Myocardial Bleeding Research Articles

Abstract 10833: 30-Day Readmissions After Primary Percutaneous Coronary Intervention in Nonagenarians: A Nationwide Analysis from the United States

Objective: To assess 30-day readmission rates and mortality at readmission in nonagenarians following primary percutaneous coronary intervention (pPCI) for ST elevation myocardial infarction (STEMI). Background: There is limited contemporary data exploring the 30-day readmission rates and mortality in nonagenarians (age greater than 90 years) with STEMI following pPCI when compared to no pPCI. Methods: We utilized the National Readmissions Database (NRD) from 2010 to 2018 to identify nonagenarians hospitalized with STEMI. We divided the total cohort into two groups based on pPCI status. We analyzed 30-day readmission rates, mortality at the time of readmission, and causes of readmissions in both study cohorts. Results: Between 2010-2018, an estimated 37,363 STEMI hospitalizations were identified in nonagenarians, of which 12,062 (32.3%) included pPCI and 25,301 (67.7%) had no pPCI. Compared to pPCI cohort, no pPCI had more women (69.8% vs 36.7%), higher elixhauser comorbidity index (13% vs 8%), palliative care consultation (12.6% vs 3.4%), and nursing home placement (48% vs 33.3%) (all p<0.01). Overall, 30-day readmission rates were higher in pPCI cohort compared with no pPCI (22.1% vs 16.2%; p<0.01). However, the in-hospital mortality rates at 30-day readmission were significantly lower in pPCI cohort compared with no pPCI (7.0% vs 14.3%; p<0.01). Heart failure is the most common cause of 30-day readmissions in both cohorts, followed by acute myocardial infarction (MI) and gastrointestinal hemorrhage. Recurrent MI rates were significantly lower in pPCI cohort compared with no pPCI (12.3% vs 18.4%; p<0.01). Conclusion: In nonagenarians with STEMI, pPCI during index hospitalization is associated with slightly higher 30-day readmissions but significantly lower mortality at the time of readmission. Given the remarkable mortality benefit with pPCI, further research is necessary to risk stratify and optimize readmission rates following STEMI in nonagenarians.

Role of biomarkers of myocardial injury and inflammation in predicting ischemia-reperfusion injury in patients with ST-segment elevation acute coronary syndrome undergoing endovascular revascularization

Aim. To evaluate the informative value of biomarkers (cardiac troponin l (cTnl), high-sensitivity C-reactive protein (hsCRP), N-terminal pro-brain natriuretic peptide (NTproBNP), stimulating growth factor (ST2)) as laboratory markers of myocardial ischemia-reperfusion injury in patients with ST-segment elevation acute coronary syndrome (STEACS) undergoing endovascular revascularization.Material and methods. The study included 115 patients with STEACS who underwent endovascular myocardial revascularization. To identify the informative value of biomarkers, the levels of cTnl, NTproBNP, hsCRP, sST2 were analyzed at baseline, as well as after reperfusion therapy on the 2nd (cTnl) and 5th (sST2, hsCRP, NTproBNP) days. Contrast-enhanced cardiac magnetic resonance imaging was performed 5 days after endovascular intervention.Results. Microvascular obstruction was detected in 54 patients (47%), of which 24 (44%) patients had a combination of microvascular obstruction and myocardial hemorrhage. ln 61 cases (53%), no microvascular damage was registered. lt was found that with an increase in the threshold initial NTproBNP levels >590 pg/ml, the odds ratio (OR) of myocardial reperfusion injury was 12,2 (95% confidence interval (CI), 4,81-30,92, p<0,001). In addition, we analyzed biomarker levels in the early period after myocardial infarction, at which threshold values of reperfusion injury parameters were established as follows: for cTnI >8,1 ng/ml, OR=7,17 (95% CI, 3,11-16,53, p=0,001); for hsCRP >14 mg/L, OR=12,71 (95% CI, 5,03-32,08, p=0,001); for NTproBNP >334 pg/ml, OR=11,8 (95% CI, 4,88-28,59, p=0,001); for sST2 >41 ng/ml, OR=7,17 (95% CI, 3,11-16,53, p=0,001). According to multivariate analysis, predictors of microvascular injury were the initial NTproBNP values, as well as the cTnI, hsCRP, and sST2 values in the early postinfarction period (sensitivity — 89,5%, specificity — 83,3%).Conclusion. Thus, the initial NTproBNP, as well as cTnI, hsCRP, sST2 values after percutaneous coronary intervention are more informative for assessing the risk of microvascular damage.

