Significant Left Ventricular Dysfunction Research Articles

Abstract 11344: Targeted Deletion of Arrdc4 Mitigates Cardiac Injury in Insulin-Deficient Diabetes

Introduction: Diabetic cardiomyopathy is an important contributor to mortality in the diabetic population. However, the pathogenesis of diabetic cardiomyopathy is unclear. Hypothesis: We recently reported that the interaction between glucose transporter 1 (GLUT1) and its adaptor protein Arrdc4 mediates metabolic stress in the ischemic heart. Here, we tested whether this mechanism plays a role in diabetic cardiomyopathy. Methods: To determine glucose responsiveness, mouse neonatal cardiomyocytes were treated with high glucose (25 mM). To investigate cardiac phenotype in vivo, we engineered Arrdc4-knockout (KO) mice by CRISPR/Cas9 technology and created an insulin-deficient diabetic model by intraperitoneal injection of streptozotocin. Results: Arrdc4 expression was robustly stimulated by D-glucose (324±10%, p<0.01) in cardiomyocytes. The glucose responsiveness was mediated by MondoA, a nutrient-sensing transcriptional factor, through a cytoplasmic-nuclear shuttling mechanism. Confocal live imaging showed that Arrdc4 triggered endocytic trafficking of GLUT1 into lysosomes. In the animal model, levels of insulin depletion were comparable between the genotypes. Nevertheless, Arrdc4-KO diabetic mice had enhanced glucose uptake in multiple organs including the heart (139±13%, p<0.01) compared to wild-type (WT) diabetic mice. Arrdc4-KO diabetic hearts had lower induction of oxidative stress, ER stress, and autophagy by hyperglycemia, leading to better mitochondrial function and less cardiomyocyte apoptosis (70±5%, p<0.01) than WT diabetic hearts. Although resting echocardiography could not detect early signs of left ventricular dysfunction, stress hemodynamic analysis uncovered the masked mechanical dysfunction by diabetes and found that Arrdc4-KO diabetic mice retained a greater cardiac response to beta-adrenergic stimulation than wild-type mice (149±5%, p<0.01). Conclusion: The metabolic rearrangements by Arrdc4 deletion improve glucose transport due to the absence of its inhibition towards GLUT1 function, protecting the heart against diabetic damage. These results provide a novel link between GLUT1 and Arrdc4 as a fundamental mechanism of the regulation of glucose homeostasis in diabetic cardiomyopathy.

Abstract 13631: Desmoplakin Cardiomyopathy in Pediatric Patients - A Distinct, Underrecognized Cohort of Arrhythmogenic Cardiomyopathy

Introduction: Arrhythmogenic cardiomyopathy is a spectrum of diagnoses including the historically recognized arrhythmogenic right ventricular cardiomyopathy. More recent literature describes predominately left ventricular (LV) or biventricular (BiV) involvement. Variants in the desmoplakin ( DSP) gene commonly cause LV and BiV phenotypes, though data in children are sparse. Hypothesis: Pediatric patients (pts) with DSP mutation have predominantly LV or BiV disease and may present with early onset malignant arrhythmia. Methods: We performed a multicenter, retrospective cohort study of pts <21 years with pathogenic or likely pathogenic DSP variants from 6 tertiary referral children’s hospitals. We describe clinical variation in DSP probands (PBs), the first affected family member prompting genetic testing due to clinical history, as compared to genotype-positive family members (FMs) <21 years of age diagnosed by familial cascade screening. Results: We identified 34 pts; 12 (35%) were PBs and 22 (65%) were FMs. Median age at genetic diagnosis was 13.3 and 12.3 years for PBs and FMs, respectively. Four PBs had LV-predominant disease; 6 had BiV disease (table 1). The most common initial diagnosis for PBs was myocarditis and dilated cardiomyopathy. ECG abnormalities were common in PBs (75%) and included left axis deviation, inferolateral T-wave inversion, and low QRS complex amplitude. The LV ejection fraction (EF) on echo was 48% and 65% for PBs and FMs, respectively. Eight PBs underwent MRI and 6 had late gadolinium enhancement involving the LV only, while 2 had BiV involvement. Six PBs underwent ICD implantation and 2 received appropriate ICD therapy (LVEF 25% and 41%). Two PBs had cardiac transplantation. Conclusion: Pediatric DSP -cardiomyopathy has predominantly LV or BiV involvement and may be misdiagnosed as myocarditis or dilated cardiomyopathy. Probands in particular, may present with early malignant ventricular arrhythmias and significant LV dysfunction.

