Genetic, clinical and imaging implications of a noncompaction phenotype population with preserved ejection fraction.

Introduction: The genotype of symptomatic left ventricular noncompaction phenotype (LVNC) subjects with preserved left ventricular ejection fraction (LVEF) and its effect on clinical presentation are less well studied. We aimed to characterize the genetic, cardiac magnetic resonance (CMR) and clinical background, and genotype-phenotype relationship in LVNC with preserved LVEF. Methods: We included 54 symptomatic LVNC individuals (LVEF: 65 ± 5%) whose samples were analyzed with a 174-gene next-generation sequencing panel and 54 control (C) subjects. The results were evaluated using the criteria of the American College of Medical Genetics and Genomics. Medical data suggesting a higher risk of cardiovascular complications were considered "red flags". Results: Of the LVNC population, 24% carried pathogenic or likely pathogenic (P) mutations; 56% carried variants of uncertain significance (VUS); and 20% were free from cardiomyopathy-related mutations. Regarding the CMR parameters, the LVNC and C groups differed significantly, while the three genetic subgroups were comparable. We found a significant relationship between red flags and genotype; furthermore, the number of red flags in a single subject differed significantly among the genetic subgroups (p = 0.002) and correlated with the genotype (r = 0.457, p = 0.01). In 6 out of 7 LVNC subjects diagnosed in childhood, P or VUS mutations were found. Discussion: The large number of P mutations and the association between red flags and genotype underline the importance of genetic-assisted risk stratification in symptomatic LVNC with preserved LVEF.

Highlights of right ventricular characteristics of left ventricular noncompaction using 3D echocardiography.

Highlights of right ventricular characteristics of left ventricular noncompaction using 3D echocardiography. The aspects of right ventricular volumes and function investigated with 3D echocardiography in a large cohort of left ventricular noncompaction morphology (LVNC) population remains unclear. The objective of our research was to study the left (LV) and right (RV) ventricular parameters using 3D echocardiography and analyze the clinical features of a LVNC population with preserved LV ejection fraction (EF > 50 %) in comparison with healthy controls (HC). We selected 41 LVNC subjects with preserved LV function (EF: 52.91 ± 3 %, male n = 26) and without any comorbidities and compared them with an age and sex-matched HC. Three dimensional endocardial contours were evaluated to determine the following LV and RV parameters: end-diastolic (EDV) and end-systolic (ESV) volumes, stroke volume, EF, LV global longitudinal and circumferential strain and RV septal and free wall longitudinal strain. Regarding the clinical characteristics, the family involvement had a notable proportion, accounting for 51%. The EF and strain values of the LVNC population were significantly decreased in both RV and LV compared to HC. Although the LV volumes of the LVNC group were significantly elevated, the RV volumetric parameters did not differ significantly compared to controls. We found significant correlations between LV and RV volumetric and functional parameters and linear regression models showed that LV EDV and LV ESV determined the RV volumetric values. While the alteration and relationship of the RV parameters may represent the potential of biventricular involvement, clinical characteristics of the LVNC group underlines the necessity of monitoring this population, even with preserved EF.

D'Atri spaces and the total scalar curvature of hemispheres, tubes and cylinders.

Csikós and Horváth proved in J Geom Anal 28(4): 3458-3476, (2018) that if a connected Riemannian manifold of dimension at least 4 is harmonic, then the total scalar curvatures of tubes of small radius about an arbitrary regular curve depend only on the length of the curve and the radius of the tube, and conversely, if the latter condition holds for cylinders, i.e., for tubes about geodesic segments, then the manifold is harmonic. In the present paper, we show that in contrast to the higher dimensional case, a connected 3-dimensional Riemannian manifold has the above mentioned property of tubes if and only if the manifold is a D'Atri space, furthermore, if the space has bounded sectional curvature, then it is enough to require the total scalar curvature condition just for cylinders to imply that the space is D'Atri. This result gives a negative answer to a question posed by Gheysens and Vanhecke. To prove these statements, we give a characterization of D'Atri spaces in terms of the total scalar curvature of geodesic hemispheres in any dimension.

Different methods, different results? Threshold-based versus conventional contouring techniques in clinical practice.

