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Background Inflammation has emerged as a new treatment target in patients with coronary artery disease, and inflammation seems to play an important role in the ischemia/reperfusion injury in ST-elevation myocardial infarction (STEMI). The pro-inflammatory cytokine interleukin-6 (IL-6) has been shown to be associated with myocardial injury and poor prognosis in patients with STEMI. Purpose The aim of the study was to further elucidate possible associations between the IL-6 trans-signalling system and final infarct size, myocardial function, adverse remodelling, and future cardiovascular events in patients with STEMI. Methods A total of 272 patients with first-time STEMI included in the POSTEMI study on ischaemic postconditioning, with symptom duration Results There was a significant increase in IL-6 levels from admission to day 1 with a subsequent decline from day 1 to 4 months (Figure 1A). No significant change in IL-6R levels were found from admission to day 1 (Figure 1B). There was no difference between patients treated by postconditioning compared to routine PCI. High levels of IL-6 (> median) at all sampling points were significantly associated with increased infarct size and reduced left ventricular ejection fraction (LVEF) measured by CMR. Additionally, high levels of IL-6 (> median) at day 1 were associated with lower myocardial salvage, more presence of microvascular obstruction and larger increase in indexed LV end diastolic volume (LVEDVi). IL-6R measured during hospitalisation was significantly associated with change in LVEDVi, but did not associate with infarct size, LVEF or myocardial salvage. High levels of IL-6 (>75th percentile) at all sampling points were associated with an increased risk of having an adverse clinical event during the first year and with long-term all-cause mortality (Figure 2), whereas there was no association between IL-6R and adverse clinical events. Conclusion Patients with high IL-6 levels during the acute phase of STEMI had larger infarct size, reduced myocardial salvage, reduced LV function and worse clinical outcome than patients with lower levels of IL-6. High levels of IL-6 measured after 4 months were associated with larger infarct size, reduced LVEF and increased all-cause mortality. IL-6R was significantly associated with increase in LVEDVi. The results add important information to the role of IL-6 in myocardial injury in acute STEMI and the IL-6 pathway as a potential treatment target. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Stein Erik Hagen Foundation for Clinical Heart Research, Oslo, Norway. Figure 1Figure 2

Born in Salzwedel, East Germany, Matthias Nahrendorf entered adulthood just as the Iron Curtain was lifting in Eastern Europe. He earned his medical degree and PhD in cardiovascular biology at Heidelberg University, and completed his residency plus fellowships in internal medicine and cardiovascular imaging at University of Wuerzburg. In 2004, a postdoctoral position at Massachusetts General Hospital’s Center for Molecular Imaging Research brought Nahrendorf to Boston. He is now a principal investigator at MGH’s Center for Systems Biology and director of the hospital’s Mouse Imaging Program. Nahrendorf, 45, is pursuing a deeper understanding of the consequences of ischemic injury, especially regarding how monocytes/macrophages impact acute healing and scar development,1–3 and how an imbalance in the process fuels prolonged inflammation and then heart failure. An associate professor of radiology at Harvard Medical School, Nahrendorf and his collaborators are also developing molecular imaging tools to noninvasively study regulators of heart failure biology and infarct healing processes.4–6 A long-term goal of the work is to devise new therapies for ischemic injury that reduce the action of inflammatory cells to what is necessary only to promote healthy healing, Nahrendorf says. If that could be achieved, “Ideally we wouldn’t have heart failure anymore.” I have one brother, he’s younger, and my parents. It was a pretty sheltered childhood. I grew up in Magdeburg, and the (Berlin) Wall came down when I was 18. Army service was compulsory in East Germany. So I spent one year in the army and then Germany reunited, so I was free to go wherever I wanted. My parents are both doctors. My dad is a cardiologist, my mom a pediatrician. I had a happy childhood. They were never telling me what to do. But I was obviously influenced by their jobs. They talked about …

