Chronic Ischemic Cardiomyopathy Research Articles

Correction: Left Ventricular Geometry and Angiogenesis Improvement in Rat Chronic Ischemic Cardiomyopathy following Injection of Encapsulated Mesenchymal Stem Cells.

In this article published in Cell J, Vol 24, No 12, 2022, on pages 741-747, the authors found that there was some mistakes in the Table 1 and we have corrected them in the following table. The authors would like to apologize for any inconvenience.

Cardiovascular toxicity of fluoropyrimidines: Experience from a quaternary referral center.

e24028 Background: Fluoropyrimidines, including 5-fluorouracil (5-FU) and capecitabine, are widely used chemotherapeutic agents. Their use has been linked to various forms of cardiovascular (CV) toxicity. We sought to analyze the rate of CV events and associated factors in patients receiving fluoropyrimidines at our institution. Methods: We included all patients who received intravenous 5-FU or oral capecitabine at the Cleveland Clinic since 2000. Diagnosis data was obtained based on ICD-10 Codes. CV events included chest pain/angina, myocardial infarction, chronic ischemic heart disease, arrhythmias, conduction disorders, cardiac arrest, cardiomyopathy, and heart failure. CV events were accounted for if they occurred during treatment or within 30 days following the latest administration of the agent. Logistic regression was performed to identify predictors of CV events. Results: A total of 17,236 patients were included, of which 9,386 (54.5) received 5-FU and 7,850 (45.5) received capecitabine. Median age at treatment was 63. The most frequent malignancies were gastrointestinal (70%) and breast cancer (12.3%). A total of 2,283 patients (13.2%) experienced at least one CV event either during treatment or within 30 days following drug administration. The most frequent CV events were chest pain/angina (35.7% of all events). On multivariable logistic regression, factors associated with increased risk of CV events were black race, smoking history, hypertension, and obesity (Table). A prior history of CV disease was also associated with increased risk of CV events (OR 1.22; 95% CI [1.09 - 1.33]). Finally, intravenous 5-FU was linked to higher odds of CV events compared to oral capecitabine (OR 1.48; 95% CI [1.34 - 1.63]). Conclusions: This large-scale cohort study provides pivotal insights into the cardiovascular risks associated with fluoropyrimidine therapy. Besides traditional risk factors, black patients were more likely to suffer from CV events. Additionally, capecitabine may offer better CV outcomes compared to 5-FU. These findings underscore the need for refined risk assessment and enhanced cardiovascular monitoring in patients treated with fluoropyrimidines. [Table: see text]

In-hospital outcomes of anterior versus non-anterior st elevation myocardial infarction complicated with complete atrioventricular block

Abstract Background Complete atrioventricular block (CAVB) is an infrequent complication of acute ST-elevation myocardial infarction (STEMI), and information on its outcomes is scarce. We aimed to address the characteristics and in-hospital outcomes of patients with anterior versus non-anterior STEMI complicated with CAVB in a contemporary, nationwide, all-comer registry, in the U.S. Methods Using the National Inpatient Sample (NIS) database, we identified patients who were hospitalized with STEMI, complicated with CAVB between 2016- 2019. Patients with any cardiac implantable electronic device (CIED) in-situ were excluded. Baseline characteristics, in-hospital procedures and outcomes including time to temporary or permanent pacemaker (PPM)/implantable cardioverter defibrillator (ICD) implantation, length of stay and mortality were collected. Results A total of 17470 patients, were hospitalized with a primary diagnosis of STEMI and concomitant diagnosis of CAVB, 2755(15.8%) with Anterior and 14715(84.2%) with non-anterior STEMI. Non-anterior STEMI patients included more women, had higher prevalence of hypertension, dyslipidemia, smoking history and chronic pulmonary disease, while anterior STEMI patients had higher prevalence of chronic kidney disease and ischemic cardiomyopathy. Anterior STEMI patient had significantly higher rate of in hospital death [955 (35%) vs 2220 (15%), p<0.001], CPR, VT/VF, cardiac arrest, acute heart failure, respiratory failure, mechanical ventilation >96 hours and acute kidney injury. In both groups 40% received temporary pacemaker, but mean time to implantation was longer in anterior STEMI patients [1.1±3.3 vs 0.3±1.2 days, p<0.001]. Rate of any permanent CIED implantation was also significantly higher in the anterior STEMI patients with longer time to PPM implantation, [3.3±3.5 vs 2.8±2.8 days, p<0.001]. Use of mechanical circulatory support devices was significantly higher in anterior STEMI patients. Conclusion In STEMI patients complicated with CAVB, in-hospital outcomes of anterior STEMI were worse comparing to non-anterior STEMI, with significantly higher rates of in-hospital death, in-hospital complications and CIED implantations.

