Myocardial Infarction Scar Research Articles

Mechanism of Ventricular Tachycardia Occurring in Chronic Myocardial Infarction Scar.

Cardiac arrest is the leading cause of death in the more economically developed countries. Ventricular tachycardia associated with myocardial infarct is a prominent cause of cardiac arrest. Ventricular arrhythmias occur in 3 phases of infarction: during the ischemic event, during the healing phase, and after the scar matures. Mechanisms of arrhythmias in these phases are distinct. This review focuses on arrhythmia mechanisms for ventricular tachycardia in mature myocardial scar. Available data have shown that postinfarct ventricular tachycardia is a reentrant arrhythmia occurring in circuits found in the surviving myocardial strands that traverse the scar. Electrical conduction follows a zigzag course through that area. Conduction velocity is impaired by decreased gap junction density and impaired myocyte excitability. Enhanced sympathetic tone decreases action potential duration and increases sarcoplasmic reticular calcium leak and triggered activity. These elements of the ventricular tachycardia mechanism are found diffusely throughout scar. A distinct myocyte repolarization pattern is unique to the ventricular tachycardia circuit, setting up conditions for classical reentry. Our understanding of ventricular tachycardia mechanisms continues to evolve as new data become available. The ultimate use of this information would be the development of novel diagnostics and therapeutics to reliably identify at-risk patients and prevent their ventricular arrhythmias.

Abstract 15206: Prevalence of Myocardial Adipose Tissue in Non-Ischemic and Ischemic Victims of Sudden Cardiac Death

Background: Recent imaging studies have shown that patients with myocardial infarction scar who have ventricular arrhythmias show more adipose tissue around the scar. Similar changes are seen in ARVC. Purpose: The aim of this study was to determine the prevalence of myocardial adipose tissue that co-localize with fibrosis in non-ischemic and ischemic sudden cardiac death (SCD) victims. Methods: The ischemic and non-ischemic subjects were derived from the FinGesture cohort, consisting of autopsy verified consecutive victims of SCD in Northern Finland between years 1998-2017 (n=5,869). Total of 48 non-ischemic, 47 ischemic and 37 accidental/intoxication related death subjects were included in the study. Hematoxylin-eosin-stained slides were digitized and fibrofatty deposits was determined using virtual microscopy software. Results: Myocardial adipose tissue was present in 51% of ischemic cases, 29% of non-ischemic cases and 14% of controls (p< 0.001). In ischemic cases, BMI seems to be associated with the presence of myocardial adipose tissue. Mean BMI was higher in subjects with myocardial adipose tissue versus subjects without (29.2 vs 24.9. p=0.022). Conclusions: The findings suggest that adipose tissue might have an influence in creation of fatal arrhythmias in SCD as it does in scar related ventricular arrhythmias. In addition, it seems that obesity is associated with ischemic scar related adipose tissue metaplasia.

Impact of cardiac history and myocardial scar on increase of myocardial perfusion after revascularization

PurposeWe sought to assess the impact of coronary revascularization on myocardial perfusion and fractional flow reserve (FFR) in patients without a cardiac history, with prior myocardial infarction (MI) or non-MI percutaneous coronary intervention (PCI). Furthermore, we studied the impact of scar tissue.MethodsSymptomatic patients underwent [15O]H2O positron emission tomography (PET) and FFR before and after revascularization. Patients with prior CAD, defined as prior MI or PCI, underwent scar quantification by magnetic resonance imaging late gadolinium enhancement.ResultsAmong 137 patients (87% male, age 62.2 ± 9.5 years) 84 (61%) had a prior MI or PCI. The increase in FFR and hyperemic myocardial blood flow (hMBF) was less in patients with prior MI or non-MI PCI compared to those without a cardiac history (FFR: 0.23 ± 0.14 vs. 0.20 ± 0.12 vs. 0.31 ± 0.18, p = 0.02; hMBF: 0.54 ± 0.75 vs. 0.62 ± 0.97 vs. 0.91 ± 0.96 ml/min/g, p = 0.04). Post-revascularization FFR and hMBF were similar across patients without a cardiac history or with prior MI or non-MI PCI. An increase in FFR was strongly associated to hMBF increase in patients without a cardiac history or with prior MI/non-MI PCI (r = 0.60 and r = 0.60, p < 0.01 for both). Similar results were found for coronary flow reserve. In patients with prior MI scar was negatively correlated to hMBF increase and independently predictive of an attenuated CFR increase.ConclusionsPost revascularization FFR and perfusion were similar among patients without a cardiac history, with prior MI or non-MI PCI. In patients with prior MI scar burden was associated to an attenuated perfusion increase.