Myocardial infarct expansion has been associated with an increased risk of infarct rupture and progression to heart failure, motivating therapies such as infarct restraint and polymer injection that aim to limit infarct expansion. However, an exhaustive review of quantitative studies of infarct remodeling reveals that only half found chronic in-plane expansion, and many reported in-plane compaction. Using a finite-element model, we demonstrate that the balance between scar stiffening due to collagen accumulation and increased wall stresses due to infarct thinning can produce either expansion or compaction in the pressurized heart – potentially explaining variability in the literature – and that loaded dimensions are much more sensitive to changes in thickness than in stiffness. Our analysis challenges the concept that in-plane expansion is a central feature of post-infarction remodeling; rather, available data suggest that radial thinning is the dominant process during infarct healing and may be an attractive therapeutic target.

Effects of white wine (WW) consumption on the expression of inflammatory markers/mediators (MMP-2, MMP-9, NF-ĸB p65 and TGF-β1) in myocardial tissue after experimentally induced permanent myocardial ischemia was investigated. Male Sprague-Dawley rats were given either a combination of WW and water or only water, for 28 days. After coronary ligation, animals were left to survive for 24 hours. Three representative areas: infarct/ischemic, peri-infarct/border zone, and control/non-ischemic zones were analyzed for expression of immunoreactivity by measuring the threshold area % of signal density. For MMP-9, significantly smaller expression was found in all 3 zones of wine drinking animals (P < 0.001). There was no difference in MMP-2 immunoreactivity between the 2 groups, except in peri-infarct zones, where the signal was significantly decreased (P < 0.001). The same pattern of expression was found for the NF-κB p65 signal, although no differences between experimental groups were observed for TGF-β1. White wine consumption decreases the expression of the 3 investigated inflammatory markers/mediators in the peri-infarct zone, suggesting its significant modulatory effect. For MMP-9 and MMP-2, expression was similar to the effect of postischemic reperfusion. No effect on TGF-β1 was observed, highlighting its role in being the master-switch, changing from the inflammatory to the proliferative stage of infarct healing.

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. Electronic supplementary material The online version of this article (doi:10.1007/s00395-017-0616-3) contains supplementary material, which is available to authorized users.

Rationale:Macrophages are involved in wound healing after myocardial infarction (MI). The role of Dectin-2, a pattern recognition receptor mainly expressed on myeloid cells, in the infarct healing remains unknown.Objective:The aim of this study is to determine whether Dectin-2 signaling is involved in the healing process and cardiac remodeling after MI and to elucidate the underlying molecular mechanisms.Methods and Results:In a mouse model of permanent coronary ligation, Dectin-2, mainly expressed in macrophages, was shown to be increased in the early phase after MI. Dectin-2 knockout mice showed an improvement in the infarct healing and cardiac remodeling, compared with wild-type mice, which was demonstrated by significantly lower mortality because of cardiac rupture, increased wall thickness, and better cardiac function. Increased expression of α-smooth muscle actin and collagen I/III was observed, whereas the levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 were decreased in the hearts of Dectin-2 knockout mice after MI. Dectin-2 deficiency inhibited the rate of apoptotic and necrotic cell death. However, Dectin-2 did not affect immune cell infiltration and macrophage polarization, but it led to a stronger activation of the Th1/interferon-γ immune reaction, through the enhancement of interleukin-12 production in the heart. Interferon-γ was shown to downregulate transforming growth factor-β–induced expression of α-smooth muscle actin and collagen I/III in isolated cardiac fibroblasts, leading to a decrease in migration and myofibroblast differentiation. Finally, Dectin-2 knockout improved myocardial ischemia–reperfusion injury and infarct healing.Conclusions:Dectin-2 leads to an increase in cardiac rupture, impairs wound healing, and aggravates cardiac remodeling after MI through the modulation of Th1 differentiation.

