF-10 β = −1.98, HAQ-DI β = 0.06, GIS 0.42, 1.47) and alcohol non-consumption (PF-10 β = −16.10, HAQ-DI β = 0.45). Gout-specific HRQOL was better in Caucasians than non-Caucasians (GIS β = −13.05, −13.48). Poorer generic HRQOL was associated with diabetes mellitus (PF-10 β = −4.33, HAQ-DI β = 0.14), stroke (PF-10 β = −12.21, HAQ-DI β = 0.37), renal failure (PF-10 β = −9.43, HAQ-DI β = 0.21), myocardial infarction (HAQ-DI β = 0.17), female gender (PF-10 β = −17.26, HAQ-DI β = 0.43), deprivation (PF-10 β = −7.80, HAQ-DI β = 0.19), and body mass index ≥35 kg/m2 (PF-10 β = −6.10, HAQ-DI β = 0.21).ConclusionsHRQOL in gout is impaired by gout-specific, comorbid, and sociodemographic characteristics, highlighting the importance of comorbidity screening and early urate-lowering therapy. Both gout-specific and generic questionnaires identify the impact of disease-specific features on HRQOL but studies focusing on comorbidity should include generic instruments.

Effects of four antiplatelet/statin combined strategies on immune and inflammatory responses in patients with acute myocardial infarction undergoing pharmacoinvasive strategy: Design and rationale of the B and T Types of Lymphocytes Evaluation in Acute Myocardial Infarction (BATTLE-AMI) study: study protocol for a randomized controlled trial

BackgroundEarly reperfusion of the occluded coronary artery during acute myocardial infarction is considered crucial for reduction of infarcted mass and recovery of ventricular function. Effective microcirculation and the balance between protective and harmful lymphocytes may have roles in reperfusion injury and may affect final ventricular remodeling.Methods/designBATTLE-AMI is an open-label, randomized trial comparing the effects of four therapeutic strategies (rosuvastatin/ticagrelor, rosuvastatin/clopidogrel, simvastatin plus ezetimibe/ticagrelor, or simvastatin plus ezetimibe/clopidogrel) on infarcted mass and left ventricular ejection fraction (LVEF) (blinded endpoints) in patients with ST-segment elevation myocardial infarction submitted to fibrinolytic therapy before coronary angiogram (pharmacoinvasive strategy). All patients (n = 300, 75 per arm) will be followed up for six months. The effects of treatment on subsets of B and T lymphocytes will be determined by flow-cytometry/ELISPOT and will be correlated with the infarcted mass, LVEF, and microcirculation perfusion obtained by cardiac magnetic resonance imaging. The primary hypothesis is that the combined rosuvastatin/ticagrelor therapy will be superior to other therapies (particularly for the comparison with simvastatin plus ezetimibe/clopidogrel) for the achievement of better LVEF at 30 days (primary endpoint) and smaller infarcted mass (secondary endpoint) at 30 days and six months. The trial will also evaluate the improvement in the immune/inflammatory responses mediated by B and T lymphocytes. Omics field (metabolomics and proteomics) will help to understand these responses by molecular events.DiscussionBATTLE-AMI is aimed to (1) evaluate the role of subsets of lymphocytes on microcirculation improvement and (2) show how the choice of statin/antiplatelet therapy may affect cardiac remodeling after acute myocardial infarction with ST elevation.Trial registrationClinicalTrials.gov, NCT02428374. Registered on 28 September 2014.

Early peripheral endothelial dysfunction predicts myocardial infarct extension and microvascular obstruction in patients with ST-elevation myocardial infarction

