Quantification Of Infarct Size Research Articles

Single-Dose Gadoterate Meglumine for 3T Late Gadolinium Enhancement MRI for the Assessment of Chronic Myocardial Infarction: Intra-Individual Comparison with Conventional Double-Dose 1.5T MRI.

ObjectiveTo intra-individually compare 3T magnetic resonance (MR) images obtained with one dose gadoterate meglumine to 1.5T MR using conventional double dose for assessment of chronic myocardial infarction.Materials and MethodsSixteen patients diagnosed with chronic myocardial infarctions were examined on single-dose 3T MR within two weeks after undergoing double-dose 1.5T MR. Representative short-axis images were acquired at three points after administration of gadoterate meglumine. Contrast-to-noise ratios between infarcted and normal myocardium (CNRinfarct-normal) and between infarct and left ventricular cavity (CNRinfarct-LVC) were calculated and compared intra-individually at each temporal scan. Additionally, two independent readers assessed relative infarct size semi-automatically and inter-observer reproducibility was evaluated using intraclass correlation coefficient.ResultsWhile higher CNRinfarct-normal was revealed at single-dose 3T at only 10 minutes scan (p = 0.047), the CNRinfarct-LVC was higher at single-dose 3T MR at each temporal scan (all, p < 0.05). Measurement of relative infarct size was not significantly different between both examinations for both observers (all, p > 0.05). However, inter-observer reproducibility was higher at single-dose 3T MR (all, p < 0.05).ConclusionSingle-dose 3T MR is as effective as double-dose 1.5T MR for delineation of infarcted myocardium while being superior in detection of infarcted myocardium from the blood cavity, and provides better reproducibility for infarct size quantification.

Role of cardiac T1 mapping and extracellular volume in the assessment of myocardial infarction.

Although late gadolinium enhancement on cardiac magnetic resonance imaging remains the reference standard for scar assessment, it does not provide quantitative information about the extent of pathophysiological changes within the scar tissue. T1 mapping and extracellular volume (ECV) mapping are steadily becoming diagnostic and prognostically useful tests for in vivo myocardial histology, influencing clinical decision-making. Quantitative native T1 maps (acquired without a contrast agent) represent the longitudinal relaxation time within the myocardium and changes with myocardial extracellular water (edema, focal, or diffuse fibrosis), fat, iron, and amyloid protein content. Post-contrast ECV maps estimate the size of the extracellular space and have sensitivity in the identification of interstitial disease. Both pre- and post-contrast T1 mapping are emerging as comprehensive tools for the assessment of numerous conditions including ischemic scarring that occurs post myocardial infarction (MI). This review outlines the current evidence and potential future role of T1 mapping in MI. We conclude by highlighting some of the remaining challenges such as quality control, standardization of image acquisition for clinical practice, and automated methods for quantifying infarct size, area at risk, and myocardial salvage post MI.

Quantification of Infarct Size in Acute and Chronic Ischaemic and Non-Ischaemic Heart Diseases: Reproducibility of Different Techniques

Background: Several techniques have been proposed for the quantification of late gadolinium enhancement (LGE), including manual planimetry, manual thresholding, the signal threshold versus reference myocardium technique (STRM) and the full width at half maximum (FWHM) technique. However, none of these approaches is considered as the optimal method for quantitative assessment of left ventricular (LV) scar. This study compares the intra- and inter-observer reproducibility of the aforementioned quantification techniques across different disease processes that give rise to LV scar, i.e. acute myocardial infarct (AMI), acute myocarditis (AMy), chronic ischaemic heart disease (CIHD), hypertrophic cardiomyopathy (HCM) and non-ischaemic cardiomyopathy (NICM). Methods: 100 patients (20 AMI patients, 20 AMy patients, 20 CIHD patients, 20 HCM patients and 20 NICM patients) who had cardiac magnetic resonance imaging and visually detectable LGE were included in the study. LGE images were analysed by two independent observers and intra- and inter-observer agreement of each technique was reported using the intraclass correlation coefficient (ICC). Results: All quantitative techniques had excellent intra- and inter-observer agreement (ICC values ≥0.95) in AMI patients, while only FWHM performed well in AMy and CIHD patients (intra- and inter-observer ICC were 0.96 and 0.92 among AMy patients and 0.95 and 0.93 among the CIHD patients). Among HCM and NICM patients, all quantitative techniques had good intra- and inter-observer agreement (ICC values ≥0.90), except manual thresholding, which had ICC values <0.90; FWHM presented the highest intra- and inter-observer ICC (0.97 and 0.94, respectively). Conclusions: FWHM technique performs well in all cardiac conditions; STRM techniques represent a valid alternative in AMI, HCM and NICM.

