Myocardial Scar Research Articles

Endogenous Sex Hormone Levels and Myocardial Fibrosis in Men and Postmenopausal Women

BackgroundSex hormone (SH) imbalances have been linked to a higher risk of heart failure in both sexes. However, mechanisms that underlie this relationship remain unclear. We examined the association of baseline SH with interstitial and replacement myocardial fibrosis in the MESA (Multi-Ethnic Study of Atherosclerosis) using cardiac magnetic resonance (CMR) T1 mapping and late gadolinium enhancement (LGE). ObjectivesThe purpose of this study was to assess the link between baseline sex hormone levels and myocardial fibrosis in the MESA cohort using CMR. MethodsA total of 2,324 participants (men and postmenopausal women [PMW]) were included in the MESA with SH measured at baseline and had underwent CMR 10 years later. All analyses were stratified by sex and age. Regression models were constructed to assess the associations of baseline SH with extracellular volume (ECV)% and native T1 time and with LGE. Higher native T1 time and ECV% are interpreted as evidence of increasing interstitial myocardial fibrosis (IMF). Given the limited number of myocardial scars present in PMW, analysis of LGE was limited to men. ResultsAmong older men (age ≥65 years), a 1-SD increment higher free testosterone was significantly associated with 2.45% lower ECV% and 21.5% lower native T1 time, while a 1-SD increment higher bioavailable testosterone was associated with 12.5% lower native T1 time. A 1-SD increment greater sex hormone-binding globulin level was associated with 1% higher ECV%. Among PMW of 55 to 64 years, a 1-SD increment higher total testosterone was associated with 9.5% lower native T1 time. Higher levels of estradiol in older men were independently associated with higher odds of having a myocardial scar (OR: 4.10; 95% CI: 1.35-12.40; P = 0.01). ConclusionsAmong older men, SH imbalances at initial evaluation were independently associated with CMR defined IMF and replacement fibrosis, respectively; while increasing total testosterone in middle-aged PMW was associated with lesser marker of IMF.

PO-03-107 MYOCARDIAL SCAR CHARACTERISTICS BY 3D-LGE CANNOT FULLY EXPLAIN DIFFERENT ARRHYTHMIC EVENT RATES IN PRIMARY AND SECONDARY PREVENTION OF SUDDEN CARDIAC DEATH

There is a noticeable difference in the incidence of ventricular arrythmias among patients receiving defibrillator devices (ICD or CRT-D) for primary vs. secondary prevention of sudden cardiac death (SCD). The underlying reasons for this difference remain to be fully explained. To assess for differences in myocardial scar characteristics between patients who had defibrillator devices implanted in primary vs. secondary prevention scenarios, and their correlation with arrhythmic events. In this single center retrospective study, patients who underwent late gadolinium enhancement (LGE) cardiac MRI for clinical purposes before the implantation of an ICD or CRT-D were included. Patients with channelopathies (n=2) or inappropriate imaging quality (n=7) were excluded. We used ADAS software to perform myocardial scar characterization in 3D-LGE datasets in all but 16 patients, in which 2D datasets were used. The primary endpoint was a composite of appropriate ICD therapy (appropriate shock or ATP), sustained ventricular tachycardia or SCD. A total of 116 patients (mean age 66±14 years, 81% male) were included, 40 (35%) with devices implanted in secondary prevention. During a median follow-up of 28 months (IQR 16-24), 23 events were identified (18 appropriate ICD therapy, 9 shocks and 9 ATP; 2 SCD; 3 sustained VT), 7 of which (30.4%) in the primary prevention group, and 16 (69.6%) in the secondary prevention group. The event rate was significantly higher in the secondary prevention setting (15.0 events per 100 persons-year [95% CI 7.7 – 22.4] vs. 4.1 events per 100 persons-year [95% CI 1.1 – 7.1]; p < 0.001). Despite a higher LVEF in the secondary prevention group (41 ± 14% vs. 30 ± 13%; p-value < 0.001), no statistically significant differences were found regarding scar tissue characteristics, namely scar and borderzone (BZ) mass, total channel mass, largest channel mass, number of channels and scar heterogeneity (BZ mass / scar mass ratio) – Table. Despite the higher event rate in patients receiving defibrillator devices in secondary vs. prevention, no differences in myocardial scar characteristics were found between both groups. These findings suggest that arrhythmic risk is unlikely to be explained solely by the anatomical substrate, and support a greater role for the interplay between substrate and transient triggers.Tabled 1Primary PreventionSecondary Preventionp-valueScar + BZ mass (g)26.2 (IQR 13.3 - 35.0)23.7 (IQR 11.4 - 33.4)p = 0.322Scar + BZ percentage (%)18.0 (IQR 11.0 – 27.0)17.0 (IQR 9.0 - 26.0)p = 0.545BZ mass (g)17.7 (IQR 11.1 - 24.2)14.8 (IQR 8.8 - 22.0)p = 0.350BZ percentage (%)13.0 (IQR 8.0 - 18.0)11.0 (IQR 6.0 - 17.0)p = 0.677Scar mass (g)6.6 (IQR 3.4 - 11.0)6.9 (IQR 2.0 - 10.3)p = 0.693Scar percentage (%)4.0 (IQR 2.0 - 9.0)5.0 (IQR 1.0 - 8.0)p = 0.695Scar heterogeneity2.4 (IQR 1.7 - 3.9)2.7 (IQR 1.5 - 4.4)p = 0.797Total channels mass (g)3.0 (IQR 0.7 - 4.9)1.8 (IQR 0.0 - 5.0)p = 0.215Biggest channel mass (g)1.4 (IQR 0.5 - 2.5)0.8 (IQR 0.0 - 3.0)p = 0.163Number of channels3.0 (IQR 1.0 - 5.0)3.0 (IQR 0.0 - 5.0)p = 0.520BZ, Borderzone Open table in a new tab