Effects of Mesenchymal Stem Cell Injection into Healed Myocardial Infarction Scar Border Zone on the Risk of Ventricular Tachycardia.

The scar border zone is a main source of reentry responsible for ischemic ventricular tachycardia (VT). We evaluated the effects of mesenchymal stem cell (MSC) injection into the scar border zone on arrhythmic risks in a post-myocardial infarction (MI) animal model. Rabbit MI models were generated by left descending coronary artery ligation. Surviving rabbits after 4 weeks underwent left thoracotomy and autologous MSCs or phosphate-buffered saline (PBS) was administered to scar border zones in two rabbits in each group. Another rabbit without MI underwent a sham procedure (control). An implantable loop recorder (ILR) was implanted in the left chest wall in all animals. Four weeks after cell injections, ventricular fibrillation was induced in 1/2 rabbit in the PBS group by electrophysiologic study, and no ventricular arrhythmia was induced in the MSC group or control. Spontaneous VT was not detected during ILR analysis in any animal for 4 weeks. Histologic examination showed restoration of connexin 43 (Cx43) expression in the MSC group, which was higher than in the PBS group and comparable to the control. In conclusion, MSC injections into the MI scar border zone did not increase the risk of VT and were associated with favorable Cx43 expression and arrangement.

The cardioprotective effects of pharmacological postconditioning with mangafodipir in ST-elevation myocardial infarction, a 4–7 years follow up study

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Futurum - the academy for health and care, Jönköping. Background/Introduction The prevalence of heart failure is increasing as more patients survive a myocardial infarction (MI). MI scar extent is a strong predictor of the development of heart failure due to left ventricular adverse remodeling. Reperfusion injury occurs in the early phase of reperfusion and is linked to the increase of reactive oxygen species (ROS) with calcium overload disrupting the mitochondrial structure, which in turn results in further cell necrosis. Manganese dipyridoxyl diphosphate (mangafodipir) has superoxide dismutase mimetics and may act as a ROS scavenger in the acute phase of myocardial ischemia, hence supporting the myocardial cells in the neutralization of the chemically reactive molecules reducing the MI extent [1–3]. Purpose Our aim was to investigate the cardioprotective role of pharmacological postconditioning with mangafidipir in patients with ST-elevation myocardial infarction (STEMI). Methods Twenty patients with acute STEMI were enrolled between 2009–2014 and followed up 2017. The subjects were randomized in the cath lab into blinded treatment with i.v mangafodipir or control treatment receiving i.v saline prior to restoration of blood flow in the occluded coronary artery. Cardiac magnetic resonance imaging (CMR) at baseline and at follow-up (4–7 years) was performed to evaluate MI scar, LV end diastolic volume (LVEDV), LV end systolic volume (LVESV), LV stroke volume (LVSV), LV ejection fraction (LVEF) and LV mass (LVM). The study was approved by the ethical review board in Linkoping (Dnr 2016/212-31) and registered in the public database at clinicaltrials.gov (NCT 00966563). Results There was no significant difference between the groups in MI scar or LV geometrical and functional properties at baseline, although the duration of ischemia was significantly longer in the mangafodipir group (206 min vs. 144 min, p &amp;lt; 0.05) and a better TIMI grade before pPCI was observed in the control group. The group that underwent pharmacological postconditioning with mangafodipir had lower volumes and higher LVEF (p &amp;lt; 0.05) at follow-up, while the placebo group showed increased LV volumes, see Table 1 and Figure 1. Conclusion Pharmacological postconditioning with mangafodipir in STEMI may have a cardioprotective role in the development of left ventricular adverse remodeling. Due to the limited number of participants, the benefit of mangafodipir needs confirmation in larger studies.

Melatonin increases collagen content accumulation and Fibroblast Growth Factor-2 secretion in cultured human cardiac fibroblasts

