Search

Pathological cardiac hypertrophy is characterized by myocyte enlargement and cardiac dysfunction. However, the pathogenesis for this disease is still poorly understood. Stimulator of interferon genes (STING) could meditate inflammation and immune response in various kinds of diseases. In this work, we demonstrated that STING was critical for pressure overload-induced cardiac hypertrophy. Results showed that STING expression was up-regulated in human and mouse hypertrophic hearts. STING knockout attenuated cardiac hypertrophy induced by aortic banding (AB). The effects of STING deficiency on the improvement of cardiac hypertrophy and dysfunction were associated with the restrained macrophage infiltration, inflammatory response and fibrosis. Moreover, ER stress was detected in hearts of AB-operated mice, as evidenced by the increased expression of phospho-protein kinase RNA-like endoplasmic reticulum kinase (PERK), phospho-eukaryotic initiation factor 2 alpha (eIF2α) and phospho-inositol-requiring kinase (IRE)-1α. Importantly, these proteins were restrained in mice with STING knockout after AB surgery. What's more, angiotensin II (Ang II)-induced STING could be accelerated by ER stress activator, while being markedly abolished by the ER stress inhibitor. We then found that whether co-treated with or without transforming growth factor-beta 1 (TGF-β1), cardiac fibroblasts cultured in the conditional medium (CM) from Ang II-incubated cardiomyocytes with STING knockdown exhibited significantly reduced fibrosis, as displayed by the clearly down-regulated expression of α-SMA, Collagen type I (Col I) and Collagen type III (Col III). Therefore, we defined STING as an important signal contributing to cardiac hypertrophy closely associated with ER stress., Competing Interests: Declaration of Competing Interest The authors see no any conflict of interest., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: Cardiomegaly on chest radiographs (CXR) in pediatric patients leads to multiple tests. We aimed to determine the positive predictive value (PPV) of cardiomegaly on CXR in predicting subsequent heart disease and to assess the utility of obtaining a B-type Natriuretic Peptide level (BNP) and/or electrocardiogram (EKG) in such patients. We hypothesized that an echocardiogram may not be appropriate in all cases of cardiomegaly on CXR, particularly in a patient with a normal EKG and BNP level., Methods: We performed a retrospective cohort study of pediatric patients with cardiomegaly on their initial CXR between January 2015-December 2017. Patients without a subsequent echocardiogram or known congenital heart disease were excluded. A patient was deemed to have heart disease if they had structural abnormalities, functional abnormalities or a pericardial effusion on echocardiogram. The PPV of CXR and the PPV/NPV of the other tests (EKG, BNP) were calculated using contingency tables., Results: Four hundred and eighty nine patients met inclusion criteria. The PPV of cardiomegaly on CXR alone without any other diagnostic testing in predicting subsequent heart disease was 15%. The PPV increased if there was either an abnormal EKG or a BNP >100 pg/ml and further increased if both of these were present. The PPV values were higher in patients <1 year of age., Conclusions: Cardiomegaly on CXR can often predict the presence of heart disease, particularly in infants. Further testing with EKG and BNP can better predict who may have heart disease, but it may not eliminate the need for echocardiography., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cantú syndrome (CS) was first described in 1982, and is caused by pathogenic variants in ABCC9 and KCNJ8 encoding regulatory and pore forming subunits of ATP-sensitive potassium (K ATP ) channels, respectively. It is characterized by congenital hypertrichosis, osteochondrodysplasia, extensive cardiovascular abnormalities and distinctive facial anomalies including a broad nasal bridge, long philtrum, epicanthal folds, and prominent lips. Many genetic syndromes, such as CS, involve facial anomalies that serve as a significant clue in the initial identification of the respective disorder before clinical or molecular diagnosis are undertaken. However, an overwhelming number of CS patients receive misdiagnoses based on an evaluation of coarse facial features. By analyzing three-dimensional images of CS faces, we quantified facial dysmorphology in a cohort of both male and female CS patients with confirmed ABCC9 variants. Morphometric analysis of different regions of the face revealed gender-specific significant differences in face shape. Moreover, we show that 3D facial photographs can distinguish between CS and other genetic disorders with specific facial dysmorphologies that have been mistaken for CS-associated anomalies in the past, hence assisting in an earlier clinical and molecular diagnosis. This optimizes genetic counseling and reduces stress for patients and parents by avoiding unnecessary misdiagnosis., (© 2020 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc.)

Alterations in connexins and specifically in 43 isoform (Cx43) in the heart have been associated with a high incidence of arrhythmogenesis and sudden death in several cardiac diseases. We propose to determine salutary effect of Cx43 mimetic peptide Gap27 in the progression of heart failure. High-output heart failure was induced by volume overload using the arterio-venous fistula model (AV-Shunt) in adult male rats. Four weeks after AV-Shunt surgery, the Cx43 mimetic peptide Gap27 or scrambled peptide, were administered via osmotic minipumps (AV-Shunt Gap27 or AV-Shunt Scr ) for 4 weeks. Cardiac volumes, arrhythmias, function and remodeling were determined at 8 weeks after AV-Shunt surgeries. At 8 th week, AV-Shunt Gap27 showed a marked decrease in the progression of cardiac deterioration and showed a significant improvement in cardiac functions measured by intraventricular pressure-volume loops. Furthermore, AV-Shunt Gap27 showed less cardiac arrhythmogenesis and cardiac hypertrophy index compared to AV-Shunt Scr . Gap27 treatment results in no change Cx43 expression in the heart of AV-Shunt rats. Our results strongly suggest that Cx43 play a pivotal role in the progression of cardiac dysfunction and arrhythmogenesis in high-output heart failure; furthermore, support the use of Cx43 mimetic peptide Gap27 as an effective therapeutic tool to reduce the progression of cardiac dysfunction in high-output heart failure.