Introduction: Cardiac remodeling post myocardial infarction (MI) can be a critical determinant of outcome for patients with MI. Well-contained inflammation results in successful infarct healing while excessive inflammation cause adverse remodeling which leads to heart failure. Macrophages are important participants in inflammation, helping resolve pro-inflammatory reactions and performing reparative processes. Reprogramming macrophages towards a resolving and reparative phenotype is a potential therapeutic approach. We hypothesized that IL4/IL13-induced, alternatively activated macrophages (M2) have an important role in cardiac remodeling post-MI, and we tested this hypothesis in a mouse model of MI using myeloid-specific IL4 receptor α knockout mice (MyIL4RaKO). Methods: MyIL4RaKO mice were generated using IL4Ra flox/flox ;LysM-Cre. MI was induced by ligating the left anterior descending coronary artery. Hearts were cut into 1mm sections, and then stained by tetrazolium chloride for infarct size measurement. Evenly spaced radians were taken through the infarct with the center of left ventricle in 5μm heart sections, and the average infarct thickness was calculated. qPCR was used to determine gene expression. Echocardiography was performed at baseline and 3 weeks post MI. Results: Initial infarct size was not affected by IL4Ra knockout but at 1-week post MI, infarct size of MyIL4RaKO mice (16.54 ± 2.433, n=11) was shown significantly smaller than that of FC mice (24.96 ± 2.005, n=15) showing changes in remodeling (p= 0.0129). Changes in remodeling continued and at 3-week post MI, infarct thickness of MyIL4RaKO mice (0.2171 ± 0.01053, n=6) was significantly increased, compared with that of FC mice (0.3508 ± 0.03629, n=8, p= 0.0094). These changes were accompanied by MyIL4RaKO mice also showed lower level of fibrosis markers: Col1A1 and Plod2. A significantly lower ejection fraction was observed in MyIL4RaKO mice (25.46 ± 3.749, n=5) compared with FC mice (37.90 ± 2.309, n=5) at 3 weeks (p= 0.0223). Conclusions: Myeloid-specific IL4Ra knockout results in alteration of remodeling, altered fibrosis and decreased cardiac function post MI, although the cardiac hypertrophy did not show significant change.

Today, cardiovascular MRI (CMR) is widely used for diagnosis and therapeutic decision making in the setting of different cardiac diseases. CMR allows to analyse anatomical and functional parameters, and enables a non-invasive, accurate and repeatable assessment of changes in myocardial tissue. For example, contrast-enhanced CMR techniques such as late gadolinium enhancement (LGE) imaging enable an accurate, however, unspecific detection of myocardial damage, caused by myocardial infarction (MI). In addition, T2 and T2*-weighted CMR techniques allow to detect myocardial oedema as well as myocardial haemorrhage (in case of acute MI) and thereby provide additional information on infarct pathology and prediction of adverse outcome—at least in some cases. Regarding the initiation of timely and adequate therapy, diagnosis of myocardial inflammation in the early phase of heart disease—before the occurrence of structural changes in the myocardium—is crucial. Unfortunately, T2-weighted CMR techniques that promise to depict myocardial oedema as the first morphological change in the sequence of events have a limited sensitivity, and are questioned with regard to their diagnostic value by some groups.1 Also novel T2-mapping techniques promise an improved diagnostic yield, neither LGE-based imaging nor T2- and T2*-weighted imaging do allow a direct visualisation of infiltrating macrophages in the infarcted myocardium, but rather depict myocardial tissue changes that are ‘associated’ with or the consequence of ongoing myocardial inflammation and healing. Hence, new and more specific CMR tools are needed to improve both early diagnosis and specificity of diagnosis. From a clinical point of view, the opportunity to directly image infiltrating macrophages in the infarcted myocardium will be of broad diagnostic as well as therapeutic value since the extent and degree of myocardial disease might be monitored more accurately and the therapeutic success be assessed more appropriately.2 In this context, two distinct phases in the process of infarct healing were described recently3: …

Infarct healing is sought to be a dynamic process occurring in the subacute and chronic phase after ST-elevation myocardial infarction (STEMI) and is preferentially investigated by means of cardiac magnetic resonance (CMR) imaging. Previous studies indicate a reduction of infarct size (IS) during

