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The global incidence of coronary artery diseases (CADs), especially myocardial infarction (MI), has drastically increased in recent years. Even though the conventional therapies have improved the outcomes, the post-MI complications and the increased rate of recurrence among the survivors are still alarming. Molecular events associated with the pathogenesis and the adaptive responses of the surviving myocardium are largely unknown. Focus on exosome-mediated signaling for cell-cell/matrix communications at the infarct zone reflects an emerging opportunity in cardiac regeneration. Also, cardiac tissue engineering provides promising insights for the next generation of therapeutic approaches in the management of CADs. In this article, we critically reviewed the current understanding on the biology of cardiac exosomes, therapeutic potential of exosomes, and recent developments in cardiac tissue engineering and discussed novel translational approaches based on tissue engineering and exosomes for cardiac regeneration and CADs.

Infarct extension involves necrosis of healthy myocardium in the border zone (BZ), progressively enlarging the infarct zone (IZ) and recruiting the remote zone (RZ) into the BZ, eventually leading to heart failure. The mechanisms underlying infarct extension remain unclear, but myocyte stretching has been suggested as the most likely cause. Using human patient-specific left-ventricular (LV) numerical simulations established from cardiac magnetic resonance imaging (MRI) of myocardial infarction (MI) patients, the correlation between infarct extension and regional mechanics abnormality was investigated by analysing the fibre stress-strain loops (FSSLs). FSSL abnormality was characterised using the directional regional external work (DREW) index, which measures FSSL area and loop direction. Sensitivity studies were also performed to investigate the effect of infarct stiffness on regional myocardial mechanics and potential for infarct extension. We found that infarct extension was correlated to severely abnormal FSSL in the form of counter-clockwise loop at the RZ close to the infarct, as indicated by negative DREW values. In regions demonstrating negative DREW values, we observed substantial fibre stretching in the isovolumic relaxation (IVR) phase accompanied by a reduced rate of systolic shortening. Such stretching in IVR phase in part of the RZ was due to its inability to withstand the high LV pressure that was still present and possibly caused by regional myocardial stiffness inhomogeneity. Further analysis revealed that the occurrence of severely abnormal FSSL due to IVR fibre stretching near the RZ-BZ boundary was due to a large amount of surrounding infarcted tissue, or an excessively stiff IZ.

BACKGROUND: In vivo imaging of oxidative stress can facilitate the understanding and treatment of cardiovascular diseases. We evaluated nitroxide-enhanced MRI with 3-carbamoyl-proxyl (3CP) for the detection of myocardial oxidative stress. METHODS: Three mouse models of cardiac oxidative stress were imaged, namely angiotensin II (Ang II) infusion, myocardial infarction (MI), and high-fat high-sucrose (HFHS) diet-induced obesity (DIO). For the Ang II model, mice underwent MRI at baseline and after 7 days of Ang II (n = 8) or saline infusion (n = 8). For the MI model, mice underwent MRI at baseline (n = 10) and at 1 (n = 8), 4 (n = 9), and 21 (n = 8) days after MI. For the HFHS-DIO model, mice underwent MRI at baseline (n = 20) and 18 weeks (n = 13) after diet initiation. The 3CP reduction rate, K(red), computed using a tracer kinetic model, was used as a metric of oxidative stress. Dihydroethidium (DHE) staining of tissue sections was performed on Day 1 after MI. RESULTS: For the Ang II model, K(red) was higher after 7 days of Ang II versus other groups (p < 0.05). For the MI model, K(red), in the infarct region was significantly elevated on Days 1 and 4 after MI (p < 0.05), whereas K(red) in the noninfarcted region did not change after MI. DHE confirmed elevated oxidative stress in the infarct zone on Day 1 after MI. After 18 weeks of HFHS diet, K(red) was higher in mice after diet versus baseline (p < 0.05). CONCLUSIONS: Nitroxide-enhanced MRI noninvasively quantifies tissue oxidative stress as one component of a multiparametric preclinical MRI examination. These methods may facilitate investigations of oxidative stress in cardiovascular disease and related therapies.

Visual Abstract, Highlights • A drop in eosinophil blood count is associated with recruitment of eosinophils to the heart during repair following clinical and experimental MI. • Genetic and pharmacological eosinophil depletion leads to increased adverse remodeling in experimental MI. • Eosinophils are required for acquisition of an anti-inflammatory macrophage phenotype, a shift to resolution of inflammation and mature scar formation during infarct repair. • IL-4 therapy is able to rescue the adverse remodeling phenotype in conditions of eosinophil deficiency., Summary In ST-segment elevation myocardial infarction of both patients and mice, there was a decline in blood eosinophil count, with activated eosinophils recruited to the infarct zone. Eosinophil deficiency resulted in attenuated anti-inflammatory macrophage polarization, enhanced myocardial inflammation, increased scar size, and deterioration of myocardial structure and function. Adverse cardiac remodeling in the setting of eosinophil deficiency was prevented by interleukin-4 therapy.