Hypertensive cardiac hypertrophy (HCH) is a common cause of heart failure (HF), a major public health problem worldwide. However, the molecular bases of HCH have not been completely elucidated. Neuron-derived orphan receptor-1 (NOR-1) is a nuclear receptor whose role in cardiac remodelling is poorly understood. The aim of the present study was to generate a transgenic mouse over-expressing NOR-1 in the heart (TgNOR-1) and assess the impact of this gain-of-function on HCH. The CAG promoter-driven transgenesis led to viable animals that over-expressed NOR-1 in the heart, mainly in cardiomyocytes and also in cardiofibroblasts. Cardiomyocytes from TgNOR-1 exhibited an enhanced cell surface area and myosin heavy chain 7 (Myh7)/Myh6 expression ratio, and increased cell shortening elicited by electric field stimulation. TgNOR-1 cardiofibroblasts expressed higher levels of myofibroblast markers than wild-type (WT) cells (α 1 skeletal muscle actin (Acta1), transgelin (Sm22α)) and were more prone to synthesise collagen and migrate. TgNOR-1 mice experienced an age-associated remodelling of the left ventricle (LV). Angiotensin II (AngII) induced the cardiac expression of NOR-1, and NOR-1 transgenesis exacerbated AngII-induced cardiac hypertrophy and fibrosis. This effect was associated with the up-regulation of hypertrophic (brain natriuretic peptide (Bnp), Acta1 and Myh7) and fibrotic markers (collagen type I α 1 chain (Col1a1), Pai-1 and lysyl oxidase-like 2 (Loxl2)). NOR-1 transgenesis up-regulated two key genes involved in cardiac hypertrophy (Myh7, encoding for β-myosin heavy chain (β-MHC)) and fibrosis (Loxl2, encoding for the extracellular matrix (ECM) modifying enzyme, Loxl2). Interestigly, in transient transfection assays, NOR-1 drove the transcription of Myh7 and Loxl2 promoters. Our findings suggest that NOR-1 is involved in the transcriptional programme leading to HCH., (© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Ventricular hypertrophy is a risk factors for arrhythmias, ischemia and sudden death. It involves cellular modifications leading to a pathological remodeling and is associated with heart failure. The activation of the G protein-coupled estrogen receptor (GPER) mediates beneficial actions in the cardiovascular system. Our goal was to prevent and regress the hypertrophy by the activation of GPER in neonatal cardiac myocytes (NRCM) and SHR male rats. Aldosterone increased the neonatal cardiomyocytes cell surface area after 48 h of incubation. The aldo-induced hypertrophy was blocked by the mineralocorticoid receptor (MR) inhibitor Eplererone or the reduction of MR expression by siRNA. The activation of GPER by the agonist G-1 totally prevented the increase surface area by Ald. The transfection of neonatal rat cardiac myocytes with a siRNA against GPER or the incubation with GPER blockers G-15 and G-36 inhibited the protection of G-1. The significant increase of cell surface area after 48 h of incubation with Ald was totally regressed in 24 h by the presence of G-1, indicating that the activation of GPER not only prevent the hypertrophy but also regress the hypertrophy when it is already established. In the in vivo model, G-1 or Vehicle was constantly infused via the minipump to SHR. The reduction of the hypertrophy by G-1 was evident by the cross-sectional area, BNP and ANP markers and by echocardiography. In this studied we demonstrated that the activation of GPER prevented and regressed the hypertrophy induced by Ald in NRCM and regressed hypertrophy in SHR rats., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Familial lipodystrophy is a rare genetic condition in which individuals have, besides metabolic changes and body fat deposits, a type of cardiomyopathy that has not been well studied. Many of the patients develop cardiovascular changes, the most commonly reported in the literature being the expression of a type of hypertrophic cardiomyopathy. This article, presented as a bibliographic review, reviews the clinical and cardiovascular imaging aspects in this scenario of cardiomyopathy in a rare metabolic disease, based on the latest scientific evidence published in the area. Despite the frequent association of congenital lipodystrophy and ventricular hypertrophy described in the literature, the pathophysiological mechanisms of this cardiomyopathy have not yet been definitively elucidated, and new information on cardiac morphological aspects is emerging in the aegis of recent and advanced imaging methods, such as cardiac magnetic resonance.

Objective: Obesity causes a variety of metabolic alterations that may contribute to abnormalities of the cardiac structure and function (obesity cardiomyopathy). In previous works, we have shown that pentamethylquercetin (PMQ) significantly improved metabolic disorders in obese mice and it inhibited pressure overload-induced cardiac remodeling in mice. However, its potential benefit in obesity cardiomyopathy remains unclear. The aim of this study was to investigate the effects of PMQ on cardiac remodeling in obese mice., Methods: We generated a monosodium glutamate-induced obese (MSG-IO) model in mice, which were treated with PMQ (5, 10, and 20 mg/kg) for 16 weeks consecutively. We examined the metabolic parameters and observed cardiac remodeling by performing cardiac echocardiography and Masson's staining. The expression levels of molecules associated with the endogenous antioxidant system, including the sestrins/kelch-like ECH-associated protein 1 (Keap1)/Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway, were analyzed by western blotting and immunofluorescent staining., Results: We found that PMQ treatment significantly ameliorated obesity phenotypes and improved metabolic disorders in MSG-IO mice. PMQ decreased the heart wall thickness and attenuated cardiac fibrosis. Further study revealed that the protective effects of PMQ might be mediated by promoting Keap1 degradation and augmenting sestrins expression and Nrf2 nuclear translocation., Conclusion: Our findings indicated that PMQ ameliorated cardiac remodeling in obese mice by targeting the sestrins/Keap1/Nrf2 signaling pathway., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Jingxia Du et al.)

Objective: To determine whether cardiac magnetic resonance imaging (CMR) could be useful in identifying previously undiagnosed cardiomyopathies in a cohort of patients with ischemic stroke who underwent standard etiologic investigation and to describe the type and frequency of these cardiomyopathies., Methods: We performed a subanalysis of a previously collected prospective cohort of patients with ischemic stroke. Patients with structural changes on echocardiography that are considered causal for stroke in the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification were excluded. A 3T CMR was performed. We compared the frequency of the cardiomyopathies that we found with reference values for the general population., Results: One hundred thirty-two patients with a mean age of 68.4 years were included. In 7 patients (5.3%, 95% confidence interval 2.59%-10.54%) CMR identified cardiomyopathy. Four patients had hypertrophic cardiomyopathy, 2 had restrictive cardiomyopathy, and 1 had noncompaction cardiomyopathy. Six of these patients had been classified after standard evaluation as having undetermined stroke and 1 patient as having cardioembolic stroke (atrial fibrillation). We found a higher frequency of hypertrophic cardiomyopathy in the entire cohort and in the undetermined cause group compared to the general population (3.03% and 5.81% vs 0.2%, respectively, p = 0.001 and p < 0.001). The frequency of noncompaction cardiomyopathy was also higher in our cohort (0.76% vs 0.05%, respectively, p < 0.001)., Conclusions: Although rare, cardiomyopathies should be considered as a possible cause of ischemic stroke classified as of undetermined etiology after standard evaluation., (© 2019 American Academy of Neurology.)

