Influence of Hypoxia Inducible Factor-1α of Endothelial Progenitor Cells on Left Ventricular Function in Experimental Myocardial Infarction

Based on the promotion of myocardial activity via endothelial progenitor cells (EPCs) subsequent to acute myocardial infarction (AMI), our research was designed to explore the influence of excessive HIF-1α expression in expanded EPCs (eEPCs) on promotion of the activity of left ventricle subsequent to MI. Isolation of EPCs from cord blood was performed before transduction with the help of retroviral vector with or without HIF-1α expression. Transplantation was performed subsequent to ligation of the left anterior descending coronary artery in mice. Ejection fraction (EF) of left ventricle was promoted via transplantation after 2 weeks. Excessive HIF-1α expression enhanced EF of left ventricle and decreased the extent of MI. It was revealed via functional studies that excessive HIF-1α expression enhanced proliferation of EPCs triggered by low oxygen concentration and suppressed cell death in the region of infarction. Moreover, markers of endothelium CD31, VEGF, and eNOS were upregulated. Transplantation of eEPCs with excessive HIF-1α expression in AMI can promote myocardial activities by increasing differentiation, generation of vessels, proliferation of eEPCs, and suppressing cell death. The above findings propose that regulation of EPCs via HIF-1α enhances the activity as well as mobilization of EPCs, indicating that reinforcement of expression of HIF-1α is beneficial for coronary heart disease.

Left ventricle reverse remodeling in chronic aortic regurgitation patients with dilated ventricle after aortic valve replacement

Background Aortic valve replacement (AVR) for chronic aortic regurgitation (AR) with a severe dilated left ventricle and dysfunction leads to left ventricle remodeling. But there are rarely reports on the left ventricle reverse remodeling (LVRR) after AVR. This study aimed to investigate the LVRR and outcomes in chronic AR patients with severe dilated left ventricle and dysfunction after AVR. Methods We retrospectively analyzed the clinical datum of chronic aortic regurgitation patients who underwent isolated AVR. The LVRR was defined as an increase in left ventricular ejection fraction (LVEF) at least 10 points or a follow-up LVEF ≥ 50%, and a decrease in the indexed left ventricular end-diastolic diameter of at least 10%, or an indexed left ventricular end-diastolic diameter ≤ 33 mm/m2. The changes in echocardiographic parameters after AVR, survival analysis, the predictors of major adverse cardiac events (MACE), the association between LVRR and MACE were analyzed. Results Sixty-nine patients with severe dilated left ventricle and dysfunction underwent isolated AVR. LV remodeling in 54 patients and no LV remodeling in 15 patients at 6–12 months follow-up. The preoperative left ventricular dimensions and volumes were larger, and the EF was lower in the LV no remodeling group than those in the LV remodeling group (all p < 0.05). The adverse LVRR was the predictor for MACE at follow-up. The mean follow-up period was 47.29 months (range 6 to 173 months). The rate of freedom from MACE was 94.44% at 5 years and 92.59% at 10 years in the remodeling group, 60% at 5 years, and 46.67% at 10 years in the no remodeling group. Conclusions The left ventricle remodeling after AVR was the important predictor for MACE. LV no remodeling may not be associated with benefits from AVR for chronic aortic regurgitation patients with severe dilated LV and dysfunction.

Left ventricle geometry, atrial strain, ventricle strain and hemodynamics across aortic valve before and after transcatheter aortic valve replacements