BackgroundThe extracellular matrix serves as a scaffold for cardiomyocytes, allowing them to work in accord. In rats, collagen metabolism within a myocardial infarction scar is regulated by melatonin. The present study determines whether melatonin influences matrix metabolism within human cardiac fibroblast cultures and examines the underlying mechanism.MethodsThe experiments were performed on cultures of cardiac fibroblasts. The Woessner method, 1,9-dimethylmethylene blue assay, enzyme-linked immunosorbent assay and quantitative PCR were used in the study.ResultsMelatonin treatment lowered the total cell count within the culture, elevated necrotic and apoptotic cell count as well as augmented cardiac fibroblast proliferation, and increased total, intracellular, and extracellular collagen within the fibroblast culture; it also elevated type III procollagen α1 chain expression, without increasing procollagen type I mRNA production. The pineal hormone did not influence matrix metalloproteinase-2 (MMP-2) release or glycosaminoglycan accumulation by cardiac fibroblasts. Melatonin increased the release of Fibroblast Growth Factor-2 (FGF-2) by human cardiac fibroblasts, but cardiotrophin release was not influenced.ConclusionWithin human cardiac fibroblast culture, collagen metabolism is regulated by melatonin. The profibrotic effect of melatonin depends on the elevation of procollagen type III gene expression, and this could be modified by FGF-2. Two parallel processes, viz., cell elimination and proliferation, induced by melatonin, lead to excessive replacement of cardiac fibroblasts.

In vivo pulsed-field ablation in healthy vs. chronically infarcted ventricular myocardium: biophysical and histologic characterization.

Data on ventricular pulsed-field ablation (PFA) are sparse in the setting of chronic myocardial infarction (MI). The objective of this study was to compare the biophysical and histopathologic characteristics of PFA in healthy and MI swine ventricular myocardium. Myocardial infarction swine (n = 8) underwent coronary balloon occlusion and survived for 30 days. We then performed endocardial unipolar, biphasic PFA of the MI border zone and a dense scar with electroanatomic mapping and using an irrigated contact force (CF)-sensing catheter with the CENTAURI System (Galaxy Medical). Lesion and biophysical characteristics were compared with three controls: MI swine undergoing thermal ablation, MI swine undergoing no ablation, and healthy swine undergoing similar PFA applications that included linear lesion sets. Tissues were systematically assessed by gross pathology utilizing 2,3,5-triphenyl-2H-tetrazolium chloride staining and histologically with haematoxylin and eosin and trichrome. Pulsed-field ablation in healthy myocardium generated well-demarcated ellipsoid lesions (7.2 ± 2.1 mm depth) with contraction band necrosis and myocytolysis. Pulsed-field ablation in MI demonstrated slightly smaller lesions (depth 5.3 ± 1.9 mm, P = 0.0002), and lesions infiltrated into the irregular scar border, resulting in contraction band necrosis and myocytolysis of surviving myocytes and extending to the epicardial border of the scar. Coagulative necrosis was present in 75% of thermal ablation controls but only in 16% of PFA lesions. Linear PFA resulted in contiguous linear lesions with no gaps in gross pathology. Neither CF nor local R-wave amplitude reduction correlated with lesion size. Pulsed-field ablation of a heterogeneous chronic MI scar effectively ablates surviving myocytes within and beyond the scar, demonstrating promise for the clinical ablation of scar-mediated ventricular arrhythmias.

Fourier analysis of collagen bundle orientation in myocardial infarction scars

Collagen bundle orientation (CBO) in myocardial infarct scars plays a major role in scar mechanics and complications after infarction. We aim to compare four histopathological methods for CBO measurement in myocardial scarring. Myocardial infarction was induced in 21 pigs by balloon coronary occlusion. Scar samples were obtained at 4 weeks, stained with Masson’s trichrome, Picrosirius red, and Hematoxylin–Eosin (H&E), and photographed using light, polarized light microscopy, and confocal microscopy, respectively. Masson’s trichrome images were also optimized to remove non-collagenous structures. Two observers measured CBO by means of a semi-automated, Fourier analysis protocol. Interrater reliability and comparability between techniques were studied by the intraclass correlation coefficient (ICC) and Bland–Altman (B&A) plots and limits of agreement. Fourier analysis showed an almost perfect interrater reliability for each technique (ICC ≥ 0.95, p < 0.001 in all cases). CBO showed more randomly oriented values in Masson’s trichrome and worse comparability with other techniques (ICC vs. Picrosirius red: 0.79 [0.47–0.91], p = 0.001; vs. H&E-confocal: 0.70 [0.26–0.88], p = 0.005). However, optimized Masson’s trichrome showed almost perfect agreement with Picrosirius red (ICC 0.84 [0.6–0.94], p < 0.001) and H&E-confocal (ICC 0.81 [0.54–0.92], p < 0.001), as well as these latter techniques between each other (ICC 0.84 [0.60–0.93], p < 0.001). In summary, a semi-automated, Fourier-based method can provide highly reproducible CBO measurements in four different histopathological techniques. Masson’s trichrome tends to provide more randomly oriented CBO index values, probably due to non-specific visualization of non-collagenous structures. However, optimization of Masson’s trichrome microphotographs to remove non-collagenous components provides an almost perfect comparability between this technique, Picrosirius red and H&E-confocal.