Successful treatment of severe subaortic stenosis with left ventricular dysfunction in children

Link of Video Abstract: https://youtu.be/tHcMqNHfLyYBackground: Subaortic stenosis (SAS) is the second most common form of left ventricular outflow obstruction, accounting for 14% of LVOT obstruction in the general population. This obstruction is in the area of the heart under the aortic valve. While only a few cases have been reported in pediatrics, SAS is a gradually progressive disorder rarely seen at birth and infancy. This case study aims to evaluate the successful treatment of severe SAS with left ventricular dysfunction in children Case Presentation: We present the case of an 8-year-old boy who presented with shortness of breath on exertion and diaphoresis 3 months ago. Transthoracic echocardiography revealed severe aortic stenosis (PG 69.86 mmHg) with discrete tissue in the anterior LVOT and left ventricular systolic function decreased (EF Teich 29.44%), with global hypokinetic. Transesophageal echocardiography (TEE) results in severe subvalvular AS with a fixed subaortic membrane (PG 51.16 mmHg; Stenotic area 0.1 cm2), anterior to the aortic valve 1 cm long. There was mild mitral regurgitation and moderate tricuspid regurgitation. The patient then undergoes successful medical treatment and surgical subaortic membrane resection with tricuspid repair. After one year's operation, the patient remained stable, in good condition and free of symptoms. Conclusion: Subaortic stenosis is a gradually progressive disorder and could develop into heart failure with significant left ventricular dysfunction. Monitoring is an important aspect, given the nature of disease progression. Successful management of a patient with subaortic stenosis involves a multidisciplinary approach, including an early diagnosis, a comprehensive understanding of cardiac pathophysiology, risk factors of recurrence, optimal medical management and surgical strategy.

Subclinical myocardial injury increases the risk of heart failure in patients with and without type 2 diabetes post-acute coronary syndrome

BackgroundLittle is known about the effect of subclinical myocardial injury (sMi) on heart failure (HF) risk after acute coronary syndrome (ACS). We examined the frequency patterns of sMi after ACS among patients with and without diabetes mellitus (DM), and the influence of sMis on HF risk at 1 year. MethodsFifty patients with ACS who underwent revascularization were prospectively enrolled. After discharge, serial study visits were conducted and high-sensitivity cardiac troponin T (hs-TnT) levels were checked at 3-month intervals for 1 year. sMi was defined as hs-TnT ≥14 ng/L without clinical symptoms. The primary endpoint was a composite of post-ACS chronic HF or significant left ventricular (LV) dysfunction without HF symptoms. A multivariable logistic regression model was used for risk evaluation. ResultsThe mean patient age was 58 years, and 90% were men. Overall, 44% of patients had DM, and the median LV ejection fraction at discharge was 56%. Patients with DM had a higher incidence of sMi than those without DM (63.6% vs. 32.1%, P < 0.05). sMi occurred at least twice in most patients, and the prevalence declined over time in DM, but not in non-DM. Fourteen patients (28%) met the primary endpoint at 1 year, and the risk was higher in patients with DM (odds ratio: 4.99) and patients with sMi (odds ratio: 6.26). However, sMi was not a mediator of the association between DM and HF risk. ConclusionsPatients with DM had a higher incidence of sMi. Nonetheless, sMi increased the risk of HF after ACS, irrespective of diabetes status.

Sacubitril/valsartan mitigates cardiac remodeling, systolic dysfunction, and preserves mitochondrial quality in a rat model of mitral regurgitation

Sacubitril/valsartan (SAC/VAL), an angiotensin receptor blocker-neprilysin inhibitor, has been widely used to treat several types of heart failure. Nevertheless, the effects of drugs in mitral regurgitation patients, from the molecular level to therapeutic effects, remain unclear. This study investigates the roles of SAC/VAL on cardiac function, mitochondrial quality, autophagy, mitophagy, and natriuretic peptides in a rat model of chronic mitral regurgitation. Male Sprague–Dawley rats underwent MR induction (n = 16) and sham surgeries (n = 8). Four weeks post-surgery confirmed MR rats were randomly divided into MR (n = 8) and SAC/VAL (n = 8) groups. The SAC/VAL group was administered SAC/VAL, whereas the MR and the sham rats received vehicle via oral gavage daily for 8 weeks. Cardiac geometry, function, and myocardial fibrosis were assessed by echocardiography and histopathology. Spectrophotometry and real-time PCR were performed to assess the pharmacological effects on mitochondrial quality, autophagy, mitophagy, and natriuretic peptides. MR rats demonstrated significant left heart dilation and left ventricular systolic dysfunction compared with the sham group, which could be significantly improved by SAC/VAL. In addition, SAC/VAL significantly reduced myocardial cardiac remodeling and fibrosis in MR rats. SAC/VAL improved the mitochondrial quality by attenuating mitochondrial reactive oxygen species production and mitochondrial depolarization compared with the MR group. Also, the upregulation of autophagy-related, mitophagy-related, and natriuretic peptide system gene expression in MR rats was attenuated by SAC/VAL treatment. In conclusion, this study demonstrated that SAC/VAL treatment could provide numerous beneficial effects in MR conditions, suggesting that this drug may be an effective treatment for MR.