PO-01-084 HIDING IN PLAIN SIGHT

Substrate based scar modification requires accurate detection and characterization of myocardial scar in sinus rhythm or using different wavefronts of activation. Mapping during ventricular tachycardia can be performed only in about 30% to 40% cases. We describe a challenging case of scar VT with discrepancy in the delineation of scar between voltage mapping and cardiac MRI and the role of Decremental Evoked Potential Mapping as a guide to a more focussed ablation in such circumstances. N/A N/A 56 year diabetic female status post Coronary artery bypass grafting in 2016 and moderate left ventricular dysfunction with recurrent episodes of hemodynamically unstable ventricular tachycardia and patient's refusal for ICD was evaluated and cardiac MRI revealed subendocardial scar in the anterior wall and patent grafts on coronary angiogram. Patient was taken up for 3D mapping and ablation using 3.5 mm tip non force sensing unidirectional irrigation ablation catheter.In view of hemodynamically unstable VT, activation mapping was not possible, hence substrate mapping was planned. Endocardial bipolar voltage mapping didnot delineate any scar in sinus rhythm and after changing the wavefront of activation to right ventricular paced rhythm. Unipolar voltage map didnot show any scar. While mapping the anterior wall , abnormal local electrograms were seen superimposed into the far field electrograms. To do a foccussed ablation we applied the concept of Decremental Evoked Potential Mapping and identified the slow conduction zone - the most critical component of the scar for initiation and maintainence of re-entry. We identified and ablated only the points with abnormal local electrograms with absolute value of decrement more than 10 ms as part of slow conduction zone. Post ablation, VT was not inducible despite induction protocol using triple extrastimuli from two different sites. Activation mapping is not possible in hemodynamically unstable VT. Substrate based mapping needs accurate delineation of myocardial scar. As the 3D mapping system is an automated system and annotates only the largest amplitude signals for color coded voltage mapping, in cases without dense scar, voltage mapping doesnot reliably identify and delineate the scar when compared to cardiac MRI, particularly with a larger tip diameter ablation catheter. Novel mapping techniques like Decremental Evoked Potential Mapping enable limited ablation in such cases.

