Ventricular Wall Hypertrophy Research Articles

8746 Primary Prevention and Early Intervention for Cardiovascular Disease in Polyglandular Autoimmune Syndrome Type 2

Abstract Disclosure: V.N. Flores-Robles: None. Y. Fuentes-Rosa: None. M. Sanchez-Cordero: None. D.A. Lopez: None. M. Carrero-Quinones: None. Introduction: Polyglandular autoimmune syndrome type 2 (PAS-2) is an autoimmune syndrome that is known for lymphocytic infiltration causing organ-specific damage. It can include primary adrenal insufficiency (Addison's disease), type 1 diabetes mellitus (T1DM), autoimmune thyroid disease-causing Grave’s disease, or hypothyroidism, and can be diagnosed when two out of these three pathologies are present. Carpenter syndrome, a type of PAS-2, is described as the triad of Addison's disease, autoimmune thyroid disease, and T1DM. Its initial manifestation can be associated with non-endocrine and endocrine disorders as in autoimmune thyroid disease, T1DM, primary hypogonadism, and diabetes insipidus. It is well documented that uncontrolled diabetes mellitus can accelerate the progression of cardiovascular disease of co-existing coronary artery disease, but documentation that Addison’s disease may accelerate the progression is scant with only ten cases documented. On the other hand, there are no documented cases of the presence of coronary artery disease in patients with PAS-2. Case report: This case involves a 66-year-old Hispanic male with a past medical history of hypertension, and PAS-2, presenting with Addison’s disease, type 1 diabetes mellitus, and hypothyroidism. The initial presentation at the hospital was that of a complete atrioventricular block that required pacemaker placement. Cardiology services were consulted as the patient also had a positive stress test and eventually cardiac catheterization was done as further workup. Cardiac catheterization showed obstruction of the left main coronary artery of 80% and left circumflex with mild disease, that required coronary artery bypass (CABG). A 2D ECHO was done for further evaluation of cardiac function and findings were pertinent for an ejection fraction of 65-70%, mild concentric hypertrophy of the left ventricular wall, and left ventricular diastolic function with impaired relaxation pattern. The patient underwent the CABG procedure without any complications. He has been followed up outpatient and remains without any symptoms or pertinent presentation. Early intervention in this patient with PAS-2 prevented any further cardiovascular complications. Conclusion: Patients with PAS-2 may have a predisposition to developing coronary artery disease due to concomitant endocrinopathies that independently increase the risk of cardiovascular disease. This promotes further investigation into the primary prevention of cardiovascular disease in patients presenting with PAS-2. Taking into consideration the increased risk and/or progression of cardiovascular disease in these patients, early intervention and evaluation by cardiology services should be suggested as it may decrease their morbidity or mortality. Presentation: 6/2/2024

The Unseen Side of Feline Hypertrophic Cardiomyopathy: Diagnostic and Prognostic Utility of Electrocardiography and Holter Monitoring.

Hypertrophic cardiomyopathy (HCM) is a common heart disease in cats, characterized by regional or diffuse hypertrophy of the left ventricular walls, with an uncertain etiology and heterogenous natural history. Several types of rhythm disturbances are often associated with the disease. This study conducts a comprehensive review of the current literature, in order to evaluate the diagnostic and prognostic effectiveness of electrocardiography and Holter monitoring in the management of feline hypertrophic cardiomyopathy. The main subjects of discussion will include general information about HCM and its connection to arrhythmias. We will explore the rhythm disturbances documented in the current literature on Holter monitoring, as well as the techniques used for Holter monitoring. Additionally, the review will cover classical electrocardiography (ECG) and its diagnostic utility. Prognostic indicators and anti-arrhythmic therapy will also be discussed in detail. The findings highlight the importance of understanding arrhythmias in feline HCM for accurate diagnosis, risk assessment, and therapeutic intervention. ECG and Holter monitoring may offer valuable insights into managing feline HCM.

Left ventricular posterior wall hypertrophy leads to poor prognosis of hypertrophic obstructive cardiomyopathy in children - a cohort study.