Perfusion contrast echocardiography is limited by the bright cavity echo artifact and poor signal to noise ratio. We present in vivo open chest pig infarct data for a novel nested phase-change agent with an acoustic response dependent on electric field generated by depolarizing myocardium in

Acoustic droplet (AD)-based delivery of plasmid DNA (pDNA) offers an alternative for non-viral gene therapy. Unlike microbubbles (MBs), ADs cross endothelial barriers. Targeted transthoracic acoustic activation of Definity nanodroplets (DNDs) may result in selective infarct zone acoustic enhancement

Background Delivering therapeutic materials, like stem cells or gene vectors, to the myocardium is difficult in the setting of ischemic heart failure because of decreased coronary flow and impaired microvascular perfusion ( MP ). The aim of this study was to determine if mechanical left ventricular ( LV ) unloading with the Impella increases coronary flow and MP in a subacute myocardial infarction. Methods and Results Anterior transmural myocardial infarction (infarct size, 26.0±3.4%) was induced in Yorkshire pigs. At 2 weeks after myocardial infarction, 6 animals underwent mechanical LV unloading by Impella, whereas 4 animals underwent pharmacological LV unloading using sodium nitroprusside for 2 hours. LV unloading with Impella significantly reduced end‐diastolic volume (−16±11%, P =0.02) and end‐diastolic pressure (EDP; −32±23%, P =0.03), resulting in a significant decrease in LV end‐diastolic wall stress ( EDWS ) (infarct: 71.6±14.7 to 43.3±10.8 kdynes/cm 2 [ P =0.02]; remote: 66.6±20.9 to 40.6±13.3 kdynes/cm 2 [ P =0.02]). Coronary flow increased immediately and remained elevated after 2 hours in Impella‐treated pigs. Compared with the baseline, MP measured by fluorescent microspheres significantly increased within the infarct zone (109±81%, P =0.003), but not in the remote zone. Although sodium nitroprusside effectively reduced LV ‐ EDWS , 2 (50%) of sodium nitroprusside–treated pigs developed profound systemic hypotension. A significant correlation was observed between the infarct MP and EDWS ( r 2 =0.43, P =0.03), suggesting an important role of EDWS in regulating MP during LV unloading in the infarcted myocardium. Conclusions LV unloading using an Impella decreased EDWS and increased infarct MP without hemodynamic decompensation. Mechanical LV unloading is a novel and efficient approach to increase infarct MP in patients with subacute myocardial infarction.

Following myocardial infarction (MI), the left ventricle (LV) undergoes a series of molecular, cellular, and functional alterations that are both part of the wound healing response to form a scar in the infarct region and the consequence of that response. Using the laws of thermodynamics as an analogy, we present here three laws for categorizing the post-MI LV remodeling process. The first law is that the LV will attempt to maintain equilibrium and compensate as a way to maximize function, the second law is that remodeling is progressive and unidirectional, and the third law is that the final goal is (ideally, but not always achievable) a stable, equilibrated scar. This comparison helps to define the boundaries of the system, whether it be the infarct zone, the LV, the heart, or the entire body. This review provides an overview for those not directly in the field and establishes a framework to help prioritize future research directions.

Background Hemorrhage is a frequent complication in acute myocardial infarction (AMI) and is speculated to be an independent predictor of adverse outcomes [1]. In addition to infarct zone remodeling, the distal remote myocardium may experience alterations vasodilator dysfunction, edema, and extracellular matrix (ECM) expansion [2-4]. The aim of our study was to understand the impact of hemorrhage on infarct as well as remote myocardial remodeling following an ischemic event. To this end, we employed quantitative T1 and T2 mapping to probe the underlying tissue alterations in a novel hemorrhagic model of AMI.

Purpose: To study the effect of exercise training on the myocardial perfusion in the postinfarct myocardium. Materials and Methods: Twenty-nine patients with stable chronic myocardial infarction were randomly assigned to either a training group (N = 17) or a control group (N = 12). The training group received a 3-month exercise program. Cardiovascular MR was first performed before the training to establish a baseline, and subsequently performed once again upon conclusion of the program. Late gadolinium enhancement was used both to define the infarct and remote zones and to quantify the ratio of the residual viable myocardium (VMR) within the infarct zone. The myocardium was divided into subendocardial and subepicardial layers with equal thickness. The interval change of myocardial perfusion reserve (MPR) was computed for each zone and layer. The association between the exercise-induced perfusion change and VMR was analyzed for layers of the infarct zone. Results: In the training group, the remote zone showed significantly increased MPR. The infarct zone showed no perfusion change in the subendocardial layer, but it demonstrated significantly increased MPR in the subepicardial layer. In the infarct zone, the change in MPR was associated with VMR. Conclusion: In chronic myocardial infarction, the exercise-induced perfusion change in the infarct zone is proportional to the amount of residual viable myocardium. J. Magn. Reson. Imaging 2011;. © 2011 Wiley-Liss, Inc.