Introduction and ObjectivesThe role of endothelial dysfunction (ED) in patients with ST-elevation myocardial infarction (STEMI) is poorly understood. Peripheral arterial tonometry (PAT) allows non-invasive evaluation of ED, but has never been used for this purpose early after primary percutaneous coronary intervention (P-PCI). Our purpose was to analyze the relation between ED assessed by PAT and both the presence of microvascular obstruction (MVO) and infarct extension in STEMI patients. MethodsED was assessed by the reactive hyperemia index (RHI), measured by PAT and defined as RHI <1.67. Infarct extension was assessed by troponin I (TnI) release and contrast-enhanced cardiac magnetic resonance (ceCMR). MVO was assessed by ceCMR and by indirect angiographic and ECG indicators. An echocardiogram was also performed in the first 12 h. ResultsWe included 38 patients (mean age 60.0±13.7 years, 29 male). Mean RHI was 1.87±0.60 and 16 patients (42.1%) had ED. Peak TnI (median 118 mg/dl, IQR 186 vs. 67/81, p=0.024) and AUC of TnI (median 2305, IQR 2486 vs. 1076/1042, p=0.012) were significantly higher in patients with ED, who also showed a trend for more transmural infarcts (63.6% vs. 22.2%, p=0.06) and larger infarct mass on ceCMR (median 17.5%, IQR 15.4 vs. 10.1/10.3, p=0.08). Left ventricular ejection fraction (LVEF) was lower and wall motion score index (WMSI) was higher on both echocardiogram and ceCMR in patients with ED. On ceCMR, MVO was more frequent in patients with RHI <1.67 (54.5% vs. 11.1%, p=0.03). ECG and angiographic indicators of MVO all showed a trend toward worse results in these patients. ConclusionsThe presence of ED assessed by PAT 24 h after P-PCI in patients with STEMI is associated with larger infarcts, lower LVEF, higher WMSI and higher prevalence of MVO.

Early peripheral endothelial dysfunction predicts myocardial infarct extension and microvascular obstruction in patients with ST-elevation myocardial infarction

Introduction and ObjectivesThe role of endothelial dysfunction (ED) in patients with ST-elevation myocardial infarction (STEMI) is poorly understood. Peripheral arterial tonometry (PAT) allows non-invasive evaluation of ED, but has never been used for this purpose early after primary percutaneous coronary intervention (P-PCI). Our purpose was to analyze the relation between ED assessed by PAT and both the presence of microvascular obstruction (MVO) and infarct extension in STEMI patients. MethodsED was assessed by the reactive hyperemia index (RHI), measured by PAT and defined as RHI <1.67. Infarct extension was assessed by troponin I (TnI) release and contrast-enhanced cardiac magnetic resonance (ceCMR). MVO was assessed by ceCMR and by indirect angiographic and ECG indicators. An echocardiogram was also performed in the first 12 h. ResultsWe included 38 patients (mean age 60.0±13.7 years, 29 male). Mean RHI was 1.87±0.60 and 16 patients (42.1%) had ED. Peak TnI (median 118 mg/dl, IQR 186 vs. 67/81, p=0.024) and AUC of TnI (median 2305, IQR 2486 vs. 1076/1042, p=0.012) were significantly higher in patients with ED, who also showed a trend for more transmural infarcts (63.6% vs. 22.2%, p=0.06) and larger infarct mass on ceCMR (median 17.5%, IQR 15.4 vs. 10.1/10.3, p=0.08). Left ventricular ejection fraction (LVEF) was lower and wall motion score index (WMSI) was higher on both echocardiogram and ceCMR in patients with ED. On ceCMR, MVO was more frequent in patients with RHI <1.67 (54.5% vs. 11.1%, p=0.03). ECG and angiographic indicators of MVO all showed a trend toward worse results in these patients. ConclusionsThe presence of ED assessed by PAT 24 h after P-PCI in patients with STEMI is associated with larger infarcts, lower LVEF, higher WMSI and higher prevalence of MVO.

Polypharmacy and Gait Performance in Community-dwelling Older Adults.

To examine the relationship between polypharmacy and gait performance during simple (normal walk (NW)) and complex (walking while talking (WWT)) locomotion. Cross-sectional. Community. Community-dwelling older adults (N = 482). Polypharmacy, defined as use of five or more medications and a cohort-specific alternate definition of eight or more medications, was examined. Velocity (cm/s) measured quantitatively during NW and WWT conditions. The 164 participants (34%) with polypharmacy of five or more medications were older (77.0 ± 6.6 vs 76.0 ± 6.4) and more likely to have hypertension, congestive heart failure, diabetes mellitus, myocardial infarction, and higher body mass index (BMI) and to have fallen within the last year than the remaining 318 without polypharmacy and walked 6 cm/s slower (P = .004) during NW and 4 cm/s slower during WWT (P = .07), adjusting for age, sex, and education. Group differences were not statistically significant after adjusting for comorbidities. Prevalence of polypharmacy of eight or more medications was 10%. This group walked 11 cm/s slower during NW (P < .001) and 8.6 cm/s slower during WWT (P = .01) than those without polypharmacy, adjusted for age, sex, and education. Participants taking eight or more medications had slower NW (8.5 cm/s; P = .01), and WWT (6.9 cm/s; P = .07), compared to those without polypharmacy, adjusting for comorbidities. Adjustments for BMI, high-risk drugs, falls, and comorbidities yielded slower NW (9.4 cm/s, P = .005) and WWT (7.9 cm/s, P = .04 among those with polypharmacy compared to those without polypharmacy). These results suggest an association between polypharmacy and locomotion that medical comorbidities only partly explained.