In Vivo Quantification of Myocardial Infarction in Mice Using Micro-CT and a Novel Blood Pool Agent.

We herein developed a micro-CT method using the innovative contrast agent ExiTron™ MyoC 8000 to longitudinally monitor cardiac processes in vivo in small animals. Experiments were performed on healthy mice and mice with myocardial infarction inflicted by ligation of the left anterior descending artery. Time-dependent signal enhancement in different tissues of healthy mice was measured and various contrast agent doses were investigated so as to determine the minimum required dose for imaging of the myocardium. Due to its ability to be taken up by healthy myocardium but not by infarct tissue, ExiTron MyoC 8000 enables detection of myocardial infarction even at a very low dose. The signal enhancement in the myocardium of infarcted mice after contrast agent injection was exploited for quantification of infarct size. The values of infarct size obtained from the imaging method were compared with those obtained from histology and showed a significant correlation (R2 = 0.98). Thus, the developed micro-CT method allows for monitoring of a variety of processes such as cardiac remodeling in longitudinal studies.

In vivo visualization and ex vivo quantification of experimental myocardial infarction by indocyanine green fluorescence imaging.

The fluorophore indocyanine green accumulates in areas of ischemia-reperfusion injury due to an increase in vascular permeability and extravasation of the dye. The aim of the study was to validate an indocyanine green-based technique of in vivo visualization of myocardial infarction. A further aim was to quantify infarct size ex vivo and compare this technique with the standard triphenyltetrazolium chloride staining. Wistar rats were subjected to regional myocardial ischemia (30 minutes) followed by reperfusion (n = 7). Indocyanine green (0.25 mg/mL in 1 mL of normal saline) was infused intravenously for 10 minutes starting from the 25th minute of ischemia. Video registration in the near-infrared fluorescence was performed. Epicardial fluorescence of indocyanine green corresponded to the injured area after 30 minutes of reperfusion. Infarct size was similar when determined ex vivo using traditional triphenyltetrazolium chloride assay and indocyanine green fluorescent labeling. Intravital visualization of irreversible injury can be done directly by fluorescence on the surface of the heart. This technique may also be an alternative for ex vivo measurements of infarct size.

Sources of variability in quantification of cardiovascular magnetic resonance infarct size - reproducibility among three core laboratories

BackgroundAcute myocardial infarct (AMI) size depicted by late gadolinium enhancement cardiovascular magnetic resonance (CMR) is increasingly used as an efficacy endpoint in randomized trials comparing AMI therapies. Infarct size is quantified using manual planimetry (MANUAL), visual scoring (VISUAL), or automated techniques using signal-intensity thresholding (AUTO). Although AUTO is considered the most reproducible, prior studies did not account for the subjective determination of endocardial/epicardial borders, which all methods require. For MANUAL and VISUAL, prior studies did not address how to treat intermediate signal intensities due to partial volume.MethodsTo assess sources of variability, AMI size was measured in 30 patients and 12 controls by 3 core-laboratories using 8 methods, each separated by more than 2 months time (n = 720 evaluations). The methods were: (1,2) AUTOSegment, AUTOFWHM (using Segment software or the full-width-at-half-maximum algorithm, respectively); (3,4) AUTO-UCSegment, AUTO-UCFWHM (user correction for endocardial border pixels, no-reflow, etc.); (5) MANUAL; (6) MANUAL-ISI (adjustment for intermediate signal-intensities); (7) VISUAL; (8) VISUAL-ISI.ResultsMean infarct size varied between 16.8% and 27.2% of LV mass depending on method. Even automated techniques with no user interaction for infarct borders resulted in significant within-patient variability given the need to subjectively trace endocardial/epicardial contours. The coefficient-of-variation (CV) was 10.6% and 14.6% for AUTOSegment and AUTOFWHM, respectively. For manual and visual categories, reproducibility was improved when intermediate signal-intensities were considered (MANUAL-ISI vs MANUAL: CV = 8.3% vs 14.4%; p = 0.03; VISUAL-ISI vs VISUAL: CV = 8.4% vs 10.9%; p = 0.01). For AUTO-UCSegment, MANUAL-ISI, and VISUAL-ISI (best technique in each category) within-patient variability due to the quantification method was less than 10% of total variability, and the required sample sizes for detecting a 5% absolute difference in infarct size were 62, 63, and 62 patients, respectively.ConclusionAmong CMR core-laboratories, an important source of variability in infarct size quantification is the subjective delineation of endocardial/epicardial borders. When intermediate signal intensities are considered in manual planimetry and visual scoring, reproducibility and impact on sample size are similar to automated techniques.