Chronic myocardial and coronary arterial effects of intracoronary supersaturated oxygen therapy in swine with normal and ischemic-reperfused myocardium

The study assessed chronic myocardial, coronary and systemic effects of intracoronary supersaturated oxygen (SSO2) therapy. Left anterior descending coronary arteries of 40 swine were stented and randomized to 90-min selective intracoronary infusion of SSO2 (pO2 760–1000 mmHg) or normoxemic saline. In 20 out of 40 animals, SSO2 delivery followed a 60-min balloon occlusion to induce myocardial infarction (MI). In both normal and MI models, intracoronary treatment with hyperoxemic SSO2 therapy showed no evidence of coronary thrombosis. There were no biologically relevant differences between treatments at either time point in regard to coronary intervention site healing and neointimal growth. No signs of any myocardial or systemic toxicity were observed after 7 or 30 days. A trend was observed toward reduced incidence of microscopic MI scars and reduced infarct size in histopathology, as well as toward better recovery of echocardiographically evaluated global and regional contractility at 30 days. No treatment related infarcts or thromboemboli were observed in the downstream organs.

Tissue Preparation Techniques for Contrast-Enhanced Micro Computed Tomography Imaging of Large Mammalian Cardiac Models with Chronic Disease.

Structural remodeling is a common consequence of chronic pathological stresses imposed on the heart. Understanding the architectural and compositional properties of diseased tissue is critical to determine their interactions with arrhythmic behavior. Microscale tissue remodeling, below the clinical resolution, is emerging as an important source of lethal arrhythmia, with high prevalence in young adults. Challenges remain in obtaining high imaging contrast at sufficient microscale resolution for preclinical models, such as large mammalian whole hearts. Moreover, tissue composition-selective contrast enhancement for three-dimensional high-resolution imaging is still lacking. Non-destructive imaging using micro-computed tomography shows promise for high-resolution imaging. The objective was to alleviate sufferance from X-ray over attenuation in large biological samples. Hearts were extracted from healthy pigs (N = 2), and sheep (N = 2) with either induced chronic myocardial infarction and fibrotic scar formation or induced chronic atrial fibrillation. Excised hearts were perfused with: a saline solution supplemented with a calcium ion quenching agent and a vasodilator, ethanol in serial dehydration, and hexamethyldisilizane under vacuum. The latter reinforced the heart structure during air-drying for 1 week. Collagen-dominant tissue was selectively bound by an X-ray contrast-enhancing agent, phosphomolybdic acid. Tissue conformation was stable in air, permitting long-duration microcomputed tomography acquisitions to obtain high-resolution (isotropic 20.7 µm) images. Optimal contrast agent loading by diffusion showed selective contrast enhancement of the epithelial layer and sub-endocardial Purkinje fibers in healthy pig ventricles. Atrial fibrillation (AF) hearts showed enhanced contrast accumulation in the posterior walls and appendages of the atria, attributed to greater collagen content. Myocardial infarction hearts showed increased contrast selectively in regions of cardiac fibrosis, which enabled the identification of interweaving surviving myocardial muscle fibers. Contrast-enhanced air-dried tissue preparations enabled microscale imaging of the intact large mammalian heart and selective contrast enhancement of underlying disease constituents.

Tissue Preparation Techniques for Contrast-Enhanced Micro Computed Tomography Imaging of Large Mammalian Cardiac Models with Chronic Disease