Microvascular obstruction (MVO) is usually seen in a proportion of patients with acute myocardial infarction following reperfusion therapy of an occluded coronary artery. It is characterized by damage and dysfunction of the myocardial microvasculature with a no-reflow phenomenon within the infarct zone. While MVO may be demonstrated via a number of different imaging modalities, cardiac MR (CMR) enables accurate identification of MVO and also permits assessment of infarct extent and overall left ventricular function during the same imaging examination. We present a pictorial review of the characteristic appearances of MVO on CMR and highlight the importance of this imaging diagnosis for patient outcome following acute myocardial infarction.

We compared two routes for myocardial delivery of therapeutics, transendocardial (TE) delivery with an intramyocardial injection catheter, and retrograde coronary venous (RCV) delivery with a balloon occlusion catheter in the interventricular vein. Methods: TE and RCV injection of 15 mu m, neutron-activatable microspheres was compared in healthy pigs (Group I, n = 3), pigs with a 1-week-old myocardial infarction (MI; group II, n = 5), and pigs with a 2-weeks-old MI (group III, n = 4). The MI was induced by a 1-hr balloon occlusion in the LAD. Both methods were compared in the same animal using different microspheres. The RCV catheter allowed for continuous measurement of distal pressure and 2.5 x 10(6) microspheres were injected in 10 ml at 300 mmHg above balloon occlusion pressure. The TE injections were targeted to the infarct zone and 2.5 x 10(6) microspheres were distributed over 10 injections of 200 mu l. Results: The retention of microspheres decreased with increase in MI age, but was comparable between devices within the groups. RCV delivery resulted in (14.3 +/- 0.9)% microsphere retention in Group I, (10.3 +/- 0.2)% in Group II, and (6.4 +/- 0.1)% in group III (P less than 0.05 versus group I). Microsphere retention after TE was (15.1 +/- 0.7)% in group I, (18.9 +/- 0.6)% in group II, (4.1 +/- 0.1)% in Group III (P less than 0.05 versus groups I and II). The RCV catheter delivered primarily to midventricular, antero-septal segments, whereas TE targeted apical areas predominantly. Conclusions: Delivery efficacy was comparable between devices in each group however RCV targeted midventricular areas whereas TE targeted apical areas.

Introduction: In acute coronary syndromes, the extent of myocardial injury can be substantially greater than the infarct zone. Existing imaging methods identify the infarct zone but do not assess “global myocardial injury” (GMI), which measures the total area of myocardium that sustained injuries including and beyond the infarct zone per se. Hypothesis: GMI can be detected based on changes in cellular membrane organization as a surrogate marker, using Tc-99m-duramycin. Methods: Balloon angioplasty was used for coronary occlusion in a pig model of myocardial ischemia and reperfusion (n = 9). Tc-99m-duramycin scans were acquired on a SPECT/CT scanner on day 1. On day 2, the infarct zone was assessed with Tc-99m-tetrofosmin. In an open-chest pig model of myocardial ischemia/reperfusion (n = 4) we used Evans Blue dye to facilitate the measurement of area-at-risk (AAR). Tc-99m-duramycin uptake was measured by gamma counting after tetrazolium (TTC) staining and physically dissecting the AAR, infarct zone and the noninfarcted-but-ischemically-damaged tissues. Histopathology was used to document cellular damages. Results: Quantitatively, Tc-99m-duramycin uptake delineated an area of myocardium that included but was substantially more extensive than the infarct zone. Under the current experimental condition, this area accounted for 81.0 ± 9.6% of the AAR, whereas the infarct zone was 25.5 ± 14.0% of the AAR. This was consistent with in vivo imaging, where the size of Tc-99m-duramycin positive tissue was visually larger than the perfusion defect in the Tc-99m-tetrofosmin scan. By histopathology, the noninfarcted-but-ischemically-damaged tissues contained features associated with cellular damages, and a heterogeneous mix of viable and dead cells. Conclusions: Tc-99m-duramycin has significant uptake in infarcted as well as noninfarcted-but-ischemically-damaged myocardium, thus reflecting global myocardial injury. The data support GMI as a new criterion independent of infarct size and AAR. The noninfarcted-but-ischemically-damaged myocardium is pathologically heterogeneous, thus a potential substrate for ventricular arrhythmias. The ability to detect such tissues may have important diagnostic and prognostic value.