Prevalence of Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus &amp; its Association with HbA1c

Objective: Diabetes mellitus progressively augmented over the previous years in India and through the world, with India subsidizing a foremost part of the global encumbrance. The current study has been aimed to assess left ventricular diastolic dysfunction in diabetic person and to evaluate the correlation of diastolic dysfunction also its HbA1c range.&#x0D; Material and methods: This prospective, cross-sectional, observational study has been performed for one year from September 2018 to August 2019 in the Bhima bhoi medical college &amp; Hospital, Balangir, Odisha. 70 patients of Type 2 DM have been enrolled in the present study. The primary objective of the present study is to evaluate the incidence of LVDD in cases with Type 2 DM without any prior cardiac complications. Glycosylated haemoglobin has been estimated by ion exchange resin method. 2D Doppler Echocardiography was used to diagnose LVDD.&#x0D; Results: A large proportion or 48.6% of the diabetics in the study were diagnosed with LVDD of grade I severity. Data revealed that increased levels of glycated haemoglobin caused the severity of LVDD to worsen. With HbA1c levels between 0-8.9 per cent, 67.4% had grade I LVDD, with HbA1c levels between 9-10.9%, majority or 76.9% had grade II dysfunction and similarly with HbA1c between 11-18%, 90.9% of patients had grade III LVDD. This correlation found to be statistically significant (p&lt;0.00001).&#x0D; Conclusion: Higher values of FPG, PPPG and HbA1c were associated with higher incidence of LVDD. Thus, optimal glycaemic control may lower the risk of having early diastolic dysfunction and its progression. This has been perceived with cases with Type 2 diabetes mellitus may remain asymptomatic despite having significant left ventricular diastolic dysfunction

Acute neurogenic stunned myocardium in a patient with Guillain-Barré syndrome: case report.

A 65-year-old man with GBS presented with reversible left ventricular systolic failure. On first presentation, our patient had no history or indications of heart malfunction. During the clinical manifestation of his autonomic dysfunction, he had electrocardiographic alterations, modestly increased cardiac enzymes, significant left ventricular systolic dysfunction, and segmental wall motion irregularity. Once the initial episode was over, these anomalies and his symptoms resolved quickly. We believe the reversible left ventricular dysfunction was caused by the toxic impact of elevated catecholamines as well as transiently injured sympathetic nerve endings in the myocardium, which was apparently caused by GBS. We recommend that echocardiography be performed in patients who exhibit clinical signs of autonomic dysfunction, particularly if they are associated with abnormal electrocardiographic findings, cardiac enzyme elevation, or hemodynamic instability, so that appropriate medical therapy can be instituted as soon as possible. GBS is a not a very rare situation in our context. Thus, doctors are supposed to know the life-threatening complications such as neurogenic stunned myocardium and be prepared to dodge it.

Pathology and pathophysiology of the aortic root.

Pathologies of the aortic root amenable to repair with valve preservation include aneurysm formation, development of aortic insufficiency (AI) and aortic dissection. In the normal aortic root, the walls are constructed of 50-70 layers of concentric lamellar units. These units consist of sheets of elastin sandwiching smooth muscle cells interspersed with collagen and glycosaminoglycans. Medial degeneration results in disruption of the extracellular matrix (ECM), loss of smooth muscle cells and pooling of proteoglycans/glycosaminoglycans. These structural changes are associated with aneurysm formation. Aortic root aneurysms are commonly linked to hereditary thoracic aortic diseases including Marfan syndrome and Loeys-Dietz syndrome. One important pathway for hereditary thoracic aortic diseases is the transforming growth factor-β (TGF-β) cell-signalling pathway. Pathogenic gene mutations affecting various levels of this pathway have been implicated in aortic root aneurysm formation. Secondary effects of aneurysm formation include AI. Severe chronic AI leads to a pressure and volume load on the heart. Once symptoms develop or significant left ventricular remodelling and dysfunction occurs, the patient's prognosis is poor without surgery. Another consequence of aneurysm formation and medial degeneration is the risk of aortic dissection. Aortic root surgery is performed in 34-41% of surgeries for type A aortic dissection. Predicting those who will experience aortic dissections remains a challenge. Finite element analysis, study of fluid-structure interactions and aortic wall biomechanics are important areas of ongoing research.