Post-procedural myocardial infarction following surgical aortic valve replacement and transcatheter aortic valve implantation

Myocardial injury assessed using cardiac biomarker release is ubiquitous following surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI), preventing accurate discrimination between focal myocardial infarction (MI) and global injury. Cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) imaging was used to compare rates of new MI following SAVR and TAVI. Identical CMR scans were obtained at baseline and six months post procedure in ninety-six patients undergoing SAVR (n=39) and TAVI (n=57). The rate of new MI was greater following SAVR than TAVI (SAVR, n=10 [26%] vs. TAVI, n=3 [5%], p=0.004). Infarct mass was similar between groups (SAVR 1.1±0.6 vs. TAVI 2.0±1.4 g, p=0.395). New MI did not impact on change in LV ejection fraction (SAVR:LGE[+]2.2±4.7 vs. LGE[-]0.9±8.0%, p=0.437, TAVI:LGE[+]-0.9±6.0 vs. LGE[-]2.0±7.8%, p=0.420). Thirty-four patients (60%) in the TAVI group had non-revascularised coronary artery disease (CAD) at the time of TAVI, of whom three (9%) had new MI. MI is an infrequent complication of TAVI but is more common following SAVR. Infarct size is small following both procedures. The low new infarct rate in TAVI, especially in the context of high rates of non-revascularised CAD, strengthens data from previous studies suggesting that coronary revascularisation pre-TAVI may be unnecessary.

Automatic high-resolution infarct detection using volumetric multiphase dual-energy CT

ObjectivesLate contrast enhancement CT (LCE-CT) visualizes the presence of myocardial infarcts. Differentiation of the contrast-enhanced infarct from blood pool is challenging. We developed a novel method using data from first pass CT angiography (CTA) imaging to enable automatic infarct detection. Materials and methodsA canine model of myocardial infarction was produced in 11 animals. Two months later, first pass CTA (90 kVp) and LCE-CT (dual energy 90 kVp/150 kVp tin filtered) were performed. Late gadolinium enhancement MRI was used as reference standard. The CTA and LCE-CT were co-registered using a fully automatic non-rigid method based on curved B-splines. The method allowed for limited elastic deformation and the considerable differences in attenuation between first-pass and delayed image. The blood pool was easily identified on the CTA image by high attenuation. Because CTA and LCE-CT were registered, the blood pool segmentation can be directly transferred to the LCE-CT – thereby solving the key problem of infarct/blood pool differentiation. The remaining segmentation of infarcted vs. noninfarcted myocardium was performed using a threshold. Automatic and MRI-guided expert segmentations of LCE-CT infarcts were compared to each other on volume and area basis (intraclass correlation coefficient, ICC) and on voxel basis (dice similarity coefficient, DSC between automatic and expert CT segmentation). CT infarct volumes were compared with the reference standard MRI. ResultsThe infarcts were mainly subendocardial (81%) and relatively small (median MRI infarct mass 7.4 g). The automatic segmentation showed excellent agreement with expert segmentation on volume and area measurements (ICC = 0.96 and 0.87, respectively). DSC showed moderately good agreement (DSC = 0.47). Compared to MRI there was modest agreement (ICC = 0.62) and excellent correlation (R = 0.9). Manual interaction was less than 1 min per exam. ConclusionWe propose an automatic method for infarct segmentation on LCE-CT using multiphase CT information, which showed excellent agreement with expert readers and favorable correlation with MRI.