The purpose of this study was to assess the value of technetium 99m sestamibi gated single photon emission computed tomography (SPECT) in predicting the evolution of left ventricular volumes in patients treated successfully in the acute phase of a myocardial infarction (MI).Twenty-nine patients with acute MI and early percutaneous transluminal coronary angioplasty (PTCA) were included in this study. A rest Tc-99m sestamibi electrocardiography (ECG)-gated SPECT study was performed 21 +/- 5 days after PTCA. The myocardial perfusion index was calculated by use of a semiautomatic sectorial analysis. All patients had contrast ventriculography performed during the acute phase and 6 months later. The patients were separated into two groups according to the absence (group I, n = 21) or presence (group II, n = 8) of end-systolic enlargement. The perfusion index in the infarct sectors was -2.29 +/- 2.90 SD in group I and -6.40 +/- 2.85 SD in group II ( P.01). With a cutoff value of -2.46 SD, the sensitivity and specificity of Tc-99m sestamibi SPECT for the prediction of end-systolic volume enlargement were 100% and 62%, respectively. When the functional data from ECG-gated acquisitions were added, specificity increased to 86%.Despite successful PTCA in the acute phase of MI, an increase in end-systolic volume was observed at 6 months in 28% of patients. Tc-99m sestamibi ECG-gated SPECT performed 3 weeks after the acute phase could predict this enlargement with a high accuracy.

Purpose To characterize the extent and distribution of left ventricular myocardial scar in delayed enhancement magnetic resonance imaging (MRI). Materials and Methods Delayed enhancement images from 18 patients were categorized into three groups based on myocardial scar appearance: discrete myocardial infarction (N = 10), diffuse fibrosis (N = 4), and circumferential endocardial scarring (N = 4). Images were segmented manually by two observers (twice by one observer) to identify nonviable myocardium. Scar was characterized by the following morphologic parameters: the relative area of nonviable myocardium (Percent Scar); a measure of scar cohesion (Patchiness); and the extent to which scar traversed the ventricle wall (Trans>50). Results The three scar parameters successfully discriminated between patient groups, although no one parameter was able to differentiate between all groups. The average bias between readers was approximately 3% for each parameter, and the average bias between repeated measurements was 1%. In addition, five patients exhibited regions of nonhyperenhanced nonviable myocardium that were expected to show hyperenhancement based upon their location within the infarct zone and appearance on cine images. Conclusion Quantitative characterization of myocardial scar showed good interobserver and intraobserver agreement. However, the appearance of nonhyperenhanced scar in chronic ischemia is problematic for segmentation of delayed enhancement images. J. Magn. Reson. Imaging 2003;18:434–441. © 2003 Wiley-Liss, Inc.

GOAL Comparison between a fluid-sensitive (HASTE-TIRM)-sequence and delayed contrast-enhancement in patients with acute myocardial infarct (AMI) in MRI. MATERIAL AND METHODS 32 patients with AMI were imaged 7 +/- 4 days after the time of infarction with a 1.5 T unit using a T2 HASTE-TIRM and a contrast-enhanced (CE) T1 turbo FLASH sequence. A threshold method (>2 SD in comparison with normal myocardium) was used to quantify the hyperintense zones in both sequences. The transmurality of the hyperintense regions was measured on a segmental basis. RESULTS The hyperintense areas were larger on the HASTE-TIRM sequence with 29.6 +/- 13.2 % of the left ventricular (LV) area as compared to the CE-MRI with 19.2 +/- 10 % of the LV area (p < 0.0001). The measured transmurality was higher with the HASTE-TIRM sequence than with the CE-MRI (p < 0.0001). While the correlation between CE-MRI and peak creatine kinase (CK max) was good (r = 0.59, p < 0.001), no correlation was found between the HASTE-TIRM sequence and CK max (r = 0.29, p = ns). CONCLUSIONS The peri-infarct edema can be depicted with a HASTE-TIRM sequence in addition to the non-viable infarct zone. The HASTE-TIRM sequence shows a higher transmurality of the hyperintense regions than the CE-MRI. The additional area depicted by the HASTE-TIRM sequence could represent functionally impaired but viable myocardium).

Acute coronary occlusion causes ST-segment elevation on the body surface ECG and on the epicardial electrogram in the territory supplied by that artery. The occurrence and significance of endocardial ST changes have not been studied. The NOGA electromechanical mapping was performed on eight anesthetized dogs at baseline, immediately after occlusion of the LAD, and again at 5 hours to assess regional changes in the ST segment. At 3 days and 4 weeks the ventricles were remapped for comparison. Regional unipolar ST-segment elevation was measured for each zone from NOGA maps at 0, 80, and 120 ms after the J point. ST segments rose immediately in the infarct zones, as demarcated by echocardiography, compared to remote zones, but by 3 days had dropped below, and at 4 weeks returned to baseline values. Immediately postocclusion, ST elevation at 120 ms best differentiated between normal versus abnormal echo scores (concordance = 0.80), probably by correcting for pressure induced ST elevation. In conclusion, acute endocardial ST-segment changes occur in the infarct zone in the dog, showing a distinctive temporal evolution.