Kiosk 9R-TA-05 - Machine Learning for Automated Detection of Normal and Abnormal Strain in Oxygenation-sensitive Cardiovascular Magnetic Resonance (OS-CMR) of Patients with Chronic Ischemic Cardiomyopathy

Kiosk 9R-TA-05 - Machine Learning for Automated Detection of Normal and Abnormal Strain in Oxygenation-sensitive Cardiovascular Magnetic Resonance (OS-CMR) of Patients with Chronic Ischemic Cardiomyopathy

Kiosk 7R-FC-03 - Prevalence, Associations, and Prognostic Relevance of Right Ventricular Dysfunction in Patients with Chronic Ischemic Cardiomyopathy Undergoing Cardiovascular Magnetic Resonance Imaging

Kiosk 7R-FC-03 - Prevalence, Associations, and Prognostic Relevance of Right Ventricular Dysfunction in Patients with Chronic Ischemic Cardiomyopathy Undergoing Cardiovascular Magnetic Resonance Imaging

What Links Chronic Kidney Disease and Ischemic Cardiomyopathy? A Comprehensive Bioinformatic Analysis Utilizing Bulk and Single-Cell RNA Sequencing Data with Machine Learning.

Chronic kidney disease (CKD) emerges as a substantial contributor to various cardiovascular disorders, including ischemic cardiomyopathy (ICM). However, the underlying molecular mechanisms linking CKD and ICM remain elusive. Our study aims to unravel these connections by integrating publicly available bulk and single-cell RNA sequencing (scRNA-seq) data. Expression profiles from two ICM datasets obtained from heart tissue and one CKD with Peripheral Blood Mononuclear Cell (CKD-PBMC) dataset were collected. We initiated by identifying shared differentially expressed genes (DEGs) between ICM and CKD. Subsequent functional enrichment analysis shed light on the mechanisms connecting CKD to ICM. Machine learning algorithms enabled the identification of 13 candidate genes, including AGRN, COL16A1, COL1A2, FAP, FRZB, GPX3, ITIH5, NFASC, PTN, SLC38A1, STARD7, THBS2, and VPS35. Their expression patterns in ICM were investigated via scRNA-seq data analysis. Notably, most of them were enriched in fibroblasts. COL16A1, COL1A2, PTN, and FAP were enriched in scar-formation fibroblasts, while GPX3 and THBS2 showed enrichment in angiogenesis fibroblasts. A Gaussian naïve Bayes model was developed for diagnosing CKD-related ICM, bolstered by SHapley Additive exPlanations interpretability and validated internally and externally. In conclusion, our investigation unveils the extracellular matrix's role in CKD and ICM interplay, identifies 13 candidate genes, and showcases their expression patterns in ICM. We also constructed a diagnostic model using 13 gene features and presented an innovative approach for managing CKD-related ICM through serum-based diagnostic strategies.

Developing and evaluating a chronic ischemic cardiomyopathy in swine model by rest and stress CMR.