The modified Morrow operation for hypertrophic obstructive cardiomyopathy (HOCM) in children has a favorable outcome, but some children still have a poor prognosis after the procedure. In this study, we aimed to investigate the application of cardiac computed tomography (CCT) to construct a three-dimensional(3D) model of the left ventricle (LV) and analyze the association between hypertrophy in different parts of the LV and poor prognosis. We retrospectively analyzed 57 children with HOCM from April 2015 to October 2022, among whom 16 underwent preoperative CCT examination. All children underwent the modified Morrow surgery in our center. We defined heart failure (HF), malignant ventricular arrhythmia, and recurrent left ventricular outflow tract obstruction (LVOTO) as adverse events. We performed a retrospective Cox analysis and conducted genetic testing. A 3D model of the LV was built through the standard 17-segment method and analyzing the high-risk factors. 17 (29.8%) had adverse events during follow-up. Multivariate Cox analysis revealed that genetic mutation (HR:5.634, 95%CI:1.663-19.086, P=0.005), Noonan syndrome (HR:3.770, 95%CI:1.245-11.419, P=0.019), preoperational systolic anterior motion (SAM)(HR:4.596, 95%CI:1.532-13.792, P=0.007)and mid-ventricular obstruction (HR:4.763, 95%CI:1.538-14.754, P=0.007) were high-risk factors, suggesting that the degree of hypertrophy in the left ventricle is associated with poor prognosis. By analyzing the CCT with 3D model, children with poor prognosis have more hypertrophy in basal-inferior (P=0.014), mid-inferoseptal(P=0.044), mid-inferior(P=0.017). It suggests that a more hypertrophied posterior left ventricular wall portends a worse prognosis. Even after modified Morrow surgery, the prognostic impact of genetic mutation remains significant. Moreover, the degree of hypertrophy of the posterior wall in the LV was also related to the postoperative prognosis through CCT combined with 3D technology. It provides surgeons guiding to evaluate the overall prognosis and the treatment plan before surgery.

High-intensity interval training improves respiratory and cardiovascular adjustments before and after initiation of exercise.

Purpose: High-intensity interval training (HIIT) may induce training-specific physiological adaptations such as improved respiratory and cardiovascular adjustments before and after the onset of high-intensity exercise, leading to improved exercise performance during high-intensity exercise. The present study investigated the effects of HIIT on time-dependent cardiorespiratory adjustment during maximal exercise and before and after initiation of high-intensity exercise, as well as on maximal exercise performance. Methods: 21 healthy male college students were randomly assigned to HIIT group (n = 11) or control group (n = 10). HIIT group performed training on a cycle ergometer once a week for 8 weeks. The training consisted of three bouts of exercise at 95% maximal work rate (WRmax) until exhaustion. Before and after the HIIT program, dynamic cardiorespiratory function was investigated by ramp and step exercise tests, and HIIT-induced cardiac morphological changes were assessed using echocardiography. Results: HIIT significantly improved not only maximal oxygen uptake and minute ventilation, but also maximal heart rate (HR), systolic blood pressure (SBP), and time to exhaustion in both exercise tests (p < 0.05). Time-dependent increases in minute ventilation (VE) and HR before and at the start of exercise were significantly enhanced after HIIT. During high-intensity exercise, there was a strong correlation between percent change (from before to after HIIT program) in time to exhaustion and percent change in HRmax (r = 0.932, p < 0.001). Furthermore, HIIT-induced cardiac morphological changes such as ventricular wall hypertrophy was observed (p < 0.001). Conclusion: We have demonstrated that HIIT at 95% WRmax induces training-specific adaptations such as improved cardiorespiratory adjustments, not only during maximal exercise but also before and after the onset of high-intensity exercise, improvement of exercise performance mainly associated with circulatory systems.

A wolf in sheep's clothing-aortic stenosis and cardiac amyloidosis: "RAISE"ing awareness in clinical practice.

Aesop's fable of the wolf in sheep's clothing encourages us to look beneath the exterior appearance of a situation and evaluate the truth that lies beneath. This concept should be applied when managing older patients with severe aortic stenosis. This population of patients is increasingly being identified as having concomitant cardiac amyloidosis, which is an underrecognized cause of common cardiac conditions. The presence of cardiac amyloidosis negatively affects the outcome of patients with aortic stenosis, these patients undergo transcatheter aortic valve replacement (TAVR) with increasing frequency and have a significantly higher overall mortality rate than patients with aortic stenosis alone. Although left ventricular wall hypertrophy is expected in patients with aortic stenosis, it should not be assumed that this is caused only by aortic stenosis. A suspicion of cardiac amyloidosis should be raised in patients in whom the degree of hypertrophy is disproportionate to the degree of aortic stenosis severity. The remodeling, age, injury, systemic, and electrical (RAISE) score was developed to predict the presence of cardiac amyloidosis in patients with severe aortic stenosis. This article highlights the value of increased clinical suspicion, demonstrates the use of the multiparameter RAISE score in daily clinical practice, and illustrates the scoring system with case studies. In elderly patients being considered for TAVR, systematic testing for cardiac amyloidosis should be considered as part of the preoperative workup.