Increased myocardial structural heterogeneity in response to ischemic injury following myocardial infarction (MI) is purported as the mechanism of ventricular arrhythmogenesis. Current modalities for in vivo assessment of structural heterogeneity for identification of arrhythmogenic substrate are limited due to the complex nature of the structural microenvironment post-MI. We investigated the utility of in vivo bio-impedance spectroscopy (BIS) in a large post-infarct animal model for differentiation between normal and infarcted tissue. We also investigated the quantitative effects of adipose and collagen on BIS assessment of myocardium. The results indicate that the degree of myocardial injury following chronic post-infarction remodeling could be reliably quantified (performed in triplicates) using BIS. Furthermore, the presence of intramyocardial adipose tissue that develops in conjunction with collagen within the infarct zone had a greater and significant influence on BIS then collagen tissue alone. These preliminary results indicate a potential role of BIS for quantitative assessment and characterization of complex arrhythmogenic substrates in ischemic cardiomyopathy.

Chronic fibrosis caused by acute myocardial infarction (MI) leads to increased morbidity and mortality due to cardiac dysfunction. We have developed a therapeutic materials strategy that aims to mitigate myocardial fibrosis by utilizing injectable polymeric microstructures to mechanically alter the microenvironment. Polymeric microstructures were fabricated using photolithographic techniques and studied in a three-dimensional culture model of the fibrotic environment and by direct injection into the infarct zone of adult rats. Here, we show dose-dependent down-regulation of expression of genes associated with the mechanical fibrotic response in the presence of microstructures. Injection of this microstructured material into the infarct zone decreased levels of collagen and TGF-β, increased elastin deposition and vascularization in the infarcted region, and improved functional outcomes after six weeks. Our results demonstrate the efficacy of these discrete anti-fibrotic microstructures and suggest a potential therapeutic materials approach for combatting pathologic fibrosis.

We recently reported that compared to Primary Reperfusion (PR), first reducing myocardial oxygen demand by activating an acute mechanical circulatory support (AMCS) pump while delaying coronary reperfusion (Primary Unloading; PU) reduces myocardial damage in models of acute myocardial infarction (

Objectives. Aim of the present study was to investigate site- and rate dependent effects of the IKs-blocking agent chromanol 293b on conduction and refractoriness in normal, infarcted, and transitional regions of in-situ canine hearts.

Background —The aim of the present study was to characterize temporal changes in cyclic variation of ultrasonic integrated backscatter (IBS), which reflects intrinsic contractile performance, in patients with reperfused acute myocardial infarction (AMI) and to elucidate the clinical value of tissue characterization in predicting myocardial viability. Methods and Results —We recorded short-axis IBS images before and 3, 7, and 21 days after reperfusion in 26 patients with AMI and obtained the cyclic variation of IBS in the normal and infarct zones. When cyclic variation showed synchrony and asynchrony, we expressed its magnitude as positive and negative values, respectively, called the phase-corrected magnitude. We also measured average wall motion score (dyskinesis, 4; normal, 0) of the infarct segments. The phase-corrected magnitude was lower in the infarct zone than in the normal zone before reperfusion (0.3±2.5 versus 5.2±1.7 dB, P P Conclusions —In patients with AMI, cyclic variation of IBS is blunted during ischemia but recovers much faster after reperfusion than the improvement in wall motion. The greater phase-corrected magnitude at day 3 may be a predictor of better functional improvement.

Our studies on the targeting of liposomes and liposome-associated pharmaceuticals within the cardiovascular system are reviewed. The delivery of diagnostic and therapeutic agents in plain liposomes, immunoliposomes, long-circulating liposomes and long-circulating immunoliposomes into the sites of vascular injuries and myocardial infarction is discussed. In vitro, ex vivo, and in vivo experiments present a general view on the advantages and limitations of using liposome-mediated targeting. Liposomes capable of targeting pathological areas of the blood vessel wall both, in vitro and ex vivo are described, as well as liposome able to be internalized by normal endothelial cells. Liposome-mediated drug targeting to compromised myocardium is reviewed with a primary impact on liposomes with anti-cardiac myosin antibodies. Targeted visualization of myocardial infarction with diagnostic liposomes is discussed. Efficient accumulation of long-circulating immunoliposomes in the infarct zone is demonstrated, a...