Abstract MP02: Proprotein Convertase Subtilisin/kexin Type 6 (PCSK6) Is Involved In Regulation Of Vasculogenesis

Background: PCSK6 cleaves and activates growth factors involved in cell differentiation and Pcsk6-/- mice exhibit 25% embryonic lethality, while surviving offspring have blindness and cyclopia. We have shown that PCSK6 localizes to vascular smooth muscle cells of intra-plaque neovessels. Hypothesis: We hypothesize that a) the processes of vasculogenesis, atherosclerosis and plaque neovascularisation share common molecular regulators and b) that PCSK6 plays a common role in vascular remodeling. Methods: Association between SNPs near the PCSK6 gene and levels of 90 plasma proteins was tested using data from 30,931 individuals in the SCALLOP consortium. Data from the FinnGen consortium (Release 3) were queried to explore the PCSK6 SNPs associated with specific disease phenotypes. Morpholino technology was used for Pcsk6 knockdown in zebrafish, coupled with vascular phenotype studies. Pcsk6-/- mice were used to study the expression of vasculogenesis related genes as well as vascular morphology. Results: Rs7178801 and rs11639051 in the PCSK6 gene were found to relate to plasma PDGFB and VEGFD levels, while rs45482895 associated with diabetic retinopathy and disorders of the choroid and retina in humans. Gross phenotypic and histological examination of zebrafish embryos with ablated PCSK6 showed improper peripheral vascular patterning of intersegmental vessels, cerebral and myocardial haemorrhage, atrial dilatation and pericardial oedema. Gene expression levels of vasculogenesis related genes, i.e. Vegfa, Vegfb, Angpt1 and Tgfb2 were altered in the heart, liver and adipose tissue in Pcsk6-/- mice. In the retinas of Pcsk6-/- mice, Pdgfb was significantly downregulated compared to controls. Staining of the retinal vasculature showed that superficial retinal vasculature had a lower number of branching points and vessel width, while deep retinal vasculature covered a significantly smaller area in Pcsk6-/- Conclusions: Here, we show that variants in the PCSK6 gene associate with growth factors implicated in vasculogenesis and retinopathy. Lack of Pcsk6 in mice and zebrafish led to vascular patterning defects. Further studies will aim to elucidate the mechanisms by which PCSK6 regulates vasculogenesis in homeostatic and pathological conditions

Acute Late-Stage Myocarditis in the Crab-Eating Macaque Model of Hemorrhagic Smallpox.

Hemorrhagic smallpox, caused by variola virus (VARV), was a rare but nearly 100% lethal human disease manifestation. Hemorrhagic smallpox is frequently characterized by secondary bacterial infection, coagulopathy, and myocardial and subendocardial hemorrhages. Previous experiments have demonstrated that intravenous (IV) cowpox virus (CPXV) exposure of macaques mimics human hemorrhagic smallpox. The goal of this experiment was to further understand the onset, nature, and severity of cardiac pathology and how it may contribute to disease. The findings support an acute late-stage myocarditis with lymphohistiocytic infiltrates in the CPXV model of hemorrhagic smallpox.

Retrospective review of 27 European cases of fatal elephant endotheliotropic herpesvirus-haemorrhagic disease reveals evidence of disseminated intravascular coagulation

Elephant endotheliotropic herpesvirus haemorrhagic disease (EEHV-HD) is widely acknowledged as the most common cause of mortality in young Asian elephants (Elephas maximus) in captivity. The objective of the current study was to perform a blinded, retrospective pathology review of European EEHV-HD fatalities, constituting the largest systematic assessment of EEHV-HD pathology to date. Findings between viral genotypes were compared with the aim to investigate if disseminated intravascular coagulation (DIC) could be substantiated as a significant complicating factor, thereby increasing the understanding of disease pathophysiology. Immunohistochemical staining confirmed endothelial cell (EC) damage and the presence of EC intranuclear inclusion bodies, demonstrating a direct viral cytopathic effect. Microthrombi were observed in 63% of cases in several organs, including lungs, which, together with widespread haemorrhage and thrombocytopenia reported in EEHV-HD case reports, supports the presence of overt DIC as a serious haemostatic complication of active EEHV infection. Death was attributed to widespread vascular damage with multi-organ dysfunction, including severe acute myocardial haemorrhage and subsequent cardiac failure. Systemic inflammation observed in the absence of bacterial infection may be caused by cytokine release syndrome. Findings reinforce the necessity to investigate cytokine responses and haemostatic status during symptomatic and asymptomatic EEHV viraemia, to potentially support the use of anti-inflammatory treatment in conjunction with anti-viral therapy and cardiovascular support.

