Impact of carbon monoxide on early cardiac development in an avian model

Carbon monoxide (CO) is a toxic gas that can be lethal in large doses and may also cause physiological damage in lower doses. Epidemiological studies suggest that CO in lower doses over time may impact on embryo development, in particular cardiac development, however other studies have not observed this association. Here, we exposed chick embryos in ovo to CO at three different concentrations (1ppm, 8ppm, 25ppm) plus air control (4 protocols in total) for the first nine days of development, at which point we assessed egg and embryo weight, ankle length, developmental stage, heart weight and ventricular wall thickness. We found that heart weight was reduced for the low and moderate exposures compared to air, and that ventricular wall thickness was increased for the moderate and high exposures compared to air. Ventricular wall thickness was also significantly positively correlated with absolute CO exposures across all protocols. This intervention study thus suggests that CO even at very low levels may have a significant impact on cardiac development.

Changes of resting cardiac marker levels due to sport adaptation

Background In acute and chronic heart diseases some cardiac necroenzymes and peptide fragments are essential during the diagnosis and following the progression of the diseases. Previous literature data are available about elevation of these cardiac markers after exhausting physical activity, but we do not have information about the resting levels in athletes. Methods In part of the extended cardiology screening of athletes in our institute, we analyzed the levels of hsTroponinT, CKMB, LDH and NT-proBNP from blood samples. All the samples were collected at least 12 hours after the last trainings or competitions. The results of the athletes were compared with a healthy sedentary non-athlete control group. After the blood collection all subject underwent echocardiography examinations and cardiopulmonary exercise testing. Depending on normality, groups were compared with two-tailed Student's t-test or Mann-Whitney U-test. Statistical analysis was processed in RStudio development environment. Results Results of 335 athletes from different sports (male: 162, age: 18.9±5.9 years, training: 15.8±5.9 hours/week) and 53 sedentary non-athletes (male: 23, age: 19.8±3.2 years, training: 2.7±2.3 hours/week) were compared. In athletes, increased level of hsTroponinT was found in 3.3% (n=11), of CKMB in 5.7% (n=18), of LDH in 2.7% (n=9) and of NT-proBNP in 1.2% (n=4). In the control group no elevation was found regarding the CKMB and hsTroponinT, while slightly elevated values of LDH and NT-proBNP were revealed in 1–1 cases. In athletes we measured higher CKMB (17.5±6.8 vs 12.3±3.4 U/l, p<0.001) and LDH values (323.7±63.3 vs 286.0±51.1 U/l, p<0.001), and lower values of NT-proBNP (27.2±29.2 vs 49 8±38.7 pg/ml, p<0.001) compared to the control group, while in the hsTroponinT levels (4.3±1.4 vs 5.6±6.3 ng/l, p=0.33) no significant changes were measured. In term of the examined laboratory parameters significant correlation was found with maximal relative aerob capacity (CKMB: r=0.23, p<0.001; LDH: r=0.18, p<0.001; hsTroponinT: r=0.23, p<0.001; NT-proBNP: r=−0.22, p<0.001), but no correlation was found with age. Significant correlation was found between NT-proBNP levels and echocardiographic measurements of ventricular diameters and left ventricular wall thickness (LVEDD r=−0.15, p<0.03; LVESD r=−0.18, p<0.03; RVD: r=−0.15, p<0.02; IVS: r=−0.22, p<0.001; PWD r=−0.27, p<0.001), CKMB levels correlated with left ventricular wall thickness (IVS: r=0.11, p<0.05; PWD r=0.14, p<0.02). Conclusions Based on our results, in connection with the sports adaptation of the heart, the resting levels of the cardiac markers also show significant changes, these changes are correlated with aerobic endurance and structural sport adaptation parameters as well. Our study draws attention to the importance of different assessment of cardiac markers in athletes. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This project was supported by a grant from the National Research, Development and Innovation Office (NKFIH) of Hungary (K 135076).Supported by the ÚNKP-20-3-I-SE-41 New National Excellence Program of the Ministry for Innovation and Technology from the Source of the National Research, Development and Innovation fund.