The goal of reperfusion strategies in patients with acute myocardial infarction is to salvage myocardium within the infarct zone at risk from the acute occlusion. The status of wall motion and thickening within the infarct zone is an imprecise guide to the extent of salvage and viability within the infarct zone, based on the well-described phenomenon of myocardial stunning. However, knowledge of significant salvage and preserved viability within an infarct zone soon after infarction has important implications regarding clinical decision making for catheterization and potential revascularization: given preserved viability, restoration of normal coronary flow in the setting of a severe residual stenosis or occlusion would be expected to result in significant recovery of regional, and possibly global left ventricular function, with attendant implications for prognosis and outcome.

Background Sympathetic hyperactivity is linked with several adverse cardiovascular events in patients with acute coronary syndrome (ACS). Sympathetic activity increases early in the process of ischemia through 2 mechanisms. One originates from the central nervous system and leads to enhanced sympathetic activity. The other mechanism originates at the infarct zone and leads to B receptor up-regulation and catecholamine supersensitivity. Nevertheless, sympathetic hyperactivity accompanied by an underlying myocardial structural damage is likely to increase the ventricular repolarization duration measured as QT interval on the body surface electrocardiogram. Purpose The aims of the current review of the literature were to examine the physiological processes underlying the use of long QT interval as a risk prediction tool in patients with ACS and to critically review and critique the existing evidence related to this matter. Conclusion The available evidence is contradictory and includes serious limitations in design and QT measurement and correction. Until accurate and reliable data are available, it is difficult to determine the additional clinical value and prognostic significance of long QT interval in patients with ACS beyond that in other patients. Clinical implications Long QT interval is not uncommon among patients with ACS. Automated continuous QT interval monitoring is superior to manual QT interval measurement with the standard 10-second electrocardiogram. Optimum care for patients with ACS requires nurses to keep monitoring the QT interval several days after the initial event.

Infarct extension, a process involving progressive extension of the infarct zone (IZ) into the normally perfused border zone (BZ), leads to continuous degradation of the myocardial function and adverse remodelling. Despite carrying a high risk of mortality, detailed understanding of the mechanisms leading to BZ hypoxia and infarct extension remains unexplored. In the present study, we developed a 3D truncated ellipsoidal left ventricular model incorporating realistic electromechanical properties and fibre orientation to examine the mechanical interaction among the remote, infarct and BZs in the presence of varying infarct transmural extent (TME). Localized highly abnormal systolic fibre stress was observed at the BZ, owing to the simultaneous presence of moderately increased stiffness and fibre strain at this region, caused by the mechanical tethering effect imposed by the overstretched IZ. Our simulations also demonstrated the greatest tethering effect and stress in BZ regions with fibre direction tangential to the BZ-remote zone boundary. This can be explained by the lower stiffness in the cross-fibre direction, which gave rise to a greater stretching of the IZ in this direction. The average fibre strain of the IZ, as well as the maximum stress in the sub-endocardial layer, increased steeply from 10% to 50% infarct TME, and slower thereafter. Based on our stress-strain loop analysis, we found impairment in the myocardial energy efficiency and elevated energy expenditure with increasing infarct TME, which we believe to place the BZ at further risk of hypoxia. Copyright © 2016 John Wiley & Sons, Ltd.

Background The natural history of persistent myocardial oedema after ST-elevation myocardial infarction (STEMI) is uncertain. Methods and ResultsPatients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI; ClinicalTrials.gov: NCT02072850). Cardiac magnetic resonance (CMR) imaging with T2-mapping of myocardial oedema was performed at 1.5 Tesla 2 days and 6 months post-MI. Myocardial oedema was defined as infarct signal intensity (S. I.) >2 standard deviations from the mean S. I. within a remote reference region. 283 STEMI patients (mean (SD) age 59 (12) years, 75% male) were enrolled. Infarct size was 18 (13)% of left ventricular (LV) mass. At 2 days, infarct zone T2 (ms) was higher than remote zone T2 (62.9 (5.2) vs. 49.7 (2.1); p Conclusion Persistence of oedema within the infarct zone affected the majority of patients at 6 months post-STEMI, and was associated with the initial severity of STEMI and adverse LV remodelling.

Summary A cardiac-tailored framework for 3D Diffusion Tensor MRI tractography is developed and used to characterize myofiber architecture in normal and remodeled myocardium. We show that myofibers in the subepicardium of the remote infarct zone become less oblique (more circumferential) as the heart dilates and remodels. This fiber realignment may play an important role in the loss of contractile function in the remote zone over time. Background

In acute myocardial infarction (AMI), the aim of any therapeutic intervention is to reduce the infarct size and attenuate adverse remodeling. The type and extent of infarction encountered clinically [transmural, hemorrhagic, heterogeneous, with microvascular obstruction (MVO)], is primarily determined by the severity of the initial ischemic insult. Understanding the in-vivo pathophysiological mechanisms after AMI as a function of severity will be key in predicting functional recovery, prognosis and assessing the efficacy of novel therapies.

