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.

Effects of blood pressure percentile, body mass index, and race on left ventricular mass in children

Objective: To evaluate the association of systolic blood pressure percentile, race, and body mass index with left ventricular hypertrophy on electrocardiogram and echocardiogram to define populations at risk. Study design: This is a retrospective cross-sectional study design utilising a data analytics tool (Tableau) combining electrocardiogram and echocardiogram databases from 2003 to 2020. Customized queries identified patients aged 2–18 years who had an outpatient electrocardiogram and echocardiogram on the same date with available systolic blood pressure and body measurements. Cases with CHD, cardiomyopathy, or arrhythmia diagnoses were excluded. Echocardiograms with left ventricle mass (indexed to height2.7) were included. The main outcome was left ventricular hypertrophy on echocardiogram defined as Left ventricle mass index greater than the 95th percentile for age. Results: In a cohort of 13,539 patients, 6.7% of studies had left ventricular hypertrophy on echocardiogram. Systolic blood pressure percentile >90% has a sensitivity of 35% and specificity of 82% for left ventricular hypertrophy on echocardiogram. Left ventricular hypertrophy on electrocardiogram was a poor predictor of left ventricular hypertrophy on echocardiogram (9% sensitivity and 92% specificity). African American race (OR 1.31, 95% CI = 1.10, 1.56, p = 0.002), systolic blood pressure percentile >95% (OR = 1.60, 95% CI = 1.34, 1.93, p < 0.001), and higher body mass index (OR = 7.22, 95% CI = 6.23, 8.36, p < 0.001) were independently associated with left ventricular hypertrophy on echocardiogram. Conclusions: African American race, obesity, and hypertension on outpatient blood pressure measurements are independent risk factors for left ventricular hypertrophy in children. Electrocardiogram has little utility in the screening for left ventricular hypertrophy.

Relationship Between Overweight and Obesity and Cardiac Dimensions and Function in a Paediatric Population.

Obesity in adults is associated with left ventricular hypertrophy, dilatation and myocardial fibrosis, as well as heart failure and coronary heart disease. These associations have been studied to a lesser extent in the paediatric population. This study aims to investigate the relationship between obesity and cardiac structure and function in the paediatric population. In a southern Spanish town, we selected all inhabitants aged 6–17 years stratifying by age, gender, and educational centres. We performed a complete transthoracic echocardiogram evaluating all the cardiac morphological and functional parameters commonly measured in an echocardiographic study. There were 212 children and adolescents included. Of them, 48,1 % were males. The mean age was 10.9 ± 3.0 years. 106 (50%) were normal weight, 57 (26.9%) overweight and 49 (23.1%) obese. Sex and age were similar in all three groups. Overweight and obesity were associated with larger left ventricular end-diastolic and end-systolic volumes (p < 0.0005), greater left ventricular mass (p < 0.0005) and smaller ejection fraction (p < 0.0005). They were also associated with larger atrial, aortic and right ventricular size. Lateral and mean E/e' ratios were higher (p = 0.007 and p = 0.01 respectively). Body mass index was independently associated with all cavity size variables as well as left ventricular ejection fraction. Conclusion: Childhood obesity is independently associated with larger heart chambers, greater left ventricle mass, and smaller left ventricle ejection fraction.

Assessment of subclinical hypertention-mediated heart damage in young adults with connective tissue dysplasia

С целью оценки особенностей опосредованного артериальной гипертензией (АГ) поражения сердца у лиц молодого возраста с АГ и дисплазией соединительной ткани (ДСТ) проведено эхокардиографическое обследование 574 человек в возрасте от 18 до 29 лет. При анализе полученных данных обнаружено, что у молодых людей с АГ и ДСТ толщина межжелудочковой перегородки, стенок левого желудочка, массы и индексированных показателей массы левого желудочка не достигают общепризнанной единой верхней границы нормы. Это ведет к систематической гиподиагностике поражения сердца как органа-мишени, некорректной оценке стадии АГ и неадекватной тактике ведения этих пациентов. In order to assess the features of hypertension-mediated heart damage in young adults with hypertension and connective tissue dysplasia (СTD), an echocardiographic examination of 574 people aged 18 to 29 years was performed. It was revealed that young adults with hypertension and CTD have lower levels of the interventricular septum and left ventricle walls thickness, left ventricle mass and its indexes than in hypertensive patients without CTD, and these parameters do not reach the generally recognized upper limit of the norm. This leads to systematic underdiagnosis of hypertension-mediated heart damage, incorrect assessment of the stage of hypertension, and inadequate management for these patients.

Total endoscopic left ventricle lipoma removal

Background Left ventricle (LV) lipoma is a very rare, benign cardiac tumor. Due to its rarity, LV lipoma is often misdiagnosed. Aspecific symptoms such as murmurs, arrhythmias, memory loss and palpitation may occur due to the mass effect. Case presentation We report a case report of a 42 year old woman who was found to have left ventricle mass after check-up for arrhytmia. By a fully endoscopic approach, the mass was successfully resected from the left ventricle without the need for sternotomy. Conclusion Total endoscopic removal of left ventricle lipoma’s can be done safely and has several advantages to conventional sternotomy. Larger studies are needed to confirm this hypothesis.