Background: Preeclampsia and fetal growth restriction share some pathophysiologic features and are both associated with placental insufficiency. Fetal cardiac remodeling has been described extensively in fetal growth restriction, whereas little is known about preeclampsia with a normally grown fetus., Objective: To describe fetal cardiac structure and function in pregnancies complicated by preeclampsia and/or fetal growth restriction as compared with uncomplicated pregnancies., Study Design: This was a prospective, observational study including pregnancies complicated by normotensive fetal growth restriction (n=36), preeclampsia with a normally grown fetus (n=35), preeclampsia with fetal growth restriction (preeclampsia with a normally grown fetus-fetal growth restriction, n=42), and 111 uncomplicated pregnancies matched by gestational age at ultrasound. Fetal echocardiography was performed at diagnosis for cases and recruitment for uncomplicated pregnancies. Cord blood concentrations of B-type natriuretic peptide and troponin I were measured at delivery. Univariate and multiple regression analysis were conducted., Results: Pregnancies complicated by preeclampsia and/or fetal growth restriction showed similar patterns of fetal cardiac remodeling with larger hearts (cardiothoracic ratio, median [interquartile range]: uncomplicated pregnancies 0.27 [0.23-0.29], fetal growth restriction 0.31 [0.26-0.34], preeclampsia with a normally grown fetus 0.31 [0.29-0.33), and preeclampsia with fetal growth restriction 0.28 [0.26-0.33]; P<.001) and more spherical right ventricles (right ventricular sphericity index: uncomplicated pregnancies 1.42 [1.25-1.72], fetal growth restriction 1.29 [1.22-1.72], preeclampsia with a normally grown fetus 1.30 [1.33-1.51], and preeclampsia with fetal growth restriction 1.35 [1.27-1.46]; P=.04) and hypertrophic ventricles (relative wall thickness: uncomplicated pregnancies 0.55 [0.48-0.61], fetal growth restriction 0.67 [0.58-0.8], preeclampsia with a normally grown fetus 0.68 [0.61-0.76], and preeclampsia with fetal growth restriction 0.66 [0.58-0.77]; P<.001). Signs of myocardial dysfunction also were observed, with increased myocardial performance index (uncomplicated pregnancies 0.78 z scores [0.32-1.41], fetal growth restriction 1.48 [0.97-2.08], preeclampsia with a normally grown fetus 1.15 [0.75-2.17], and preeclampsia with fetal growth restriction 0.45 [0.54-1.94]; P<.001) and greater cord blood B-type natriuretic peptide (uncomplicated pregnancies 14.2 [8.4-30.9] pg/mL, fetal growth restriction 20.8 [13.1-33.5] pg/mL, preeclampsia with a normally grown fetus 31.8 [16.4-45.8] pg/mL and preeclampsia with fetal growth restriction 37.9 [15.7-105.4] pg/mL; P<.001) and troponin I as compared with uncomplicated pregnancies., Conclusion: Fetuses of preeclamptic mothers, independently of their growth patterns, presented cardiovascular remodeling and dysfunction in a similar fashion to what has been previously described for fetal growth restriction. Future research is warranted to better elucidate the mechanism(s) underlying fetal cardiac adaptation in these conditions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Left atrial disease is an independent risk factor for ischemic stroke and can be used to predict atrial fibrillation (AF). We examine whether left atrial enlargement (LAE) could predict stroke recurrence in patients with embolic stroke of undetermined source (ESUS)., Materials and Methods: Sixty-four patients with a confirmed diagnosis of ESUS were followed for a median of 22 months. Clinical data and echocardiogram findings were recorded. The echocardiogram interpretation was performed centrally and blindly. The Brown ESUS - AF score was used to categorize patients into high (human resource planning [HRP]: score > 2) and low-risk patients (non-HRP score 0-1). Stroke recurrence was the primary outcome., Results: The median age was 62 years (range: 22-85 years); and 33 (51.6%) were men. The median initial NIHSS score was three points (range: 0-27). Twelve (18.8%) patients were categorized as HRP. We found a significant tendency toward recurrence among HRP versus non-HRP patients. Three (25%) HRP versus 2 (3.8%) non-HRP experienced recurrence (OR: 8.3 95% CI 1.2-57; p=0.042); this association was related to severe atrial dilatation (OR: 14.5 95% CI 0.78-277, p = 0.02) and age > 75 years (OR: 12.7 95% CI 1.7-92.2, p = 0.03). We found no differences in recurrence in a univariate analysis., Conclusions: Patients with severe LAE who are 75 years old or older have a significant tendency to experience stroke recurrence., (Copyright: © 2020 Permanyer.)