Assessment of segmental agreement of T2 mapping versus triple inversion recovery in detection of acute myocardial edema

BackgroundThere are some limitations using the different sequences of clinical cardiac magnetic resonance (cardiac MR) in detection of edema in patients presenting with acute myocardial injury. The purpose of this study is to evaluate the myocardial segmental agreement between the different edema sequences: T2 mapping and turbo inversion recovery magnitude (TIRM) in detection of acute myocardial edema.ResultsThirty-seven patients presented with acute infarction were sent to cardiac MR to assess myocardial edema. All cardiac MR studies were scanned using cine, TIRM, and late gadolinium enhancement (LGE) in short axis views (SAX). Position of the T2 mapping slices were copied from the TIRM. The left ventricle (LV) was divided into apical, mid, and basal segments per visualization of the papillary muscles. Edema mass was assessed separately in each segment as well as the total edema mass in both the TIRM and T2 mapping. Twenty-four patients of whom 12.5% had multi-territorial coronary lesions and edema were assessed. Myocardial edema was not assessed in thirteen patients (35%) due to significant intra myocardial hemorrhage (T2 mapping < 60 ms). No statistical significance was found between the TIRM and the T2 mapping neither in the total amount of edema (p = 0.79), nor in the LV basal, mid, and apical segments’ edema (p = 0.69, 0.5, and 0.8 respectively). The upper and lower limits of agreements were tested between the TIRM and the T2 mapping of total edema mass, basal segments, mid, and apical ventricular segments were = 18 and − 7.7 g, 11.3 and − 5.1 g, 12.3 and − 5.2 g, and 15.5 and − 7.8 g respectively.ConclusionThis study supports the proof of the principle that there is no statistical significant difference per myocardial segments between the T2 mapping and routine edema’s sequences. Larger studies are recommended to assess the impact in clinical outcome.

Abstract P444: Myocardial Infarction and Subarachnoid Hemorrhage. Frequency and Impact on Outcome

Introduction/background: Subarachnoid hemorrhage is known to be associated with systemic complications including neurogenic pulmonary edema and Talkotsubo cardiomyopathy. We set to establish the frequency of myocardial infarction (MI) and its impact on outcome among patients with subarachnoid hemorrhage (SAH) Methods: We analyzed the data from Nationwide Inpatient Sample (2005-2014) for all subarachnoid hemorrhage (ICH) patients. Myocardial infraction (MI) was identified using the International Classification of Disease, 9th Revision, Clinical Modification codes. Baseline characteristics, discharge outcomes (mortality, moderate to severe disability at dischagre, length of stay and in-hospital charges) were compared between the two groups. Results: Of the 325923 patients with SAH, 12720 (3.90%) had in-hospital myocardial infraction. SAH patients with MI were older (64.6 years versus 59.0 years, P &lt;.0001) compared to SAH patients without MI but there was no difference in-term of proportion of females between the two groups. The in-hospital mortality was also higher (49.8% versus 23.9%, p≤.0001) among patients with MI in both univariate and multivariate analysis (OR = 1.75 (1.59 -1.93), P&lt;.0001) after adjusting for potential confounders. SAH patients with MI had higher (68.5% versus 40.9%, P &lt;.0001) proportion of moderate to severe disability at discharge compared to ones without. Similarly, mean length of in-hospital stay (13.2 days versus 11.8 days, P &lt;.0001) and mean hospital charges ($188845 versus $150062, P &lt;.0001) were also higher in SAH patients with MI Conclusions: While MI was reported in only 3.9% of SAH cases it had a significant impact on outcome with a one fold increase in morality and about 75% increase risk of severe disability.

Quantification of myocardial hemorrhage using T2* cardiovascular magnetic resonance at 1.5T with ex-vivo validation