PO-05-148 VENTRICULAR DYSFUNCTION IN SARCOIDOSIS CARDIOMYOPATHY: INFLAMMATION IS NOT ALWAYS THE ONE TO BLAME

Clinical presentation A 63-year-old female was admitted after repeated syncopal events. She had a previous history of type 1 diabetes and hypertension. ECG on admission showed sinus rhythm with prolonged PR interval (320ms) and normal QRS duration. Imaging work up Coronary angiography revealed patent arteries. Echocardiography showed regional wall motion abnormalities but preserved left ventricular ejection fraction (LVEF). Cardiac magnetic resonance displayed patchy contrast retention following a non-coronary distribution. Whole-body positron emission tomography showed intense, multifocal tracer uptake in the myocardium and in the thoracic lymph nodes, in a pattern consisting with sarcoidosis. Diagnosis and Initial Treatment A clinical diagnosis of cardiac sarcoidosis (CS) was made. Following the implantation of a biventricular defibrillator, she was discharged from the hospital, and systemic immunosuppression with 30 mg prednisone daily was initiated. Follow-up Six months after diagnosis, interval PET showed reduction in the degree of myocardial inflammation, and no major change in the extent of myocardial scarring as based on myocardial perfusion (Table 1). Nevertheless, LVEF had dropped from 53% to 36%. Device interrogation revealed a high burden of PVCs. PVC-mediated cardiomyopathy was suspected, and amiodarone was initiated. Also because of uncertainty for the precipitous decline of LVEF and concern that it was multifactorial, additional immunosuppression with infliximab was instituted. After four months with amiodarone (but only one dose of infliximab), the PVC burden was reduced to 1%, biventricular pacing improved to target, and LVEF was restored to normal. These outcomes are maintained two years on. Interpretation

MR guided cardiac ablation: how to build an interventional magnetic resonance suite and what's the role of the imaging.

Magnetic resonance (MR) represents a new interesting imaging approach for guiding electrophysiology (EP)-based ablation procedures of atrial flutter and typical atrial fibrillation. This new approach permits to reach good results if compared with conventional EP ablation. Tissue characterization by MR permits to detect cardiac anatomy and pathological substrate like myocardial scars well visualized with late gadolinium enhancement (LGE) sequences. Intra-procedural imaging is useful to real-time follow the catheter during the ablation procedure and at the same time to visualize cardiac anatomy in addition to understanding if the ablation is correctly performed using oedema sequences. Performing cardiac ablations inside an MR room permits to reduce radiation exposure and occupational illnesses.

Scarring/arrhythmogenic cardiomyopathy.

The designation of 'arrhythmogenic cardiomyopathy' reflects the evolving concept of a heart muscle disease affecting not only the right ventricle (ARVC) but also the left ventricle (LV), with phenotypic variants characterized by a biventricular (BIV) or predominant LV involvement (ALVC). Herein, we use the term 'scarring/arrhythmogenic cardiomyopathy (S/ACM)' to emphasize that the disease phenotype is distinctively characterized by loss of ventricular myocardium due to myocyte death with subsequent fibrous or fibro-fatty scar tissue replacement. The myocardial scarring predisposes to potentially lethal ventricular arrhythmias and underlies the impairment of systolic ventricular function. S/ACM is an 'umbrella term' which includes a variety of conditions, either genetic or acquired (mostly post-inflammatory), sharing the typical 'scarring' phenotypic features of the disease. Differential diagnoses include 'non-scarring' heart diseases leading to either RV dilatation from left-to-right shunt or LV dilatation/dysfunction from a dilated cardiomyopathy. The development of 2020 upgraded criteria ('Padua criteria') for diagnosis of S/ACM reflected the evolving clinical experience with the expanding spectrum of S/ACM phenotypes and the advances in cardiac magnetic resonance (CMR) imaging. The Padua criteria aimed to improve the diagnosis of S/ACM by incorporation of CMR myocardial tissue characterization findings. Risk stratification of S/ACM patients is mostly based on arrhythmic burden and ventricular dysfunction severity, although other ECG or imaging parameters may have a role. Medical therapy is crucial for treatment of ventricular arrhythmias and heart failure. Implantable cardioverter defibrillator (ICD) is the only proven life-saving treatment, despite its significant morbidity because of device-related complications and inappropriate shocks. Selection of patients who can benefit the most from ICD therapy is one of the most challenging issues in clinical practice.

JOINT DEEP LEARNING FOR IMPROVED MYOCARDIAL SCAR DETECTION FROM CARDIAC MRI.

Automated identification of myocardial scar from late gadolinium enhancement cardiac magnetic resonance images (LGE-CMR) is limited by image noise and artifacts such as those related to motion and partial volume effect. This paper presents a novel joint deep learning (JDL) framework that improves such tasks by utilizing simultaneously learned myocardium segmentations to eliminate negative effects from non-region-of-interest areas. In contrast to previous approaches treating scar detection and myocardium segmentation as separate or parallel tasks, our proposed method introduces a message passing module where the information of myocardium segmentation is directly passed to guide scar detectors. This newly designed network will efficiently exploit joint information from the two related tasks and use all available sources of myocardium segmentation to benefit scar identification. We demonstrate the effectiveness of JDL on LGE-CMR images for automated left ventricular (LV) scar detection, with great potential to improve risk prediction in patients with both ischemic and non-ischemic heart disease and to improve response rates to cardiac resynchronization therapy (CRT) for heart failure patients. Experimental results show that our proposed approach outperforms multiple state-of-the-art methods, including commonly used two-step segmentation-classification networks, and multitask learning schemes where subtasks are indirectly interacted.