BACKGROUND: The quantitative differences of left and right ventricular (LV, RV) parameters of using different cardiac MRI (CMR) post-processing techniques and their clinical impact are less studied. We aimed to assess the differences and their clinical impact between the conventional contouring (CC) and the threshold-based (TB) methods using 70% and 50% thresholds in different hypertrabeculated conditions. METHODS: This retrospective study included 30 dilated cardiomyopathy, 30 left ventricular non-compaction (LVNC), 30 arrhythmogenic cardiomyopathy patients, 30 healthy athletes and 30 healthy volunteers. All participants underwent CMR imaging on 1.5 T. Cine sequences were used to derive measures of the cardiac volumes, function, total muscle mass (TMi) and trabeculae and papillary muscle mass (TPMi) using CC and TB segmentation methods. RESULTS: Comparing the CC and the 70% and 50% threshold TB methods, the LV and RV volumes were significantly lower, the ejection fraction (EF) and the TMi were significantly higher with the TB methods. Between the two threshold setups, only TPMi was significantly higher with the 70% threshold. Regarding the clinical benefits, the LVNC was the only group in whom all the diagnostic and therapeutic decisions and risk stratification were influenced using the TB method. Diagnostic changes occurred in three-quarters of the population, and all the cardiomyopathy groups were affected regarding the decision-making about pharmaco- and device therapy. CONCLUSIONS: Using the TB method, only TPMi was significantly higher with the 70% threshold than the 50% setup, and both of them differed significantly from the CC technique, with relevant clinical impacts in all patient groups.

Cardiopulmonary examinations of athletes returning to high-intensity sport activity following SARS-CoV-2 infection.

After SARS-CoV-2 infection, strict recommendations for return-to-sport were published. However, data are insufficient about the long-term effects on athletic performance. After suffering SARS-CoV-2 infection, and returning to maximal-intensity trainings, control examinations were performed with vita-maxima cardiopulmonary exercise testing (CPET). From various sports, 165 asymptomatic elite athletes (male: 122, age: 20y (IQR: 17-24y), training:16 h/w (IQR: 12-20 h/w), follow-up:93.5 days (IQR: 66.8-130.0 days) were examined. During CPET examinations, athletes achieved 94.7 ± 4.3% of maximal heart rate, 50.9 ± 6.0 mL/kg/min maximal oxygen uptake (V̇O2max), and 143.7 ± 30.4L/min maximal ventilation. Exercise induced arrhythmias (n = 7), significant horizontal/descending ST-depression (n = 3), ischemic heart disease (n = 1), hypertension (n = 7), slightly elevated pulmonary pressure (n = 2), and training-related hs-Troponin-T increase (n = 1) were revealed. Self-controlled CPET comparisons were performed in 62 athletes: due to intensive re-building training, exercise time, V̇O2max and ventilation increased compared to pre-COVID-19 results. However, exercise capacity decreased in 6 athletes. Further 18 athletes with ongoing minor long post-COVID symptoms, pathological ECG (ischemic ST-T changes, and arrhythmias) or laboratory findings (hsTroponin-T elevation) were controlled. Previous SARS-CoV-2-related myocarditis (n = 1), ischaemic heart disease (n = 1), anomalous coronary artery origin (n = 1), significant ventricular (n = 2) or atrial (n = 1) arrhythmias were diagnosed. Three months after SARS-CoV-2 infection, most of the athletes had satisfactory fitness levels. Some cases with SARS-CoV-2 related or not related pathologies requiring further examinations, treatment, or follow-up were revealed.

Sex- and age- specific normal values of left ventricular functional and myocardial mass parameters using threshold-based trabeculae quantification.

BACKGROUND: The threshold-based (TB) trabeculated and papillary muscle mass (TPM) quantification method for cardiac MRI (CMR) calculates different values than conventional contouring techniques. We aimed to identify the sex- and age-related normal reference ranges for left ventricular (LV) myocardial mass values, volumetric and functional parameters and the correspondence of these parameters using the TB method. METHODS: Healthy European adults (n = 200, age: 39.4 ± 12 years, males: 100) were examined with CMR and evaluated with a TB postprocessing method. They were stratified by sex and age (Group A: 18-29, Group B: 30-39, Group C: 40-49, Group D: >50 years). The calculated parameters were indexed to body surface area (i). RESULTS: The normal reference ranges for the studied parameters were assessed in each age group. Significant biometric differences in LV parameters and mass-to-volume ratios were found between males and females, and the left ventricular compacted myocardial mass (LVCMi) and TPMi differences remained significant after stratification by age. Unlike other LV volumetric and functional parameters and mass-to-volume ratios, the TPMi, the LVCMi and the TPMi-to-LVCMi ratio did not differ among age groups in males or females. This finding was strengthened by the lack of correlation between TPMi and age. CONCLUSIONS: Age- and sex-related normal reference ranges for LV volumetric and functional parameters and LVCMi and TPMi values were established using a TB postprocessing method. TPMi, LVCMi and their ratio did not change over time. The TPMi-to-LVCMi and the mass-to-volume ratios might have clinical utility in the differential diagnosis of conditions with LV hypertrabeculation.