Effect of standard phlebotomy on myocardial and hepatic iron levels in newly diagnosed cardiac asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.

Effect of standard phlebotomy on myocardial and hepatic iron levels in newly diagnosed cardiac asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.

Microvascular obstruction identifies a subgroup of patients who benefit from stem cell therapy following ST-elevation myocardial infarction

Microvascular obstruction (MVO) is associated with greater infarct size, adverse left-ventricular (LV) remodeling and reduced ejection fraction following ST-elevation myocardial infarction (STEMI). We hypothesized that patients with MVO may constitute a subgroup of patients that would benefit from intracoronary stem cell delivery with bone marrow mononuclear cells (BMCs) given previous findings that BMCs tended to improve LV function only in patients with significant LV dysfunction. We analyzed the cardiac MRIs of 356 patients (303 M, 53 F) with anterior STEMIs who received autologous BMCs or placebo / control as part of 4 randomized clinical trials that included the Cardiovascular Cell Therapy Research Network (CCTRN) TIME trial and its pilot, the multicenter French BONAMI trial and SWISS-AMI trials. A total of 327 patients had paired imaging data at 1 year. All patients received 100 to 150 million intracoronary autologous BMCs or placebo / control 3 to 7 days following primary PCI and stenting. LV function, volumes, infarct size and MVO were assessed prior to infusion of BMCs and 1 year later. Patients with MVO (n = 210) had reduced LVEF and much greater infarct size and LV volumes compared to patients without MVO (n=146) (P < .01). At 12 months, patients with MVO who received BMCs had significantly greater recovery of LVEF compared to those patients with MVO who received placebo (absolute difference=2.7%; P < .05). Similarly, left-ventricular end-diastolic (LVEDVI) and end-systolic volume indices (LVESVI) demonstrated significantly less adverse remodeling in patients with MVO who received BMCs compared to placebo. In contrast, no improvement in LVEF or LV volumes was observed in those patients without MVO who received BMCs compared to placebo. The presence of MVO on cardiac MRI following STEMI identifies a subgroup of patients who benefit from intracoronary stem cell therapy.

Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function on Cardiovascular Death

Background Coronary microvascular dysfunction (CMD) has been considered as a possible cause of cardiac diastolic dysfunction. The current study evaluated the association between cardiac diastolic dysfunction and CMD, and their prognostic implications in patients without significant left ventricular systolic dysfunction and epicardial coronary stenosis. Methods and Results A total of 330 patients without left ventricular systolic dysfunction (ejection fraction ≥50%) and significant epicardial coronary stenosis (fractional flow reserve >0.80) were analyzed. Cardiac diastolic dysfunction was defined by echocardiographic parameters (early diastolic transmitral flow velocity/early diastolic mitral annular velocity, e' velocity, tricuspid regurgitation velocity, and left atrial volume index). Overt CMD was defined as coronary flow reserve <2.0 and index of microcirculatory resistance ≥25 U. The primary end point was cardiovascular death or admission for heart failure during 5 years of follow-up. In patients without left ventricular systolic dysfunction and significant epicardial coronary stenosis, prevalence of cardiac diastolic dysfunction and overt CMD was 25.5% and 11.2%, respectively. Overt CMD was independently associated with cardiac diastolic dysfunction (adjusted odds ratio, 3.440 [95% CI, 1.599-7.401]; P=0.002). Patients with cardiac diastolic dysfunction showed significantly higher risk of the primary outcome than those without (adjusted hazard ratio [HR], 2.996 [95% CI, 1.888-4.755]; P<0.001). Patients with overt CMD also showed significantly higher risk of the primary outcome than those without (adjusted HR, 2.939 [95% CI, 1.642-5.261]; P<0.001). Presence of overt CMD was associated with significantly increased risk of cardiovascular death among the patients with cardiac diastolic dysfunction (43.8% versus 14.5%; P=0.006) but not in patients without cardiac diastolic dysfunction (interaction P<0.001). Inclusion of overt CMD into the model with cardiac diastolic dysfunction significantly improved predictive ability for cardiovascular death or heart failure admission (conconrdance index, 0.719 versus 0.737; P for comparison=0.034). Conclusions There was significant association between the presence of cardiac diastolic dysfunction and overt CMD. Both cardiac diastolic dysfunction and overt CMD were associated with increased risk of cardiovascular death or admission for heart failure. Integration of overt CMD into cardiac diastolic dysfunction showed improvement of the risk stratification in patients without significant left ventricular systolic dysfunction and epicardial coronary stenosis. Registration DIAST-CMD (Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function) registry; Unique identifier: NCT05058833.