BackgroundT2* cardiovascular magnetic resonance (CMR) is commonly used in the diagnosis of intramyocardial hemorrhage (IMH). For quantifying IMH with T2* CMR, despite the lack of consensus studies, two different methods [subject-specific T2* (ssT2*) and absolute T2* thresholding (aT2* < 20 ms)] are interchangeably used. We examined whether these approaches yield equivalent information.MethodsST elevation myocardial infarction (STEMI) patients (n = 70) were prospectively recruited for CMR at 4–7 days post revascularization and for 6-month follow up (n = 43). Canines studies were performed for validation purposes, where animals (n = 20) were subject to reperfused myocardial infarction (MI) and those surviving the MI (n = 16) underwent CMR at 7 days and 8 weeks and then euthanized. Both in patients and animals, T2* of IMH and volume of IMH were determined using ssT2* and aT2* < 20 ms. In animals, ex-vivo T2* CMR and mass spectrometry for iron concentration ([Fe]Hemo) were determined on excised myocardial sections. T2* values based on ssT2* and absolute T2* threshold approaches were independently regressed against [Fe]Hemo and compared. A range of T2* cut-offs were tested to determine the optimized conditions relative to ssT2*.ResultsWhile both approaches showed many similarities, there were also differences. Compared to ssT2*, aT2* < 20 ms showed lower T2* and volume of IMH in patients and animals independent of MI age (all p < 0.005). While T2* determined from both methods were highly correlated against [Fe]Hemo (R2 = 0.9 for both), the slope of the regression curve for ssT2* was significantly larger as compared to aT2* < 20 ms (0.46 vs. 0.32, p < 0.01). Further, slightly larger absolute T2* cut-offs (patients: 23 ms; animals: 25 ms) showed similar IMH characteristics compared to ssT2*.ConclusionCurrent quantification methods have excellent capacity to identify IMH, albeit the T2*of IMH and volume of IMH based on aT2* < 20 ms are smaller compared to ssT2*. Thus the method used to quantify IMH from T2* CMR may influence the diagnosis for IMH.

Effect of coronary flow on intracoronary alteplase: a prespecified analysis from a randomised trial

ObjectivesPersistently impaired culprit artery flow (<TIMI 3) during primary percutaneous coronary intervention is a surrogate for failed myocardial perfusion. We evaluated the effects of intracoronary alteplase according to TIMI flow...

Cardiotoxic Effects of Hemiscorpius Lepturus Scorpion Venom Fractions in Rats

Background: Scorpion stings are responsible for many deaths in humans; however, the toxicity mechanisms of the venoms from many species are not well studied. We investigated the cardiotoxicity of the crude venom from H. lepturus scorpion and its isolated fractions, F-I to F-VI. Methods: The scorpion’s venom was extracted into six fractions by chromotagraphy. Healthy male Wistar rats (N=72) were equally divided into eight groups of nine: G1: Controls (0.5ml. normal saline), G2: Crude venom (1000µg/kg), G3: F-I (120µg/kg), G4: F-II (430µg/kg), G5: F-III (80 µg/kg), G6: F-IV (180µg/kg), G7: F-V (60µg/kg), and G8: F-VI (130µg/kg). Blood samples were obtained by cardiac puncture at 1, 3 and 24 hours after the venom injection. The serum levels of AST, LDH, CPK, CK-MB and troponin-I were determined. Upon euthanasia, the hearts were removed from the rats and examined microscopically for histopathology. Results: In groups receiving crude venom and F-VI, we observed multifocal fragmentation of myocardial fibers, hemorrhage, degeneration and disappearance of striations in cardiac muscles as compared to the controls. The findings showed that AST and LDH activity in groups 2, 4 and 8, CPK activity in groups 2, 4, 6 and 8 and CK-MB activity and troponin-I levels in groups 2 and 8 increased significantly compared to those in the control group. Conclusion: There was evidence of significant cardiotoxicity in the group receiving crude venom and F-VI. Although alterations in the enzymatic and troponin-I levels were observed in other groups, the greatest cardiotoxicity of H. lepturus venom was caused by fraction VI.

Effect of Cadmium chloride on the Liver, kidney and heart tissues and the protective role of pomegranate seed oil in male Albino rats.

This experiment was designed to identify the protective role of pomegranate seed oil against the toxicity of Cadmium chloride on the tissues of the liver, kidneys and heart, as it distributed 24 male rats to four groups. The results of microscopic examination of the target organs tissues many of histological lesions after treating animals with Cadmium chloride represented by necrosis, fatty degeneration and fibrosis around the central vein in the liver tissue, swelling of the glomeruli, necrosis of kidney tissue, necrosis within the myocardial fibers and hemorrhage within heart tissue .&#x0D; Mention the present result shown the results of the group treated with pomegranate seed oil with Cadmium chloride have been shown, returned of most tissues to the semi-normal state, with some negative effects of Cadmium chloride remaining

Cardiopulmonary Lesions in Sheep Produced by Experimental AcuteClostridium PerfringensType D Enterotoxemia