Cor Triatriatum Sinistrum Combined with Changes in Atrial Septum and Right Atrium in a 60-Year-Old Woman

Background and Objectives: A rare case of cor triatriatum sinistrum in combination with anomalies in the atrial septum and in the right atrium of a 60-year-old female body donor is described here. Materials and Methods: In addition to classical dissection, ultrasound and magnetic resonance imaging, computer tomography and cinematic rendering were performed. In a reference series of 59 regularly formed hearts (33 men, 26 women), we looked for features in the left and right atrium or atrial septum. In addition, we measured the atrial and ventricular wall thickness in 15 regularly formed hearts (7 men, 8 women). Results: In the case described, the left atrium was partly divided into two chambers by an intra-atrial membrane penetrated by two small openings. The 2.5 cm-high membrane originated in the upper level of the oval fossa and left an opening of about 4 cm in diameter. Apparently, the membrane did not lead to a functionally significant flow obstruction due to the broad intra-atrial communication between the proximal and distal chamber of the left atrium. In concordance with this fact, left atrial wall thickness was not elevated in the cor triatriatum sinistrum when compared with 15 regularly formed hearts. In addition, two further anomalies were found: 1. the oval fossa was deepened and arched in the direction of the left atrium; 2. the right atrium showed a membrane-like structure at its posterior and lateral walls, which began at the lower edge of the oval fossa. It probably corresponds to a strongly developed eustachian valve (valve of the inferior vena cava). Conclusions: The case described suggests that malformations in the development of the atrial septum and in the regression of the valve of the right sinus vein are involved in the pathogenesis of cor triatriatum sinistrum.

Mutant Single Nucleotide Polymorphism rs189037 in Ataxia-Telangiectasia Mutated Gene Is Significantly Associated With Ventricular Wall Thickness and Human Lifespan

In the current study, we aimed to determine the association of single nucleotide polymorphism rs189037 in ataxia-telangiectasia mutated (ATM) gene with cardiac structure and human longevity. Based on the China Hainan Centenarian Cohort Study performed in 18 cities and counties of Hainan Province, China, the current study enrolled 547 centenarians, 250 young participants aged 20–45 years, and 250 middle-aged and elderly participants aged 46–90 years. The frequency of TT genotype was significantly higher and that of CC genotype was significantly lower in middle-aged and elderly participants than in young (P = 0.012) and centenarian (P = 0.041) participants. There were no significant differences in the genotype and allele frequencies of SNP rs189037 between young and centenarian participants. Compared with CT genotype, TT genotype was positively and significantly associated with interventricular septum thickness (IVST) and left ventricular posterior wall thickness (LVPWT) in centenarian (IVST: P = 0.049; LVPWT: P = 0.047) and middle-aged and elderly (IVST: P = 0.008; LVPWT: P = 0.004) participants. Compared with CC genotype, TT genotype was positively and significantly associated with LVPWT in centenarian (P = 0.030) and middle-aged and elderly (P = 0.013) participants. Compared with CC genotype, CT genotype was negatively and significantly associated with left ventricular end-diastolic diameter (LVEDD) in centenarian (P = 0.011) and middle-aged and elderly (P = 0.040) participants. The current study demonstrated that mutant rs189037 in the ATM gene was more commonly identified in middle-aged and elderly participants than in young and centenarian participants, was significantly associated with increased left ventricular wall thickness and volume, and could induce left ventricular eccentric hypertrophy and shorten human lifespan. Therefore, rs189037 without mutation might be an indicator of youth health and successful aging, whereas mutant rs189037 might hinder human longevity.

Hypertrophic Cardiomyopathy and Primary Restrictive Cardiomyopathy: Similarities, Differences and Phenocopies

Hypertrophic cardiomyopathy (HCM) and primary restrictive cardiomyopathy (RCM) have a similar genetic background as they are both caused mainly by variants in sarcomeric genes. These “sarcomeric cardiomyopathies” also share diastolic dysfunction as the prevalent pathophysiological mechanism. Starting from the observation that patients with HCM and primary RCM may coexist in the same family, a characteristic pathophysiological profile of HCM with restrictive physiology has been recently described and supports the hypothesis that familiar forms of primary RCM may represent a part of the phenotypic spectrum of HCM rather than a different genetic cardiomyopathy. To further complicate this scenario some infiltrative (amyloidosis) and storage diseases (Fabry disease and glycogen storage diseases) may show either a hypertrophic or restrictive phenotype according to left ventricular wall thickness and filling pattern. Establishing a correct etiological diagnosis among HCM, primary RCM, and hypertrophic or restrictive phenocopies is of paramount importance for cascade family screening and therapy.