Myocardial Scar Detection Using High-Resolution Free-Breathing 3D Dark-Blood and Standard Breath-Holding 2D Bright-Blood Late Gadolinium Enhancement MRI: A Comparison of Observer Confidence.

To compare observer confidence for myocardial scar detection using 3 different late gadolinium enhancement (LGE) data sets by 2 observers with different levels of experience. Forty-one consecutive patients, who were referred for 3D dark-blood LGE MRI before implantable cardioverter-defibrillator implantation or ablation therapy and who underwent 2D bright-blood LGE MRI within a time frame of 3 months, were prospectively included. From all 3D dark-blood LGE data sets, a stack of 2D short-axis slices was reconstructed. All acquired LGE data sets were anonymized and randomized and evaluated by 2 independent observers with different levels of experience in cardiovascular imaging (beginner and expert). Confidence in detection of ischemic scar, nonischemic scar, papillary muscle scar, and right ventricular scar for each LGE data set was scored using a using a 3-point Likert scale (1 = low, 2 = medium, or 3 = high). Observer confidence scores were compared using the Friedman omnibus test and Wilcoxon signed-rank post hoc test. For the beginner observer, a significant difference in confidence regarding ischemic scar detection was observed in favor of reconstructed 2D dark-blood LGE compared with standard 2D bright-blood LGE (p = 0.030) while for the expert observer, no significant difference was found (p = 0.166). Similarly, for right ventricular scar detection, a significant difference in confidence was observed in favor of reconstructed 2D dark-blood LGE compared with standard 2D bright-blood LGE (p = 0.006) while for the expert observer, no significant difference was found (p = 0.662). Although not significantly different for other areas of interest, 3D dark-blood LGE and its derived 2D dark-blood LGE data set showed a tendency to score higher for all areas of interest at both experience levels. The combination of dark-blood LGE contrast and high isotropic voxels may contribute to increased observer confidence in myocardial scar detection, independent of observer's experience level but in particular for beginner observers.

Cardiac rupture during acute myocardial infarction : Autopsy study (2004–2020)

IntroductionCardiac rupture is a rare but critical complication of myocardial infarction with an incidence of 1 to 3% of cases. We aimed in this autopsy study to analyze the anatomical, epidemiological, cardiac, and coronary profiles of cardiac rupture in the Monastir region. MethodsWe conducted a descriptive study with retrospective data collection of all cases of myocardial infarction complicated by a cardiac rupture over seventeen years (2004–2020). ResultsThirty-one cases were included in this study. The mean age of the cases was 67 years with a male predominance. Sixteen cases (57%) had cardiovascular risk factors. The most common symptomatology reported before death was acute chest pain in 57% of cases. Fourteen cases (45%) corresponded to the definition of sudden cardiac death. At autopsy, the heart had a mean weight of 452.78 grams. A large hemopericardium was associated in 90% of cases. Myocardial rupture involved the posterior wall of the left ventricle in 50% of cases. The myocardial rupture occurred at a site of acute myocardial infarction in 86% of cases and on a myocardial scar in 14% of cases. The coronary study showed double or triple vessel atherosclerotic coronary artery disease in 57% of cases with fresh thrombi at the infarct-related coronary in 11% of cases. ConclusionsOur analysis found that cardiac rupture mostly involved elderly subjects with underlying cardiovascular risk factors. Our findings sustain that age is a determining prognostic factor after acute coronary syndrome with the need for further education and awareness-raising efforts to speed up access to care for these patients.

Cardiovascular Manifestations of the Long COVID Syndrome.

While most coronavirus 2019 (COVID-19) survivors have had complete resolution of symptoms, a significant proportion have suffered from incomplete recovery. Cardiopulmonary symptoms, such as dyspnea, chest pain, and palpitations are responsible for a substantial symptom burden in COVID-19 survivors. Studies have revealed persistent myocardial injury with late gadolinium enhancement and myocardial scar on cardiac magnetic resonance in a significant proportion of patients. Evidence of myocardial edema, active inflammation, left ventricular dysfunction, and right ventricular dysfunction, is limited to a minority of patients. Large observational studies of COVID-19 survivors have indicated an increased risk of cardiovascular disease compared to the general population, including the risk of coronary artery disease, cardiomyopathy, and arrhythmias. Management of long COVID is focused on supportive therapy to reduce systemic inflammation. Patients with high cardiovascular risk, namely, those who had cardiovascular complications during acute illness, patients who have new onset cardiopulmonary symptoms in the postinfectious period, and competitive athletes, should be evaluated by a cardiovascular specialist. Management of cardiovascular sequelae is currently based on general expert guideline recommendations given the lack of evidence specific to long COVID syndrome. In this review, we outline the cardiovascular manifestations of long COVID, the current evidence supporting cardiac abnormalities in the postinfectious period, and the recommended management of these patients.