Cardiac, Macro-, and Micro-Circulatory Abnormalities in Association With Individual Metabolic Syndrome Component: The Northern Shanghai Study

Objective: This study investigated the association of metabolic syndrome (MS) and its components with cardiac, macro-, and micro-circulatory abnormalities in an elderly Chinese population.Methods: This cross-sectional study was conducted using data for 1,958 participants from the Northern Shanghai Study aged over 65 years without a history of cardiovascular disease. MS was defined according to the National Cholesterol Education Program Adult Treatment Panel III in 2005 (NCEPIII 2005). Asymptomatic cardiovascular impairment parameters, including the left ventricle mass index (LVMI), peak transmitral pulsed Doppler velocity/early diastolic tissue Doppler velocity (E/Ea), carotid-femoral pulse wave velocity (cf-PWV), ankle-brachial index (ABI), carotid intima-media thickness (CIMT), arterial plaque, and urinary albumin–creatinine rate (UACR), were evaluated.Results: LVMI, E/Ea, cf-PWV, and the proportion of UACR &gt; 30 mg/g exhibited increasing trends while ABI exhibited a decreasing trend according to the number of MS components (all p for trend &lt; 0.01). Logistic regression analysis revealed that MS was significantly associated with LV hypertrophy (LVH), LV diastolic dysfunction, arteriosclerosis, and microalbuminuria (all p &lt; 0.001). Central obesity and high blood pressure were associated with all cardiovascular abnormalities (all p &lt; 0.05), whereas elevated plasma glucose was associated with arteriosclerosis and microalbuminuria (both p &lt; 0.001). In addition, high triglyceride levels were associated with microalbuminuria (p &lt; 0.05).Conclusions: MS is significantly associated with cardiac, macro-, and micro-circulatory abnormalities in elderly Chinese. Moreover, the presence of individual MS components may have specific prognostic significance.

Left Ventricle Intramuscular Haemangioma

Cardiac haemangiomas are rare cardiac tumours that are usually asymptomatic and detected incidentally while imaging the heart with echocardiogram. Cardiovascular magnetic resonance (CMR) is a non-ionising imaging modality that allows the diagnosis of cardiac haemangiomas prior to surgery. We report a 36-year old male patient who was referred to the Adult Cardiology Clinic at the Royal Hospital, Muscat, Oman, in 2006 with a history of a left ventricle mass detected on echocardiogram. Further assessment of the mass by CMR revealed that the mass within the left ventricle apical septum contained features that were consistent with a cardiac haemangioma. Due to the surgical risk of ventricular septal defect and the stability of the mass, the patient was managed conservatively and upon followup the patient’s condition remained stable. Keywords: Heart Neoplasms; Hemangioma; Heart, Neoplasm; Magnetic Resonance Imaging; Cardiovascular; Left Ventricle; Coronary Angiography; Case Report; Oman.

Total Endoscopic Left Ventricle Lipoma Removal: A Case Report

Background: Left ventricle (LV) lipoma is a very rare, benign cardiac tumor. Due to its rarity, LV lipoma is often misdiagnosed. Aspecific symptoms such as murmurs, arrhythmias, memory loss and palpitation may occur due to the mass effect. Case presentation: We report a case report of a 42 year old woman who was found to have left ventricle mass after check-up for arrhytmia. By a fully endoscopic approach, the mass was successfully resected from the left ventricle without the need for sternotomy. Conclusion: Total endoscopic removal of left ventricle lipoma’s can be done safely and has several advantages to conventional sternotomy. Larger studies are needed to confirm this hypothesis.

Effective influence of sacubutril/valsartan on systolic function of left ventricle in patients with heart failure and a reduced ejеction fraction

Aim: We evaluated the influence of sacubitril/valsartan on the left ventricle function and clinical status of patients with heart failure and a reduced ejection fraction. Materials and methods: From 2018 to 2020, patients cured with 50-200 mg sacubitril/valsartan after coronary bypass grafting or coronary stenting for ischemic heart disease and HFrEF (aged 54-70 years) were enrolled in this prospective study. Results: There was no death case. There was a female prevalence with female to male ratio of 1,7:1. the value of ejection fraction high significantly increased (p=0,035), whereas the indices of left ventricle end-diastolic volume (p=0,015) and end-diastolic volume index (p=0,022) as well as left ventricle mass index were high significantly decreased (p=0,001) that indicate the amelioration of left ventricle systolic function. Correspondingly, the clinical status of all patients improved according to New York Heart Association Class (p=0,001). Conclusion: The post-CABG or PCI patients with HFrEF should be cured with sacubitril/valsartan basing on its implementation instruction. Nevertheless, future studies should focus on a larger cohort of post-CABG or PCI patients to compare the effectiveness and safety of sacubitril/valsartan usage raising from its adverse event in comparison to conventional therapy.