A large animal model of chronic coronary artery disease (CAD) is crucial for the understanding the underlying pathophysiological processes of chronic CAD and consequences for cardiac structure and function. The goal of this study was to develop a chronic model of CAD in a swine model and to evaluate the changes of myocardial structure, myocardial motility, and myocardial viability during coronary stenosis. A total of 30 swine (including 24 experimental animals and 6 controls) were enrolled. The chronic ischemia model was constructed by using Ameroid constrictor in experimental group. The 24 experimental animals were further divided into 4 groups (6 animals in each group) and were sacrificed at 1, 2, 3 and 4 weeks after operation for pathological examination, respectively. Cardiac magnetic resonance (CMR) was performed preoperatively and weekly postoperatively until sacrificed both in experimental and control group. CMR cine images, rest/adenosine triphosphate (ATP) stress myocardial contrast perfusion and LGE were performed and analyzed. The rest wall thickening (WT) score was calculated from rest cine images. The MPRI (myocardial perfusion reserve index) and MPR (myocardial perfusion reserve) were calculated based on rest and stress perfusion images. Pathology staining including triphenyltetrazolium chloride, HE and picrosirus red staining were performed after swine were sacrificed and collagen volume fraction (CVF) was calculated. The time to formation of ischemic, hibernating, and infarcted myocardium was recorded. In experimental group, from 1w to 4w after surgery, the rest WT score decreased gradually from 35.2 ± 2.0%, 32.0 ± 2.9% to 30.5 ± 3.0% and finally 29.06 ± 1.78%, p < 0.001. Left ventricular ejection fraction was gradually impaired after modeling (58.9 ± 12.6%, 56.3 ± 10.1%, 55.3 ± 9.0%, 53.8 ± 9.9%, respectively). And the MPR and MPRI also decreased stepwise with extent of surgery time (MPRI dropped from 2.1 ± 0.4, 2.0 ± 0.2 to 1.8 ± 0.3 and finally 1.7 ± 0.1, p = 0.004; MPR dropped from 2.3 ± 0.4, 2.1 ± 0.2 to 1.9 ± 0.4 and finally 1.8 ± 0.1, p < 0.001). Stronger associations between MPR, MPRI and CVF were paralleled lower wall thickening scores in fibrosis-affected areas. The ischemic myocardium was first appeared in the first week after surgery (involving ten segments), hibernated myocardium was first appeared in the second week after surgery (involving seventeen segments). LGE was first appeared in eight swine in the third weeks after surgery (16 segments). At 4w after surgery, average 9.6g scar tissue was found among 6 swine. At the same time, histological analysis established the presence of fibrosis and ongoing apoptosis in the infarcted area. In conclusion, our study provided valuable insights into the pathophysiological processes of chronic CAD and its consequences for cardiac structure and function in a large animal model through combining myocardial motion and stress perfusion.

Current concepts of treatment for left ventricular thrombus: A sys-tematic meta-analysis comparing direct oral anticoagulants versus vitamin K-antagonists