Optimized Heart Sampling and Systematic Evaluation of Cardiac Therapies in Mouse Models of Ischemic Injury: Assessment of Cardiac Remodeling and Semi-Automated Quantification of Myocardial Infarct Size.

Cardiac therapies are commonly tested preclinically in small-animal models of myocardial infarction. Following functional evaluation, post-mortem histological analysis is essential to assess morphological and molecular alterations underlying the effectiveness of treatment. However, non-methodical and inadequate sampling of the left ventricle often leads to misinterpretations and variability, making direct study comparisons unreliable. Protocols are provided for representative sampling of the ischemic mouse heart followed by morphometric analysis of the left ventricle. Extending the use of this sampling to other types of in situ analysis is also illustrated through the assessment of neovascularization and cellular engraftment in a cell-based therapy setting. This is of interest to the general cardiovascular research community as it details methods for standardization and simplification of histo-morphometric evaluation of emergent heart therapies. © 2015 by John Wiley & Sons, Inc.

Sulfonylurea use is associated with larger infarct size in patients with diabetes and ST-elevation myocardial infarction

BackgroundAnimal models have demonstrated that sulfonylureas increase the size of myocardial infarction; however, data in humans is scarce. This study evaluated the association between sulfonylurea use and infarct size in diabetes patients with ST-elevation myocardial infarction (STEMI). MethodsConsecutive STEMI patients admitted in Edmonton, Canada between 2006 and 2011 were enrolled in a regional prospective registry program. Patients with type 2 diabetes were identified from this group and the maximum recorded troponin I (max cTnI) within the first 48h of chest pain onset was used as the primary outcome to quantify infarct size. The relationship between preadmission sulfonylurea use and max cTnI was assessed using multivariable linear regression to adjust for patient demographics, cardiovascular risk factors, clinical data on admission, ischemia time, reperfusion therapy and preadmission drugs. ResultsThere were 560 STEMI patients with type 2 diabetes; mean (standard deviation; SD) age was 63.3 (12.8) years, 395 (70.5%) were male, 216 (38.6%) received primary percutaneous intervention, and 211 (37.7%) received thrombolysis. The max cTnI was higher in 146 sulfonylurea users compared to 414 non-sulfonylurea users (mean (SD): 49.8 (74.3) ng/mL versus 39.9 (50.4) ng/mL, respectively; adjusted between-group difference: 12.9ng/mL; 95% CI 0.3–25.5; p=0.044). ConclusionThis study adds further evidence to the proposed causal relationship between sulfonylureas and adverse cardiovascular events by observing a significant difference in infarct size among type 2 diabetes patients presenting with STEMI. Clinicians should consider this association when prescribing sulfonylureas to manage patients with type 2 diabetes.