Cardiac ischemia and reperfusion in mice: a comprehensive hemodynamic, electrocardiographic and electrophysiological characterization

Malignant ventricular arrhythmias (VA) after acute myocardial infarction remain a major threat. Aim of this study was to characterize the electrophysiological and autonomic sequelae of cardiac ischemia and reperfusion (I/R) in mice during the first week post incident. Left ventricular function was serially assessed using transthoracic echocardiography. VA were quantified by telemetric electrocardiogram (ECG) recordings and electrophysiological studies on the 2nd and 7th day after I/R. Cardiac autonomic function was evaluated by heart rate variability (HRV) and heart rate turbulence (HRT). Infarct size was quantified by planimetric measures. I/R caused significant myocardial scarring and diminished left ventricular ejection fraction. The ECG intervals QRS, QT, QTc, and JTc were prolonged in I/R mice. Both spontaneous VA scored higher and the inducibility of VA was raised in I/R mice. An analysis of HRV and HRT indicated a relative reduction in parasympathetic activity and disturbed baroreflex sensitivity up to 7 days after I/R. In summary, during the first week after I/R, the murine heart reflects essential features of the human heart after myocardial infarction, including a greater vulnerability for VA and a decreased parasympathetic tone accompanied by decelerated depolarization and repolarization parameters.

Allogeneic biomaterial: a fibrosis inhibitor in ischemic myocardial damage

Injectable allogeneic decellularized biomaterials are being developed both as scaffolds for delivery of cellular products and as independent pharmacological agents that affect the cascade of tissue reactions during the period of post-ischemic myocardial remodeling. Biomaterial degradation products can affect cellular processes and modulate cytokine effects, thus determining the healing strategy of damaged tissue. In this work, the influence of biomaterial on the expression of key fibrogenic factors by the cells of tissue bed was demonstrated, and the degree of damage to the myocardium during its ischemic damage was experimentally determined. The aim of our study was to determine the area of myocardial scar degeneration and detection of key fibrogenic factors (bFGF-1, TGFb1, MMP-9), as well as TIMP-2 (MMP-9 antagonist) at the acute and subacute stages of myocardial infarction after implantation of allogeneic powder-like biomaterial in an experimental model.In the course of experiments, the left ventricular coronary artery was ligated in male Wistar rats (experimental group). All animals were divided into 3 groups: experimental group I (n = 50), experimental group II (n = 50), and controls (n = 50). In experimental group I, the artery ligation was simultaneously accompanied by intramyocardial administration of powder-like biomaterial suspension (2 mg). In experimental group II, the allogeneic powder-like biomaterial was administered 5 days after coronary occlusion, and only physiological saline was administered in the control group. The animals were withdrawn from experiment on days +3, +7, +14, +30, and +45. Standard histological assessment (hematoxylin and eosin staining, according to Mallory) and immunohistochemical examination (MMP-9, TGFb1, bFGF-1, TIMP-2) were made, and statistical evaluation was performed. The cells with positive staining were counted, and the scar area index was calculated.We have found that administration of dispersed allogeneic biomaterial was followed by a five-fold decrease in the degree of scar degeneration in both experimental groups at the acute and subacute stages of ischemic myocardial damage as compared to the control group. A significantly decreased expression of fibrogenic factors (MMP-9, TGFb1, bFGF-1) by the local cells was found, along with increased activity of metalloproteinase inhibitor (TIMP-2) in connective tissue cells.Decellularized allogeneic powder-like biomaterial serves as a fibrosis inhibitor and promotes cardioprotection during myocardial remodeling at the initial stages after ischemic injury.

Prognostic Value of Left Ventricular Longitudinal Function and Myocardial Fibrosis in Patients With Ischemic and Non-Ischemic Dilated Cardiomyopathy Concomitant With Type 2 Diabetes Mellitus: A 3.0 T Cardiac MR Study.