Abstract Background/Introduction Left ventricular thrombus (LVT) is a dreaded complication after myocardial infarction (MI) and is traditionally treated with Vitamin K antagonists (VKAs) for 3-6 months. Despite a gap of evidence, the broad use of direct oral anticoagulants (DOACs) for other thromboembolic disorders has triggered an increasing off-label use for DOACs in LVTs and has stimulated for expanding research focusing on DOAC´s utility for patients with LVT. Purpose To assess the safety and efficacy of DOACs versus VKAs for the treatment of LVT with a systematic meta-analysis. Methods We conducted a systematic search according to the PRISMA guidelines to identify all existing studies comparing DOACs and VKAs for the treatment of LVT. Forest plots and pooled odds ratios have been calculated for major bleeding events, strokes and systemic embolism, and for thrombus resolution. Results We have included a total of 13 studies with a pooled sample size of 2243 patients. 601 patients (26.8%) were treated with DOACs and 1642 patients (73.2%) with VKAs. The mean age was 55 and 59 years in the DOACs and VKAs group and sex was equally distributed with a male predominance of 81% in both groups. As underlying heart disease, most patients suffered from acute or chronic ischemic cardiomyopathy and presented with a mean left ventricular ejection fraction (LVEF) of 32% at admission. Baseline characteristics of patients included in each primary study are summarized in table 1. The pooled odds ratio of stroke or systemic embolism in patients treated with DOACs versus VKAs was 0.84 (95% CI 0.59-1.19) (p= 0.32). Compared to VKAs, we suggest that the use of DOACs may be associated with a reduced risk for major bleeding incidents without reaching statistical significance (OR 0.63 (95% CI 0.39-1.04) (p = 0.07). LVT resolution was similar and independent of the antithrombotic regimen (OR 0.91 (95% CI 0.7-1.19), p=0.50). Conclusions Based on our meta-analysis we conclude that DOACs seem to be non-inferior to VKAs for the treatment of LVT in terms of thrombus resolution, stroke and systemic embolism, and bleeding incidents. Despite these promising findings, several important aspects such as the duration of anticoagulation, and the type and dosing of the DOAC agent are still poorly understood. To close the lack of evidence for DOACs in LVTs, an adequately powered, randomized trial is needed.

Repeated Intravenous Administration of Mesenchymal Stromal Cells Produces Cumulative Beneficial Effects in Chronic Ischemic Cardiomyopathy.

Repeated Intravenous Administration of Mesenchymal Stromal Cells Produces Cumulative Beneficial Effects in Chronic Ischemic Cardiomyopathy.

Bone Marrow and Wharton’s Jelly Mesenchymal Stromal Cells are Ineffective for Myocardial Repair in an Immunodeficient Rat Model of Chronic Ischemic Cardiomyopathy

BackgroundAlthough cell therapy provides benefits for outcomes of heart failure, the most optimal cell type to be used clinically remains unknown. Most of the cell products used for therapy in humans require in vitro expansion to obtain a suitable number of cells for treatment; however, the clinical background of the donor and limited starting material may result in the impaired proliferative and reparative capacity of the cells expanded in vitro. Wharton’s jelly mesenchymal cells (WJ MSCs) provide a multitude of advantages over adult tissue-derived cell products for therapy. These include large starting tissue material, superior proliferative capacity, and disease-free donors. Thus, WJ MSC if effective would be the most optimal cell source for clinical use.ObjectivesThis study evaluated the therapeutic efficacy of Wharton’s jelly (WJ) and bone marrow (BM) mesenchymal stromal cells (MSCs) in chronic ischemic cardiomyopathy in rats.MethodsHuman WJ MSCs and BM MSCs were expanded in vitro, characterized, and evaluated for therapeutic efficacy in a immunodeficient rat model of ischemic cardiomyopathy. Cardiac function was evaluated with hemodynamics and echocardiography. The extent of cardiac fibrosis, hypertrophy, and inflammation was assessed with histological analysis.ResultsIn vitro analysis revealed that WJ MSCs and BM MSCs are morphologically and immunophenotypically indistinguishable. Nevertheless, the functional analysis showed that WJ MSCs have a superior proliferative capacity, less senescent phenotype, and distinct transcriptomic profile compared to BM MSC. WJ MSCs and BM MSC injected in rat hearts chronically after MI produced a small, but not significant improvement in heart structure and function. Histological analysis showed no difference in the scar size, collagen content, cardiomyocyte cross-sectional area, and immune cell count.ConclusionsHuman WJ and BM MSC have a small but not significant effect on cardiac structure and function when injected intramyocardially in immunodeficient rats chronically after MI.Graphical

Prevalence, hematological parameters, and coagulation profiles: Cardiovascular diseases statistics in the Asir region, Saudi Arabia.