The impact of methodological and temporal variation on infarct size quantification in acute myocardial infarction with late enhancement CMR

Methods 55 patients with reperfused, first acute ST-elevation AMI underwent LGE-CMR on a Philips Achieva 3T scanner at 1 week and 6 months post AMI. IS was expressed as a percentage of LV volume and measured at both time points using: manual planimetry, signal intensity threshold indicating LGE set at 2, 3 and 5 standard deviations (SD) above the remote myocardium and the full width at half maximum (FWHM) technique, which uses half the maximal signal within the scar as the threshold. The relationship between all measures of IS and final (6 month) LV ejection fraction (LV EF) and LV end diastolic volume (LV EDV) was evaluated using Spearman correlations.

Sources of variability in quantification of CMR infarct size and their impact on sample size calculations - reproducibility among three core laboratories

Background Infarct size is increasingly used as an efficacy endpoint in randomized trials comparing acute myocardial infarct (AMI) therapies. Infarct size, depicted by delayedenhancement-CMR, is quantified using manual planimetry (MANUAL), visual scoring (VISUAL), or automated techniques using signal-intensity thresholding to define infarct borders (AUTO). Although AUTO is considered the most reproducible, prior studies did not account for the subjective determination of endocardial/epicardial borders, which all methods require. For MANUAL and VISUAL, prior studies have not explicitly defined how to treat intermediate signal-intensities due to partial volume. We wanted to assess sources of variability among 6 methods in quantification of AMI size, and illustrate the significance of these findings on sample size calculations for clinical trials.

A small molecule activator of AKT does not reduce ischemic injury of the rat heart.

BackgroundActivation of protein kinase AKT is required for cardioprotection by ischemic preconditioning, and transgenic overexpression of AKT protects the heart against ischemia. However, it is unknown whether acute pharmacological activation of AKT alone, using a therapeutically relevant strategy, induces cardioprotection. In this study we provide the first evidence to clarify this question.MethodsWe used a recently described specific activator of AKT, the small molecule SC79, to treat rat hearts submitted to ischemia and reperfusion. Initially, isolated rat hearts were perfused with increasing doses of SC79 to verify the magnitude of AKT activation. Low and high doses were determined and used to treat hearts submitted to ischemia (35 minutes) and reperfusion (60 minutes), in a randomized and blinded design. AKT activation was verified by western immunobloting. Metabolic profile was determined by cardiac ATP content and mitochondrial enzyme activity, while cytosolic levels of cytochrome C and caspase-3 activity were used as markers of apoptosis. Ischemic injury was assessed by quantification of infarct size and cardiac release of creatine kinase and lactate dehydrogenase.ResultsSC79 activated cardiac AKT within 30 minutes in a dose-dependent fashion. ATP content was largely reduced by ischemia, but was not rescued by SC79. Similarly, mitochondrial enzyme activity was not affected by SC79. SC79 administered before ischemia or at reperfusion did not prevent cytosolic accumulation of cytochrome C and overactivation of caspase-3. Finally, SC79 failed to reduce infarct size or release of cardiac injury biomarkers at reperfusion.ConclusionWe conclude that selective AKT activation by the synthetic molecule SC79 does not protect the rat heart against ischemic injury, indicating that acute pharmacological activation of AKT is not sufficient for cardioprotection.

Abstract 16161: Bone Marrow Characteristics are Associated With Changes in Infarct Size Following STEMI: A Biorepository Evaluation From the CCTRN TIME Trial