Poorly controlled type 2 diabetes mellitus (T2DM) is known to result in left ventricular (LV) dysfunction, myocardial fibrosis, and ischemic/nonischemic dilated cardiomyopathy (ICM/NIDCM). However, less is known about the prognostic value of T2DM on LV longitudinal function and late gadolinium enhancement (LGE) assessed with cardiac MRI in ICM/NIDCM patients. To measure LV longitudinal function and myocardial scar in ICM/NIDCM patients with T2DM and to determine their prognostic values. Retrospective cohort. Two hundred thirty-five ICM/NIDCM patients (158 with T2DM and 77 without T2DM). 3T; steady-state free precession cine; phase-sensitive inversion recovery segmented gradient echo LGE sequences. Global peak longitudinal systolic strain rate (GLPSSR) was evaluated to LV longitudinal function with feature tracking. The predictive value of GLPSSR was determined with ROC curve. Glycated hemoglobin (HbA1c) was measured. The primary adverse cardiovascular endpoint was follow up every 3 months. Mann-Whitney U test or student's t-test; Intra and inter-observer variabilities; Kaplan-Meier method; Cox proportional hazards analysis (threshold = 5%). ICM/NIDCM patients with T2DM exhibited significantly lower absolute value of GLPSSR (0.39 ± 0.14 vs. 0.49 ± 0.18) and higher proportion of LGE positive (+) despite similar LV ejection fraction, compared to without T2DM. LV GLPSSR was able to predict primary endpoint (AUC 0.73) and optimal cutoff point was 0.4. ICM/NIDCM patients with T2DM (GLPSSR < 0.4) had more markedly impaired survival. Importantly, this group (GLPSSR < 0.4, HbA1c ≥ 7.8%, or LGE (+)) exhibited the worst survival. In multivariate analysis, GLPSSR, HbA1c, and LGE (+) significantly predicted primary adverse cardiovascular endpoint in overall ICM/NIDCM and ICM/NIDCM patients with T2DM. T2DM has an additive deleterious effect on LV longitudinal function and myocardial fibrosis in ICM/NIDCM patients. Combining GLPSSR, HbA1c, and LGE could be promising markers in predicting outcomes in ICM/NIDCM patients with T2DM. 3 TECHNICAL EFFICACY: 5.

Coronary CT Angiography for Coronary Artery Disease: The Current Status and Future Challenges

Coronary computed tomographic angiography, often known as CCTA, is quickly becoming the diagnostic technique of choice for determining the existence of coronary artery disease (CAD). In the future, CCTA may play an essential part as a "one-stop shop" in the screening, diagnosis, decision making, and treatment planning processes. Plaque burden, high-risk plaque, non-invasive angiography, perfusion with hyperemia, fractional flow reserve (FFR), percent of myocardium at risk, inflammation, myocardial scar, wall motion analysis, and risk scores are some of the many measures that are utilized.

9 Cardio-Omentopexy to Reduce Myocardial Scarring and Promote Regeneration

OBJECTIVES/GOALS: While the current management of single ventricle repairs has drastically prolonged life expectancy, the repair fails over time primarily through pathologic inflammation and fibrosis. Our goal is to demonstrate that cardio-omentopexy can decrease inflammation and fibrosis in swine after cryoinjury. METHODS/STUDY POPULATION: A cryoinjury is created using a liquid nitrogen cooled probe to the right ventricle of 20kg swine. In half the groups the omentum is attached to the heart over the area of the injury. The swine are recovered and monitored for 4 or 8 weeks at which time they are euthanized. The injured area is evaluated via histological and immunohistochemical testing for markers of inflammation and scarring including collagen type, scar area, macrophage activity. RESULTS/ANTICIPATED RESULTS: We anticipate that the addition of omentopexy to cryoinjury will decrease scar area, fibrosis and markers of chronic inflammation. Additionally, we expect an increase in myocytes in the area of injury. We expect that this will occur through the anti-inflammatory and protective mechanism of the omentum. DISCUSSION/SIGNIFICANCE: Cardio-omentopexy, if able to decrease fibrosis and preserve myocytes, may provide a useful adjunct to the treatment of single ventricle repair by prolonging the longevity of the repair. Additionally, as these repairs often require a ventriculotomy, decreasing the operative scar may preserve myocardial function.

QRS Fragmentation in Preserved Ejection Fraction Heart Failure: Functional Insights, Pathological Correlates, and Prognosis.