To determine the prevalence of cardiovascular disease (CVD) types in the Asir region of Saudi Arabia and the importance of hematological testing for CVD patients in the context of disease management. This retrospective study comprised 416 CVD patients, and samples were divided based the type of CVD. The Mann Whitney U test was used to compare patients' hematological markers and coagulation profiles to those of healthy controls. The rate of ischemic heart disease (IHD) was 80.7% that of other CVDs, and the rate of ST-elevation myocardial infarction (STEMI) was 37.3% the rate of CVD. Significant differences were observed in the hematological and coagulation parameters of CVD patients compared to the control group. White blood cells (WBC) were significantly higher in STEMI, non-ST-elevation myocardial infarction (NSTEMI), unstable angina (UA), and heart failure (HF) groups. Red blood cells (RBC) were significantly lower in STEMI, NSTEMI, UA, chronic coronary syndrome (CCS), HF, dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM). Red distribution width (RDW) was significantly greater in the HF, DCM, and ICM groups. Prothrombin time (PT) was significantly higher in the STEMI, HF, and DCM groups. ST-elevation myocardial infarction has a higher prevalence rate among CVD patients in the Asir region. Both coagulation and hematological indicators have high potential utility as CVD diagnostic and prognostic markers.

Transarterial Embolization of Ruptured Pancreaticoduodenal Artery Pseudoaneurysm Related to Chronic Pancreatitis

We presented a 67-year-old woman with lightheadedness, diaphoresis, and acute epigastric and right hypochondrium pain, with a past medical history including stage 2 essential hypertension, chronic ischemic cardiomyopathy, and class 1 obesity. An abdominal contrast-enhanced CT scan showed an extensive hematoma (3 × 4 cm2 in size) located intra-abdominally, adjacent to the duodenojejunal area, with hyperdensity around the duodenum, positioned inferior to the pancreas (30-59 HU). Moreover, the CT scan also revealed an enhancing lesion as a pseudoaneurysm of the inferior pancreaticoduodenal artery, measuring 5 × 8 × 8 mm3 with active bleeding and associated hematoma. Following these investigations of the abdominal area, a decision was made to proceed with an endovascular intervention within the interventional radiology department. With the patient under conscious sedation, via a right common femoral artery approach, the superior mesenteric artery was catheterized. While injecting the contrast agent to obtain a better working projection, the pseudoaneurysm ruptured, and acute extravasation of the contrast agent was noted, followed by injection of a mixture of 1 mL Glubran 2 with 2 mL Lipiodol until complete obliteration of the pseudoaneurysm was obtained. The patient was hemodynamically stable at the end of the procedure and was discharged 6 days later in a good condition without active bleeding signs.

68Ga]Ga-NODAGA-E[(cRGDyK)]2 and [64Cu]Cu-DOTATATE PET Predict Improvement in Ischemic Cardiomyopathy.

An increasing number of patients are living with chronic ischemic cardiomyopathy (ICM) and/or heart failure. Treatment options and prognostic tools are lacking for many of these patients. Our aim was to investigate the prognostic value of imaging angiogenesis and macrophage activation via positron emission tomography (PET) in terms of functional improvement after cell therapy. Myocardial infarction was induced in rats. Animals were scanned with [18F]FDG PET and echocardiography after four weeks and randomized to allogeneic adipose tissue-derived stromal cells (ASCs, n = 18) or saline (n = 9). Angiogenesis and macrophage activation were assessed before and after treatment by [68Ga]Ga-RGD and [64Cu]Cu-DOTATATE. There was no overall effect of the treatment. Rats that improved left ventricular ejection fraction (LVEF) had higher uptake of both [68Ga]Ga-RGD and [64Cu]Cu-DOTATATE at follow-up (p = 0.006 and p = 0.008, respectively). The uptake of the two tracers correlated with each other (r = 0.683, p = 0.003 pre-treatment and r = 0.666, p = 0.004 post-treatment). SUVmax at follow-up could predict improvement in LVEF (p = 0.016 for [68Ga]Ga-RGD and p = 0.045 for [64Cu]Cu-DOTATATE). High uptake of [68Ga]Ga-RGD and [64Cu]Cu-DOTATATE PET after injection of ASCs or saline preceded improvement in LVEF. The use of these tracers could improve the monitoring of heart failure patients in treatment.