Enterotoxemia caused by Clostridium perfringens type D is one of the most prevalent clostridial diseases of sheep. The lesions of the acute form of this disease, particularly the cerebral lesions, are well characterized; however, detailed descriptions of the cardiac and pulmonary lesions are lacking. Here we describe cardiopulmonary lesions in experimental acute type D enterotoxemia in sheep and determine the role of epsilon toxin (ETX) in the development of these lesions. Four groups of 6 sheep were intraduodenally inoculated with either a wild-type C. perfringens type D strain; its etx knockout mutant, which is unable to produce ETX; the etx mutant complemented with the wild-type etx gene, which regains the ETX toxigenic ability; or sterile culture medium as a control. All sheep were subjected to postmortem examination within 24 hours of inoculation. Lesion scores were compared between groups for pulmonary edema; hydrothorax; ascites; hydropericardium; endocardial, myocardial and epicardial hemorrhages; microscopic lesions of acute myocardial degeneration and necrosis; and myocardial, endocardial, and epicardial edema, hemorrhage, and inflammation. Only sheep inoculated with the wild-type and complemented ETX-toxigenic bacterial strains developed cardiopulmonary lesions, which were present in varying degrees of severity and proportions. These lesions were not present in sheep inoculated with the etx mutant or in the negative control. We conclude that severe acute cardiopulmonary lesions in sheep with experimental enterotoxemia are associated with the capacity of the strains to produce ETX. These changes are likely contributors to the clinical signs and even death of affected animals.

Hemorrhage promotes chronic adverse remodeling in acute myocardial infarction: a T1 , T2 and BOLD study.

Hemorrhage is recognized as a new independent predictor of adverse outcomes following acute myocardial infarction. However, the mechanisms of its effects are less understood. The aim of our study was to probe the downstream impact of hemorrhage towards chronic remodeling, including inflammation, vasodilator function and matrix alterations in an experimental model of hemorrhage. Myocardial hemorrhage was induced in the porcine heart by intracoronary injection of collagenase. Animals (N = 18) were subjected to coronary occlusion followed by reperfusion in three groups (six/group): 8 min ischemia with hemorrhage (+HEM), 45 min infarction with no hemorrhage (I - HEM) and 45 min infarction with hemorrhage (I + HEM). MRI was performed up to 4 weeks after intervention. Cardiac function, edema (T2 , T1 ), hemorrhage (T2 *), vasodilator function (T2 BOLD), infarction and microvascular obstruction (MVO) and partition coefficient (pre- and post-contrast T1 ) were computed. Hemorrhage was induced only in the +HEM and I + HEM groups on Day 1 (low T2 * values). Infarct size was the greatest in the I + HEM group, while the +HEM group showed no observable infarct. MVO was seen only in the I + HEM group, with a 40% occurrence rate. Function was compromised and ventricular volume was enlarged only in the hemorrhage groups and not in the ischemia-alone group. In the infarct zone, edema and matrix expansion were the greatest in the I + HEM group. In the remote myocardium, T2 elevation and matrix expansion associated with a transient vasodilator dysfunction were observed in the hemorrhage groups but not in the ischemia-alone group. Our study demonstrates that the introduction of myocardial hemorrhage at reperfusion results in greater myocardial damage, upregulated inflammation, chronic adverse remodeling and remote myocardial alterations beyond the effects of the initial ischemic insult. A systematic understanding of the consequences of hemorrhage will potentially aid in the identification of novel therapeutics for high-risk patients progressing towards heart failure.