First-Phase Left Ventricular Ejection Fraction as an Early Sign of Left Ventricular Dysfunction in Patients with Stable Coronary Artery Disease.

Left ventricular (LV) systolic function is often measured with echocardiography using LV ejection fraction (LVEF) or global longitudinal peak systolic strain (GLPSS). Global wasted work (GWW), global work efficiency (GWE), and first-phase ejection fraction (LVEF-1) are newer LV systolic function indices. We examined these parameters in 45 healthy individuals and 50 patients with stable coronary artery disease (CAD), normal LV contractility, and LVEF > 50%. Compared to healthy individuals, CAD patients had similar LVEF but increased GLPSS and GWW and reduced GWE and LVEF-1. The highest area under the receiver operating characteristic for detecting CAD was found for LVEF-1 (0.84; 95% CI 0.75-0.91; p < 0.0001), and it was significantly larger than for GLPSS (+0.166, p = 0.0082) and LVEF (+0.283, p = 00001). For LVEF-1 < 30%, the odds ratio for the presence of CAD was 22.67 (95% CI 6.47-79.44, p < 0.0001) in the logistic regression adjusted for age, sex, and body mass index. Finding LVEF-1 < 30% in an individual with normal LV myocardial contraction and preserved LVEF strongly suggests the presence of CAD.

Dang Gui Bu Xue Tang, a conventional Chinese herb decoction, ameliorates radiation-induced heart disease via Nrf2/HMGB1 pathway.

Introduction: Radiation-induced heart disease (RIHD), characterized by cardiac dysfunction and myocardial fibrosis, is one of the most common complications after cardiothoracic radiotherapy. Dang Gui Bu Xue Tang (DBT) is a conventional Chinese herb decoction composed of Radix Astragali membranaceus (RAM) and Radix Angelicae sinensis (RAS) at a ratio of 5:1, famous for its "blood-nourishing" effect. In this study, we aimed to investigate the cardioprotective effect of DBT on RIHD. Methods: C57BL mice at 8 weeks of age were divided into five groups, namely Control, Radiation, RDBT51 (Radiation with DBT, RAM:RAS = 5:1), RDBT11 (Radiation with DBT, RAM:RAS = 1:1), and RDBT15 (Radiation with DBT, RAM:RAS = 1:5). Results: We mainly found that radiation in the cardiothoracic region led to significant left ventricular systolic dysfunction, myocardial fibrotic lesions and cardiac injury accompanied by abnormally increased myocardial HMGB1 protein levels. Administration of conventional DBT significantly ameliorated left ventricular systolic dysfunction, alleviated myocardial fibrosis, and counteracted cardiac injury, all of which supported the protective effect of DBT on RIHD, involving upregulation of myocardial Nrf2 protein levels and downregulation of HMGB1 protein levels as underlying mechanisms. Conclusions: DBT exerts a significant protective effect on RIHD, and the Nrf2/ HMGB1 pathway probably plays an important role in this protective effect.

Prediction of Left Ventricle Function from Pre-Operative Left Ventricle End-Systolic Dimension in Mitral Valve Replacement

Rheumatic heart disease is an endemic in developing countries. The most common valve affected is the mitral valve for which mitral valve replacement is done. Left Ventricle Function (LVEF) is used to measure the prognosis of patients after MVR. Patients with a good LVEF perform better with less morbidity and mortality in comparison to patients with low post-operative EF. Therefore, prediction of post-operative EF is mandatory in patient’s selection and post-operative management. Objective: To determine the effect of pre-operative left ventricular end-systolic dimension in predicting postoperative LV function in mitral valve replacement. Methods: A total of 100 patients with mitral valve replacement were selected for the research. The study was conducted at the cardiac surgery department of National Institute of Cardiovascular Diseases, Karachi from April 2022 to October 2022. Results: The mean age of patients was 37 ± 10 years, LVESD: 34.7 ± 8.4mm, LVEDD: 51.1 ± 9.1mm, PASP: 44 ± 11mmHg, and EF of 55 ± 9%. Patients having Left ventricular end-systolic dimension (LVESD)&gt; 38 mm had a significant post-operative left ventricular dysfunction after mitral valve replacement than patients having a pre-operative LVESD &lt; 38mm (p= 0.003). Moreover, patients having a pre-operative LV dysfunction (EF &lt;55%) were more prone to post-operative LV dysfunction(p=0.02). However, pre-operative LVESD is a more sensitive predictor of post-operative LV dysfunction than pre-operative LVEF (0.003&lt;0.02). Conclusion: Left Ventricular End-Systolic Dimension (LVESD) is a more sensitive parameter as compared to pre-operative LV ejection fraction (LVEF) in predicting post-operative LV ejection fraction (LVEF) after mitral valve replacement (MVR).