Novel Approach for Assessing Postinfarct Myocardial Injury and Inflammation Using Hybrid Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.

Novel Approach for Assessing Postinfarct Myocardial Injury and Inflammation Using Hybrid Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.

290 A UNIQUE CASE OF AORTIC VALVE LEAFLET'S ANEURYSM DETECTED BY CARDIAC COMPUTED TOMOGRAPHIC ANGIOGRAPHY-CCTA

Abstract Heart valve leaflet's aneurysm is a rare finding and literature about this topic is sparse. Early recognition is important because their rupture can lead to catastrophic valve regurgitation. An 84 years old male with chronic ischemic cardiomyopathy was admitted to coronary-intensive-care-unit for non-ST-elevation-myocardial-infarction. Baseline transthoracic-echocardiography showed normal biventricular function with inhomogeneous thickening of aortic leaflets with moderate aortic regurgitation. Because acoustic window was limited, a trans-esophageal echocardiography was performed detecting a small mass in the right aortic coronary cusp with moderate regurgitation (orifice regurgitation area: 0,54 cm2; med/max gradient: 16/32 mmHg). Endocarditis was ruled out. Because of the rapid worsening of patient's conditions, requiring mechanical ventilation and hemofiltration, and the potential hazard of an urgent coronary angiography, a cardiac computed tomographic angiography (CCTA) was performed. Detailed spatial reconstructions highlighted a bilobed cavitation in the commissure between right-left aortic coronary cusps. Diagnosis of aortic leaflets’ aneurysm was made. A “wait and see” strategy was chosen and patient's general conditions gradually improved and now he is stable and uneventful. To date no aortic leaflet's aneurysm were described in literature.

Left Ventricular Geometry and Angiogenesis Improvement in Rat Chronic Ischemic Cardiomyopathy following Injection of Encapsulated Mesenchymal Stem Cells.

Injection of hydrogel and cells into myocardial infarction (MI) patients is one of the emerging treatment techniques, however, it has some limitations such as a lack of electromechanical properties and neovascularization. We investigated the therapeutic potential of new electroactive hydrogel [reduced graphene oxide (rGO)/Alginate (ALG)] encapsulated human bone marrow mesenchymal stem cells (BMSCs). The experimental study involved ligating the left anterior descending coronary artery (LAD) in rat models of chronic ischemic cardiomyopathy. Echocardiograms were analyzed at 4 and 8 weeks after MI treatment. In the eighth week after injection in the heart, the rats were sacrificed. Histological and immunohistochemical analyses were performed using Hematoxylin and Eosin (H and E) staining, Masson's trichrome staining and anti-CD31 antibody to analyze tissue structure and detect neovascularization. In comparison to the control and other treatment groups, MSCs encapsulated in rGO-ALG showed significant improvements in fractional shortening (FS), ejection fraction (EF), wall thickness and internal diameters (P<0.05). The morphological observation showed several small blood vessels formed around the transplantation site in all treated groups especially in the MSC-ALG-rGO group 8 weeks after the transplantation. Also, Masson's trichrome staining indicated an increased amount of collagen fibers in rGO-ALG-MSC. Microvessel density was significantly higher using MSC-ALG-rGO compared to controls (P<0.01). This study demonstrates that intramyocardial injection of rGO/ALG, a bio-electroactive hydrogel, is safe for increasing LV function, neovascularization, and adjusting electrical characteristics following MI. The results confirm ALG promising capability as a natural therapeutic for cardiac regeneration.

Autologous CD133 + Cells and Laser Revascularization in patients with severe Ischemic Cardiomyopathy.