Structural remodeling is a common consequence of chronic pathological stresses imposed on the heart. Understanding the architectural and compositional properties of diseased tissue is critical to determine their interactions with arrhythmic behavior. Microscale tissue remodeling, below the clinical resolution, is emerging as an important source of lethal arrhythmia, with high prevalence in young adults. Challenges remain in obtaining high imaging contrast at sufficient microscale resolution for preclinical models, such as large mammalian whole hearts. Moreover, tissue composition-selective contrast enhancement for three-dimensional high-resolution imaging is still lacking. Non-destructive imaging using micro-computed tomography shows promise for high-resolution imaging. The objective was to alleviate sufferance from X-ray over attenuation in large biological samples. Hearts were extracted from healthy pigs (N = 2), and sheep (N = 2) with either induced chronic myocardial infarction and fibrotic scar formation or induced chronic atrial fibrillation. Excised hearts were perfused with: a saline solution supplemented with a calcium ion quenching agent and a vasodilator, ethanol in serial dehydration, and hexamethyldisilizane under vacuum. The latter reinforced the heart structure during air-drying for 1 week. Collagen-dominant tissue was selectively bound by an X-ray contrast-enhancing agent, phosphomolybdic acid. Tissue conformation was stable in air, permitting long-duration microcomputed tomography acquisitions to obtain high-resolution (isotropic 20.7 µm) images. Optimal contrast agent loading by diffusion showed selective contrast enhancement of the epithelial layer and sub-endocardial Purkinje fibers in healthy pig ventricles. Atrial fibrillation (AF) hearts showed enhanced contrast accumulation in the posterior walls and appendages of the atria, attributed to greater collagen content. Myocardial infarction hearts showed increased contrast selectively in regions of cardiac fibrosis, which enabled the identification of interweaving surviving myocardial muscle fibers. Contrast-enhanced air-dried tissue preparations enabled microscale imaging of the intact large mammalian heart and selective contrast enhancement of underlying disease constituents.

Serum collected from rats with myocardial infarction increases extracellular matrix accumulation by myofibroblasts isolated from myocardial infarction scar

Abstract The effect on extracellular matrix content is believed to be an average of several serum derived compounds acting in opposition. The aim of the study is to determine whether whole serum of rats with myocardial infarction may modify the accumulation of extracellular matrix in cultures of myofibroblasts isolated from the myocardial infarction scar. A second aim is to determine whether the tested serum can also degranulate the mast cells. Serum was collected from rats with sham myocardial infarction, rats with myocardial infarction induced by coronary artery ligation and control animals. The experiments were carried out on myocardial infarction scar myofibroblasts or mast cells from the peritoneal cavity. The cultures were divided into three groups containing eight cultures each: one treated with serum from control rats, from animals after sham operation or from those after myocardial infarction. In all groups, the serum was used at concentrations of 10%, 20% or 30%. The total collagen content (Woesner method) glycosaminoglycan level (Farandale method), cell proliferation (BrdU), histamine secretion from mast cells (spectrofluorymetry), β1 integrin and α-smooth muscle actin expression (flow cytometry) were evaluated. Isolated cells were α-smooth muscle actin positive and identified as myofibroblasts. Serum derived from rats with myocardial infarction increased collagen and glycosaminoglycan content in the cultures and modified myofibroblast proliferation in a concentration-dependent manner. The serum also results in an imbalance between collagen and glycosaminoglycan levels. The content of β1 integrin was not influenced by myocardial infarction serum. The serum of rats with myocardial infarction is involved in regulation of collagen and glycosaminoglycan content in myofibroblast cultures, as well as the modification of their proliferation. These changes were not accompanied with integrin β1 density variations. The serum of the myocardial infarction rats did not influence the mast cell degranulation.

Myocardial Perfusion Imaging After Severe COVID-19 Infection Demonstrates Regional Ischemia Rather Than Global Blood Flow Reduction.

Background: Acute myocardial damage is common in severe COVID-19. Post-mortem studies have implicated microvascular thrombosis, with cardiovascular magnetic resonance (CMR) demonstrating a high prevalence of myocardial infarction and myocarditis-like scar. The microcirculatory sequelae are incompletely characterized. Perfusion CMR can quantify the stress myocardial blood flow (MBF) and identify its association with infarction and myocarditis.Objectives: To determine the impact of the severe hospitalized COVID-19 on global and regional myocardial perfusion in recovered patients.Methods: A case-control study of previously hospitalized, troponin-positive COVID-19 patients was undertaken. The results were compared with a propensity-matched, pre-COVID chest pain cohort (referred for clinical CMR; angiography subsequently demonstrating unobstructed coronary arteries) and 27 healthy volunteers (HV). The analysis used visual assessment for the regional perfusion defects and AI-based segmentation to derive the global and regional stress and rest MBF.Results: Ninety recovered post-COVID patients {median age 64 [interquartile range (IQR) 54–71] years, 83% male, 44% requiring the intensive care unit (ICU)} underwent adenosine-stress perfusion CMR at a median of 61 (IQR 29–146) days post-discharge. The mean left ventricular ejection fraction (LVEF) was 67 ± 10%; 10 (11%) with impaired LVEF. Fifty patients (56%) had late gadolinium enhancement (LGE); 15 (17%) had infarct-pattern, 31 (34%) had non-ischemic, and 4 (4.4%) had mixed pattern LGE. Thirty-two patients (36%) had adenosine-induced regional perfusion defects, 26 out of 32 with at least one segment without prior infarction. The global stress MBF in post-COVID patients was similar to the age-, sex- and co-morbidities of the matched controls (2.53 ± 0.77 vs. 2.52 ± 0.79 ml/g/min, p = 0.10), though lower than HV (3.00 ± 0.76 ml/g/min, p< 0.01).Conclusions: After severe hospitalized COVID-19 infection, patients who attended clinical ischemia testing had little evidence of significant microvascular disease at 2 months post-discharge. The high prevalence of regional inducible ischemia and/or infarction (nearly 40%) may suggest that occult coronary disease is an important putative mechanism for troponin elevation in this cohort. This should be considered hypothesis-generating for future studies which combine ischemia and anatomical assessment.