P1476IRON PARAMETERS PREDICT CARDIOVASCULAR EVENTS IN MAINTENANCE HEMODIALYSIS PATIENTS

Abstract Background and Aims Previous studies revealed the association between iron deficiency and thromboembolic events, whereas the association between high serum ferritin and poor prognosis of cerebral haemorrhage was reported in the general population. Since few reports have revealed the relationship between iron parameters and cardiovascular events in hemodialysis (HD) patients so far, our purpose was to examine whether iron parameters predict cardiovascular events in HD patients based on the nation-wide database of patients undergoing dialysis in Japan. Method We enrolled 126,560 patients aged between 20 and 100 who had been on maintenance HD more than 1 year and three times weekly at the end of 2012. We divided baseline transferrin saturation (TSAT) levels into 3 categories (T1: &amp;lt;20, T2: 20-25, T3: &amp;gt;25%) and serum ferritin levels into quartile (Q1: &amp;lt;31, Q2: 31-73, Q3: 73-158, Q4: &amp;gt;158 ng/mL). The study outcomes were new onset of myocardial infarction (MI), cerebral infarction (CIF), and cerebral haemorrhage (CHM) and death due to these three diseases between 2012 and 2013. We performed multivariate logistic regression for the incident events and also employed Cox proportional hazards analyses for death. Multiple imputation method with 5 data sets was performed for missing values. Results During a 1-year follow-up, a total of 2,087 MI (373 deaths), 2,930 CIF (283 deaths), and 1,371 (359 deaths) CHM occurred. After adjustment for demographic and clinical factors, odd ratios (ORs) for MI and CIF were significantly higher among patients with T1 of TSAT than those with T3 (OR; 1.19 (95% confidence interval (CI), 1.07-1.33), 1.16 (95% CI, 1.06-1.27, respectively), and serum ferritin levels were not associated with those outcomes. On the other hand, TSAT was not associated with CHM, however, stepwise increase of OR with the increase of ferritin quartile was observed; patients with Q4 of ferritin had the highest risk for CHM (OR; 1.32 (95% CI, 1.12-1.57) as compared to Q1). In the multivariable Cox regression models, the hazard ratios (HRs) for death due to MI and CIF of the patients with T1 of TSAT were 1.28 (95% CI, 1.00-1.65) and 1.40 (95% CI, 1.06-1.86) as compared to T3, respectively. HR for death due to CHM in patients with Q1-Q4 of ferritin was 1.00 (Reference), 1.59 (95% CI, 1.12-2.25), 1.90 (95% CI, 1.35-2.67), 1.61 (95% CI, 1.13-2.29), respectively (Figure). Furthermore, high dose of erythropoietin stimulating agents was a risk factor of all three cardiovascular events and mortality. Conclusion Low TSAT levels predicted MI and CIF and high serum ferritin levels predicted CHM in HD patients. These results suggest that functional iron deficiency could affect thromboembolic events, while increase in storage iron could affect microvascular fragility.

Interventionist videothermometry: a new model of cardiac ischemia evaluation

BackgroundThe purpose of the present study was to evaluate, through videothermometry, the temperature variation in the hearts of rabbits, that underwent induced myocardial ischemia and reperfusion.ResultsA total of 20 female rabbits were divided into two groups: a treated group and a sham group, the treatment group underwent 5 min of cardiac arrest and reperfusion, using the inflow occlusion technique. Throughout the experiment, the animals were monitored by videothermometry, observing the thermal variations of the myocardial tissue. During the experiment, at different times, blood gas tests and tests to evaluate the lactate concentrations were performed. At the end of the experiment, each heart was submitted to histopathological evaluation. In the treated group, there was a reduction in temperature of the myocardial tissue during the circulatory arrest compared to the sham group. Additionally, a colder area next to the caudal vena cava ostium and the right atrium was observed. Notably, despite the 5 min of cardiac arrest in the treated group, both the lactate and bicarbonate levels were maintained without significant variation. However, there was an increase in PaCO2 and pH reduction, featuring respiratory acidosis. In relation to the histopathological study, the presence of hydropic degeneration in the myocardium of animals in the treated group was observed.ConclusionsBased on these results, the videothermometry was efficient in identifying the range of myocardial tissue temperature, suggesting that the first areas to suffer due to cardiac arrest were the caudal vena cava ostium and the right atrium. However, in regard to the angiographic coronary thermography, the study was not feasible due to the small size of the coronary. There was no variation between the groups regarding the presence of myocardial infarction, myocardial congestion, myocardial edema and myocardial hemorrhage.