Left ventricular characteristics of noncompaction phenotype patients with good ejection fraction measured with cardiac magnetic resonance.

OBJECTIVE: We describe left ventricular (LV) volumes, myocardial and trabeculated muscle mass and strains with Cardiac magnetic resonance of a large cohort (n=81) who fulfilled the morphologic criteria of left ventricular noncompaction (LVNC) and had good ejection fraction (EF >55%) and compare them with healthy controls (n=81). Male and female patients were compared to matched controls and to each other. We also investigated the LV trabeculated muscle mass cutoff in male and female patients with LVNC. METHODS: 81 participants with LVNC and 81 healthy controls were included. Male and female patients were compared to matched controls and to each other. We also investigated the left ventricular trabeculated muscle mass cut-off in male and female LVNC patients. RESULTS: The LV parameters of the LVNC population were normal, but they had significantly higher volumes, myocardial and trabeculated muscle mass, and a significantly smaller EF than the controls. Similar differences were observed after stratifying by sex. The optimal LV trabeculated muscle mass cutoffs were 25.8 g/m2 in men (area under the curve: 0.81) and 19.0 g/m2 in women (area under the curve: 0.87). The patients had normal global strains but a significantly worse global circumferential strain (patients vs controls: -29.9±4.9 vs. -35.8±4.7%, p<0.05) and significantly higher circumferential mechanical dispersion than the controls (patients vs. controls: 7.6±4.2 vs. 6.1±2.8%; p<0.05). No disease-related strain differences were noted between men and women. CONCLUSION: The LV functional and strain characteristics of the LVNC cohort differed significantly from those of healthy participants; this might be caused by increased LV trabeculation, and its clinical relevance might be questionable. The LV trabeculated muscle mass was very different between men and women; thus, the use of sex-specific morphologic diagnostic criteria should be considered.

Oral Epithelial Cells Distinguish between Candida Species with High or Low Pathogenic Potential through MicroRNA Regulation.

Oral epithelial cells monitor microbiome composition and initiate immune response upon dysbiosis, as in the case of Candida imbalances. Candida species, such as C. albicans and C. parapsilosis, are the most prevalent yeasts in the oral cavity. Comparison of healthy oral epithelial cell responses revealed that while C. albicans infection robustly activated inflammation cascades, C. parapsilosis primarily activated various inflammation-independent pathways. In posttranscriptional regulatory processes, several miRNAs were altered by both species. For C. parapsilosis, the dose of yeast cells directly correlated with changes in transcriptomic responses with higher fungal burdens inducing significantly different and broader changes. MicroRNAs (miRNAs) associated with carbohydrate metabolism-, hypoxia-, and vascular development-related responses dominated with C. parapsilosis infection, whereas C. albicans altered miRNAs linked to inflammatory responses. Subsequent analyses of hypoxia-inducible factor 1α (HIF1-α) and hepatic stellate cell (HSC) activation pathways predicted target genes through which miRNA-dependent regulation of yeast-specific functions may occur, which also supported the observed species-specific responses. Our findings suggest that C. parapsilosis is recognized as a commensal at low doses by the oral epithelium; however, increased fungal burden activates different pathways, some of which overlap with the inflammatory processes robustly induced by C. albicans IMPORTANCE A relatively new topic within the field of immunology involves the role of miRNAs in innate as well as adaptive immune response regulation. In recent years, posttranscriptional regulation of host-pathogenic fungal interactions through miRNAs was also suggested. Our study reveals that the distinct nature of human oral epithelial cell responses toward C. parapsilosis and C. albicans is possibly due to species-specific fine-tuning of host miRNA regulatory processes. The findings of this study also shed new light on the nature of early host cell transcriptional responses to the presence of C. parapsilosis and highlight the species' potential inflammation-independent host activation processes. These findings contribute to our better understanding of how miRNA deregulation at the oral immunological barrier, in noncanonical immune cells, may discriminate between fungal species, particularly Candida species with high or low pathogenic potential.