Intermittent pacing therapy favorably modulates infarct remodeling

Despite early revascularization, remodeling and dysfunction of the left ventricle (LV) after acute myocardial infarction (AMI) remain important therapeutic targets. Intermittent pacing therapy (IPT) of the LV can limit infarct size, when applied during early reperfusion. However, the effects of IPT on post-AMI LV remodeling and infarct healing are unknown. We therefore investigated the effects of IPT on global LV remodeling and infarct geometry in swine with a 3-day old AMI. For this purpose, fifteen pigs underwent 2 h ligation of the left circumflex coronary artery followed by reperfusion. An epicardial pacing lead was implanted in the peri-infarct zone. After three days, global LV remodeling and infarct geometry were assessed using magnetic resonance imaging (MRI). Animals were stratified into MI control and IPT groups. Thirty-five days post-AMI, follow-up MRI was obtained and myofibroblast content, markers of extracellular matrix (ECM) turnover and Wnt/frizzled signaling in infarct and non-infarct control tissue were studied. Results showed that IPT had no significant effect on global LV remodeling, function or infarct mass, but modulated infarct healing. In MI control pigs, infarct mass reduction was principally due to a 26.2 ± 4.4% reduction in infarct thickness (P ≤ 0.05), whereas in IPT pigs it was mainly due to a 35.7 ± 4.5% decrease in the number of infarct segments (P ≤ 0.05), with no significant change in infarct thickness. Myofibroblast content of the infarct zone was higher in IPT (10.9 ± 2.1%) compared to MI control (5.4 ± 1.6%; P ≤ 0.05). Higher myofibroblast presence did not coincide with alterations in expression of genes involved in ECM turnover or Wnt/frizzled signaling at 5 weeks follow-up. Taken together, IPT limited infarct expansion and altered infarct composition, showing that IPT influences remodeling of the infarct zone, likely by increasing regional myofibroblast content.

Effect and mechanism of cardiosphere-derived cells in the treatment of rats with acute myocardial infarction after reperfusion

Objective To investigate whether cardiosphere-derived cells (CDCs) can protect ischemia-reperfusion in acute myocardial infarction, and to explore its mechanism. Methods 7-10 week-old female Wistar-Kyoto (WKY) rats were used for all in vivo experiment.Ischemia was induced for 45 min to allow reperfusion.Twenty minutes (or two hours) later, CDCs (or PBS control) were injected into the LV cavity with an aortic cross-clamp.After 48 hours and 2 weeks, representative echocardiography long-axis images of the left ventricular (LV) systolic and diastolic dimensions, the protein level of activated caspase-3 were observed, the apoptosis rate of myocardial cells and the infarct area of the heart were determined in those groups. Results Rats underwent 45 minutes of ischemia, followed by either 20 minutes or 120 minutes (delayed injection) of reperfusion prior to infusion of CDCs (cells per 100μL) or PBS control (100μL) into the LV cavity during aortic cross-clamp.Ejection fraction, as measured by echocardiography, was significantly preserved in CDCs-treated animals at 48 hours with a 20-minute, but not a 120-minute, delay of infusion(28.0% vs 38.0%, χ2=7.340, P=0.008). CDCs-treated animals reduced percentage of infarct mass(6.2% vs 13.4%, χ2=4.226, P=0.002; 6.2% vs 13.5%, χ2=1.853, P=0.003), infarct mass(6.2% vs 13.4%, χ2=2.220, P=0.002; 6.2% vs 13.5%, χ2=3.119, P=0.003) treated with PBS control.CDC-treated animals reduced infarct size, relative to those of animals treated with PBS control(45.0% vs 24.0%, χ2=4.825, P=0.008), less thinning of the LV anterior wall(1.96mm vs 1.45mm, t=0.897, P=0.028). Protein expressions of MMP-8 and CXGL7 were elevated in the infarct zone of hearts treated with CDCs(MMP-8: 0.74 vs 0.56, t=0.657, P=0.014; CXGL7: 0.44 vs 0.81, t=0.791, P=0.010). Conclusion CDCs is suggested to be a promising cell source to repair acute myocardial infarction through inhibiting apoptosis and reduce proinflammatory cytokine expression. Key words: Myocardial infarction; Ischemia reperfusion; Cardiosphere-derived cells

Protective Effects of Ticagrelor on Myocardial Injury After Infarction.