We present the case of an infant with prenatal diagnosis, at 32 weeks gestation, of Ebstein's anomaly without anterograde flow from right ventricular to pulmonary atresia (PA)-functional PA with flow reversal in the ductus arteriosus. Prostaglandin E1 was started after birth. Chest X-ray showed severe cardiomegaly and echocardiogram confirmed Ebstein's anomaly with a thickened non-opening pulmonary valve without anterograde flow but with mild regurgitation. Multidisciplinary team decision was to progressively reduce prostaglandins and have an expectant attitude. Peripheral oxygen saturation above 85% was maintained and serial echocardiograms documented progressive reduction of the ductus arteriosus and the opening of the pulmonic valve cusps, with the development of anterograde flow. The newborn was discharged at day 19 of life without the need for any intervention, and at last follow-up remains asymptomatic, with anterograde normal flow in the pulmonary valve., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Athlete's heart is a term used to describe physiological changes in the hearts of athletes, but its early development has not been described in longitudinal studies. This study aims to improve our understanding of the effects of endurance training on the developing heart., Methods: Cardiac morphology and function in 48 cross-country skiers were assessed at age 12 years (12.1 ± 0.2 years) and then again at age 15 years (15.3 ± 0.3 years). Echocardiography was performed in all subjects including two-dimensional speckle-tracking strain echocardiography and three-dimensional echocardiography. All participants underwent cardiopulmonary exercise testing at both ages 12 and 15 years to assess maximal oxygen uptake and exercise capacity., Results: Thirty-one (65%) were still active endurance athletes at age 15 years and 17 (35%) were not. The active endurance athletes had greater indexed maximal oxygen uptake (62 ± 8 vs. 57 ± 6 mL/kg/min, P  < 0.05) at follow-up. There were no differences in cardiac morphology at baseline. At follow-up the active endurance athletes had greater three-dimensional indexed left ventricular end-diastolic (84 ± 11 mL/m 2 vs. 79 ± 10 mL/m 2 , P  < 0.05) and end-systolic volumes (36 ± 6 mL/m 2 vs. 32 ± 3 mL/m 2 , P  < 0.05). Relative wall thickness fell in the active endurance athletes, but not in those who had quit (-0.05 ΔmL/m 2 vs. 0.00 mL/m 2 , P  = 0.01). Four active endurance athletes had relative wall thickness above the upper reference values at baseline; all had normalised at follow-up., Conclusion: After an initial concentric remodelling in the pre-adolescent athletes, those who continued their endurance training developed eccentric changes with chamber dilatation and little change in wall thickness. Those who ceased endurance training maintained a comparable wall thickness, but did not develop chamber dilatation.

Objective: The prognostic value of left atrial (LA) dimensions may differ between patients with and without atrial fibrillation (AF)., Methods: MEDLINE and EMBASE were searched for studies that investigated the association between LA echocardiographic parameters measured by transthoracic echocardiography and cardiovascular outcomes in patients with or without AF. Data were independently abstracted by two reviewers and pooled using random-effects meta-analysis. The primary outcome was incident stroke or thromboembolic events. Secondary outcomes were heart failure, all-cause mortality and major adverse cardiac events (MACE)., Results: Twenty-three studies of patients with AF (14 939 patients) and 68 studies of patients without AF (50 720 patients) in this systematic review. Increasing LA diameter was significantly associated with stroke and thromboembolic events in patients without AF (risk ratio (RR) 1.38, 95% CI 1.02 to 1.87; p=0.03), but not in patients with AF (RR 1.02, 95% CI 0.98 to 1.07; p=0.27; p for difference=0.05). Increasing LA diameter index was significantly associated with MACE in patients with AF (RR 1.13, 95% CI 1.09 to 1.17; p<0.001) and in patients without AF (RR 2.98, 95% CI 1.90 to 4.66; p<0.001), with stronger effects in non-AF populations (p for difference <0.001). Greater LA volume index was significantly associated with the risk of MACE in patients with AF (RR 1.01, 95% CI 1.00 to 1.02; p=0.03) and in non-AF populations (RR 1.08, 95% CI 1.05 to 1.10; p<0.001), the association being stronger in individuals without AF (p for difference <0.001)., Conclusions: Larger LA parameters were associated with various adverse cardiovascular events. Many of these associations were stronger in individuals without AF, highlighting the potential importance of LA myopathy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Heart failure is the leading cause of death among diabetic people. Cellular and molecular entities leading to diabetic cardiomyopathy are, however, poorly understood. Coupling of cardiac carbonic anhydrase II (CAII) and Na + /H + exchanger 1 (NHE1) to form a transport metabolon was analyzed in obese type 2 diabetic mice (ob -/- ) and control heterozygous littermates (ob +/- ). Echocardiography showed elevated systolic interventricular septum thickness and systolic posterior wall thickness in ob -/- mice at 9 and 16 weeks. ob -/- mice showed increased left ventricular (LV) weight/tibia length ratio and increased cardiomyocyte cross sectional area as compared to controls, indicating cardiac hypertrophy. Immunoblot analysis showed increased CAII expression in LV samples of ob -/- vs. ob +/- mice, and augmented Ser 703 phosphorylation on NHE1 in ob -/- hearts. Reciprocal co-immunoprecipitation analysis showed strong association of CAII and NHE1 in LV samples of ob -/- mice. NHE1-dependent rate of intracellular pH (pH i ) normalization after transient acid loading of isolated cardiomyocytes was higher in ob -/- mice vs. ob +/- . NHE transport activity was also augmented in cultured H9C2 rat cardiomyoblasts treated with high glucose/high palmitate, and it was normalized after CA inhibition. We conclude that the NHE1/CAII metabolon complex is exacerbated in diabetic cardiomyopathy of ob -/- mice, which may lead to perturbation of pH i and [Na + ] and [Ca 2+ ] handling in these diseased hearts., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Sudden cardiac death (SCD) in the young is rare and should always lead to suspicion of a genetic cardiac disorder. We describe a family, in which the proband was a girl deceased by sudden cardiac death in the playground at thirteen years of age. The index-patient had short stature, cleft palate but no previous cardiac symptoms. We found an uncommon cause of cardiomyopathy, due to a congenital disorder of glycosylation (CDG), previously described to cause a variable range of usually mild symptoms, and not previously found to cause SCD as the first symptom of the condition., Methods: The index patient underwent postmortem genetic testing/molecular autopsy for genes known to cause SCD, without a detection of causative agent, why two siblings of similar phenotype as the deceased sister underwent clinical-exome genetic sequencing (next generation sequencing). All first-degree relatives underwent clinical examination including cardiac ultrasound, Holter-ECG, exercise stress test and biochemistry panel., Results: A genetic variant in the gene for phosphoglucomutase 1 (PGM1) was identified in the index patient and her two brothers, all were found to be homozygous for the genetic variant (G230E) NM&#95;002633.2:c.689 G > A in PGM1. This variant has been linked to a congenital disorder of glycosylation (PGM1-CDG), explaining the clinical picture of short stature, cleft palate, liver engagement and cardiomyopathy. During follow-up one of the brothers died unexpectedly after physical exertion during daily life at the age of twelve years. The other brother fainted during similar circumstances at the age of thirteen years. Both parents and three other siblings were found to be heterozygous gene carriers without risk for the disease., Conclusion: Our findings suggest that there is a need of multidisciplinary discussion and genetic testing after unexpected cardiac death in the young. We have to be more flexible in our evaluation of diseases and to consider even uncommon diseases including rare recessive inherited disorders. Our findings also suggest that the autosomal recessive PGM1-CDG might be highly associated with life-threatening cardiomyopathy with arrhythmia or sudden cardiac death as the first symptom presenting from childhood and adolescence., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: To determine whether chest radiographs can contribute to prognosis in patients with acute heart failure (AHF)., Material and Methods: Consecutive patients with AHF were enrolled by the participating emergency departments. Radiographic variables assessed were the presence or absence of evidence of cardiomegaly and pleural effusion and the pulmonary parenchymal pattern observed (vascular redistribution, interstitial edema, and/or alveolar edema). We gathered variables for the AHF episode and the patient's baseline state. Outcomes were in-hospital and 1-year mortality; hospital stay longer than 7 days, and a composite of events within 30 days of discharge (revisit, rehospitalization, and/or death). Crude and adjusted hazard ratios were calculated for the 3 categories of radiographic variables. The variables were also studied in combination., Results: A total of 2703 patients with a mean (SD) age of 81 (19) years were enrolled; 54.5% were women. Cardiomegaly was observed in 1711 cases (76.8%) and pleural effusion in 992 (36.7%). A pulmonary parenchymal pattern was observed in all cases, as follows: vascular redistribution in 1672 (61.9%), interstitial edema in 629 (23.3%) and alveolar edema in 402 (14.9%). The adjusted hazard ratios showed that cardiomegaly lacked prognostic value. However, the presence of pleural effusion was associated with a 23% (95% CI, 2%-49%) higher rate of the 30- day composite outcome; in-hospital mortality was 89% (30%-177%) higher in the presence of alveolar edema, and 1-year mortality was 38% (14%-67%) higher in association with vascular redistribution. The results for the variables in combination were consistent with the results for individual variables., Conclusion: A diagnostic chest radiograph can also contribute to the prediction of adverse events. Pleural effusion is associated with a higher rate of events after discharge, and alveolar edema is associated with higher mortality.