To evaluate the role of dobutamine echocardiography for early assessment of myocardial viability and ischemia in acute myocardial infarction (MI), 59 patients with thrombolyzed acute MI underwent low- (5-10 micrograms/kg/min, 8 patients) and high-dose (20-40 micrograms/kg/min, 51 patients) dobutamine echocardiography at a mean of 8 +/- 4 days after acute MI. Myocardial viability in the infarct zone was documented in 43 of 59 (73%) patients (group 1), in whom mean asynergy score index decreased from 1.6 +/- 0.3 at baseline to 1.3 +/- 0.2 (p0.001), after low-dose dobutamine. No viability was present in 16 of 59 (27%) patients (group 2). At follow-up, recovery of regional contractile function was observed in group 1 (asynergy score index decreased from 1.6 +/- 0.3 to 1.4 +/- 0.3; p0.001), but not in group 2 patients. Sensitivity, specificity, and negative and positive predictive values of low-dose dobutamine echocardiography in predicting spontaneous recovery of function were 79%, 68%, 50%, and 89%, respectively. Of the 51 patients who underwent high-dose dobutamine, 26 of 36 (72%) group 1 patients showed a deterioration of contractility in the infarct zone indicative of myocardial ischemia compared with only 1 of 15 (7%) group 2 patients. At follow-up, recovery of regional function was greater in patients with no evidence of myocardial ischemia at high doses than in those with an ischemic response.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess regional myocardial perfusion in patients with chronic myocardial infarction (MI) in relationship to the extent of residual viable myocardium.The study was approved by the local ethics committee; written informed consent was obtained from each participant. Twenty-nine patients with first onset of MI who underwent successful primary percutaneous coronary intervention at least 6 months thereafter were studied. Delayed enhancement magnetic resonance (MR) imaging was performed to define the infarct zone and its viable myocardial ratio (VMR), quantified by the percentage of the nonscarred pixels relative to the total pixels in the infarct zone. First-pass contrast material-enhanced MR imaging was performed to estimate regional perfusion and myocardial perfusion reserve (MPR) in the infarct region. Paired comparisons in perfusion and MPR were tested with nonparametric Wilcoxon matched-pairs test. A difference with P.05 was considered significant. Correlation was tested with Pearson analysis.The infarct region showed significant impairment of regional perfusion at rest (mean, 0.966 [mL x min(-1)]/g +/- 0.271 [standard deviation] vs 1.151 [mL x min(-1)]/g +/- 0.282; P = .024) and during stress (mean, 1.789 [mL x min(-1)]/g +/- 0.732 vs 2.753 [mL x min(-1)]/g +/- 0.806; P.0001) and a reduced MPR (mean, 1.923 +/- 0.678 vs 2.486 +/- 0.836; P.0001) as compared with remote myocardium. The estimated perfusion, with stress, of the residual viable myocardium was preserved (2.993 [mL x min(-1)]/g +/- 1.451 vs 2.753 [mL x min(-1)]/g +/- 0.806), and the difference was not significant. Furthermore, stress perfusion (R = 0.385; P = .039) and MPR (R = 0.434; P = .018) in the infarct zone were significantly correlated with VMR, suggesting that preservation of myocardial perfusion in the infarct region reflects the amount of viable myocardium.Reduced perfusion in the infarct zone is related to the extent of the viable myocardium.

Prolongation or reestablishment of stem cell homing through the expression of SDF-1 in the myocardium has been shown to lead to homing of endothelial progenitor cells to the infarct zone with a subsequent increase in vascular density and cardiac function. While the increase in vascular density is important, there could clearly be other mechanisms involved. In a recent study we demonstrated that the infusion of mesenchymal stem cells (MSC) and MSC that were engineered to overexpress SDF-1 led to significant decreases in cardiac myocyte apoptosis and increases in vascular density and cardiac function compared to control. In that study there was no evidence of cardiac regeneration from either endogenous stem cells or the infused mesenchymal stem cells. In this study we performed further detailed immunohistochemistry on these tissues and demonstrate that the overexpression of SDF-1 in the newly infracted myocardium led to recruitment of small cardiac myosin-expressing cells that had proliferated within 2 weeks of acute MI. These cells did not differentiate into mature cardiac myocytes, at least by 5 weeks after acute MI. However, based on optical mapping studies, these cells appear capable of depolarizing. We observed greater optical action potential amplitude in the infarct border in those animals that received SDF-1 overexpressing MSC than observed in noninfarcted animals and those that received control MSC. Further immunohistochemistry revealed that these proliferated cardiac myosin-positive cells did not express connexin 43, but did express connexin 45. In summary, our study suggests that the prolongation of SDF-1 expression at the time of acute MI leads to the recruitment of endogenous cardiac myosin stem cells that may represent cardiac stem cells. These cells are capable of depolarizing and thus may contribute to increased contractile function even in the absence of maturation into a mature cardiac myocyte.