Abstract 10915: Microvascular Obstruction Identifies a Subgroup of Patients Who Benefit From Intracoronary Stem Cell Delivery Following ST-Elevation Myocardial Infarction

Aims: Microvascular obstruction (MVO) following ST-elevation myocardial infarction (STEMI) is associated with greater infarct size, adverse left-ventricular (LV) remodeling and reduced ejection fraction. We hypothesized that patients with MVO may constitute a subgroup of patients that would benefit from intracoronary stem cell delivery with bone marrow mononuclear cells (BMCs) given previous findings that BMCs tended to improve LV function only in patients with significant LV dysfunction. Methods and Results: We analyzed the cardiac MRIs of 356 patients (303 M, 53 F) with anterior STEMIs who received autologous BMCs as part of 3 clinical trials that included the Cardiovascular Cell Therapy Research Network (CCTRN) TIME trial and its pilot (n=157), the multi-center French BONAMI trial (n=91) and the SWISS-AMI trial (n=108). All patients received 100 - 150 million intracoronary autologous BMCs or placebo / control 3 - 7 days following primary PCI and stenting. LV function, volumes, infarct size and MVO were assessed prior to infusion of BMCs and 1 year later. Patients with MVO (n=210) had reduced LVEF and much greater infarct size and LV volumes compared to patients without MVO (n=146) (all p &lt; 0.01) (TABLE). At 12 months, patients with MVO who received BMCs had significantly greater recovery of LVEF compared to those patients with MVO who received placebo (absolute difference = 2.7 %; p &lt; 0.05). Similarly, the changes in left-ventricular end-diastolic (LVEDV) and end-systolic volumes (LVESV) were consistent with significantly less adverse remodeling in patients with MVO who received BMCs compared to placebo ( % change; LVEDV = -9.7%; p &lt; 0.05 and LVESVI = -14.7 %; p = 0.006). In contrast, patients without MVO experienced no benefit of BMC administration compared to placebo. Conclusion: The presence of MVO on cardiac MRI following STEMI identifies a subgroup of patients who may benefit from intracoronary stem cell delivery of BMCs.

Structural and functional changes of the left ventricle in the aluminum industry workers

Introduction. Identification of early signs of left ventricular dysfunction even before the development of their clinical manifestations will allow to identify patients at risk of heart failure for its timely prevention. The study aims to evaluate the structural and functional changes of the left ventricle in workers of the main professions of the aluminum industry. Material and methods. The study included 87 employees of the main professions of aluminum production - the main group and 69 employees of the Ministry of Emergency Situations - the comparison group. The average age of the main group was 48.49±0.51 years, the comparison group was 47.15±0.57 years (p=0.082). All of them underwent echocardiography according to modern recommendations for the quantitative assessment of the structure and function of the chambers of the heart. Results. In the main group, we have detected concentric remodeling of the left ventricle in 40% of people with arterial hypertension and in 10.3% with normal blood pressure (p=0.0019), diastolic dysfunction with impaired relaxation of the left ventricle in 73.3% and 43.6%, respectively (p=0.0056). Early echocardiographic indicators of left ventricular systolic dysfunction - GLS, S - had not only significant differences in the main group depending on the presence of hypertension but were also significantly lower in the main group in subjects with normal blood pressure than in the comparison group. In the main group, the researchers have identified a decrease in the longitudinal deformation of the left ventricle in 58.5% of people with arterial hypertension and in 28.2% with normal blood pressure (p=0.0063). In the studied groups without arterial hypertension, we have found a decrease in longitudinal deformation significantly more often in aluminum industry workers (p=0.001). Limitations. This study is limited to a sample of employees of the main professions of the aluminum industry undergoing periodic medical examination at the Research Institute of Complex Hygiene Problems and Occupational Diseases. Conclusion. Arterial hypertension in workers of the main professions of the aluminum industry leads to concentric remodeling, reduction of longitudinal deformation and development of diastolic dysfunction of the left ventricle. In aluminum production workers without arterial hypertension, the researchers have identified a violation of the systolic function of the left ventricle in the form of a decrease in the longitudinal deformation of the left ventricle and the systolic peak of the mitral ring movement at the level of the interventricular septum and the lateral wall of the left ventricle. Ethics. We have conducted the study in compliance with the standards of the Bioethical Committee of the Research Institute of Complex Problems of Hygiene and Occupational Diseases, established in accordance with the Helsinki Declaration of the World Association "Ethical Principles of Scientific Medical Research with Human Participation" as amended in 2013 and the "Rules of Clinical Practice in the Russian Federation", approved by Order of the Ministry of Health of the Russian Federation No. 266 dated 06.19.2003. All the subjects signed an informed consent to participate in the study.