A 12-year-old neutered female American cocker spaniel weighing 9.9 kg was presented for evaluation with a 2-day history of dyspnea and anorexia. Echocardiography revealed severe pulmonary hypertension (estimated systolic pulmonary arterial pressure, 93.4 mmHg) with right heart enlargement, pulmonary arterial dilation, and right ventricular dysfunction. The dilation of left heart and congenital cardiac shunt were not observed. Pulmonary thromboembolism (PTE) was confirmed by computed tomographic angiography. After treatment with antiplatelet and anticoagulant, the clinical sign and the echocardiographic abnormality of right heart were improved. These echocardiographic findings are not specific for PTE, but it can be useful as a rule-in test for PTE when other causes of pulmonary hypertension are excluded and a monitor of therapeutic efficacy.

Increase of myocardial oxidative stress is closely related to the occurrence and development of cardiac hypertrophy. Cordycepin, also known as 3'-deoxyadenosine, is a natural bioactive substance extracted from Cordyceps militaris (which is widely cultivated for commercial use in functional foods and medicine). Since cordycepin suppresses oxidative stress both in vitro and in vivo, we hypothesized that cordycepin would inhibit cardiac hypertrophy by blocking oxidative stress-dependent related signalling. In our study, a mouse model of cardiac hypertrophy was induced by aortic banding (AB) surgery. Mice were intraperitoneally injected with cordycepin (20 mg/kg/d) or the same volume of vehicle 3 days after-surgery for 4 weeks. Our data demonstrated that cordycepin prevented cardiac hypertrophy induced by AB, as assessed by haemodynamic parameters analysis and echocardiographic, histological and molecular analyses. Oxidative stress was estimated by detecting superoxide generation, superoxide dismutase (SOD) activity and malondialdehyde levels, and by detecting the protein levels of gp91 phox and SOD. Mechanistically, we found that cordycepin activated activated protein kinase α (AMPKα) signalling and attenuated oxidative stress both in vivo in cordycepin-treated mice and in vitro in cordycepin treated cardiomyocytes. Taken together, the results suggest that cordycepin protects against post-AB cardiac hypertrophy through activation of the AMPKα pathway, which subsequently attenuates oxidative stress., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: There are some evidences supporting the relation between gestational diabetes mellitus (GDM) and diastolic dysfunction. The aim of our study was to investigate the effect of well-controlled GDM on morphological and functional myocardium., Materials and Methods: We designed a prospective cross-sectional study to evaluate left ventricular (LV) diastolic function of 60 neonates born from mothers with well-controlled GDM (case group) on days of 3-5 after birth. The infants of diabetic mothers (IDM) group were divided into two groups: diabetic mothers treated only with diet (class A) and group of mothers on medical therapy by insulin or metformin (class B). Traditional echocardiography and pulsed-wave Doppler (PWD), tissue Doppler imaging (TDI) were performed for all the neonates., Results: The study group consisted of 60 neonates as males (M) = 32, (0.53%) and females (F) = 28, (0.46%). Using M-mode echocardiography, interventricular septum thickness (IVS), and LV mass were significantly higher in IDM than control group (p = .0001). The PWD showed both a significantly more peak mitral flow at early diastolic wave (E) and an early filling deceleration time (E-DT) (p = .0001). Tissue Doppler echocardiography parameters A' (cm/s) (p = .0001), E' (cm/s) (p = .002), and E'/A' ratio (p = .0001), left ventricular myocardial performance index (LVMPI), and isovolumetric relaxation time (IVRT) were outstandingly different between the two groups (p = .0001, respectively). Evaluating the GDM group mothers of class A and class B, no significant difference was noted in PWD or TDI parameters compared with the healthy ones., Conclusions: It seems that neonates of mothers with well-controlled GDM are still at increased risk of cardiac hypertrophy, subclinical diastolic dysfunction, and impaired left ventricular relaxation. This can be interpreted that focusing only on glycemic control is not enough to prevent cardiac dysfunction.