Передчасно закрита артеріальна протока: можливі ризики для новонародженого

Premature closure of the fetal ductus arteriosus is a rare phenomenon that results in increased right ventricular pressure, leading to the development of isolated right ventricular hypertrophy, high pulmonary hypertension, and even death. Purpose - to present a rare clinical case of prenatally closed ductus arteriosus in a newborn boy, that clinically manifested by severe respiratory failure immediately after birth. Clinical case. The child was admitted to the neonatal intensive care unit 5 hours after delivery with clinical signs of severe respiratory failure, child was oxygen-dependent. It is known from the anamnesis that the child was delivered by urgent cesarean section on the basis of a prenatally diagnosed prematurely closed arterial duct. A week before the delivery, the mother had an acute respiratory viral infection accompanied by high fever, which was treated with high doses of over-the-counter ibuprofen. The 2D echocardiography showed severe hypertrophy of the right ventricular wall and tricuspid insufficiency, which was caused by premature closure of the ductus arteriosus. The flow through the ductus arteriosus was not determined. Aortic coarctation as a possible cause of right ventricular hypertrophy in the newborn period was excluded. The infant was switched to constant positive pressure artificial ventilation (CPAP) to reduce pulmonary vascular resistance and afterload of the right ventricle. Over the next 3-4 weeks of oxygen therapy, the child's general condition improved significantly. Hypertrophy of the right ventricular wall regressed to normal size, the child grows and develops according to age. Conclusions. Premature prenatal closure of the arterial duct can be idiopathic or caused drugs intake that suppress prostaglandin production late in the pregnancy. Pregnant women should be counseled about the potential side effects on the fetus caused by the use of NSAIDs, especially in the third trimester of pregnancy. Urgent delivery and oxygen therapy contribute to the regression of intracardiac changes and significantly improve general condition of the child. The study was conducted in accordance with the principles of the Declaration of Helsinki. The informed consent of the child’s parents was obtained for the study. No conflict of interests was declared by the authors.

Coronaro Cameral Fistula: Literature Review, Diagnosis and Management, about a Case

A coronary fistula is defined as a direct connection between a coronary artery and a heart chamber, great vessel, or other vascular structure that "bypasses" the myocardial capillary bed. This is a rare pathology that is usually not discovered until later in life, and exceptionally not during childhood. We report the case of a young patient who was hospitalized for chest pain and shortness of breath and who was found to have a coronary fistula on angiography.&#x0D; A 66-year-old patient. Hypertension on dual therapy for 16 years and diabetes on OAD (Oral Antidiabetic) for 4 years. He was hospitalized with typical angina pectoris and dyspnea, and the stress test was positive. Laboratory examination revealed a good general condition with NYHA stage 3 dyspneic angina pectoris extending to the upper extremities and no evidence of heart failure. Looking at the balance, we see a slight increase in troponin. ECG returns to regular sinus rhythm, with electrical LVH (left ventricular hypertrophy) and ambient negative waves, no rhythm or conduction abnormalities. Transthoracic echocardiography (TTE) reverses hypertensive heart disease with good global and partial contractility without significant valvular disease associated with systolic pulmonary arterial pressure (SPAP) at 35 mmHg. Coronary angiography is performed and shows evidence of minor involvement of the central CX artery and a coronary camera fistula from the first diagonal artery draining into the left ventricle.&#x0D; Management was about optimizing medical care. The patient received an appointment and was declared discharged.&#x0D; Coronary camera fistulae are rare, found in approximately 0.3% of coronary angiographic studies performed. Most are congenital and may occur primarily due to trauma, erosive infection of the vessel wall, or iatrogenicity during transluminal coronary angioplasty, myocardial biopsy, or valve replacement. In many cases, simple but complex forms can be described. The gold standard for confirming the diagnosis remains coronary angiography, which highlights both the affected arteries and drainage sites. Cardiac scanners occupy an increasingly important position, especially as they provide morphologically accurate information. Surgical or percutaneous treatment of the fistula with a coil is recommended in symptomatic adult patients, especially those with significant or complicated right-to-left shunts. The authors suggest treatment with β-blockers when multiple sinusoidal fistulas associated with ventricular wall hypertrophy are present. Close monitoring is recommended for asymptomatic small fistula.&#x0D; Corneal fistula is a rare congenital or acquired condition that is mostly asymptomatic and discovered in adulthood. Coronary angiography and heart scan can be used to confirm the diagnosis. Treatment is usually surgical or endovascular. However, in some cases, drug treatment with beta-blockers may help.