Changes in strain parameters at different deterioration levels of left ventricular function: A cardiac magnetic resonance feature-tracking study of patients with left ventricular noncompaction.

BACKGROUND: There is a lack of cardiac MRI information on left ventricular (LV) strain and rotational parameters of left ventricular noncompaction (LVNC) patients with reduced ejection fraction (EF). Thus, we sought to use feature tracking (FT) to describe these changes at different levels of EF deterioration. METHODS: We included 31 adult LVNC patients with reduced LV EF (Group B, EF < 50%) without any comorbidities or concomitant cardiac diseases, 31 age- and sex-matched LVNC patients with good EF (Group A, EF > 50%) and 31 healthy controls. Group B was divided according to LV EF into two subgroups (Group B-1: EF 35-50%, Group B-2: EF < 35%). Their global longitudinal, circumferential (GCS), and radial (GRS) strains; LV segmental strains; LV apical and basal rotation values; and patterns and degree of LV dyssynchrony were measured. RESULTS: All of the global and mean segmental strain parameters were significantly worse in Groups B, B-1 and B-2 than in Group A and in the controls. The LV mechanical dispersion increased as LV EF decreased. The degree of apical rotation was the highest in the control group, almost the same in Group A and the lowest and in the reverse direction in Group B-2. A rotational pattern, clockwise-directed rigid body rotation (RBR), was found in 39% of the Group B patients, and a counterclockwise-directed RBR was found in 26% of the Group A patients. CONCLUSIONS: The strain values and rotational parameters changed as the EF decreased. These changes affected the global LV, and we did not identify an LVNC-specific strain pattern.

Candida albicans Enhances the Progression of Oral Squamous Cell Carcinoma In Vitro and In Vivo.

Oral squamous cell carcinoma (OSCC) is associated with oral Candida albicans infection, although it is unclear whether the fungus promotes the genesis and progression of OSCC or whether cancer facilitates fungal growth. In this study, we investigated whether C. albicans can potentiate OSCC tumor development and progression. In vitro, the presence of live C. albicans, but not Candida parapsilosis, enhanced the progression of OSCC by stimulating the production of matrix metalloproteinases, oncometabolites, protumor signaling pathways, and overexpression of prognostic marker genes associated with metastatic events. C. albicans also upregulated oncogenes in nonmalignant cells. Using a newly established xenograft in vivo mouse model to investigate OSCC-C. albicans interactions, oral candidiasis enhanced the progression of OSCC through inflammation and induced the overexpression of metastatic genes and significant changes in markers of the epithelial-mesenchymal transition. Finally, using the 4-nitroquinoline 1-oxide (4NQO) murine model, we directly correlate these in vitro and short-term in vivo findings with the progression of oncogenesis over the long term. Taken together, these data indicate that C. albicans upregulates oncogenes, potentiates a premalignant phenotype, and is involved in early and late stages of malignant promotion and progression of oral cancer. IMPORTANCE Oral squamous cell carcinoma (OSCC) is a serious health issue worldwide that accounts for 2% to 4% of all cancer cases. Previous studies have revealed a higher yeast carriage and diversity in oral cancer patients than in healthy individuals. Furthermore, fungal colonization in the oral cavity bearing OSCC is higher on the neoplastic epithelial surface than on adjacent healthy surfaces, indicating a positive association between oral yeast carriage and epithelial carcinoma. In addition to this, there is strong evidence supporting the idea that Candida contributes to carcinogenesis events in the oral cavity. Here, we show that an increase in Candida albicans burden promotes an oncogenic phenotype in the oral cavity.

The effect of contrast agents on left ventricular parameters calculated by a threshold-based software module: does it truly matter?