Pathological cardiac hypertrophy is a debilitating condition characterized by deleterious thickening of the myocardium, dysregulated Ca 2+ signaling within cardiomyocytes, and contractile dysfunction. Importantly, the nanoscale organization, localization, and patterns of expression of critical Ca 2+ handling regulators including dihydropyridine receptor (DHPR), ryanodine receptor 2 (RyR2), phospholamban (PLN), and sarco/endoplasmic reticulum Ca 2+ -ATPase 2A (SERCA2A) remain poorly understood, especially during pathological hypertrophy disease progression. In the current study, we induced cardiac pathological hypertrophy via transverse aortic constriction (TAC) on 8-week-old CD1 mice, followed by isolation of cardiac ventricular myocytes. dSTORM super-resolution imaging was then used to visualize proteins at nanoscale resolution at two time points and we quantified changes in protein cluster properties using Voronoi tessellation and 2D Fast Fourier Transform analyses. We showed a decrease in the density of DHPR and RyR2 clusters with pressure-overload cardiac hypertrophy and an increase in the density of SERCA2A protein clusters. PLN protein clusters decreased in density in 2-week TAC but returned to sham levels by 4-week TAC. Furthermore, 2D-FFT analysis revealed changes in molecular organization during pathological hypertrophy, with DHPR and RyR2 becoming dispersed while both SERCA2A and PLN sequestered into dense clusters. Our work reveals molecular adaptations that occur in critical SR proteins at a single molecule during pressure overload-induced cardiomyopathy. Nanoscale alterations in protein localization and patterns of expression of crucial SR proteins within the cardiomyocyte provided insights into the pathogenesis of cardiac hypertrophy, and specific evidence that cardiomyocytes undergo significant structural remodeling during the progression of pathological hypertrophy.

The aim of the study was to characterize if the development of cardiac hypertrophy (CH) caused by severe left ventricle (LV) volume overload (VO) from chronic aortic valve regurgitation (AR) in male rats was influenced by androgens. We studied Wistar rats with/without orchiectomy (Ocx) either sham-operated (S) or with severe AR for 26 weeks. Loss of testosterone induced by Ocx decreased general body growth. Cardiac hypertrophy resulting from AR was relatively more important in intact (non-Ocx) animals than in Ocx ones compared to their respective S group (60% vs. 40%; P = 0.019). The intact AR group had more LV dilation, end-diastolic LV diameter being increased by 37% over S group and by 17% in AROcx rats (P < 0.0001). Fractional shortening (an index of systolic function) decreased only by 15% in AROcx compared to 26% for intact AR animals (P = 0.029). Changes in LV gene expression resulting from CH were more marked in intact rats than in AROcx animals, especially for genes linked to extracellular matrix remodeling and energy metabolism. The ratio of hydroxyacyl-Coenzyme A dehydrogenase activity over hexokinase activity, an index of the shift of myocardial substrate use toward glucose from the preferred fatty acids, was significantly decreased in the AR group but not in AROcx. Finally, pJnk2 LV protein content was more abundant in AR than in AROcx rats, indicating decreased activation of this stress pathway in the absence of androgens. In summary, testosterone deficiency in rats with severe LV VO resulted in less CH and a normalization of the LV gene expression profile., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Giant left atrium (GLA) is a rare entity in the pediatric population. GLA carries a significant mortality risk; once its existence is established, it needs to be evaluated with intention to treat. We report a 14-month-old boy with GLA presenting with symptoms of cough and stridor because of compressed airways. The child underwent successful surgical resection for the same., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The transcription factor Sox9 has been associated with cardiac injury and remodeling. Studies of mammalian hearts confirm Sox9 upregulation in fibroblasts following ischemic insults associated with enhanced fibrosis. The role of cardiomyocyte-specific Sox9 remains unclear. This study aimed to evaluate the role of cardiomyocyte-specific Sox9 in development and progression of left ventricular (LV) hypertrophy and fibrosis., Methods: In male conditional Sox9 knockout mice (Sox9-KO) or floxed littermates (control group) transverse aortic constriction (TAC) was performed to induce LV hypertrophy. LV function and wall thickness were assessed weekly using echocardiography. LV mRNA- and protein expression levels of hypertrophy-, fibrosis-, and remodeling-associated genes were analyzed for each time point. Histological sections were stained for fibrosis and Sox9 expression., Results: Only one week after TAC, the control group showed significantly enhanced heart weights and thickened LV posterior walls accompanied by elevated Anp- and Lox-mRNA levels. Simultaneously, Col1a1- and Col3a1-levels as well as Sox9 expression were strongly upregulated, Contrary, Sox9-KO mice did not develop cardiac hypertrophy until 4 weeks after TAC. Collagen and Sox9 expression also peaked at that later time point. Ejection fraction declined similarly in both groups after TAC. However, the control group showed a slightly better cardiac performance at 2 weeks after TAC., Conclusions: Cardiomyocyte-specific Sox9 mediates hypertrophy and early fibrosis, following cardiac pressure-overload. Loss of Sox9 delays cardiac growth and remodeling processes, however, does not preserve the cardiac function. We suggest that cardiomyocyte-driven Sox9 initiates a pro-hypertrophic cascade, possibly involving a cross-talk between myocytes and fibroblasts., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Emerging studies have recently shown the potential importance of ketone bodies in cardio-metabolic health. However, techniques to determine myocardial ketone body utilization in vivo are lacking. In this work, we developed a novel method to assess myocardial ketone body utilization in vivo using hyperpolarized [3- 13 C]acetoacetate and investigated the alterations in myocardial ketone body metabolism in diabetic rats. Within a minute upon injection of [3- 13 C]acetoacetate, the production of [5- 13 C]glutamate and [1- 13 C] acetylcarnitine can be observed real time in vivo. In diabetic rats, the production of [5- 13 C]glutamate was elevated compared to controls, while [1- 13 C]acetylcarnitine was not different. This suggests an increase in ketone body utilization in the diabetic heart, with the produced acetyl-CoA channelled into the tricarboxylic acid cycle. This observation was corroborated by an increase activity of succinyl-CoA:3-ketoacid-CoA transferase (SCOT) activity, the rate-limiting enzyme of ketone body utilization, in the diabetic heart. The increased ketone body oxidation in the diabetic hearts correlated with cardiac hypertrophy and dysfunction, suggesting a potential coupling between ketone body metabolism and cardiac function. Hyperpolarized [3- 13 C]acetoacetate is a new probe with potential for non-invasive and real time monitoring of myocardial ketone body oxidation in vivo, which offers a powerful tool to follow disease progression or therapeutic interventions.