C60 MYOCARDIAL T1 MAPPING IN ANDERSON–FABRY DISEASE AND ITS CORRELATION WITH GENETIC ANOMALITIES

Abstract Objective Cardiac involvement in Anderson–Fabry Disease is possible even in mild forms, and new analytical methods and the quantitative value evident with the T1 Native sequence for Mapping study demonstrated a linear correlation with disease severity compared with traditional MR sequences. GLA gene alterations on the X chromosome are very heterogeneous and correlated with decreased or absent alpha–galactosidase enzyme, resulting in different timing of manifestation and clinical evolution. In addition to the classic form of central nervous system, kidney and heart involvement there is a variant with only cardiac involvement, also found in our study. Materials and Methods We retrospectively analyzed 18 consecutive Cardiac MRI examinations performed in patients with established Anderson–Fabry disease at the University Radiology Department of Policlinico Riuniti di Foggia from August 2019 to January 2022. Native T1 sequences for T1 Mapping study are currently the gold standard for evaluation of cardiac involvement in Anderson–Fabry disease. Results T1 Mapping values were lower with characteristic normality of ECV after mdc. In PSIR sequences acquired after mdc for the study of "Late Gadolinium Enhancement" usually a mesocardial signal hyperintensity of the infero–lateral wall of the left ventricle characterized by fibrotic deposits is evident but this sign usually occurs when the heart is already hypertrophied. Instead, reduced Native T1 values serve as an early marker of myocardial involvement, even before the development of hypertrophy as also found in our study population. In fact in 10 out of 18 patients the only value indicating myocardial involvement was reduced T1 Mapping Native values below 1000 in at least 3 out of 17 segments. In 6 cases there was concentric left ventricular wall hypertrophy and in 2 cases mesocardial hyperintensity was evident in the PSIR sequences for the "Late Gadolinium Enhancement" study of the basal segments of the infero–lateral left ventricular wall. Conclusions Magnetic resonance imaging plays a key role in the study of cardiac involvement in Anderson–Fabry disease with potential to predict the extent of detectable accumulation at the cardiac level based on the genetic abnormality.

Pathological mechanism of heart failure with preserved ejection fraction in rats based on iTRAQ technology.

Heart failure with preserved ejection fraction (HFpEF) is a public health problem worldwide. Treatments for the patients with HFpEF are not satisfactory because there is no unified understanding of the pathological mechanism of HFpEF. This study aims at investigating the potential pathological mechanism for the effective diagnosis and treatment of HFpEF. Ten adult male Dahl salt sensitive rats (180-200 g) were divided into control and model groups. The rats in model group were fed with high salt diet (8% NaCl) to induce HFpEF for this comparative study. Behavioral changes, biochemical parameters, and histopathological changes of the rats were detected. iTRAQ technology combined with bioinformatics analysis was employed to study the differentially expressed proteins (DEPs) and their enrichment in signaling pathways. Echocardiography detection showed decreased LVEF, indicating impaired cardiac function (P<0.01), increased LVPWd, indicating ventricular wall hypertrophy (P<0.05), prolonged duration of IVRT and decreased E/A ratio, indicating diastolic dysfunction (P<0.05) of the rats in model group. 563 DEPs were identified in the rats of both groups, with 243 up-regulated and 320 down-regulated. The expression of PPAR signaling pathway in the rats of model group was down-regulated, with PPARα most significantly decreased (91.2%) (P<0.01), PPARγ obviously decreased (63.60%) (P<0.05), and PPARβ/δ decreased (45.33%) (P<0.05). The DEPs enriched in PPAR signaling pathway were mainly related to such biological processes as fatty acid beta-oxidation, such cellular components as peroxisome, and such molecular functions as lipid binding. NaCl high salt diet is one of the factors to increase the incidence of HFpEF in rats. PPARα, PPARγ and PPAR β/δ might be the targets of HFpEF. The findings may provide a theoretical basis for the treatment of HFpEF in clinical practice.

Cardiac magnetic resonance-feature tracking technique can assess cardiac function and prognosis in patients with myocardial amyloidosis

To quantitatively assess cardiac functions in patients with cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) using cardiac magnetic resonance-feature tracking (CMR-FT) technique and evaluate the prognostic value of CMR-FT in patients with CA. We retrospectively collected the data from 31 CA patients with systemic amyloidosis confirmed by Congo red staining and serum immunohistochemistry after extracardiac tissue biopsy undergoing CMR at our hospital from March, 2013 to June, 2021.Thirty-one age and gender matched patients with asymmetric left ventricular wall hypertrophy and 31 healthy individuals without organic or functional heart disease served as the controls.Radial, circumferential and longitudinal strains and strain rates of the left ventricle at the global level and in each myocardial segment (basal, middle and apical) were obtained with CMR-FT technique and compared among the 3 groups.The predictive value of myocardial strains and strain rates for all-cause mortality in CA patients was analyzed using a stepwise COX regression model. The left ventricular volume, myocardial mass, ejection fraction and cardiac output differed significantly among the groups (P < 0.05).Except for apical longitudinal strain, the global and segmental strains were all significantly lower in CA group than in HCM group (P < 0.05).The global and segmental strains were all significantly lower in CA group than in the healthy individuals (P < 0.05).The basal strain rates in the 3 directions were significantly lower in CA group than in the healthy individuals (P < 0.05), but the difference in apical strain rates was not statistically significant between the two groups.Multivariate stepwise COX analysis showed that troponin T (HR=1.05, 95%CI: 1.01-1.10, P=0.017) and middle peak diastolic circumferential strain rate (HR=6.87, 95%CI: 1.52-31.06, P=0.012) were strong predictors of death in CA patients. Strain and strain rate parameters derived from CMR-FT based on cine sequences are new noninvasive imaging markers for assessing cardiac impairment in CA and cardiac function changes in HCM, and provide independent predictive information for all-cause mortality in CA patients.