Background—Postinfarction cardiac repair is regulated through timely activation and repression of inflammatory pathways, followed by transition to fibrous tissue deposition and formation of a scar. The transforming growth factor-β/Smad3 pathway is activated in healing infarcts and may regulate cellular events critical for the inflammatory and the fibrotic responses.Methods and Results—We examined the effects of Smad3 gene disruption on infarct healing and the pathogenesis of cardiac remodeling. In the absence of injury, Smad3-null hearts had comparable function to and similar morphology as wild-type hearts. Smad3-null animals had suppressed peak chemokine expression and decreased neutrophil recruitment in the infarcted myocardium but showed timely repression of inflammatory gene synthesis and resolution of the inflammatory infiltrate. Although myofibroblast density was higher in Smad3-null infarcts, interstitial deposition of collagen and tenascin-C in the remodeling myocardium was markedly reduced. Compared with wild-type animals, Smad3−/−mice exhibited decreased dilative remodeling and attenuated diastolic dysfunction; however, infarct size was comparable between groups. Transforming growth factor-β–mediated induction of procollagen type III and tenascin-C in isolated cardiac fibroblasts was dependent on Smad3, which suggests that decreased fibrotic remodeling in infarcted Smad3-null hearts may be due to abrogation of the profibrotic transforming growth factor-β responses.Conclusions—Smad3 loss does not alter the time course of resolution of inflammation in healing infarcts, but it prevents interstitial fibrosis in the noninfarcted myocardium and attenuates cardiac remodeling. Thus, the Smad3 cascade may be a promising therapeutic target for the treatment of myocardial infarction.

Although large collagen fibers in myocardial infarct scar are highly organized, little is known about mechanisms controlling this organization. The preexisting extracellular matrix may act as a scaffold along which fibroblasts migrate. Conversely, deformation within the ischemic area could guide fibroblasts so new collagen is oriented to counteract the stretch. To investigate these potential mechanisms, we infarcted three groups of pigs. Group 1 served as infarct controls. Group 2 had the endocardium slit longitudinally to alter local systolic deformation. Group 3had a plug sectioned from ischemic tissue and rotated 90°. The slit altered systolic deformation in the infarcted tissue, changing circumferential strain from expansion to compression and increasing radial strain and shears and the variability of collagen fiber angles but not the mean angle. In the plug pigs, when deformation, matrix orientation, and continuity are altered in the infarct area, the result is complete disarray in the organization of collagen within the infarct scar.

Wnt/frizzled signaling in the adult heart is quiescent under normal conditions; however it is reactivated after myocardial infarction (MI). Any intervention at the various levels of this pathway can modulate its signaling. Several studies have targeted Wnt/frizzled signaling after MI with the majority of them indicating that the inhibition of the pathway is beneficial since it improves infarct healing and prevents heart failure. This suggests that blocking the Wnt/frizzled signaling pathway could be a potential novel therapeutic target to prevent the adverse cardiac remodeling after MI.

Summary To test the hypothesis that fibrotic burden in remote myocardium quantified by CMR during early period of infarct healing is a strong determinant of the cardiac remodeling outcome. Background After acute myocardial infarction (AMI), co-existing myocardial stunning, ischemia, and architectural alteration may yield variable patterns of ventricular remodeling with potential long-term prognostic implications. We hypothesize that CMR quantification of fibrotic content, based on R1 (1/T1) assessment, in non-infarct myocardium early after infarction and during the infarct healing phases may provide novel prediction of the final infarct size and alteration of ventricular functions during infarct healing. Methods

