Comparison of cardiac morphology and function in small for gestational age fetuses and fetuses with late-onset fetal growth retardation

Objectives To compare cardiac structural and functional findings of fetuses with fetal growth restriction (FGR) and small for gestational age (SGA). Methods In this prospective cohort study, patients were classified into three groups using Delphi procedure according to fetal weight, umbilical, uterine artery Doppler and cerebroplacental ratio. Fetal cardiac ultrasonographic morphology and Doppler examination was performed to all pregnant women at 36 weeks of gestation. Results Seventy three patients were included in the study. There were one (6.7%) patient in the control group, 2 (13.3%) in the SGA group and 12 (80%) in the FGR group who needed neonatal intensive care unit (NICU) and NICU requirement was significantly higher in FGR fetuses (p<0.001). Left spherical index was found to be lower only among FGR fetuses (p=0.046). Left ventricular wall thickness was decreased and the right/left ventricular wall ratio was increased in FGR fetuses (p=0.006, p<0.001). Tricuspid/mitral valve ratio and mitral annular plane systolic excursion value was lower in FGR fetuses (p=0.034, p=0.024 respectively). Also, myocardial performance index was remarkably higher in FGR group (p=0.002). Conclusions We detected cardiac morphological changes in cases of both SGA and FGR—more pronounced in the FGR cases. Findings related to morphological changes on the left side in FGR cases were considered secondary to volume increase in FGR cases as an indicator of a brain-protective effect. In the FGR group, both systolic and diastolic dysfunctions were detected in the left heart.

The Myosin Myocardial Mesh Interpreted as a Biological Analogous of Nematic Chiral Liquid Crystals

There are still grey areas in the understanding of the myoarchitecture of the ventricular mass. This is despite the progress of investigation methods since the beginning of the 21st century (diffusion tensor magnetic resonance imaging, microcomputed tomography, and polarised light imaging). The objective of this article is to highlight the specificities and the limitations of polarised light imaging (PLI) of the unstained myocardium embedded in methyl methacrylate (MMA). Thus, to better differentiate our method from other PLI modes, we will refer to it by the acronym PLI-MMA. PLI-MMA shows that the myosin mesh of the compact left ventricular wall behaves like a biological analogous of a nematic chiral liquid crystal. Results obtained by PLI-MMA are: the main direction of the myosin molecules contained in an imaged voxel, the crystal liquid director n, and a regional isotropy index RI that is an orientation tensor, the equivalent of the crystal liquid order parameter. The vector n is collinear with the first eigenvector of diffusion tensor imaging (DTI-MRI). The RI has not been confounded with the diffusion tensor of DTI that gives information about the three eigenvectors of the ellipsoid of diffusion. PLI-MMA gives no information about the collagen network. The physics of soft matter has allowed the revisiting of Streeter’s conjecture on the myoarchitecture of the compact left ventricular wall: “geodesics on a nested set of toroidal surfaces”. Once the torus topology is understood, this characterisation of the myoarchitecture is more accurate and parsimonious than former descriptions. Finally, this article aims to be an enthusiastic invitation to a transdisciplinary approach between physicists of liquid crystals, anatomists, and specialists of imaging.

Early post-septal myectomy outcomes for hypertrophic obstructive cardiomyopathy

Background We aimed to evaluate early outcomes of septal myectomy in patients with hypertrophic cardiomyopathy. Methods We retrospectively analyzed data collected over a 9-year period from 583 patients who underwent septal myectomy for hypertrophic cardiomyopathy at our institution. Results The mean age was 55.7 ± 13.1 years, and 338 (58%) patients were in New York Heart Association class III or IV. There were 11 (1.9%) early deaths, including 3 (0.5%) intraoperative deaths. Early mortality was lowest after isolated septal myectomy (0.8%) and highest after concomitant mitral valve replacement (6.1%). There were 4 (0.7%) and 9 (1.5%) patients with left ventricular wall rupture and ventricular septal defect, respectively, after myectomy. New pacemaker implantation caused by atrioventricular disturbances was required in 29 (5.0%) patients, and was associated with previous alcohol septal ablation (odds ratio 3.34, 95% confidence interval 1.02–11.0, P = 0.047). Left ventricular wall rupture, intraoperative residual (15.5% moderate, 0.3% severe) mitral regurgitation, and pre-discharge residual outflow tract gradient >30 mm Hg (4.6%) occurrences were surgeon-dependent. Conclusions The early results are consistent with example targets reported in the 2020 American College of Cardiology/American Heart Association guidelines for septal reduction therapy outcomes. Septal myectomy safety and efficacy are surgeon-dependent. Previous alcohol septal ablation increases the risk of permanent pacemaker implantation due to postoperative complete atrioventricular block. Therefore, continuous education, mentoring, and learning by doing may play an important role in achieving reasonable septal myectomy safety and efficacy.

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&lt;0.001) and LDH values (323.7±63.3 vs 286.0±51.1 U/l, p&lt;0.001), and lower values of NT-proBNP (27.2±29.2 vs 49 8±38.7 pg/ml, p&lt;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&lt;0.001; LDH: r=0.18, p&lt;0.001; hsTroponinT: r=0.23, p&lt;0.001; NT-proBNP: r=−0.22, p&lt;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&lt;0.03; LVESD r=−0.18, p&lt;0.03; RVD: r=−0.15, p&lt;0.02; IVS: r=−0.22, p&lt;0.001; PWD r=−0.27, p&lt;0.001), CKMB levels correlated with left ventricular wall thickness (IVS: r=0.11, p&lt;0.05; PWD r=0.14, p&lt;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.

A systems approach using Diversity Outbred mice distinguishes the cardiovascular effects and genetics of circulating GDF11 from those of its homolog, myostatin

Growth differentiation factor 11 (GDF11) is a member of the TGF-β protein family that has been implicated in the development of cardiac hypertrophy. While some studies have suggested that systemic GDF11 protects against cardiomyocyte enlargement and left ventricular wall thickening, there remains uncertainty about the true impact of GDF11 and whether its purported effects are actually attributable to its homolog myostatin. The present study was conducted to resolve the statistical and genetic relationships among GDF11, myostatin, and cardiac hypertrophy in a mouse model of human genetics, the Diversity Outbred (DO) stock. In the DO population, serum GDF11 concentrations positively correlated with cardiomyocyte cross sectional area, while circulating myostatin levels were negatively correlated with body weight, heart weight, and left ventricular wall thickness and mass. Genetic analyses revealed that serum GDF11 concentrations are modestly heritable (0.23) and identified a suggestive peak on murine chromosome 3 in close proximity to the gene Hey1, a transcriptional repressor. Bioinformatic analyses located putative binding sites for the HEY1 protein upstream of the Gdf11 gene in the mouse and human genomes. In contrast, serum myostatin concentrations were more heritable (0.57) than GDF11 concentrations, and mapping identified a significant locus near the gene FoxO1, which has binding motifs within the promoter regions of human and mouse myostatin genes. Together, these findings more precisely define the independent cardiovascular effects of GDF11 and myostatin, as well as their distinct regulatory pathways. Hey1 is a compelling candidate for the regulation of GDF11 and will be further evaluated in future studies.

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.