OBJECTIVE: Despite significant interest in bone marrow cell mononuclear cell (BMC) therapy for ischemic heart disease, current techniques have shown only modest benefit. However, select patients show improvements after autologous BMC therapy for unknown reasons. The purpose of this study was to identify BMC characteristics associated with infarct size reduction following STEMI. METHODS: This study evaluated prospectively the cohort of patients enrolled in the CCTRN TIME trial who agreed to their BMCs being stored and used for further analyses at the CCTRN Biorepository. Analyses were pre-specified and the core laboratories were blinded to clinical data and treatment assignments. The changes in infarct size between baseline (three days after PCI) and 6 months was measured by cMRI. BMC product underwent phenotype analysis using FACS identifying cells expressing CD45, CD34, CD31, CD133, CXCR4, CD3, CD11, CD14, and CD19 and functional analysis with the CFU-Hill, ECFC and CFU-F assays. RESULTS: Quantification of BMC characteristics and infarct size was available in 101 patients. The patients’ mean age was 56.5 years, with a mean screening ejection fraction of 37% and mean baseline cMRI ejection fraction of 45%. At 6 months, 75 (74.3%) patients had reductions in infarct size (mean -21.0% ± 17.6%). Multiple regression analysis revealed that, regardless of treatment allocation, an increased percentage of BMC that expressed CD31 (p=0.046) was associated with greater reductions in infarct size. Greater reductions in infarct size also were associated with more rapid growth rates for BMC functional assays (CFU-Hill, ECFC) (p=0.033, p=0.032, respectively). CONCLUSIONS: This study demonstrates a correlation between characteristics of BMCs in the acute STEMI phase and subsequent changes in infarct size. These data suggest that resident BMCs (specifically, endothelial precursors) play an important role in regenerating infarcted myocardium irrespective of treatment with autologous BMC transplantation.

Abstract 95: Longitudinal In Vivo Quantification of Infarct Size and Cardiac Function in a Murine Model of Myocardial Infarction using Novel Compact High-Performance MRI

Intro: Delayed Enhancement Imaging (DEI) characterizes MI and predicts therapeutic efficacy following coronary revascularization, stem cell transplantation, or other procedures. Typically gadolinium-based (Gd) contrast agents are injected intravenously and accumulate in the lesion, differentiating between normal and diseased myocardium. Traditionally, DEI has been explored using superconducting high-field MRI. Using a novel compact MRI at 1 Tesla, there is increased sensitivity to Gd-based contrast agents compared with higher-field MRI systems. Hypothesis: In this study, DEI on a compact MRI system was employed with spatial intensity analysis to measure infarct size. Tagged cine MRI assessed myocardial strain using the HARP method. Post-mortem histology of Masson Trichrome staining estimated infarct size. Correlation analysis determined relationships between infarct size measured via DEI and histology. Methods: C57BL/6 MI mice had ligation of the left anterior descending artery. Four sham control and five MI mice we imaged using compact MRI (ICON compact MRI, Billerica, MA) and monitored longitudinally over 21 days for infarct progression and cardiac function in vivo. DE imaging was performed 10-20 minutes post injection of 2 μL Gd contrast agent (ProHance, 0.5 mmol/ml). Images were acquired in short axis, 1 mm superior to the apex. Post-processing analysis (pcVirtue, Diagnosoft, Morrisville, NC) measured cardiac function and infarct size. Results and Conclusions: Analyses of DEI data indicate an average infarct size of 24.85 +/- 15.09 % in the left ventricle. One week after MI induction, a much lower EF was observed in MI mice with respect to control (35.3 +/- 7.567% vs. 67.3 +/- 1.6 %), with a slight recovery of cardiac function in MI mice by week 3 (EF = 45.5 +/- 3.1%). Strain analysis also indicated significantly lower average peak strain in MI vs control mice (6.9 +/- 4.3 vs. 21.5 +/- 0.4 %). Preliminary results demonstrate successful monitoring of cardiac function while performing DEI to visualize and quantify MI at 1 Tesla and leverage the benefits of the increased sensitivity of Gd-based contrast imaging with novel compact MRI. Such imaging and analysis techniques could be used to test efficacy of multiple therapeutic interventions.

131 Comparison of Semi-automated Methods to Quantify Infarct Size and Myocardial Salvage by Cardiac MRI at 1.5T and 3.0T Field Strengths

IntroductionThere is no consensus on the optimal method of quantifying infarct size (IS) on late gadolinium imaging (LGE) or area at risk (oedema, [AAR]) on T2-weighted STIR (T2wSTIR) in patients...