Background Fat suppressed T2-weighted black blood turbo spin echo (BBTSE) imaging can detect myocardial edema developed after acute myocardial infarction (MI) and characterize the extent of myocardium at risk in comparison to late gadolinium enhancement (LGE) imaging. Purpose We hypothesized that T2-extent at baseline and changes during follow-up are associated with dynamic changes of infarct heterogeneity during the convalescence phase of infarct healing. We further explored the strength of association in quantifying T2-based myocardial edema, using a semi-automated method and manual tracing. Methods Fifty-one patients (40 men) underwent 3T cardiac MRI both at 18±10 days and 7.7±1.1 months after an acute MI, including: 3 short-axis slices of T2-weighted fat-suppressed BBTSE, LV function assessment by SSFP and LGE imaging. Area of hyperintensity on T2 images was assessed by a semi-automated method using a threshold of mean signal intensity in the remote ROI ± 2 SD and by manual tracing. In further analyses, correlations of T2 extent, expressed as the percentage of total myocardium, and other MRI results were assessed by Spearman correlation. Results Correlations between the T2 extent, LV parameters, infarct heterogeneity and their respective changes are displayed in the table. At baseline, hyperintense T2 myocardium was demonstrated in 50 patients (98%) and represented 20.5±14.0% of total myocardium. Baseline T2 size was inversely correlated with LVEF and was directly correlated with total MI size. Hyperintense T2 areas persisted in 12 patients (24%) at follow-up. Manual-tracing was correlated well with the semi-automated method (Spearman’s rho 0.84; P

Background Diffusion tensor MRI (DTI) has been used to investigate infarct healing and remodeling in several species. Tractography of the myocardium has also recently been reported. However, these prior studies were conducted ex-vivo on excised hearts. Here, we use in-vivo DTI of the mouse heart to follow microstructural changes in the myocardium in response to ischemia. Mean diffusivity (MD) and fractional anisotropy (FA) were measured 24 hours and 2-3 weeks after ischemia-reperfusion. In addition, 3D diffusion MRI tractography of the mice hearts was performed in-vivo.

To the Editor: We read with great interest the article by Westermann et al1 in which the authors showed that biglycan expression was strongly increased in the myocardium after permanent coronary occlusion in wild-type mice. In the hearts of bgn −/ 0 mice 21 days after coronary occlusion, however, collagen matrix organization was impaired, and several parameters of left ventricular function were deteriorated. Furthermore, these animals showed increased mortality rates after infarction. The authors conclude that the complete absence of biglycan is deleterious and prevents the establishment of a stable infarct scar and hemodynamic adaptation, suggesting that biglycan is required for proper infarct healing. Although the observations of the authors are most valuable, the major conclusion of the authors1 is …

Objective: The MRL mouse strain shows extraordinary wound healing capacities. Some years ago, Leferovich et al. (Proc Natl Acad Sci U. S. A. 2001;98:9830-35) have reported the absence of scar formation after cryogenically-induced right ventricular myocardial infarcts in adult MRL mice. An independent group (Oh et al., Cardiovasc Pathol 2004; 13:203-6) found that MRL mice repair left ventricular ischemic infarcts after coronary artery ligation with regular scar formation. Given the divergent outcomes in infarct healing in MRL mice reported by those two studies, we have investigated whether MRL mice heal myocardial infarcts, without scar both in the cryoinjury and in the coronary ligation model. Methods and Results: Four different protocols of cryogenically induced right and left ventricular injury, as well as permanent ligation of the left anterior descending coronary artery, were tested in adult MRL and control C57Bl/6 mice. At 60 days after experimental infarction, MRL mice showed pronounced scarring of the affected right and left ventricular areas, with no significant differences in infarct size and thickness between MRL and C57Bl/6 mice using any of the five experimental protocols. Analysis of cell proliferation by 5-bromo-2' -deoxyuridine (BrdU) incorporation into the DNA did not show any difference between the two strains of mice after infarction. Histological analysis of infarct areas using picrosirius red staining did not show differences in extent of collagen and distribution between the two mouse strains. Conclusions: NIRL mice heal myocardial infarcts with scar formation in response to ischemic as well as to cryogenic injuries. (c) 2008 Elsevier Inc. All rights reserved.

s S59 implantation attenuated the decline of fractional shortening after MI and the scar was significantly thicker in both BMMC groups compared to the media injected controls (p

Background Late gadolinium enhancement (LGE) with infarct tissue heterogeneity characterized by cardiac magnetic resonance imaging (CMR) has been shown to be associated with arrhythmogenic substrates and increased mortality. Preliminary data suggests that areas of heterogeneous signal intensity (SI) within an infarct may represent an admixture of myocardial fibrosis, ischemic cellular apoptosis and viable myocytes potentially capable of functional recovery.