Myocardial ischemia and previous infarction contribute to left ventricular dyssynchrony in patients with coronary artery disease

AimsThe aim of this study was to characterize determinants of left ventricular mechanical dyssynchrony (LVMD) in patients with coronary artery disease (CAD). MethodsMedical records and results of myocardial perfusion SPECT/CT studies were evaluated in 326 patients with previously diagnosed CAD. LVMD was assessed with the phase analysis of ECG-gated myocardial SPECT. Dyssynchrony was described with phase histogram bandwidth (PHBW), standard deviation (PHSD) or entropy (PHE) values above limit of the highest normal. ResultsPrevalence of LVMD was 29% in CAD patients. Size of the infarction scar and ischemia extent correlated significantly with PHBW, PHSD and PHE (P < 0.001 for all). Independent predictors of LVMD were myocardial infarction scar (P = 0.004), ischemia extent (P = 0.003), and QRS duration (P = 0.003). Previous percutaneous coronary intervention and coronary artery bypass grafting did not independently predict dyssynchrony. ConclusionsAlmost one-third of CAD patients had significant LVMD. Dyssynchrony was associated with earlier myocardial infarction and presence of myocardial ischemia. Previous percutaneous coronary intervention and coronary artery bypass grafting did not independently predict dyssynchrony.

Determining anatomical and electrophysiological detail requirements for computational ventricular models of porcine myocardial infarction

BackgroundComputational models of the heart built from cardiac MRI and electrophysiology (EP) data have shown promise for predicting the risk of and ablation targets for myocardial infarction (MI) related ventricular tachycardia (VT), as well as to predict paced activation sequences in heart failure patients. However, most recent studies have relied on low resolution imaging data and little or no EP personalisation, which may affect the accuracy of model-based predictions. ObjectiveTo investigate the impact of model anatomy, MI scar morphology, and EP personalisation strategies on paced activation sequences and VT inducibility to determine the level of detail required to make accurate model-based predictions. MethodsImaging and EP data were acquired from a cohort of six pigs with experimentally induced MI. Computational models of ventricular anatomy, incorporating MI scar, were constructed including bi-ventricular or left ventricular (LV) only anatomy, and MI scar morphology with varying detail. Tissue conductivities and action potential duration (APD) were fitted to 12-lead ECG data using the QRS duration and the QT interval, respectively, in addition to corresponding literature parameters. Paced activation sequences and VT induction were simulated. Simulated paced activation and VT inducibility were compared between models and against experimental data. ResultsSimulations predict that the level of model anatomical detail has little effect on simulated paced activation, with all model predictions comparing closely with invasive EP measurements. However, detailed scar morphology from high-resolution images, bi-ventricular anatomy, and personalized tissue conductivities are required to predict experimental VT outcome. ConclusionThis study provides clear guidance for model generation based on clinical data. While a representing high level of anatomical and scar detail will require high-resolution image acquisition, EP personalisation based on 12-lead ECG can be readily incorporated into modelling pipelines, as such data is widely available.

Impact of myocardial scars on left ventricular deformation in type 2 diabetes mellitus after myocardial infarction by contrast-enhanced cardiac magnetic resonance