The acquisition of short-axis (SA) cine magnetic resonance (MR) images after the administration of contrast agent (CA) is a common, time-saving technique, but a decreased difference in the blood-myocardium contrast on these steady-state free precession (SSFP) cine scans could change the calculated parameters when using threshold-based papillary and trabecular muscle (PTM) quantification. We studied the effect of CA on the parameters calculated from pre- and post-CA SA cine images in noncompaction cardiomyopathy (NC-CMP) and healthy (H) participants using a threshold-based module. A total of 39 individuals (20 patients and 19 healthy) were included prospectively in this study. After the pre-CA SA images were acquired, i.v. gadobutrol (GA) or gadobenate dimeglumine (GD) (GA vs. GD: NC-CMP = 12 vs. 8; C = 12 vs. 7) was administered, and SA scans were repeated after two minutes. A threshold-based PTM software was used for postprocessing. Pre-CA and post-CA SA images were analyzed, and the parameters were compared in both the NC-CMP and H groups. The left ventricular volumes were significantly larger, while the left ventricular myocardial (LVmass) and trabecular mass (LVtrab) values were significantly smaller on the post-CA scans (NC-CMP: pre-CA vs. post-CA, EDV: 74.0 ± 13.6 vs. 81.1 ± 16.3 ml/m2, ESV: 25.3 ± 7.3 vs. 30.1 ± 11.2 ml/m2, LVmass-ED: 82.5 ± 17.5 vs. 75.7 ± 15.9 g/m2, LVtrab-ED: 25.0 ± 6.6 vs. 18.9 ± 4.7 g/m2; Healthy: preCA vs. post-CA, EDV: 69.7 ± 11.9 vs. 72.2 ± 10.7 ml/m2, ESV: 22.6 ± 5.7 vs. 23.9 ± 6.3 ml/m2, LVmass-ED: 71.3 ± 13.6 vs. 68.7 ± 13.9 g/m2, LVtrab-ED: 19.4 ± 2.6 vs. 16.2 ± 3.0 g/m2; p < 0.05). The decreased blood-myocardium contrast difference on post-CA SSFP SA cine images leads to altered cardiac parameters when using threshold-based software for evaluation.

Association Between Serum Lipid Profile and Obstructive Respiratory Events During REM and Non-REM Sleep.

PURPOSE: Obstructive sleep apnoea (OSA) represents a risk for dyslipidaemia. Obstructive respiratory events during rapid eye movement (REM) sleep are more strongly related to the development of hypertension and diabetes than in non-REM. However, the relationship between sleep phases and serum lipid profile is unclear. We aimed to analyse the relationship between obstructive respiratory events in REM and non-REM sleep as well as serum lipid profile. METHODS: Polysomnography was performed in 94 adult subjects who did not take any lipid-modifying medications. Fasting venous blood sample was taken the following morning for total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, lipoprotein(a), apoprotein A1 (ApoA1) and for apoprotein B (ApoB) measurements. Lipid profiles were correlated with apnoea-hypopnoea index (AHI) during REM (AHIREM) and non-REM (AHINREM) stages in all subjects. In addition, lipid profiles were compared between REM-dependent OSA patients (AHIREM ≥ 5/h, but AHINREM < 5/h) and control subjects (both AHIREM and AHINREM < 5/h). RESULTS: AHIREM correlated only with triglyceride concentrations (p = 0.04, Spearman's rho, ρ = 0.21). In contrast, there was a significant association between AHINREM and triglyceride (p = 0.02, ρ = 0.23), ApoB (p = 0.03, ρ = 0.21), HDL-C (p < 0.01, ρ = - 0.32) as well as ApoA1 levels (p = 0.04, ρ = - 0.21). However, these correlations were not present after adjustment for BMI (all p > 0.05). There was no difference in the lipid profile of REM-dependent OSA subjects and healthy controls (p > 0.05). CONCLUSIONS: Altered serum lipid profile is equally associated with a disturbed REM and non-REM sleep in OSA. Obesity must be considered as a strong covariate when interpreting lipid data in sleep apnoea.

Current efforts to monitor and conserve the Eastern Imperial Eagle Aquila heliaca in Hungary.

The globally threatened Eastern Imperial Eagle Aquila heliaca has been one of the flagship species of Hungarian bird conservation efforts since the 1980s. Due to these conservation activities and positive land-use changes during the last 2 decades, the Hungarian Imperial Eagle population increased from as few as approximately 20 pairs in the early 1980s to 81 pairs by 2006. Between 2002 and 2005 as part of a LIFE-Nature project, MME/Birdlife Hungary carried out particularly intensive monitoring, conservation, research, and public awareness actions. The main goal of the project was to secure the long-term sustainable increase in the Imperial Eagle population after Hungary's European Union accession in 2004. New methods were developed and applied to census and monitor the breeding and wintering population sizes. Standardized baseline land-use mapping and surveys were introduced to detect long-term land-use and prey density changes in priority areas for Imperial Eagles and to monitor the effects of key mortality factors, such as electrocution. Historical information and data gathered before and during the project period were assimilated using a Geographic Information System and incorporated into a comprehensive set of Imperial Eagle Management Guidelines.