Background Fragmented QRS (fQRS) morphology as a surrogate marker of the possible presence of myocardial scarring has been shown to confer a higher risk in patients with reduced ejection fraction heart failure. We aimed to investigate the pathophysiological correlates and prognostic implications of fQRS in patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results We consecutively studied 960 patients with HFpEF (76.4±12.7 years, men: 37.2%). fQRS was assessed using a body surface ECG during hospitalization. QRS morphology was available and classified into 3 categories among 960 subjects with HFpEF as non-fQRS, inferior fQRS, and anterior/lateral fQRS groups. Despite comparable clinical features in most baseline demographics among the 3 fQRS categories, anterior/lateral fQRS showed significantly higher B-type natriuretic peptide/troponin levels (both P<0.001), with both the inferior and anterior/lateral fQRS HFpEF groups demonstrating a higher degree of unfavorable cardiac remodeling, greater extent of myocardial perfusion defect, and slower coronary flow phenomenon (all P<0.05). Patients with anterior/lateral fQRS HFpEF exhibited significantly altered cardiac structure/function and more impaired diastolic indices (all P<0.05). During a median of 657 days follow-up, the presence of anterior/lateral fQRS conferred a doubled HF re-admission risk (adjusted hazard ratio 1.90, P<0.001), with both inferior and anterior/lateral fQRS having a higher risk of cardiovascular and all-cause death (all P<0.05) by using Cox regression models. Conclusions The presence of fQRS in HFpEF was associated with more extensive myocardial perfusion defects and worsened mechanics, which possibly denotes a more severe involvement of cardiac damage. Early recognition in such patients with HFpEF likely benefits from targeted therapeutic interventions.

Adult Bone Marrow-Derived Mesenchymal Stem Cells Seeded on Tissue-Engineered Cardiac Patch Contribute to Myocardial Scar Remodeling and Enhance Revascularization in a Rabbit Model of Chronic Myocardial Infarction.

Although the transplantation of tissue-engineered cardiac patches with adult bone marrow-derived mesenchymal stem cells (MSCs) can enhance cardiac function after acute or chronic myocardial infarction (MI), the recovery mechanism remains controversial. This experiment aimed to investigate the outcome measurements of MSCs within a tissue-engineered cardiac patch in a rabbit chronic MI model. This experiment was divided into four groups: left anterior descending artery (LAD) sham-operation group (N = 7), sham-transplantation (control, N = 7), non-seeded patch group (N = 7), and MSCs-seeded patch group (N = 6). PKH26 and 5-Bromo-2'-deoxyuridine (BrdU) labeled MSCs-seeded or non-seeded patches were transplanted onto chronically infarct rabbit hearts. Cardiac function was evaluated by cardiac hemodynamics. H&E staining was performed to count the number of vessels in the infarcted area. Masson staining was used to observe cardiac fiber formation and to measure scar thickness. Four weeks after transplantation, a remarkable improvement in cardiac functionality could be distinctly observed, which was most significant in the MSCs-seeded patch group. Moreover, labeled cells were detected in the myocardial scar, with most of them differentiated into myofibroblasts, some into smooth muscle cells, and only a few into cardiomyocytes in the MSCs-seeded patch group. We also observed significant revascularization in the infarct area implanted in either MSCs-seeded or non-seeded patches. In addition, there were significantly greater numbers of microvessels in the MSCs-seeded patch group than in the non-seeded patch group.

Review on Cardiac Arrhythmias with ECG Interpretation on Different Myocardial Regions

Electrocardiogram (ECG) is one of the major diagnostics tools for Cardiac Arrhythmias (CA). ECG interpretation is more important to provide specific treatment of different arrhythmic myocardial regions. In this article the aim is to focus on detailed normal and abnormal ECG interpretation with different myocardial regions. Contraction and Relaxation Process (CRP) during cardiac cycle generates complex ECG with addition of each conduction node electrical vector activity in cardiac conduction system. Epinephrine stimulates Beta1 adrenergic receptors to produce more G stimulation proteins and thus leads to increase calcium level in the cell that provides frequent production of Action Potential (AP) like sinus tachycardia, Early Afterdepolarization (EAD) and Delayed Afterdepolarization (EAD). Myocardial scar regions, AP cannot move because of blockage, in turns moving rapidly around the dead area in a circular way to lead reentrant arrhythmias. On the other hand of respiration cycle, vagus outflow fluctuates (inspiration) the Sinus Node (SN) to increase heart rate (R-R distance will decrease, more P wave and QRS complex will be produced) and to decrease heart rate during expiration (R-R distance will be more). Finally conclude that different myocardial dysfunction regions are the major cause of multi-classified cardiac arrhythmias.