BackgroundType 2 diabetes mellitus (T2DM) is a major risk factor for coronary artery disease and myocardial infarction (MI). The interaction of diabetic cardiomyopathy and MI scars on myocardial deformation in T2DM patients is unclear. Therefore, we aimed to evaluate myocardial deformation using cardiac magnetic resonance (CMR) in T2DM patients with previous MI and investigated the influence of myocardial scar on left ventricular (LV) deformation.MethodsOverall, 202 T2DM patients, including 46 with MI (T2DM(MI+)) and 156 without MI (T2DM(MI−)), and 59 normal controls who underwent CMR scans were included. Myocardial scars were assessed by late gadolinium enhancement. LV function and deformation, including LV global function index, LV global peak strain (PS), peak systolic strain rate (PSSR), and peak diastolic strain rate (PDSR), were compared among these groups. Correlation and multivariate linear regression analyses were used to investigate the relationship between myocardial scars and LV deformation.ResultsDecreases were observed in LV function and LV global PS, PSSR, and PDSR in the T2DM(MI+) group compared with those of the other groups. Reduced LV deformation (p < 0.017) was observed in the T2DM(MI+) group with anterior wall infarction. The increased total LV infarct extent and infarct mass of LV were related to decreased LV global PS (radial, circumferential, and longitudinal directions; p < 0.01) and LV global PSSR (radial and circumferential directions, p < 0.02). Multivariate analysis demonstrated that NYHA functional class and total LV infarct extent were independently associated with LV global radial PS (β = − 0.400 and β = − 0.446, respectively, all p < 0.01; model R2 = 0.37) and circumferential PS (β = 0.339 and β = 0.530, respectively, all p < 0.01; model R2 = 0.41), LV anterior wall infarction was independently associated with LV global longitudinal PS (β = 0.398, p = 0.006).ConclusionsThe myocardial scarring size in T2DM patients after MI is negatively correlated with LV global PS and PSSR, particularly in the circumferential direction. Additionally, different MI regions have different effects on the reduction of LV deformation, and relevant clinical evaluations should be strengthened.

Prognostic Value of Vasodilator Stress Perfusion Cardiovascular Magnetic Resonance in Patients With Prior Myocardial Infarction

ObjectivesThis study sought to assess the incremental prognostic value of vasodilator stress cardiovascular magnetic resonance (CMR) in patients with prior myocardial infarction (MI). BackgroundRecurrent MI is a major cause of mortality and morbidity among MI survivors. MethodsBetween 2008 and 2019, consecutive patients with prior MI referred for stress CMR were followed up for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular mortality or recurrent nonfatal MI. Uni- and multivariable Cox regressions were performed to determine the prognostic value of inducible ischemia and the extent of myocardial scar. ResultsAmong 1,594 patients with prior MI and myocardial scar on CMR, 1,401 (92%) (68.2 ± 11.0 years; 61.4% men) completed the follow-up (median: 6.2 years), and 205 had MACE (14.6%). Patients without inducible ischemia experienced a lower annual rate of MACE (3.1%) than those with 1–2 (4.9%), 3–5 (21.5%), or ≥6 segments of ischemia (45.7%) (all p < 0.01). Using Kaplan-Meier analysis, the presence of inducible ischemia and the extent of scar were associated with MACE (hazard ratio [HR]:3.52; 95% confidence interval [CI]: 2.67 to 4.65 and HR: 1.66; 95% CI: 1.53 to 2.18, respectively; both p < 0.001). In multivariable stepwise Cox regression, the presence of ischemia and the extent of scar were independent predictors of MACE (HR: 2.84; 95% CI: 2.14 to 3.78 and HR: 1.57; 95% CI: 1.44 to 1.72, respectively; both p < 0.001). These findings were significant in both symptomatic and asymptomatic patients. The addition of CMR parameters to the model including traditional risk factors resulted in a better discrimination for MACE (C-statistic: 0.76 vs. 0.62). ConclusionsIn patients with prior MI, vasodilator stress CMR has independent and incremental prognostic value over traditional risk factors.