A Rodent Model of Reperfused Hemorrhagic Myocardial Infarction

BackgroundIntramyocardial hemorrhage following reperfusion is strongly associated with major adverse cardiovascular events (MACE) in myocardial infarction (MI) patients. Previous work from by us and others have shown that prolonged ischemic periods prior to reperfusion drives the development of intramyocardial hemorrhage in large animal models, characterized by the presence of iron composites within the infarct zones in the acute and chronic periods following MI. Yet the mechanisms contributing to the adverse outcomes associated with hemorrhagic myocardial infarction (hMI) is not well understood, partly due to the lack of small animal models of hMI. Here, we demonstrate a novel rodent model that mimics reperfused hMI.Methods &amp; ResultsSprague‐Dawley rats underwent either a 90‐min ischemia and then reperfusion (I/R) (n=22), a 60‐min I/R (n=20) or 30‐min I/R (n=18) of the left anterior descending coronary artery. Sham rats were used as controls. 90‐min I/R always yielded hMI, while 30‐min I/R consistently yielded non‐hMI with no reflow. But, 60‐min I/R resulted in both hMIs (60%) and non‐hMI (40%), with both groups showing evidence for zones of no reflow within MI. Ex‐vivo late‐gadolinium‐enhancement (LGE) and T2* cardiac MRI performed on excised hearts from 90‐min I/R rats revealed colocalization of iron deposits with the scarred tissue. Histological studies verified tissue damage (H&amp;E) detected on LGE and the presence of iron (Perl’s stain) observed on T2*‐CMR. Protein expression of proinflammatory markers (TNF‐α, IL‐1β and MMP‐9) were increased in the 90‐min I/R group when compared to sham‐controls and 30‐min I/R groups. Further, transmission electron microscopy performed on 90‐min I/R myocardium showed accumulation of granular iron particles within the phagosomes.ConclusionShort (30‐min) and long (90‐min) ischemic periods before reperfusion consistently resulted in non‐hMI and hMI respectively in rats. This novel rodent model can be a useful tool to elucidate the molecular mechanisms of cardiovascular pathology associated with reperfused hemorrhagic myocardial infarctions.Late Reperfusion Leads to Development of hMIRepresentative LGE and T2*‐w images from ex‐vivo cardiac MRI showing myocardial infarction and hemorrhage respectively from late‐reperfusion (90‐min I/R) and early‐reperfusion (30‐min I/R) groups. Histological images of H&amp;E staining from regions negative for MI (green box) and H&amp;E and Perl’s stained images from regions positive for MI (blue box) are shown.Figure 1

Insights from examination of hearts from adults dying suddenly to the understanding of congenital cardiac malformations.

Congenital heart disease is a rare but important finding in adults who experience sudden death. Examination of the congenitally malformed heart has historically been considered esoteric and best left to those with expertise. The Cardiac Risk in the Young cardiovascular pathology laboratory based at St George's University of London has now received over 6,000 cases. Of these, 21 congenitally malformed hearts were retained for research and educational purposes. Hearts were assessed using sequential segmental analysis, and causes of death were adjudicated based on thorough macroscopic examination and histology. Congenital malformations that were encountered included atrial septal defects, ventricular septal defects, tetralogy of Fallot, and transposition of the great arteries in both its regular and congenitally corrected variants. Findings also included hearts with mirror-imaged and isomeric atrial appendages. Direct causes of death included myocardial fibrosis, pulmonary hypertension, and hemorrhage. A small but notable proportion did not reveal a substrate for arrhythmia, raising the question of whether the terminal event was due to the congenital heart disease itself, or an underlying channelopathy. Here, we demonstrate the value of simple sequential segmental analysis in describing and categorizing the cases, with the concept of the "morphological method" serving to identify the distinguishing features of the cardiac components. Clin. Anat. 33:394-404, 2020. © 2019 Wiley Periodicals, Inc.

Flow-targeted pediatric ex vivo heart perfusion in donation after circulatory death: A porcine model

The optimal blood flow and pressure to perfuse pediatric hearts from donation after circulatory death (DCD) on the ex vivo perfusion system has not been elucidated. This study sought to investigate the optimal perfusion strategy for pediatric DCD hearts by using a juvenile porcine model comparing pressure- vs flow-targeted strategy. The hearts of the juvenile DCD pigs were explanted, and the coronary arteries were perfused for 2 hours by the ex vivo heart perfusion system with 2 different perfusion strategies; pressure-targeted perfusion (target coronary perfusion pressure: 40 mm Hg, group A) and flow-targeted perfusion (target coronary perfusion flow: 10 ml/kg/min, group B). The working model heart perfusion was used to assess systolic and diastolic myocardial performance. The body weight, warm and cold ischemic time, and ex vivo perfusion time were comparable between the groups. In the working model, group B showed significantly preserved cardiac output (A: 70.5 ± 15.3 ml/kg/min vs B: 113.8 ± 15.0 ml/kg/min, p < 0.01), stroke volume (A: 0.4 ± 0.1 ml/kg vs B: 0.7 ± 0.1 ml/kg, p < 0.01), and ejection fraction (A: 18.8% ± 5.9% vs B: 35.0% ± 10.6%, p < 0.01). E/e' and Tei index were also significantly preserved in group B. The percentage gain of heart weight after ex vivo (net increase of the heart weight divided by heart weight at baseline) was significantly smaller in group B (A: 20.0% ± 5.3% vs B: 11.6% ± 5.0%, p < 0.05). Troponin-I, myocardial hemorrhage, oxidative stress markers; myeloperoxidase and 8-hydroxy-2'-deoxyguanosine were also significantly lower after ex vivo perfusion in group B (p < 0.05). The tightly controlled flow-targeted myocardial perfusion strategy for DCD donor hearts achieved better myocardial performance by causing less myocardial edema and limiting myocardial reperfusion injury.