Background: Transcatheter Aortic Valve Replacements (TAVR) has become widespread throughout the world. To date there are no echocardiographic study of TAVR patients from Southeast Asia (SEA). We sought to evaluate 1) changes in echocardiographic and strain values pre and post TAVR 2) relationship between aortic stenosis (AS) severity and strain values, 3) left ventricle geometry in severe AS 4) relationship of flow rate to dimensionless index (DVI) and acceleration time (AT) and 5) effect of strains on outcome. Methods: Retrospective study of 112 TAVR patients in our center from 2009 to 2020. The echocardiographic and strain images pre (within 1 months), post (day after) and 6 months post TAVR were analyzed by expert echocardiographer. Results: The ejection fraction (EF) increased at 6 months (53.02 ± 12.12% to 56.35 ± 9.00%) (p=0.044). Interventricular septal thickness in diastole (IVSd) decreased (1.27 ± 0.21cm to 1.21 ± 0.23cm) (p=0.038) and left ventricle internal dimension in diastole (LVIDd) decreased from 4.77 ± 0.64cm to 4.49 ± 0.65cm (p = 0.001). No changes in stroke volume index (SVI pre vs 6 months p =0.187), but the flow rate increases (217.80 ± 57.61mls/s to 251.94 ± 69.59mls/s, p<0.001). Global Longitudinal Strain (GLS) improved from -11.44 ± 4.23% to -13.94 ± 3.72% (p <0.001), Left Atrial Reservoir strain (Lar-S) increased from 17.44 ± 9.16% to 19.60 ± 8.77% (p=0.033). 8 patients (7.5%) had IVSd < 1.0cm, and 4 patients (3.7%) had normal left ventricle (LV) geometry. There was linear relationship between IVSd and mean PG (r=0.208, p=0.031), between GLS to aortic valve area (AVA) and aortic valve area index (AVAi) (r = – 0.305, p=0.001 and r= – 0.316, p = 0.001). There was also relationship between AT (r=-0.20, p=0.04) and DVI (r=0.35, p< 0.001) with flow rate. Patients who died late (after 6 months) had lower GLS at 6 months. (Alive; -13.94 ± 3.72% vs Died; -12.43 ± 4.19%, p= 0.001) Conclusion: At 6 months TAVR cause reverse remodeling of the LV with reduction in IVSd, LVIDd and improvement in GLS and LAr-S. There is linear relationship between GLS and AVA and between IVSd and AVA.

Clinical and Echocardiographic Assessment of Patients with Dilated Cardiomyopathy

Introduction: Cardiomyopathy is the disorder of the heart muscles which can be dilated, hypertrophic or restrictive type. Dilated cardiomyopathy is caused by genetic and non-genetic causes but many of the causes are still not known. Echocardiography is an important imaging technique to diagnose and manage dilated cardiomyopathy. Aims: This study aims to assess the clinical and echocardiographic findings among patients with dilated cardiomyopathy. Methods: This is a cross-sectional, observational study conducted in Nepalgunj Medical College from January 2021 to June 2021. A total of 61 patients with dilated Cardiomyopathy were enrolled after obtaining written informed consent. Clinical examination and echocardiographic findings were recorded and data analysis was done using Statistical Package for Social Sciences. Results: The participants included 31 men and 30 women with dilated cardiomyopathy. The mean age of the participants was 58.49 + 15.46 years. The most common complaint was shortness of breath 84.5% and the most common clinical presentation was bilateral basal crepitation 98.4%. The patients mostly had diastolic left ventricle internal diameter of 5.5-6 cm and ejection fraction of 21-30%. Mitral regurgitation was observed among most 58(95.1%) of the patients. Conclusion: This study concludes that shortness of breath and bilateral basal crepitation are the most common presentation. Left ventricle dilation, reduced ejection fraction and mitral regurgitation are seen among majority of the patients.

Cap analysis of gene expression reveals alternative promoter usage in a rat model of hypertension

The role of alternative promoter usage in tissue-specific gene expression has been well established; however, its role in complex diseases is poorly understood. We performed cap analysis of gene expression (CAGE) sequencing from the left ventricle of a rat model of hypertension, the spontaneously hypertensive rat (SHR), and a normotensive strain, Brown Norway to understand the role of alternative promoter usage in complex disease. We identified 26,560 CAGE-defined transcription start sites in the rat left ventricle, including 1,970 novel cardiac transcription start sites. We identified 28 genes with alternative promoter usage between SHR and Brown Norway, which could lead to protein isoforms differing at the amino terminus between two strains and 475 promoter switching events altering the length of the 5′ UTR. We found that the shift in Insr promoter usage was significantly associated with insulin levels and blood pressure within a panel of HXB/BXH recombinant inbred rat strains, suggesting that hyperinsulinemia due to insulin resistance might lead to hypertension in SHR. Our study provides a preliminary evidence of alternative promoter usage in complex diseases.