Differences in Myocardial Remodeling and Tissue Characteristics in Chronic Isolated Aortic and Mitral Regurgitation.

The left ventricular hemodynamic load differs between aortic regurgitation (AR) and primary mitral regurgitation (MR). We used cardiac magnetic resonance to compare left ventricular remodeling patterns, systemic forward stroke volume, and tissue characteristics between patients with isolated AR and isolated MR. We assessed remodeling parameters across the spectrum of regurgitant volume. Left ventricular volumes and mass were compared against normal values for age and sex. We calculated forward stroke volume (planimetered left ventricular stroke volume-regurgitant volume) and derived a cardiac magnetic resonance-based systemic cardiac index. We assessed symptom status according to remodeling patterns. We also evaluated the prevalence of myocardial scarring using late gadolinium enhancement imaging, and the extent of interstitial expansion via extracellular volume fraction. We studied 664 patients (240 AR, 424 primary MR), median age of 60.7 (49.5-69.9) years. AR led to more pronounced increases in ventricular volume and mass compared with MR across the spectrum of regurgitant volume (P<0.001). In ≥moderate regurgitation, AR patients had a higher prevalence of eccentric hypertrophy (58.3% versus 17.5% in MR; P<0.001), whereas MR patients had normal geometry (56.7%) followed by myocardial thinning with low mass/volume ratio (18.4%). The patterns of eccentric hypertrophy and myocardial thinning were more common in symptomatic AR and MR patients (P<0.001). Systemic cardiac index remained unchanged across the spectrum of AR, whereas it progressively declined with increasing MR volume. Patients with MR had a higher prevalence of myocardial scarring and higher extracellular volume with increasing regurgitant volume (P value for trend <0.001), whereas they were unchanged across the spectrum of AR (P=0.24 and 0.42, respectively). Cardiac magnetic resonance identified significant heterogeneity in remodeling patterns and tissue characteristics at matched degrees of AR and MR. Further research is needed to examine if these differences impact reverse remodeling and clinical outcomes after intervention.

Ventricular tachycardia ablation through radiation therapy (VT-ART) consortium: Concept description of an observational multicentric trial via matched pair analysis.

Monomorphic ventricular tachycardia (VT) is a life-threatening condition often observed in patients with structural heart disease. Ventricular tachycardia ablation through radiation therapy (VT-ART) for sustained monomorphic ventricular tachycardia seems promising, effective, and safe. VT-ART delivers focused, high-dose radiation, usually in a single fraction of 25 Gy, allowing ablation of VT by inducing myocardial scars. The procedure is fully non-invasive; therefore, it can be easily performed in patients with contraindications to invasive ablation procedures. Definitive data are lacking, and no direct comparison with standard procedures is available. The aim of this multicenter observational study is to evaluate the efficacy and safety of VT-ART, comparing the clinical outcome of patients undergone to VT-ART to patients not having received such a procedure. The two groups will not be collected by direct, prospective accrual to avoid randomization among the innovative and traditional arm: A retrospective selection through matched pair analysis will collect patients presenting features similar to the ones undergone VT-ART within the consortium (in each center independently). Our trial will enroll patients with optimized medical therapy in whom endocardial and/or epicardial radiofrequency ablation (RFA), the gold standard for VT ablation, is either unfeasible or fails to control VT recurrence. Our primary outcome is investigating the difference in overall cardiovascular survival among the group undergoing VT-ART and the one not exposed to the innovative procedure. The secondary outcome is evaluating the difference in ventricular event-free survival after the last procedure (i.e., last RFA vs. VT-ART) between the two groups. An additional secondary aim is to evaluate the reduction in the number of VT episodes comparing the 3 months before the procedure to the ones recorded at 6 months (from the 4th to 6th month) following VT-ART and RFA, respectively. Other secondary objectives include identifying the benefits of VT-ART on cardiac function, as evaluated through an electrocardiogram, echocardiographic, biochemical variables, and on patient quality of life. We calculated the sample size (in a 2:1 ratio) upon enrolling 149 patients: 100 in the non-exposed control group and 49 in the VT-ART group. Progressively, on a multicentric basis supervised by the promoting center in the VT-ART consortium, for each VT-ART patient enrollment, a matched pair patient profile according to the predefined features will be shared with the consortium to enroll a patient that has not undergone VT-ART. Our trial will provide insight into the efficacy and safety of VT-ART through a matched pair analysis, via an observational, multicentric study of two groups of patients with or without VT-ART in the multicentric consortium (with subgroup stratification into dynamic cohorts).