6030Effects of adjunctive treatment with low-dose alteplase during primary percutaneous coronary intervention according to ischaemic time

Abstract Background Microvascular obstruction affects half of patients with acute ST-segment elevation myocardial infarction and confers an adverse prognosis. Purpose We aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intra-coronary alteplase infused early after coronary reperfusion associates with ischaemic time. Methods We conducted a prospective, multicentre, parallel group, 1:1:1 randomised, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischaemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified sub-group of interest. Between March 17, 2016, and December 21, 2017, 440 patients presenting at 11 hospitals in the UK were enrolled with follow up to 3 months. Patients with acute myocardial infarction due to occlusion of a major coronary artery presenting ≤6 hours from symptom onset were randomly assigned to treatment with placebo, alteplase 10mg or alteplase 20mg. The primary outcome was the amount of microvascular obstruction disclosed by cardiac magnetic resonance imaging at 2–7 days. Secondary outcomes included infarct size, myocardial haemorrhage, left ventricular ejection fraction, and troponin T area-under-the curve. Results 440 patients were randomized (figure), the primary endpoint was achieved in 396 (90%), seventeen (3.9%) withdrew and all other patients were followed up to 3 months. In the primary analysis, the amount of microvascular obstruction did not differ between the groups. Their ischaemic times were: ≤2 hours, n=98; ≥2–&lt;4 hours, n=215; and ≥4–6 hours, n=83. In patients with an ischaemic time ≥4 hours, treatment with alteplase (10 mg, n=26; 20 mg, n=30) was associated with a dose dependent increase in the amount (mean) of microvascular obstruction (% left ventricular mass) compared to placebo (n=27) 1.14 vs. 3.11 vs. 5.20; mean difference on square root scale 0.81 (95% CI 0.21, 1.42), p=0.009. The interaction test between ischaemic time and treatment (active vs. placebo) was not statistically significant p=0.06, however when the interaction was assessed for a trend across treatment groups this did reach statistical significance, p=0.018. Furthermore, a higher proportion of patients presenting ≥4–6 hours treated with 20 mg of alteplase had myocardial haemorrhage (59.3%) compared to the placebo group (28.0%), odds ratio 3.81 (95% CI 1.19, 12.25), p=0.025. The amount of haemorrhage was also greater; estimated mean difference 3.49 (95% CI 1.22, 5.75), p=0.0026. No between-treatment group differences for myocardial haemorrhage were observed in patients presenting with shorter ischaemic times. Study flow diagram Conclusions In patients presenting with an ischaemic time ≥4 hours, adjunctive treatment with low-dose intra-coronary alteplase during primary PCI was associated with increases in microvascular obstruction and myocardial haemorrhage. The mechanism may involve haemorrhagic transformation within the infarct core. Acknowledgement/Funding NIHR EME programme (reference: 12/170/45); British Heart Foundation (BHF reference FS/16/74/32573)

Efficacy of methylprednisolone on T-2 toxin-induced cardiotoxicity in vivo: A pathohistological study

Our aim was to compare the protective efficacy of two different formulations of methylprednisolone in T-2 toxin-induced cardiomyopathy. Methylprednisolone (soluble form, Lemod-solu® and/or depot form, Lemod-depo®, a total single dose of 40 mg/kg im) was given immediately after T-2 toxin (1 LD50 0.23 mg/kg sc). The myocardial tissue samples were examinated by using histopathology, semiquantitative and imaging analyses on day 1, 7, 14, 21, 28 and 60 of the study. Therapeutic application of Lemod-solu® significantly decreased the intensity of myocardial degeneration and haemorrhages, distribution of glycogen granules in the endo- and perimysium, a total number of mast cells and the degree of their degranulation was in correlation with the reversible heart structural lesions (p < 0.01 vs. T-2 toxin). These changes were completely abolished by the therapeutic use of Lemod-solu® plus Lemod-depo® (p < 0.001 vs. T-2 toxin). Our results show that a significant cardioprotective efficacy of methylprednisolone is mediated by its anti-inflammatory activity.