Background A variety of CMR methods for detecting intramyocardial haemorrhage (IMH) has been proposed, including T2-weighted imaging (T2w), T2-mapping and T2* mapping. IMH detected by T2w imaging is associated with adverse LV remodelling and adverse outcome post acute myocardial infarction (MI). We compare the sensitivity, specificity, CNR and SNR of the three IMH imaging techniques. Methods Twenty patients underwent CMR at 3T (Achieva TX system, Philips Healthcare, Best, The Netherlands) within 3 days following reperfused ST-elevation MI. Black blood, cine, T2w, T2-mapping, T2*-mapping and LGE imaging (0.1 mmol/kg gadolinium DTPA) were performed in identical short axis locations using the ‘3 of 5’ approach. Data were evaluated offline using commercial software (cvi42 v4.1.5, Circle Cardiovascular Imaging Inc., Calgary, Canada). On the LGE images showing the largest infarct volume, infarct size was determined by using a semi-automated histogram-based thresholding method. This slice was evaluated for visual presence of IMH by the three methods. Signal intensity (SI) and respective standard deviation of SI (SD) were measured for the infarcted myocardium, remote myocardium and any IMH (if present). SNR was computed for each using the formula = 0.655((SI)/(SD)). CNR was determined comparing contrast-to-noise of infarcted myocardium to IMH (SNRi-SNRIMH). Results Of the twenty patients, 55% (n = 11) had IMH on T2w-imaging. The mean (±standard deviation) SNR and CNR values are listed in Table 1. The visual assessment of T2w imaging correlated strongly to T2-maps (r = 0.69; p = 0.001) and to the T2*-maps (r = 0.60; p = 0.005). The SNR for IMH and infarct zone were significantly different for only T2w imaging (Figure 1). Quantitative CNR for T2w imaging correlated strongly to visual assessment of all three imaging modalities (T2w- r = 0.650; p = 0.002, T2-map- r = 0.454; p = 0.04, T2*-map- r = 0.603; p = 0.005). The CNR for T2-maps and T2*-maps did not show similar correlation to the visual assessment. Conclusion Quantitative and qualitative T2w-imaging assessment for IMH is superior to T2-mapping and T2*mapping.

Background The clinical significance of extracellular volume (ECV) expansion in infarcted myocardium post-STEMI is unknown. Myocardial ECV can be estimated by cardiac magnetic resonance imaging (CMR) using T1 MOLLI maps before and after contrast. We repeatedly measured infarct ECV in STEMI survivors, and assessed the relationships between ECV, peak troponin T and baseline infarct size. Methods Acute STEMI survivors were enrolled in a single-centre cohort study (BHF MR-MI study – NCT02072850). Contrast-enhanced CMR was performed at 1.5 Tesla (Siemens MAGNETOM Avanto) 2 days and 6 months post-MI. T1 mapping with MOLLI was performed before and 15 min after contrast (0.15 mmol/kg gadoterate meglumine). ECV analysis was performed by outlining regions of interest (ROIs) in infarcted myocardium and left ventricular (LV) blood pool. ROIs were representative of the infarct including microvascular obstruction. ECV was calculated as the relaxation rate (R1=1/T1) for myocardium and LV blood pool before vs. after contrast, corrected for haematocrit. Infarct size was measured using late gadolinium images and expressed as a percentage of LV mass. Infarct ECV at baseline and follow up was compared with peak troponin T measured at presentation and infarct size at baseline. Peak troponin T was log-transformed to improve normality and linearity. Results 201 STEMI patients (mean age 58 ± 11 years; 156 (77%) male) were enrolled. Infarct ECV was similar at baseline and follow-up (51.3 ± 9.5% vs. 50.3 ± 12.0%, p = 0.097). Peak troponin T was widely variable (4256.7 ug/L ± 4020.8 ug/L). Peak troponin T was positively associated with infarct ECV at baseline (p Conclusion High peak troponin T and a large infarct size are predictors of higher infarct ECV at baseline and follow-up. Infarct ECV is associated with clinical and MRI measures of MI severity in survivors of STEMI.

Left ventricular (LV) remodeling after myocardial infarction (MI) may lead to congestive heart failure, disability and death. It consists of expansion of the infarct zone and dilatation of the non-infarcted myocardium, causing shape distortion and ventricular enlargement. Experimental studies have shown that treatment with growth hormone (GH) stimulates cardiac repair, resulting in increased infarct zone collagen scar formation and possibly enhanced proteinosynthesis. These actions may ameliorate the process of LV remodeling. We hypothesize that these beneficial effects may be more prominent, if GH is delivered selectively in the infarct area, during the early phase of acute MI. Experimental and clinical studies are necessary to validate this hypothesis.