A transgenic mouse model mimicking human cardiac amyloidosis

Abstract Background Heart failure (HF) pathophysiology complicating cardiac amyloidosis (CA) is poorly explored due to the lack of relevant animal model. A recently transgenic mouse expressing an amyloidogenic variant of human apolipoprotein AII was developed that showed ubiquitous amyloid deposit but limited data on cardiac involvement. Purpose To investigate heart structure and function in transgenic mice expressing an amyloidogenic variant of human apolipoprotein AII Methods Seventy-nine mice ageing 2 to 3 months were included in this study as follow: amyloidosis group (n=44) and sham (i.e. genetic mutation without phenotypic expression, n=35). Both were serially imaged by echocardiography (Vevo3100 Fujifilm) and cardiac magnetic resonance imaging (CMR, Biospec 4.7 tesla), and invasively explored by left–sided catheterization (pressure-volume loop [PV loop], Millar Catheterization), before sacrifice and histological investigations. Results As soon as 2–3 months of age, the amyloidosis group demonstrated significant left ventricular (LV) hypertrophy, diastolic dysfunction and left atrial dilatation compared with sham group (p&amp;lt;0.01). Left ventricular ejection fraction was initially normal in both groups but deteriorated in amyloidosis mice (p&amp;lt;0.001) before right ventricular function collapses (p&amp;lt;0.001). In amyloidosis group, PV loops showed significant LV end-diastolic pressure increase (p&amp;lt;0.001), stiffer LV (p&amp;lt;0.01) and reduced systolic function LV elastance (p&amp;lt;0.05). Invasive and non-invasive abnormalities paralleled severe CA deposits and subendocardial fibrosis matrix remodeling, both labeling by Congo red and Red Sirius coloration (p&amp;lt;0.001). CMR analysis showed significant T1 (p&amp;lt;0.05) and T2 (p&amp;lt;0.01) signal increase and significant decrease in myocardial perfusion (p&amp;lt;0.01) in the amyloidosis group. Clinically, mice with amyloidosis covered less distance during exercise test (p&amp;lt;0.001) and died earlier (log-rank test, p&amp;lt;0.01). Conclusion By mimicking human cardiac amyloidosis, the model of transgenic mouse expressing an amyloidogenic variant of human apolipoprotein AII is promising to investigate the underlying pathophysiology of heart failure due to amyloidosis. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Pfizer grant

WELLENS SYNDROME - REPORT OF TWO CASES IN A PATIENT WITH MULTIVESSEL CORONARY ARTERY DISEASE

Acute coronary syndrome is a leading cause of death and increased morbidity in developed countries.Wellens syndrome as a high-risk of acute coronary syndrome is characterized by changes in the ST-T segment in theprecordial leads, indicating critical stenosis of the left anterior descending artery (LAD). This syndrome belongs tothe subgroup of patients with unstable angina pectoris who have inverted T waves in the anterior precordial leads onthe electrocardiogram (ECG). In our paper, we presented two cases of Wellens syndrome with critical LAD stenosis,performed coronary angiography and LAD stent placement. Wellens' syndrome can be a marker of critical LADstenosis in both its proximal and midsection. Changes can be temporary, last for months or disappear afterrevascularization treatment. Coronary angiography of the patient may also reveal critical stenosis of RCA (80%),LCx (100%), and diagonal-1 (90%). Failure to recognize this syndrome can cause a delay in referring patients forurgent coronary angiography and revascularization therapy that can lead to anterior myocardial infarction,significant left ventricular dysfunction, and even death. About 75% of patients with Wellens syndrome treated withconservative management alone will develop an extensive anterior myocardial infarction within a few days, with anaverage of 8.5 days from the onset of symptoms. This case study concludes that clinicians should be aware of ECGchanges in Wellens syndrome, which may occur during the pain-free period. For the definitive management ofWellens syndrome, the treatment of choice is cardiac catheterization with percutaneous coronary intervention (PCI),to relieve the patient of the symptoms of Wellens syndrome, as well as a number of complications of this acutecondition.