Objective: Dilated cardiomyopathy (DCM) is a disorder featuring left ventricular dysfunction, heart failure, and a poor prognosis. The etiology is still unclear, despite diagnostic and therapeutic developments. This study was an evaluation of factors affecting the life span of a group of idiopathic DCM patients., Methods: A total of 79 patients from between October 2005 and October 2017 with a diagnosis of idiopathic DCM were evaluated retrospectively. Demographic characteristics, clinical information, left ventricular function, treatment, and follow-up of the patients were reviewed based on hospital records. Age, gender, parental consanguinity, cardiomegaly on telecardiography, reduced ejection fraction (EF) and shortening fraction (SF), degree of mitral regurgitation, and intracardiac thrombosis were determined to affect prognosis., Results: The patients were aged 20+-60 months, and the male/female ratio was 1.02/1. The patients most frequently presented with heart failure signs and symptoms (n=59, 74.7%). The most common physical examination findings were a murmur (n=53, 67.1%) and tachycardia (n=48, 60.8%). Cardiomegaly was observed on telecardiography in 73.4% of the patients. The EF and SF values were 35.7+-12.6% and 17.3+-6.5%, respectively. In all, 42 (53.2%) patients had mitral regurgitation of grade 2 or higher. The duration of follow-up was between 1 and 156 months (20+-34.9 months). Intracardiac thrombosis was detected in 4 (5.1%) patients. The mortality rate was 36.7%. When the prognostic factors were compared according to survival time, it was determined that survival was reduced in cases of parental consanguinity, low EF, and cardiomegaly., Conclusion: The most important negative markers affecting the length of survival of DCM patients were parental consanguinity, cardiomegaly detected on telecardiography, and a reduced EF level.

Background: MicroRNAs (miRNAs) have been shown to commonly contribute to cardiac hypertrophy (CH). The aim of this study was to test the hypothesis that miR-200c plays an important role in the progression of CH by targeting myosin light chain kinase (MLCK/MYLK)., Methods and Results: Cardiac hypertrophy was induced by aortic banding (AB) in rats. Cellular hypertrophy in neonatal rat cardiomyocytes (NCMs) was induced by AngII treatment. Echocardiography, histology and molecular measurements were used to assess the results of the experiments. The levels of apoptosis and reactive oxygen species (ROS) were also measured. Quantitative real-time PCR (qRT-PCR) and Western blotting were used to measure mRNA and protein levels respectively. The present results showed that miR-200c expression was increased in response to CH both in vivo and in vitro. The down-regulation of miRNA-200c by a specific inhibitor markedly ameliorated CH resulting from AngII treatment, and the mRNA levels of atrial natriuretic peptide, brain natriuretic peptide and β-myosin heavy chain were simultaneously decreased. Notably, minimal apoptosis and ROS accumulation were identified in AngII-induced hypertrophic cardiomyocytes. Conversely, the up-regulation of miR-200c using specific mimics reversed these effects. Mechanistic investigations demonstrated that the MLCK gene is a direct target of miR-200c; an increase in miR-200c levels led to a decrease in the expression of MLCK and its downstream effector, p-MLC2, while miR-200c inhibition increased the expression of these proteins. Furthermore, inhibiting MLCK impaired the anti-hypertrophic effects contributions produced by the knockdown of miR-200c., Conclusion: Our studies suggest that miR-200c may serve as a potential therapeutic target that could delay hypertrophy. We have also uncovered a relationship between miR-200c and MLCK, identifying MLCK as a direct mediator of miR-200c., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: The heart responds to hemodynamic overload through cardiac hypertrophy and activation of the fetal gene program. However, these changes have not been thoroughly examined in individual cardiomyocytes, and the relation between cardiomyocyte size and fetal gene expression remains elusive. We established a method of high-throughput single-molecule RNA imaging analysis of in vivo cardiomyocytes and determined spatial and temporal changes during the development of heart failure., Methods and Results: We applied three novel single-cell analysis methods, namely, single-cell quantitative PCR (sc-qPCR), single-cell RNA sequencing (scRNA-seq), and single-molecule fluorescence in situ hybridization (smFISH). Isolated cardiomyocytes and cross sections from pressure overloaded murine hearts after transverse aortic constriction (TAC) were analyzed at an early hypertrophy stage (2 weeks, TAC2W) and at a late heart failure stage (8 weeks, TAC8W). Expression of myosin heavy chain β (Myh7), a representative fetal gene, was induced in some cardiomyocytes in TAC2W hearts and in more cardiomyocytes in TAC8W hearts. Expression levels of Myh7 varied considerably among cardiomyocytes. Myh7-expressing cardiomyocytes were significantly more abundant in the middle layer, compared with the inner or outer layers of TAC2W hearts, while such spatial differences were not observed in TAC8W hearts. Expression levels of Myh7 were inversely correlated with cardiomyocyte size and expression levels of mitochondria-related genes., Conclusions: We developed a new image-analysis pipeline to allow automated and unbiased quantification of gene expression at the single-cell level and determined the spatial and temporal regulation of heterogenous Myh7 expression in cardiomyocytes after pressure overload., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Competing interests: None declared.

The mitral valve morphology in patients with pectus excavatum (PE) has not been fully investigated. Thirty-five patients with PE, 46 normal controls, and patients with hypertrophic cardiomyopathy (HCM) who underwent 2 leaflet length measurements of Carpentier classification P2 and A2 using a transthoracic echocardiography were retrospectively investigated. The coaptation lengths and depths, papillary muscle tethering length, and mitral annular diameters were also measured. The P2 and A2 lengths were separately compared between 2 groups: older than 16 years and 16 years or younger. Furthermore, the correlations between actual P2 or A2 lengths and Haller computed tomography index, an index of chest deformity, were investigated in patients with PE exclusively. Among subjects older than 16 years, patients with PE had significantly shorter P2, longer A2, shorter copatation depth, and longer papillary muscle tethering length compared with normal controls. Similarly, patients with PE had significantly shorter P2 and shorter coaptation depth even compared with patients with HCM, while no significant difference was found in A2 length and papillary muscle tethering length. The same tendency was noted between 4 normal controls and 7 age- and sex-matched patients with PE ≤ 16 years old. No significant difference regarding A2/P2 ratio was found between patients with PE older and younger than 16 years. No significant correlation between the Haller computed tomography index and actual mitral leaflet lengths in patients with PE older than 16 years was noted; the same was observed for A2/P2 in all patients with PE. In conclusion, the characteristic features of the shorter posterior mitral leaflet, the longer anterior mitral leaflet, the shorter coaptation depth, and the longer papillary muscle tethering length in patients with PE was demonstrated. This finding might provide a clue regarding the etiology of mitral valve prolapse in PE at its possible earliest form., Competing Interests: The authors have declared that no competing interests exist.