Coronary occlusion (CO) of 1 h or longer causes transmural myocardial infarction (MI) in the rabbit. We studied how reperfusion of an infarct affected myocardial blood flow (MBF) acutely and after 3 wk of healing. CO was performed in rabbits for 60 or 180 min (n = 22) followed by reperfusion, and MBF to normal and infarcted zones was determined by radioactive microspheres. In a separate series (n = 23), MBF was measured at 21-25 days post-CO in three groups that had either permanent CO or reperfusion after 60 or 180 min of CO. MBF to the infarct was approximately 8 +/- 3% (+/-SE) of normal MBF (3.8 +/- 0.5 ml.min-1.g-1) during 60-180 min of CO but 3 wk later had increased to 33 +/- 6% of normal MBF (P less than 0.005). Reperfusion after 60 or 180 min of CO resulted in 74 +/- 6% and 41 +/- 5% return of normal MBF, respectively, but 3 wk later, MBF had decreased to 25 +/- 5% (P less than 0.001) and 24 +/- 4% (P less than 0.025) of normal MBF, respectively. Thus after 3 wk of postinfarction healing, MBF to the permanently occluded infarcts increased fourfold, whereas MBF decreased by 50% in the reperfused infarcts so that MBF to the scar tissue was comparable among the three groups and was not influenced by acute post-MI reperfusion.

The electrophysiologic and anatomic basis for fractionated electrograms were investigated in superfused epicardial preparations from infarcted canine hearts. Fractionated bipolar electrograms were frequently recorded in preparations from infarcts 2 weeks to 18 months old but only rarely in preparations from 5-day-old infarcts. The fractionated electrograms were not caused by movement artifacts. They were not associated with depressed transmembrane resting or action potentials (which were found in the 5-day-old infarcts), but rather transmembrane potentials recorded in the vicinity of the bipolar electrodes were normal. Despite the normal transmembrane potentials, activation time in regions where fractionated electrograms occurred was prolonged. However, prolonged activation time by itself did not cause fractionation, since fractionated electrograms were not recorded from normal preparations in which conduction was markedly slowed by a superfusate containing 16 mM potassium and epinephrine. Unipolar electrograms recorded with glass microelectrodes (tip size 1 to 5 microns) showed that activation in regions where fractionated electrograms were recorded was inhomogeneous. Prepotentials were found preceding the upstrokes of some action potentials in regions where double potentials were recorded, suggesting the possibility of electrotonic transmission across high resistance or inexcitable gaps, but no electrotonic potentials were seen in regions with multicomponent fractionated electrograms. Fractionated electrograms were recorded in regions where infarct healing caused wide separation of individual myocardial fibers while distorting their orientation. The anatomic changes probably caused slow and inhomogeneous activation.

Recent studies show that proton nuclear magnetic resonance (NMR) imaging can detect myocardial ischemia and acute myocardial infarction (AMI) in animal models1–3 and in humans.4–6 The area of AMI appears as increased signal intensity on the spin-echo NMR images and most likely reflects the regional edema associated with tissue necrosis.1 Thus, the time course of regional edema and the evolution of infarct healing may be revealed by serial NMR studies. In a recent canine study, Pflugfelder et al7 examined the time course of the increased NMR signal intensity associated with AMI. They found that the relative signal intensity increased between the day of AMI and 2 weeks after AMI and subsequently decreased by the 20th day. We examined the early time course of NMR changes in humans.

Myocardial infarcts are wounds inflicted by ischemic injury of the heart muscle. As in any other wound, a sufficient healing process after acute injury is prerequisite to the recovery and integrity of the organ's function. If infarct healing derails, fibrosis may be insufficient or too widespread

The use of methylprednisolone to limit the myocardial damage of acute myocardial infarction (AMI) may retard the progression of infarct healing and cause scar thinning. 1,2 It is unknown whether biochemical alterations in scar formation also accompany defective healing. To better understand the nature of altered healing in the evaluation of potential therapeutic interventions, we investigated experimentally whether alterations in collagen content, major genetic subtypes and cross-links occur late during healing, following early treatment with methylprednisolone after AMI.