Cardiac Magnetic Resonance as a diagnostic tool in arrhythmias

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Etiology of cardiac arrhythmias is often difficult to determine.As the gold standard to anatomical and functional cardiac evaluation,Cardiac Magnetic Resonance(CMR)can be a fundamental technique for accurate assessment of myocardial arrhythmic substrates or for arrhythmias management. Purpose The aim of this study is to determine diagnostic and arrhythmic risk stratification impact of CMR performed in patients with suspected or confirmed arrhythmias. Methods We performed a six-years prospective study of patients with suspected or confirmed arrhythmias which evaluation with other techniques did not provide a definitive diagnosis.These patients underwent CMR for diagnostic and risk stratification assessment.We applied a protocol to evaluate both ventricles’ morphology and functional and late gadolinium enhancement (LGE) presence. Results A total of 93 patients were included,of which 66% were male, with a mean age of 45 ± 17 years old. The indications for patients with suspected or confirmed arrhythmias performing CMR evaluation were the following: 33% (n = 31) of the patients had very frequent premature ventricular complexes, 23% (n = 21) had sustained ventricular tachycardia (VT), 5%(n = 5) non-sustained VT, 17%(n = 16) suspected structural heart disease with high arrhythmic potential,10%(n = 9) unexplained recurrent syncope,9 %(n = 8) supraventricular tachycardia and 3% (n = 3) aborted sudden cardiac death. Depressed ejection fraction (EF)(&amp;lt;50%) was present in 10% (n = 9) for LV(mean EF 38 ± 9%) and 15%(n = 14) for RV (mean EF 42 ± 7%). Dilation of LV was found in 25% of patients (n = 23, mean LV volume: 115 ± 7ml/m²), with RV dilation being present in only 1 patient, who had right ventricle arrhythmogenic dysplasia (RVAD) (RV volume: 152ml/m²). In total, 16%had interventricular septum hypertrophy (mean 15 ± 4mm/m2).We found slight anterior leaflet prolapse of mitral valve in 10% (n = 9) of the cases and mild mitral regurgitation in 15% (n = 14). Left atrium dilation was observed in 17% (n = 16) of patients (mean area of 18 ± 2cm2/m2), as right atrium was dilated in only two. In 20% of the patients, CMR contributed to establish a previously unknown diagnosis: 6% (n = 5) have hypertrophic cardiomyopathy,4%(n = 4)a myocarditis sequelae and 2%(n = 2)had RVAD. LV non-compaction,a silent myocardial infarction scar and non-ischemic dilated cardiomyopathy were diagnosed in 3%of the cases each. In 15%(n = 14)we found nonspecific variations, which deserve follow-up. On the remaining patients, CMR was considered normal. Conclusion As a high reproducible, accurate and versatile technique, CMR allowed an increase on diagnosis in 20% of the patients with suspected or confirmed arrhythmias. Consequently, it contributed to the risk stratification of our study population with suspected high arrhythmic potential when the first-line complementary exams were inconclusive.

Large- and Medium-sized Arteries Remaining in Transmural Scar Distal to Permanent Coronary Ligation Undergo Neointimal Hyperplasia and Inward Remodeling.

This study aimed to investigate the structural integrity and dynamic changes in chronically occluded residual arteries found in post-myocardial infarction (MI) scar. A transmural MI was induced in middle-aged, male Sprague-Dawley rats by left coronary artery ligation. The rats were euthanized 3 days and 1, 2, 4, 8, and 12 weeks after MI, and their hearts were processed into paraffin for histology, immunohistochemistry, and quantitative morphometry. It has been found that large- and medium-sized arteries were able to survive inside the transmural scars for 12 post-MI weeks. Furthermore, most residual arteries preserved their structural integrity for up to 2 weeks post-MI, but gradually all disused vessels had undergone neointimal hyperplasia and inward remodeling at later time periods. In addition, the replacement of vascular smooth muscle cells in the wall of residual arteries by extracellular matrix components led to a disruption of the vessel integrity and progressive obliteration of their lumen between 4 and 12 post-MI weeks. Taken together, this study demonstrate that residual arteries in post-infarcted region were capable of maintaining their structural integrity, including the patent lumen, during two post-MI weeks, suggesting that during this period they can be used as potential conduits for conceivable reflow of arterial blood within the scarred region of the heart.

Estimating cardiac active tension from wall motion-An inverse problem of cardiac biomechanics.

The contraction of the human heart is a complex process as a consequence of the interaction of internal and external forces. In current clinical routine, the resulting deformation can be imaged during an entire heart beat. However, the active tension development cannot be measured in vivo but may provide valuable diagnostic information. In this work, we present a novel numerical method for solving an inverse problem of cardiac biomechanics-estimating the dynamic active tension field, provided the motion of the myocardial wall is known. This ill-posed non-linear problem is solved using second order Tikhonov regularization in space and time. We conducted a sensitivity analysis by varying the fiber orientation in the range of measurement accuracy. To achieve RMSE <20% of the maximal tension, the fiber orientation needs to be provided with an accuracy of 10°. Also, variation was added to the deformation data in the range of segmentation accuracy. Here, imposing temporal regularization led to an eightfold decrease in the error down to 12%. Furthermore, non-contracting regions representing myocardial infarct scars were introduced in the left ventricle and could be identified accurately in the inverse solution (sensitivity >0.95). The results obtained with non-matching input data are promising and indicate directions for further improvement of the method. In future, this method will be extended to estimate the active tension field based on motion data from clinical images, which could provide important insights in terms of a new diagnostic tool for the identification and treatment of diseased heart tissue.