The elite judo female athlete's heart.

Purpose: There is a paucity of data on physiological heart adaptation in elite-level judo female athletes. This study aimed to assess left ventricular morphology and function in highly trained elite female judokas. Methods: The study prospectively included 18 females aged 23.5 ± 2.25 years, nine elite level judokas, and nine healthy non-athlete volunteers. All participants underwent a medical examination, electrocardiogram, and transthoracic 2D echocardiogram. Left ventricular diastolic and systolic diameters and volumes were determined, and parameters of left heart geometry and function (systolic and diastolic) were measured, calculated, and compared between groups. Results: When groups were compared, judokas had significantly increased left ventricular cavity dimensions p < 0.01, left ventricular wall thickness p < 0.01, and volumes p < 0.01. Elite female judokas exhibited left ventricular dilatation demonstrated as high prevalence increased end-diastolic volume/index, and increased end-systolic volume/index in 88.9% of judokas vs. 0% in controls, p < 0.01. Left ventricle mass/index was significantly increased in judokas, p < 0.01), with a 43.3% difference between groups. The majority (77.7%) of judokas had normal left ventricular geometry, although eccentric hypertrophy was revealed in 2 (22.2%) of judokas. Conclusion: Elite, highly trained female judokas exhibit significant changes in left heart morphology as a result of vigorous training compared to non-athletes. These findings suggest that female judokas athletes’ heart follows a pattern toward chamber dilatation rather than left ventricular wall hypertrophy.

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model.

Familial hypertrophic cardiomyopathy (HCM, OMIM: 613690) is the most common cardiomyopathy in China. However, the underlying genetic etiology of HCM remains elusive. We previously identified a myosin heavy chain 7 (MYH7) gene heterozygous variant, NM_000257.4: c.G2468A (p.G823E), in a large Chinese Han family with HCM. In this family, variant G823E cosegregates with an autosomal dominant disorder. This variant is located in the lever arm domain of the neck region of the MYH7 protein and is highly conserved among homologous myosins and species. To verify the pathogenicity of the G823E variant, we produced a C57BL/6N mouse model with a point mutation (G823E) at the mouse MYH7 locus with CRISPR/Cas9-mediated genome engineering. We designed gRNA targeting vectors and donor oligonucleotides (with targeting sequences flanked by 134 bp of homology). The p.G823E (GGG to GAG) site in the donor oligonucleotide was introduced into exon 23 of MYH7 by homology-directed repair. A silenced p.R819 (AGG to CGA) was also inserted to prevent gRNA binding and re-cleavage of the sequence after homology-directed repair. Echocardiography revealed left ventricular posterior wall (LVPW) hypertrophy with systole in MYH7 G823E/- mice at 2 months of age. These results were likewise validated by histological analysis (Figure 3). These results demonstrate that the G823E variant plays an important role in the pathogenesis of HCM. Our findings enrich the spectrum of MYH7 variants linked to familial HCM and may provide guidance for genetic counseling and prenatal diagnosis in this Chinese family.

Single-cell transcriptome reveals effects of semaglutide on non-cardiomyocytes of obese mice

Non-cardiomyocytes (nonCMs) play an important part in cardiac fibrosis pathophysiology, but the underlying molecular pathways are unknown. Semaglutide has cardioprotective properties, but it is still unclear whether it helps with cardiac fibrosis and what the processes are. The goal of this study is to use single cell transcriptomics approaches to investigate the molecular mechanism of semaglutide's cardioprotective action in obese mice. We found 15 non-CMs, with fibroblasts making up the majority of them. We found eight DEGs that altered significantly following semaglutide treatment by screening for differentially expressed genes (DEGs). DEGs were shown to have biological activities primarily related to extracellular matrix and collagen synthesis and distribution, with Serpinh1 and Pcolce expression being the most dramatically altered. Serpinh1 and Pcolce were mostly found in fibroblasts, which play a key role in the fibrosis of the heart. Furthermore, we discovered that semaglutide lowered cardiac collagen content and alleviated obesity-induced ventricular wall hypertrophy. As a result, our findings show that Serpinh1 and Pcolce, which are expressed by fibroblasts, may play a role in the development of obese cardiac fibrosis. By reducing Serpinh1 and Pcolce expression and delaying cardiac fibrosis, semaglutide may have a cardioprotective effect.