Bipolar Electroporation Across theInterventricular Septum: Electrophysiological, Imaging, and Histopathological Characteristics.

Pulsed electric field (PEF) ablation is an emerging modality for the treatment of cardiac arrhythmias. Data regarding effects on the interventricular septum are limited, and the optimal delivery protocol and electrode configuration remain undefined. This study sought to evaluate the electrophysiological, imaging, and histological characteristics of bipolar direct-current PEF delivered across the interventricular septum. PEF was applied between identical solid-tip ablation catheters positioned on either side of the septum in a chronic canine model. Intracardiac and surface electrophysiological data were recorded following delivery. In 4 animals, cardiac magnetic resonance (CMR) was performed early (6 ± 2days) and late (30 ± 2days) postablation. After 4weeks of survival, cardiac specimens were sectioned for histopathological analysis. In 8 canines, PEF was delivered in 27 separate septal sites (45 ± 17 J/site) with either microsecond or nanosecond PEF. Acute complications included transient complete atrioventricular block in 5 animals (63%) after delivery at the anterobasal septum, with right bundle branch block persisting in 3 (38%). Ventricular fibrillation occurred in 1animal during microsecond but not nanosecond PEF. Postprocedural CMR showed prominent edema and significant left ventricular systolic dysfunction, which recovered with late imaging. At 4weeks, 36 individual well-demarcated lesions were demonstrated by CMR and histopathology. Lesion depth measured by histology was 2.6 ± 2.1mm (maximum 10.9mm and near transmural). Bipolar PEF ablation of the interventricular septum is feasible and can produce near transmural lesions. Myocardial stunning, edema, and conduction system injury may occur transiently. Further studies are required to optimize safe delivery and efficacious lesions.

Cardiac Assessment in Children with MIS-C: Late Magnetic Resonance Imaging Features.

Multisystem Inflammatory Syndrome (MIS-C) is a new entity that emerges 2–4 weeks after the SARS-CoV-2 infection in children. MIS-C can affect all systems, the most severe of which is cardiac involvement. The duration of the cardiac symptoms is still uncertain and may be persistent or prolonged. The American College of Rheumatology Clinical Guidelines recommends cardiac magnetic resonance imaging (MRI) 2–6 months after the diagnosis of MIS-C in patients presenting with significant transient left ventricular (LV) dysfunction in the acute phase of illness (LV ejection fraction 50%) or persistent LV dysfunction. There are a few studies investigating cardiac MRI findings in MIS-C patients. In this study, we aimed to evaluate cardiac MRI findings, at the earliest 3 months after diagnosis, and compare these findings with the echocardiograms in children with MIS-C. A retrospective study including 34 MIS-C patients was conducted at a tertiary-level University Hospital between June 2020 and July 2021. Centers for Disease Control and Prevention criteria were used in the diagnosis of MIS-C. Cardiac MRI was performed at least 3 months after MIS-C diagnosis. The study included 17 (50%) boys and 17 (50%) girls with a mean age of 9.31 ± 4.72 years. Initial echocardiographic evaluation revealed cardiac abnormality in 13 (38.2) patients; 4 (11.8%) pericardial effusion, 4 (11.8%) left ventricular ejection fraction (LVEF) < 55%, and 5 (14.7%) coronary artery dilatation. Echocardiography showed normal LV systolic function in all patients during follow-up; coronary dilatation persisted in 2 of 5 (40%) patients at the 6th-month visit. Cardiac MRI was performed in 31 (91.2%) patients, and myocardial hyperemia was not detected in any patients (T1 relaxation time was < 1044 ms in all children). However, 9 (29%) patients’ MRI showed isolated elevated T2 levels, and 19 (61.3%) revealed at least one of the following findings: pericardial effusion, right ventricular dysfunction, or LVEF abnormality. In patients with MIS-C, a high rate of cardiac involvement, particularly pericardial effusion was determined by cardiac MRI performed at the earliest 2–6 months after diagnosis. Even if echocardiography does not reveal any abnormality in the initial phase, cardiac MRI should be suggested in MIS-C patients in the late period. This is the first study reporting cardiac MRI findings in the late period of MIS-C patients.