Background The role of infarct size on left ventricular (LV) remodeling in heart failure after an acute ST-segment elevation myocardial infarction (STEMI) is well recognized. Infarct size, as determined by cardiovascular magnetic resonance (CMR), decreases over time. The amount, rate, and duration of infarct healing are unknown. Methods A total of 66 patients were prospectively enrolled after reperfusion for an acute STEMI. Patients underwent a CMR evaluation within 1 week, 4 months, and 14 months after STEMI. Results Mean infarct sizes for the 66 patients at baseline (acute necrosis), early follow-up (early scar), and late follow-up (late scar) were 25 ± 17 g, 17 ± 12 g, and 15 ± 11 g, respectively. Patients were stratified in tertiles, based on infarct size, with the largest infarcts having the greatest absolute decrease in mass at early and late scar. The percent reduction of infarct mass was independent of initial infarct size. There was an 8 g or 32% decrease in infarct mass between acute necrosis and early scar (p Conclusions Infarct healing is a continuous process after reperfusion for STEMI, with greatest reduction in infarct size in the first few months. The dynamic nature of infarct healing through the first year after STEMI indicates that decisions based on infarct size, and interventions to reduce infarct size, must take into consideration the time frame of measurement.

Background Quantitative T1 and T2 cardiovascular magnetic resonance (CMR) approaches have been utilized to detect edema post acute myocardial infarction (AMI). However, a systematic comparison between the two measures is currently lacking. Furthermore, these relaxation measurements may also be confounded by opposing effects of intramyocardial hemorrhage that is typically not taken into account. The purpose of our study was to compare regional and serial fluctuations in T1 and T2 post-AMI and additionally quantify T2* that is a more specific marker of hemorrhage. Methods A porcine model of myocardial infarction was employed involving a 90 min LAD occlusion followed by reperfusion. Pigs (N=3) were imaged on a 1.5T scanner (GE Healthcare) in a healthy state (control) and at day 2 and week 4 post-AMI. The following sequences were utilized for quantification: T2 with multi-echo fast-spin-echo (4 echo’s; TE=5.6-105 ms); apparent T1 by modified look-locker with saturation recovery (TI=50-3000 ms); T2* by gradient echo (2 echo’s; TE=1.4, 15 ms; TR=18ms). Measurements were reported in two regionsof-interest (ROI): 1) infarct zone defined from late gadolinium enhancement images; and 2) remote uninfarcted myocardium. Two short-axis slices were analyzed for each study; the anatomical location was identical for all three sequences. Results Fig. 1 a shows the linear regression between T1 and T2 values when taken across all ROI’s and time points. Both T1 and T2 were significantly elevated at day 2 (p=0.0003, p=0.0001) and week 4 (p=0.01, p=0.005) post-AMI compared to control, respectively; see Fig. 1b and 1c. Reduced T2* at day 2 (p=0.05) suggested the presence of hemorrhage in all animals; see Fig. 1d. Percent change in T2 (relative to control) was significantly greater than that for T1 at both day 2 (25±12 vs. 13±3 %, p=0.05) and week 4 (62±36 vs. 20±13 %, p=0.03). A lower apparent change at day 2m ay be suggestive of influence from hemorrhage on both T1 and T2. Conclusions T1 and T2 are highly correlated in AMI; however, T2 is a more sensitive parameter to detect the underlying alterations following AMI. In the early sub-acute phase, both T1 and T2 may be affected by counteracting effects of edema and hemorrhage, unlike T2*. Furthermore, in the late phase when hemorrhage has resolved, sensitivity of T2 towards edema appears to be greater in comparison to T1; T1 may possibly be reduced due to chronic remodeling. Simultaneous characterization of these relaxation parameters may potentially offer useful insights into the complex remodeling processes that follow AMI.