Предиктори трирічного виживання в госпіталізованих пацієнтів з тріпотінням передсердь

Мета роботи – проаналізувати виживання пацієнтів з тріпотінням передсердь (ТП) після індексної госпіталізації протягом трирічного спостереження та визначити його незалежні предиктори.Матеріали і методи. До одноцентрового проспективного дослідження залучили 126 пацієнтів з різними формами ТП, зокрема 86 (68,3 %) чоловіків і 40 (31,7 %) жінок, медіана віку – 65,5 (квартилі 55–73) року. Медіана тривалості спостереження становила 26 (квартилі 1–46) місяців з моменту індексної госпіталізації. Аналіз впливу на виживання проводили методом регресії Кокса для неперервних характеристик, шляхом оцінки кривих Каплана – Мейєра з допомогою модуля «порівняння кількох груп» і розрахунку χ2 для рангових характеристик (при кількості рангів більше 2) та з допомогою F-критерію Кокса для альтернативних (бінарних) характеристик. Результати. За трирічний період померли 22 (17,5 %) пацієнти. Кумулятивна частка виживання на 36-й місяць спостереження становила 80,9 %. Незалежні предиктори фатальних виходів у пацієнтів з ТП за даними багатофакторного аналізу за методом регресії Кокса: зниження фракції викиду лівого шлуночка, гіпертрофія стінок лівого шлуночка, наявність попередніх епізодів ТП, порушення гемодинаміки на тлі пароксизму та хронічна хвороба нирок (p&lt;0,05).Висновки. Кумулятивна частка виживання пацієнтів з ТП на 36-й місяць спостереження становила 80,9 %. Незалежними предикторами гіршого виживання є зниження фракції викиду лівого шлуночка та гіпертрофія його стінок, повторні епізоди ТП, порушення гемодинаміки на тлі пароксизму та наявність хронічної хвороби нирок.

Outcomes and phenotypic expression of rare variants in hypertrophic cardiomyopathy genes in over 200,000 adults

Abstract Background Hypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomere-encoding genes, but little is known about the clinical significance of these variants in the general population. Purpose To determine the population prevalence of HCM-associated sarcomeric variants, characterise their phenotypic manifestations, estimate penetrance, and identify associations between sarcomeric variants and clinical outcomes, we performed an observational study of 218,813 adults in the UK Biobank (UKBB), of whom 200,584 have whole exome sequencing (WES). Methods We carried out an integrated analysis of WES and cardiac magnetic resonance (CMR) imaging in UK Biobank participants stratified by sarcomere-encoding variant status. Computer vision techniques were used to automatically segment the four chambers of the heart (Figure 1). Cardiac motion analysis was used to derive strain and strain rates. Regional analysis of left ventricular wall thickness was performed using three-dimensional modelling of these segmentations. Results Median age at recruitment was 58 (IQR 50–63 years), and participants were followed up for a median of 10.8 years (IQR 9.9–11.6 years) with a total of 19,507 primary clinical events reported. The prevalence of rare variants (allele frequency &amp;lt;0.ehab724.17314) in HCM-associated sarcomere-encoding genes in 200,584 participants was 2.9% (n=5,727; 1 in 35), and the prevalence of pathogenic or likely pathogenic variants (SARC-P/LP) was 0.24% (n=474, 1 in 423). SARC-P/LP variants were associated with increased risk of death or major adverse cardiac events (MACE) compared to controls (HR 1.68, 95% CI 1.37–2.06, p&amp;lt;0.001), mainly due to heart failure endpoints (Figure 2: cumulative hazard curves with zoomed plots for lifetime risk of A) death and MACE or B) heart failure, stratified by genotype; genotype negative (SARC-NEG), carriers of indeterminate sarcomeric variants (SARC-IND) or SARC-P/LP; C) Forest plot of comparative lifetime risk of clinical endpoints by genotype). While males had a higher overall risk of adverse outcomes, the incremental genetic risk from SARC-P/LP mutations was greater in females (HR for females: 2.18 CI 1.65–2.89, p&amp;lt;0.001; HR for males: 1.42 CI 1.05–1.9, p=0.02). In 21,322 participants with CMR, SARC-P/LP were associated with asymmetric increase in left ventricular maximum wall thickness (10.9±2.7 vs 9.4±1.6 mm, p&amp;lt;0.001) but hypertrophy (≥13mm) was only present in 16% (n=7/43, 95% CI 7–31%). Other rare sarcomere-encoding variants had a weak effect on wall thickness (9.5±1.7 vs 9.4±1.6 mm, p=0.002) with no combined excess cardiovascular risk. Conclusions In the general population, SARC-P/LP variants have low aggregate penetrance for overt HCM but are associated with increased risk of adverse cardiovascular outcomes and a sub-clinical cardiomyopathic phenotype. Although absolute event rates are low, identification of these variants may enhance risk stratification beyond familial disease. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The study was supported by the Medical Research Council, UK (MC-A651-53301); National Institute for Health Research (NIHR) Imperial College Biomedical Research Centre; NIHR Royal Brompton Cardiovascular Biomedical Research Unit; British Heart Foundation (NH/17/1/32725, RG/19/6/34387, RE/18/4/34215).