Cardiac glycosaminoglycans and structural alterations during chronic stress-induced depression-like behavior in mice

Major depressive disorder (MDD) is an independent risk factor for cardiovascular disease (CVD) and its complications; however, causal mechanisms remain unclear. In the present study, we investigate cardiac structural and functional alterations and associated changes in myocardial glycosaminoglycans (GAGs) disaccharide profile in mice that exhibit depression-like behavior. Mice were assigned to chronic mild stress group (CMS) and non-stress control group (CT). The CMS group was exposed to a series of mild, unpredictable stressors for 7 weeks. Mice in CMS group show a significant decrease in protein expression of hippocampal brain-derived neurotrophic factor (BDNF), and exhibit depression-like behavioral changes such as learned helplessness and decreased exploration behavior as compared to the control group. While cardiac function remained unchanged between the groups, echocardiography analysis showed slightly increased left ventricular wall thickness in the CMS group. Furthermore, CMS group shows an increase in cardiomyocyte cross-sectional area when compared to control mice. GAG disaccharide analysis of the left ventricles of the CMS and CT mice revealed an elevation in heparan (HS) and chondroitin sulfate (CS) content in the CMS hearts (35.3% and 17.9%, respectively vs. control group). Furthermore, we also observed that unsulfated or monosulfated disaccharides were the most abundant units; however, we did not find any significant difference in mole % or sulfation pattern of HS/CS disaccharides between the groups. The current investigation highlights a need for further research to explore the relationship between cardiac GAGs biology and myocardial remodeling as a causal mechanism that underlie cardiovascular complications in MDD patients.

Injury caused by alcoholic cardiomyopathy in spontaneous ethanol drinking rats

ABSTRACTWhen speaking of pathologies caused or aggravated by the constant ingestion of ethanol, people with liver and central nervous system diseases soon come to mind, however, the acute intake of large amounts of ethanol and chronic abuse induce toxic effects in the majority of tissues. The heart is highlighted, since alcoholic cardiomyopathy (AC) has prevalence among alcoholics of 23 to 40% and occurs more frequently in men than in women. AC is characterized by dilation and poor contraction of one or both ventricles in the presence of increased ventricular wall thickness, along with a long history of ethanol abuse and no other cause identified. Our aim is to quantify the rate of cardiac tissue replacement, collagen fiber deposition and pro inflammatory cytokines in the left ventricle myocardium of volunteer ethanol drinking rats.

Discordant clinical features of identical hypertrophic cardiomyopathy twins

Hypertrophic cardiomyopathy (HCM) is a disease of heart muscle, which affects ∼1 in 500 individuals and is characterized by increased left ventricular wall thickness. While HCM is caused by pathogenic variants in any one of eight sarcomere protein genes, clinical expression varies considerably, even among patients with the same pathogenic variant. To determine whether background genetic variation or environmental factors drive these differences, we studied disease progression in 11 pairs of monozygotic HCM twins. The twin pairs were followed for 5 to 14 y, and left ventricular wall thickness, left atrial diameter, and left ventricular ejection fraction were collected from echocardiograms at various time points. All nine twin pairs with sarcomere protein gene variants and two with unknown disease etiologies had discordant morphologic features of the heart, demonstrating the influence of nonhereditable factors on clinical expression of HCM. Whole genome sequencing analysis of the six monozygotic twins with discordant HCM phenotypes did not reveal notable somatic genetic variants that might explain their clinical differences. Discordant cardiac morphology of identical twins highlights a significant role for epigenetics and environment in HCM disease progression.

Prognostic effect of increased left ventricular wall thickness in severe aortic stenosis

Background It is unclear whether increased left ventricular (LV) thickness is associated with worse clinical outcomes in severe aortic stenosis (AS). The aim of this study was to determine the effect of increased LV wall thickness (LVWT) on major clinical outcomes in patients with severe AS. Methods and results This study included 290 severe AS patients (mean age 69.4 ± 11.0 years; 136 females) between January 2008 and December 2018. For outcome assessment, the endpoint was defined as death from all causes, cardiovascular death, and the aortic valve replacement (AVR) surgery rate. During follow-up (48.7 ± 39.0 months), 157 patients had AVR, 43 patients died, and 28 patients died from cardiovascular causes. Patients with increased LVWT underwent AVR surgery much more than those without LVWT (60.0% vs. 39.0%, p < 0.001). Furthermore, in patients with increased LVWT, the all-cause and cardiovascular death rates were significantly lower in the AVR group than in the non-AVR group (8.8% vs. 27.3%, p < 0.001, 4.8%, vs. 21.0%, p < 0.001). Multivariate analysis revealed that increased LVWT, age, dyspnea, and AVR surgery were significantly correlated with cardiovascular death. Conclusions In patients with severe AS, increased LVWT was associated with a higher AVR surgery rate and an increased rate of cardiovascular death independent of other well-known prognostic variates. Thus, these findings suggest that increased LVWT might be used as a potential prognostic factor in severe AS patients.