The sympathetic nervous system is the main stimulator of cardiac function. While acute activation of the β-adrenoceptors exerts positive inotropic and lusitropic effects by increasing cAMP and Ca 2+ , chronically enhanced sympathetic tone with changed β-adrenergic signaling leads to alterations of gene expression and remodeling. The CREB-regulated transcription coactivator 1 (CRTC1) is activated by cAMP and Ca 2+ . In the present study, the regulation of CRTC1 in cardiomyocytes and its effect on cardiac function and growth was investigated. In cardiomyocytes, isoprenaline induced dephosphorylation, and thus activation of CRTC1, which was prevented by propranolol. Crtc1-deficient mice exhibited left ventricular dysfunction, hypertrophy and enlarged cardiomyocytes. However, isoprenaline-induced contractility of isolated trabeculae or phosphorylation of cardiac troponin I, cardiac myosin-binding protein C, phospholamban, and ryanodine receptor were not altered, suggesting that cardiac dysfunction was due to the global lack of Crtc1. The mRNA and protein levels of the Gα q GTPase activating protein regulator of G-protein signaling 2 (RGS2) were lower in hearts of Crtc1-deficient mice. Chromatin immunoprecipitation and reporter gene assays showed stimulation of the Rgs2 promoter by CRTC1. In Crtc1-deficient cardiomyocytes, phosphorylation of the Gα q -downstream kinase ERK was enhanced. CRTC1 content was higher in cardiac tissue from patients with aortic stenosis or hypertrophic cardiomyopathy and from two murine models mimicking these diseases. These data suggest that increased CRTC1 in maladaptive hypertrophy presents a compensatory mechanism to delay disease progression in part by enhancing Rgs2 gene transcription. Furthermore, the present study demonstrates an important role of CRTC1 in the regulation of cardiac function and growth., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Brain renin-angiotensin system (RAS) hyperactivity has been implicated in sympathetic hyperactivity and progressive left ventricular (LV) dysfunction after myocardial infarction (MI). Angiotensin III, generated by aminopeptidase A (APA), is one of the main effector peptides of the brain RAS in the control of cardiac function. We hypothesized that orally administered firibastat (previously named RB150), an APA inhibitor prodrug, would attenuate heart failure (HF) development after MI in mice, by blocking brain RAS hyperactivity. Two days after MI, adult male CD1 mice were randomized to three groups, for four to eight weeks of oral treatment with vehicle (MI + vehicle), firibastat (150 mg/kg; MI + firibastat) or the angiotensin I converting enzyme inhibitor enalapril (1 mg/kg; MI + enalapril) as a positive control. From one to four weeks post-MI, brain APA hyperactivity occurred, contributing to brain RAS hyperactivity. Firibastat treatment normalized brain APA hyperactivity, with a return to the control values measured in sham group two weeks after MI. Four and six weeks after MI, MI + firibastat mice had a significant lower LV end-diastolic pressure, LV end-systolic diameter and volume, and a higher LV ejection fraction than MI + vehicle mice. Moreover, the mRNA levels of biomarkers of HF (Myh7, Bnp and Anf) were significantly lower following firibastat treatment. For a similar infarct size, the peri-infarct area of MI + firibastat mice displayed lower levels of mRNA for Ctgf and collagen types I and III (markers of fibrosis) than MI + vehicle mice. Thus, chronic oral firibastat administration after MI in mice prevents cardiac dysfunction by normalizing brain APA hyperactivity, and attenuates cardiac hypertrophy and fibrosis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

TRIM63 mutations have been described as a potential cause for cardiac and skeletal myopathy in only one family so far. We describe a new patient carrying the same homozygous TRIM63 nonsense mutation c.739 C>T p.Q247X, that was originally reported in two members of a Spanish family manifesting cardiac hypertrophy. One of these original patients also had an additional heterozygous mutation in TRIM54 and a much more severe phenotype also involving skeletal muscles, and a digenic inheritance was therefore suggested. Our case report confirms the role of TRIM63 as a new cardiac myopathy gene, although it is unclear whether the homozygous p.Q247X mutation alone is sufficient to cause an additional skeletal myopathy.

Background: The left ventricular (LV) hypertrophy increases the risk of heart failure. Hypertension and infiltrative cardiomyopathies are the well-known reasons of LV hypertrophy. The growing interest of scientists in this issue affects hereditary haemochromatosis (HH), which is characterised by the excess deposition of iron mostly due to HFE gene mutation. The aim of our study was to investigate the possible influence of HH on LV parameters in patients with early-diagnosed (early HH) and long-lasting and long-treated (old HH) disease., Materials and Methods: Thirty nine early HH and 19 old HH patients were prospectively enrolled in the study; age- and sex-matched healthy volunteers constituted the appropriate control groups. All participants had echocardiography performed (including three-dimension volume and mass analysis); the iron turnover parameters were measured at the time of enrolment in every HH patients., Results: Echocardiographic parameters regarding to left atrium (LA), LV thickness, mass and long axis length were significantly higher, whereas LV ejection fraction was lower in early HH in comparison to healthy persons. In old HH patients the differences were similar to those mentioned before, except LV ejection fraction. The presence of hypertension in both HH groups did not influence echo parameters, as well as diabetes in old HH. The strongest correlation in all HH group was found between the time from HH diagnosis and LA, LV thickness and volumes parameters, but the correlations between iron turnover and echo parameters were non-existent., Conclusions: Hereditary haemochromatosis, not only long-lasting, but also early-diagnosed, could lead to exacerbation of LV wall thickness and cardiac hypertrophy. This effect is not simply connected with hypertension and diabetes that are frequent additional diseases in these patients, but with the time from HH diagnosis.