Spontaneous Occlusion of the Sinus Node Artery: A Case Report

Introduction: Occlusion of the sinus node artery is a rare situation. It is responsible for sinus node dysfunction and often occurs accidentally during percutaneous coronary intervention of a proximal lesion of the right coronary artery Case Report: This is a sixty-year-old woman with high blood pressure treat by dual therapy (an enzyme conversion inhibitor and a thiazide diuretic), who presented to the cardiological emergency room for a typical angina pain that had been evolving for 48 hours without a lull. Her clinical examination was normal apart from grade 3 arterial hypertension. The 18-lead surface electrocardiogram showed an electrical left ventricular hypertrophy with undershift of the ST segment in lateral and posterior territories, with an overshift of the ST segment in the antero-septal without any sign of necrosis. Biologically, the ultra-sensitive troponinemia was 88 times normal. The diagnosis of NSTEMI with troponin was retained with an intermediate ischaemic risk. Transthoracic Doppler echocardiography showed concentric hypertrophy of the left ventricular walls and dyskinesia of the right ventricle infero-apical wall. The coronary angiography showed an occlusion of the sinus node artery and a left coronary artery atheromatous with an intermediate lesion in the middle segment of the anterior interventricular artery. Conclusion: The present clinical case highlights the diversity in the expression of a sinus node artery occlusion that can occur spontaneously outside of a percutaneous coronary intervention.

Changes in miR 21 and 23b expression in postnatal hypertrophic heart derived from gestational diabetes precede dilated cardiomyopathy

Gestational diabetes mellitus (GDM) increases the risk of fetal congenital ventricular hypertrophic cardiomyopathy (HCM). We explored the effects and mechanisms of the postnatal progression of fetal hypertrophic failure in rat pups with STZ-induced Gestational Diabetes (GD). The hearts of rat pups (newborn [NB], 8, 15, 25 and 35 days postnatal) were obtained. Histological characteristics and expression of collagen were evaluated. In-gel-gelatin zymography for MMP-9 activation was performed. Adrenergic receptors (α2AR and β3AR), myosins (Myc6 and Myc7), Bcl-2 and Bax mRNA expression were quantified by qRT-PCR. Fetal hypertrophy of the left ventricular lateral wall (LVLW) in rat pups with DG persists until day 8, although this process appears to be reversed during the postnatal stage. The temporal continuity of the study demonstrated a thinning of the ventricular wall, similar to dilated cardiomyopathy (DCM). This ventricular remodeling process is associated with the expression of β3 adrenergic receptors and miR-21, -23b. The Bax/Bcl2 ratio was significantly reduced only at early ages. In addition, the increase in interstitial space in all ages, as well as the predominance of early ages expression of Col2 and increased expression of Col3, MMP-9 and Cx43 in late ages, is the result of an active extracellular remodeling in the hearts of rat pups with GD.