Receptor interacting protein kinase-3 promotes both myopathy and cardiomyopathy in dystrophin-deficient mice

Background Duchenne muscular dystrophy (DMD) is a muscle degenerative disorder that is caused by the absence of dystrophin. From early childhood, multiple rounds of myofibre necrosis and regeneration lead to fibrosis and fat deposition, irreversibly disturbing skeletal muscle function and impairing locomotion. Cell necrosis also affects respiratory muscles and cardiomyocytes, ultimately responsible for the death of DMD boys by respiratory or heart failure. Necroptosis is a genetically programmed form of necrosis requiring the receptor-interacting serine/threonine-protein kinase (RIPK)3 and is a promising new therapeutic target for multiple degenerative disorders. We previously demonstrated that necroptosis mediates hindlimb myofibre degeneration in distinct muscular dystrophies, including in DMD. However, this pathway was recently found to be required for myogenesis. Its prevention might therefore lead to detrimental side effects on muscle repair. Whether necroptosis also participates in the pathogenesis of respiratory and cardiac muscle dysfunction, and whether its long-term inhibition would ultimately be beneficial or detrimental to mdx mice are addressed here. Methods Herein, we examined the effects of RIPK3 depletion on an advanced stage of pathogenesis in mdx mice. Dystrophic mice aged 12 to 18 months were submitted to forced treadmill running to assess their locomotor function. mdx cardiomyopathy was also examined by echocardiography in 40-week-old mice. Limb skeletal muscles, diaphragm and heart were analyzed by histology and molecular biology to compare the phenotype of mdxRipk3+/+ mdxRipk3-/- mice. Results In 18-month-old mdxRipk3-/- mice, we found no sign of muscle regeneration defect compared to mdxRipk3+/+ littermates. mdxRipk3-/- mice had decreased fibrosis in limb muscles, without evidence of muscle atrophy. The size of diaphragm myofibres was slightly reduced and affected by less variability than mdx littermates. Fibrosis was also reduced in the diaphragm of RIPK3-deficient mdx mice. Notably, heart hypertrophy and left ventricle fibrosis were reduced in mdxRipk3-/- mice, and using echocardiography, we found a significant decrease of markers of cardiomyopathy by such as a reduction of the relative wall thickness and left ventricle mass. Conclusions Our data suggest that necroptosis is involved together in the pathogenic phenotype of locomotor, respiratory, and cardiac muscles in dystrophin-deficient mice. The long-term genetic ablation of RIPK3 does not generate evidence of sarcopenia or muscle impairment in mdx mice. Our data suggest that necroptosis may represent a new therapeutic target susceptible to improving the phenotype of myopathy and cardiomyopathy.

Concomitant Repair For Mild Aortic Insufficiency And Implantation Of Left Ventricle Mechanical Support

Aortic valve regurgitation in patients undergoing LVAD implantation is a significant complication which occurs in up to 10% of patients in the INTERMACS database. Patients who have aortic valve regurgitation at the time of implant have been handled by several methods, including aortic valve leaflets approximation, to aortic valve replacement or even valve closure. We report a case where we used HAART Ring to repair a regurgitant aortic valve during LAVD implant for destination therapy.

Pediatric cardiac tamponade caused by metallic wire penetration into the heart: A case report and literature review

Thin, metallic wires can easily penetrate the gastrointestinal system if ingested and cause serious cardiac issues in children. We report a pediatric case of such an object that caused cardiac tamponade after lodging in the left ventricle. The wire was extracted without cardiopulmonary bypass and a full recovery was made. Cardiac issues after ingestion of foreign objects are rare but immediate surgery is required for resolution.