Bilirubin loading of the heart: a novel treatment for ischemia‐reperfusion injury (667.5)

Cardiovascular Disease (CVD) is the world’s greatest killer, claiming the lives of around 17.2 million men and women per year. Bilirubin is a novel antioxidant, which has been cited to reduce ischemia‐reperfusion injury in various tissues; however research into cardiac ischemia‐reperfusion injury is yet to be completed. The aim of this research was to determine whether exogenous bilirubin is capable of reducing ischemia‐reperfusion injury, in the heart. Young male (12 weeks old) Wistar isolated rat hearts were treated with bilirubin (50mM) for a period of 30 minutes before (Pre) or after (Post) a 30 minute no flow ischemic period. As well as functional recovery, tissue damage was measured by collecting effluent samples and quantifying infarct size. The left atria was removed from each heart after their respective treatment periods to allow analysis, through Pearson's correlation, of recovery and bilirubin concentration in the tissue. Diastolic pressure in both Pre and Post treated hearts was most significantly reduced after 90 minutes of reperfusion (Control, 81.01±14.73 mmHg, Pre, 58.92±14.23 mmHg, Post, 64.74±13.21 mmHg). The pre‐treated hearts revealed a significant recovery in left ventricular developed pressure (LVDP) in comparison to controls (Control, 34.72±12.67 %, Pre, 54.32±12.87 %). In addition, biomarkers of tissue damage, as well as infarct area, were significantly reduced in both pre‐treated and post‐treated hearts, in comparison to controls. Although the mechanisms are still unclear, this data suggests that bilirubin loading on the heart, either before or after ischemic insult, can preserve heart tissue and function.

Comparison of two methods to automatically quantify infarct size in rat isolated hearts following global ischemia and reperfusion (1154.6)

Infarct size (IS) remains the gold standard to estimate cardiac injury in many animal models. 2,3,5‐triphenyltetrazolium chloride (TTC) staining delineates infarcted from non‐infarcted tissue. Here, we compare manual image analysis to commercially available software using Bayesian differentiation and a newly developed automated freeware algorithm using color thresholding. As part of a study on genome‐dependent cardioprotection we analyzed 855 slices from 156 isolated rat hearts subject to 30/120 min ischemia/reperfusion after different protective treatments. Hearts were cut into 2 mm transverse slices and TTC‐stained, slices scanned on green background and infarcted areas measured manually and automatically by VisiomorphTM and Image J (NIH) whose color threshold T was varied from 125 to 133 to determine the best differentiation for IS. Statistics: linear regression; alpha 0.05. VisiomorphTM correlated well with manual measurements as did Image J where T129 provided the best agreement. IS measurement by either software provides equal results to manual measurements. Both methods enable fast, operator‐independent and reliable IS assessment. Potential shortcomings such as lack of discrimination are offset by significant time‐ and cost‐savings and a better longitudinal resolution by analyzing more slices per heart. Supported by Department of Veterans Affairs (CARA‐026‐10F) and NIH.Grant Funding Source: Supported by Department of Veterans Affairs and NIH.

Anatomical and functional imaging of myocardial infarction in mice using micro‐CT and eXIA 160 contrast agent

Noninvasive small animal imaging techniques are essential for evaluation of cardiac disease and potential therapeutics. A novel preclinical iodinated contrast agent called eXIA 160 has recently been developed, which has been evaluated for micro-CT cardiac imaging. eXIA 160 creates strong contrast between blood and tissue immediately after its injection and is subsequently taken up by the myocardium and other metabolically active tissues over time. We focus on these properties of eXIA and show its use in imaging myocardial infarction in mice. Five C57BL/6 mice were imaged ~2 weeks after left anterior descending coronary artery ligation. Six C57BL/6 mice were used as controls. Immediately after injection of eXIA 160, an enhancement difference between blood and myocardium of ~340 HU enabled cardiac function estimation via 4D micro-CT scanning with retrospective gating. Four hours post-injection, the healthy perfused myocardium had a contrast difference of ~140 HU relative to blood while the infarcted myocardium showed no enhancement. These differences allowed quantification of infarct size via dual-energy micro-CT. In vivo micro-SPECT imaging and ex vivo triphenyl tetrazolium chloride (TTC) staining provided validation for the micro-CT findings. Root mean squared error of infarct measurements was 2.7% between micro-CT and SPECT, and 4.7% between micro-CT and TTC. Thus, micro-CT with eXIA 160 can be used to provide both morphological and functional data for preclinical studies evaluating myocardial infarction and potential therapies. Further studies are warranted to study the potential use of eXIA 160 as a CT molecular imaging tool for other metabolically active tissues in the mouse.