Disfuncția tiroidiană la pacientul cu sindrom coronarian acut

Purpose. The study aims to determine the impact of dystyroidism on the type of acute coronary syndrome, on vascular function and coronary impairment, as well as on the myocardium and last but not least the general biological resonance of these hormones, emphasizing the role of thyroid hormones in the cardiovascular system. Methods. We introduced in the study 100 patients recently diagnosed with acute coronary syndrome, without history of ischemic heart disease or thyroid disease, hospitalized in the Cardiology Clinic of the Emergency Clinical Hospital Bagdasar-Arseni Bucharest, for the interventional treatment of acute coronary syndrome. The studied patients were hospitalized between November 2014 - April 2015, with follow-up up to 5 years, evaluated clinically, bio-humorally, by echocardiography, coronary angiography with SYNTAX score calculation and electrocardiogram and pulse wave. The obtained data were integrated in Excel sheets and statistically processed with the Python program. Results. The prevalence of dystyroidism in the study group was 44% (44 patients). Hypothyroidism is predominant (34 patients; 77%), and subclinical hypothyroidism occurs in 20 (59%) of subjects with hypothyroidism. Unstable angina is the predominant type of acute coronary syndrome, both in the whole group (54 patients; 54%) and in the group of patients with hyperthyroidism (7 patients; 70%), while acute myocardial infarction without ST-segment elevation was the type majority of presentation in patients with hypothyroidism (19 patients, 56%). Coronary heart disease varied as follows: in the total group unicoronary lesion (31 subjects; 31%), in patients with hyperthyroidism unicoronary lesion (5 subjects; 50%), in patients with hypothyroidism bicoronary lesion (10 subjects; 29%). And the calculated SYNTAX score is higher in the group of patients with dysthyroidism compared to the group of patients with euthyroidism. Discussions. Unstable angina (p = 0.006) and ventricular wall hypertrophy (p = 0.008) are predictive factors for dysthyroidism. Hypothyroidism correlates with high LDL-cholesterol levels (p = 0.0176) and hyposideremia (p = 0.0083), while hyperthyroidism correlates with thrombocytosis (p = 0.0122) and a significant nonspecific inflammatory syndrome (p = 0.0043). Dystyroidism has a direct correlation with the presence of kinetic disorders (Person correlation coefficient 0.21). Conclusion. Thyroid disease, with hypothyroidism or hyperthyroidism, can also be a risk factor for cardiovascular disease, and especially for ischemic heart disease.

Hypertrophic Cardiomyopathy with masked Atrioventricular Block. Report of 2 cases

Background. Hypertrophic cardiomyopathy is the most common genetic cardiac disorder in Algeria, although syncope is often caused by ventricular arrhythmias or left outflow tract obstruction, it may also be related to complete atrioventricular block; the latter is rarely reported in the literature, the diagnosis is not so obvious, and should be thoroughly researched in presence of syncope. We report two cases of patients with hypertrophic cardiomyopathy and atrioventricular block revealed by syncope. Cases’ presentation. We reported two patients who presented hypertrophic cardiomyopathy, with recurrent syncope; one patient presented an accessory pathway that masked the complete atrioventricular block and the other patient presented an alternating occurrence of right bundle branch block and left bundle branch block at the ECG monitoring over a 48 hour. Echocardiography showed hypertrophy of left ventricular walls, but no left ventricular outflow tract gradient was detected. Extensive fibrosis especially in the septum was detected by late gadolinium enhancement. The two patients were implanted with dual-chamber pacemakers. During follow-up, one patient had developed refractory heart failure and died in 2014. Conclusions. The accessory pathway may mask complete atrioventricular block, also alternating bundle branch block could be the only proof of complete atrioventricular block. Fibrosis is the principal substrate of the reentry phenomenon, but septal fibrosis can also damage the atrioventricular conduction system. Non-obstructive hypertrophic cardiomyopathy could be related to fibrosis, and/or asynchrony. Keywords: Convulsive Syncope, Sudden Cardiac Death, Alternating Bundle Branch Block, Accessory Pathway.

Hypertrophic Cardiomyopathy in Infants from the Perspective of Cardiomyocyte Maturation.

Hypertrophic cardiomyopathy (HCM) is characterized by ventricular wall hypertrophy with diastolic dysfunction. Pediatric HCM is distinguished from the adult in many aspects. Most children with HCM do not present clinically until the adolescent period, even when they are born with genetic mutations. Some infants with early-onset HCM present with massive progressive myocardial hypertrophy in the first few months of life, which is often fatal. The mortality of pediatric HCM peaks during the infantile and adolescent periods. These periods roughly correlate with children's growth spurt. Non-sarcomeric causes of HCM are more frequent in pediatric HCM, while sarcomeric causes are more common in adults. From the perspective of cardiac development, the fetal heart has immature cardiomyocytes, which are characterized by proliferation and exit their cell cycles with a decreased regenerative property after birth. In the perinatal period, there is a dynamic change in maturation of cardiomyocytes from immature to mature cells. Infants who are treated with steroids or born to mothers with diabetes or hyperthyroidism often show phenotypes of HCM, which gradually resolve. With remarkable advancement of molecular biology, understanding on maturation of cardiomyocytes has increased. Neonates undergo abrupt environmental changes during the transitional circulation, which is affected by oxygen, metabolic and hormonal fluctuations. Derangement in physiological transition to the normal postnatal environment may influence maturation of proliferative immature cardiomyocytes during early infancy. This article reviews updates of infantile HCM and recent molecular studies related to maturation of cardiomyocytes from the clinical point of view of identifying distinct characteristics of infantile HCM.