We tested the hypothesis that targeted TMLR combined with intramyocardial injection of autologous CD 133+ progenitor cells is safe and feasible in patients with chronic ischemic cardiomyopathy (ICM) and no revascularization options. Eight male patients (age 62 ± 2.4years) with multivessel severe ischemic heart disease and no revascularization options were enrolled. Autologous CD 133 + endothelial progenitor cells were derived and purified from the bone marrow on the day of surgery using the clinical-grade closed CliniMACS system. Using a lateral thoracotomy approach, TMLR was performed, followed by transmyocardial transplantation of purified CD133 + cells (mean number of transplanted cells: 12.5 × 106) in the region surrounding the TMLR sites. These sites were selected based on ischemia on pre-procedure perfusion imaging. We performed clinical and myocardial perfusion imaging pre-procedure and then at 6- and 12-month follow-up. No major complications or death occurred during the procedure or during the peri-operative hospital stay. One patient died of cardiac cause 6months post-procedure. There was a reported short-term improvement in anginal and heart failure symptoms and a modest reduction in the ischemic score as assessed by perfusion imaging. Our phase 1 clinical study examining the combination therapy of targeted transmyocardial laser revascularization therapy and autologous CD133 + endothelial progenitor cells in patients with chronic ICM and no revascularization options demonstrates the feasibility and short-term safety of this combined approach and warrants future larger phase 2 randomized clinical studies.

Abstract 10128: Recombinant Human Placental Growth Factor-2 Treatment in Porcine Ischemic Cardiomyopathy

Background: Placental growth factor (PlGF)-2 induces neovascularization and improves myocardial function in atherosclerotic rodent myocardial ischemia models without stimulating plaque angiogenesis. This promising therapeutic profile of PlGF-2 warrants a double blind, randomized, and placebo-controlled feasibility and efficacy study in a large animal model, representative of human disease. Methods: We induced myocardial infarction (MI) in domestic pigs using a 75 min balloon occlusion of the mid-LAD followed by reperfusion. After 4 w, we randomized pigs with marked LV dysfunction (LVEF&lt;40%) to continuous IV infusion of 5, 15, 45 μg/kg/day rhPlGF-2 or PBS (CON) for 2 w using osmotic pumps. We evaluated treatment effect 8 w after MI using comprehensive MRI analysis of LV function and structure and performed postmortem histological analyses of LV vascularization and fibrotic remodeling. Results: In the pilot study (3 pigs/dose), PIGF plasma concentrations showed stable and sustained dose-dependent increases for 28 days without organ-specific side effects or systemic toxicity. Myocardial Ischemia/reperfusion induced LV dysfunction at 4 w (infarct size, 16±4 % of LV mass, n=42; LVEF, 34±4 %, range 19%-40%). In the dose escalation study using 5 (n=10), 15 or 45 μg/kg/day PlGF (n=11 per group), global LV function, and regional myocardial blood flow at rest or during stress, and infarct size did not differ between CON (n=10) and PlGF (Figure 1). Capillary densities and extent of LV interstitial fibrosis in infarct core and border zone were comparable between CON and PlGF. Conclusions: In this blinded randomized controlled trial, rhPIGF-2 did not improve global cardiac function in a porcine model of chronic ischemic cardiomyopathy, and failed to recapitulate therapeutic neovascularization reported in rodents. Our data emphasize the critical need for robust double blind, placebo controlled trials in representative large animal models before clinical translation.

Direct oral anticoagulants compared to vitamin K antagonists for the treatment of left ventricular thrombi