The P2Y12 receptor antagonist ticagrelor has been shown to be clinically superior to clopidogrel. Although the underlying mechanisms remain elusive, ticagrelor may exert off-target effects through adenosine-related mechanisms. We aimed to investigate whether ticagrelor reduces myocardial injury to a greater extent than clopidogrel after myocardial infarction (MI) at a similar level of platelet inhibition and to determine the underlying mechanisms. Pigs received the following before MI induction: (1) placebo-control; (2) a loading dose of clopidogrel (600 mg); (3) a loading dose of ticagrelor (180 mg); or (4) a loading dose of ticagrelor followed by an adenosine A1/A2-receptor antagonist [8-(p-sulfophenyl)theophylline, 4 mg/kg intravenous] to determine the potential contribution of adenosine in ticagrelor-related cardioprotection. Animals received the corresponding maintenance doses of the antiplatelet agents during the following 24 hours and underwent 3T-cardiac MRI analysis. Platelet inhibition was monitored by ADP-induced platelet aggregation. In the myocardium, we assessed the expression and activation of proteins known to modulate edema formation, including aquaporin-4 and AMP-activated protein kinase and its downstream effectors CD36 and endothelial nitric oxide synthase and cyclooxygenase-2 activity. Clopidogrel and ticagrelor exerted a high and consistent antiplatelet effect (68.2% and 62.2% of platelet inhibition, respectively, on challenge with 20 μmol/L ADP) that persisted up to 24 hours post-MI (P<0.05). All groups showed comparable myocardial area-at-risk and cardiac worsening after MI induction. 3T-Cardiac MRI analysis revealed that clopidogrel- and ticagrelor-treated animals had a significantly smaller extent of MI than placebo-control animals (15.7 g left ventricle and 12.0 g left ventricle versus 22.8 g left ventricle, respectively). Yet, ticagrelor reduced infarct size to a significantly greater extent than clopidogrel (further 23.5% reduction; P=0.0026), an effect supported by troponin-I assessment and histopathologic analysis (P=0.0021). Furthermore, in comparison with clopidogrel, ticagrelor significantly diminished myocardial edema by 24.5% (P=0.004), which correlated with infarct mass (r=0.73; P<0.001). 8-(p-Sulfophenyl)theophylline administration abolished the cardioprotective effects of ticagrelor over clopidogrel. At a molecular level, aquaporin-4 expression decreased and the expression and activation of AMP-activated protein kinase signaling and cyclooxygenase-2 increased in the ischemic myocardium of ticagrelor- versus clopidogrel-treated animals (P<0.05). These protein changes were not observed in those animals administered the adenosine receptor blocker 8-(p-sulfophenyl)theophylline. Ticagrelor, beyond its antiplatelet efficacy, exerts cardioprotective effects by reducing necrotic injury and edema formation via adenosine-dependent mechanisms.

A comparison of infarct mass by cardiac magnetic resonance and real time myocardial perfusion echocardiography as predictors of major adverse cardiac events following reperfusion for ST elevation myocardial infarction

Infarct mass as assessed by myocardial-delayed enhancement imaging on cardiac magnetic resonance (CMR) and myocardial blood flow as assessed by real time myocardial perfusion echocardiography (RT-MPE) have been shown to predict adverse events following ST elevation myocardial infarction (STEMI). There has been no published comparison of quantitative assessment using these modalities as predictors of clinical outcomes to date. We compared RT-MPE with CMR for prediction of cardiac events in reperfused STEMI patients. Consecutive STEMI patients with early reperfusion were studied. RT-MPE and CMR were performed. Perfusion score indices (PSIRT-MPE and PSICMR ) were calculated [sum of segmental perfusion scores/number of segments]. CMR infarct mass (g) and RT-MPE myocardial blood flow (MBF dB/s) were quantified. Patients were followed for cardiac events (death, nonfatal MI, revascularization, angina, and heart failure). All 27 patients (age 62±14; follow-up 3.5±2.6years) had thrombolysis in myocardial infarction (TIMI) grade 3 flow of infarct vessel. Cardiac events occurred in 17 (63%). Cardiac event patients had higher PSIRT-MPE , PSICMR , infarct mass, and lower MBF. PSIRT-MPE cutoff of 0.3 had an AUC of 0.856 (82% sensitivity, 70% specificity), while a PSICMR cutoff of 0.2 had an AUC of 0.765 (76% sensitivity, 60% specificity). Infarct mass and MBF were independent predictors of cardiac events after adjusting for risk factors (hazard ratios: 20.9 [95% CI 1.8-256] P=.02 and 8.1 [95% CI 1.5-78] P=.01, respectively). Quantitative RT-MPE performed comparably to CMR for prediction of MACE in STEMI patients supporting a prognostic role for this noninvasive, bedside imaging method.