Automated scar quantification by CMR: a step in the right direction.

Cardiovascular imaging techniques have advanced our understanding of the pathophysiology of acute and chronic myocardial infarction (MI). Infarct size is intimately related to adverse LV remodeling, heart failure and clinical outcomes (1,2). Rapid, robust, and reproducible quantification of infarct size is therefore desirable in both clinical and research settings. The late gadolinium enhancement (LGE) technique using cardiovascular magnetic resonance is the gold standard method because of its high spatial resolution and excellent contrast (3). The technique uses a chelated gadolinium contrast agent, which acts as an extracellular tracer. This accumulates in areas where cell membranes are not intact (cells destined to die in acute MI) or where there is replacement fibrosis (chronic MI). Gadolinium, which shortens T1, causes the infarct to appear bright (white) on a T1 weighted image (4). Infarction imaged in this way correlates accurately with histological specimens in ex vivo animal studies (3,5) and is prognostic in multiple human studies (1). It guides therapy and is used as a surrogate endpoint in many acute infarct trials.

Serial measurement of hFABP and high-sensitivity troponin I post-PCI in STEMI: how fast and accurate can myocardial infarct size and no-reflow be predicted?

The objective of this study was to compare heart-specific fatty acid binding protein (hFABP) and high-sensitivity troponin I (hsTnI) via serial measurements to identify early time points to accurately quantify infarct size and no-reflow in a preclinical swine model of ST-elevated myocardial infarction (STEMI). Myocardial necrosis, usually confirmed by hsTnI or TnT, takes several hours of ischemia before plasma levels rise in the absence of reperfusion. We evaluated the fast marker hFABP compared with hsTnI to estimate infarct size and no-reflow upon reperfused (2 h occlusion) and nonreperfused (8 h occlusion) STEMI in swine. In STEMI (n = 4) and STEMI + reperfusion (n = 8) induced in swine, serial blood samples were taken for hFABP and hsTnI and compared with triphenyl tetrazolium chloride and thioflavin-S staining for infarct size and no-reflow at the time of euthanasia. hFABP increased faster than hsTnI upon occlusion (82 ± 29 vs. 180 ± 73 min, P < 0.05) and increased immediately upon reperfusion while hsTnI release was delayed 16 ± 3 min (P < 0.05). Peak hFABP and hsTnI reperfusion values were reached at 30 ± 5 and 139 ± 21 min, respectively (P < 0.05). Infarct size (containing 84 ± 0.6% no-reflow) correlated well with area under the curve for hFABP (r(2) = 0.92) but less for hsTnI (r(2) = 0.53). At 50 and 60 min reperfusion, hFABP correlated best with infarct size (r(2) = 0.94 and 0.93) and no-reflow (r(2) = 0.96 and 0.94) and showed high sensitivity for myocardial necrosis (2.3 ± 0.6 and 0.4 ± 0.6 g). hFABP rises faster and correlates better with infarct size and no-reflow than hsTnI in STEMI + reperfusion when measured early after reperfusion. The highest sensitivity detecting myocardial necrosis, 0.4 ± 0.6 g at 60 min postreperfusion, provides an accurate and early measurement of infarct size and no-reflow.

Imaging Biomarkers for Intra-arterial Stroke Therapy.

Despite high rates of early revascularization with intra-arterial stroke therapy, the clinical efficacy of this approach has not been clearly demonstrated. Neuroimaging biomarkers will be useful in future trials for patient selection and for outcomes evaluation. To identify patients who are likely to benefit from intra-arterial therapy, the combination of vessel imaging, infarct size quantification and degree of neurologic deficit appears critical. Perfusion imaging may be useful in specific circumstances, but requires further validation. For measuring treatment outcomes, surrogate biomarkers that appear suitable are angiographic reperfusion as measured by the modified Thrombolysis in Cerebral Infarction scale and final infarct volume.