Abstract Background Left ventricular thrombus (LVT) complicates around one in six cases of acute and chronic left ventricular systolic dysfunction and is associated with an increased risk of stroke, major systemic embolism and death, believed to be ameliorated by anticoagulation. Off-label use of direct oral anticoagulants (DOACs) for LVT has steadily increased, largely based on favourable outcomes in atrial fibrillation and venous thromboembolism, but the safety and efficacy of DOACs versus vitamin K antagonists (VKA) for LVT remains uncertain. Purpose The main aim of our study was to compare treatment of LVT with VKA to DOAC, focusing on all-cause mortality, stroke, major systemic emboli and major bleeding. Methods We conducted a retrospective observational longitudinal study of patients presenting to two large quaternary centres between 2011 and 2021 with a diagnosis of LVT. Patients were eligible if they had a documented LVT and received anticoagulation with either VKA or DOAC. Baseline data, thrombus characteristics, treatment type and duration, follow up imaging and clinical events were recorded using electronic health care records. Outcome measures included thrombus resolution, stroke and systemic embolism (SSE), major bleeding and mortality. Results A total of 955 patients were identified, of whom 901 received treatment with either a VKA (567 pts, 62.9%) or a DOAC (334 pts, 37.1%) and were included in the analysis. Underlying aetiologies included acute myocardial infarction (AMI) (38.3%), chronic ischaemic cardiomyopathy (38.0%) and non-ischaemic cardiomyopathy (23.7%). Rivaroxaban (43.4%) was the most frequently prescribed DOAC followed by apixaban (35.9%), and the remaining on edoxaban (20.7%). AMI related LVT was more commonly treated with DOAC (53.0%) and chronic ischaemic cardiomyopathy with VKA (72.9%). There was a lower baseline LVEF in the VKA cohort (29.5±13.2 vs 33.1±14.2, p&amp;lt;0.0001). Other demographic features were comparable. Median follow up was 2.5 years (IQR: 1–3.5). There were no differences in follow up duration between the two treatments (p=0.17). Greater rates of thrombus resolution were seen in the DOAC group compared to VKA (1 year: 78.4% vs 51.4%, p&amp;lt;0.0001), with higher rates of persistent thrombus over the follow-up period seen in the VKA group (25.1% vs 12.9%, p&amp;lt;0.0001). Rates of stroke and systemic embolization were similar between the groups (VKA 9.3% vs 9.6% DOAC, p=0.93). Higher rates of bleeding (BARC &amp;gt;3, 8.1% VKA, 3.6% DOAC, p=0.031) (Figure 1A) and mortality (VKA 18.5%, DOAC 10.2%, p=0.001) (Figure 1B) were seen in the VKA group over the follow-up period. Conclusions In a large multi-centre registry of LVT of mixed aetiology, anticoagulation with DOAC was associated with earlier and greater rates of thrombus resolution and consequential reduced adverse events (major bleeding and mortality) during follow up. A funding application to support a multi-centre randomised control trial is underway. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): This work was supported by the British Heart Foundation (Fellowship FS/CRTF/21/24190 to HM) and the National Institute for Health Research (Biomedical Research Centre Award to Guy's and St Thomas' NHS FT and King's College London).

Ventricular Tachycardia Electrical Storm

&#x0D; &#x0D; &#x0D; The term “electrical storm” (ES) indicates a life-threatening clinical condition characterized by the recurrence of hemodynamically unstable ventricular tachycardia (VT) and/or ventricular fibrillation (VF). We are presenting a case of ES in hemodynamically unstable VT treated at pre-hospital and hospital level.&#x0D; Seventy-one-year-old patient with a previous history of hypertension, insulin-dependent diabetes, congestive stroke and myocardial infarction, severe three-vessel coronary artery disease and myocardial revascularization, diabetic nephropathy, chronic kidney failure, and chronic ischemic cardiomyopathy, collapses at home. After examination and diagnostic procedures, the emergency medical physician (EMS) diagnoses hemodynamically unstable VT, which he treats with medication and gets the patient urgently transported to a hospital. In the next 24 h, during hospitalization, there are five more separate episodes of VT with pulse treated with DC shock and antiarrhythmics. On the twelfth day of hospitalization, an implantable cardioverter-defibrillator is implanted to prevent sudden cardiac death. On the seventeenth day, the patient is discharged from hospital in stable condition.&#x0D; The question arises of further best pharmacological and non-pharmacological therapy of ES in hemodynamically unstable VT. It is necessary to educate EMS physicians in the practical application of synchronized cardioversion at the prehospital level.&#x0D; &#x0D; &#x0D;