Prevalence of Bicuspid Aortic Valve in Turner Syndrome Patients Receiving Cardiac MRI and CT: A Meta-Analysis

Turner syndrome (TS) is a rare disorder affecting 25–50 in 100000 female newborns. Bicuspid aortic valve (BAV) is assumed to be the most common congenital heart defect (CHD) in TS. In literature, reported BAV prevalence in TS ranges between 14% and 34%. The specific BAV prevalence in TS is still unknown. The aim of this study was to give a more precise estimation of BAV prevalence in TS by conducting a meta-analysis of TS-studies, which detected BAV by either cardiac magnetic resonance imaging (MRI) or cardiac computed tomography (CT). We searched PubMed, Cochrane Library, and Web of Science databases to collect observational studies including the prevalence of BAV identified by cardiac MRI or cardiac CT in TS patients up to June 4th, 2021. After screening for inclusion, data extraction, and quality assessment by two independent reviewers, the meta-analysis was performed with R 4.1.1 software. Results are shown as proportion and weighted mean difference with 95% confidence intervals (95% CI). In total, 11 studies involving 1177 patients were included. Pooled data showed that the prevalence of BAV in TS patients was 23.7% (95% CI: 21.3% to 26.1%). No high heterogeneity was found between the included studies. The current meta-analysis reveals that BAV can be detected in 23.7% of TS patients receiving cardiac MRI or cardiac CT. Therefore, BAV can be considered as the most common CHD in TS. Compared to TTE, cardiac MRI and cardiac CT might represent superior imaging modalities in BAV assessment of adult TS patients

Energy Drinks and Their Acute Effects on Arterial Stiffness in Healthy Children and Teenagers: A Randomized Trial

Adolescents are the main consumer group of energy drinks (ED). Studies suggest that acute ED consumption is associated with increased peripheral blood pressure. Little is known of the ED-induced effects on arterial stiffness. Therefore, this study aimed to investigate the acute effects of ED consumption on arterial stiffness in healthy children and teenagers by conducting a prospective, randomized, single-blind, placebo-controlled, crossover clinical trial. Study participants (n = 27, mean age = 14.53 years) consumed a body-weight-adjusted amount of an ED or a placebo on two consecutive days. Arterial stiffness was evaluated sonographically by two-dimensional speckle tracking of the common carotid artery (CCA) at baseline and up to four hours after beverage consumption. The ED intake led to a significantly decreased peak circumferential strain of the CCA (11.78 +/- 2.70% vs. 12.29 +/- 2.68%, p = 0.043) compared with the placebo. The results of this study indicate that the acute ED consumption might be associated with increased arterial stiffness in healthy children and teenagers. Minors, particularly those with increased cardiovascular morbidity, should be discouraged from ED consumption

MicroRNA-126-3p/5p and Aortic Stiffness in Patients with Turner Syndrome

Background: Turner Syndrome (TS) is a relatively rare X-chromosomal disease with increased cardiovascular morbidity and mortality. This study aimed to identify whether the circulating miR-126-3p/5p are involved in the pathophysiology of vascular dysfunction in TS. Methods: Using the RT-qPCR, the abundance levels of miR-126-3p and miR-126-5p were determined in 33 TS patients and 33 age-matched healthy volunteers (HVs). Vascular screening, including the assessment of blood pressure, pulse wave velocity, augmentation index, aortic deformation, arterial distensibility, and arterial elastance, was conducted in TS patients and HVs. Results: The abundance levels of miR-126-3p and miR-126-5p were significantly higher in TS patients compared to HVs (p < 0.0001). Within the TS cohort, miR-126-3p/5p correlated significantly with aortic deformation (r = 0.47, p = 0.01; r = 0.48, p < 0.01) and arterial distensibility (r = 0.55, p < 0.01; r = 0.48, p < 0.01). In addition, a significant negative correlation was demonstrated between miR-126-3p and arterial elastance (r = −0.48, p = 0.01). The receiver operating characteristic analysis showed that miR-126-3p and miR-126-5p separated the tested groups with high sensitivity and specificity. Conclusions: The abundance levels of miR-126-3p and miR-126-5p were significantly higher in TS patients compared to HVs. Within the TS cohort, a lower abundance level of miR-126-3p and miR-126-5p was linked with a significantly higher aortic stiffness

Insights from circulating microRNAs in cardiovascular entities in turner syndrome patients

Background Turner syndrome (TS) is a chromosomal disorder, in which a female is partially or entirely missing one of the two X chromosomes, with a prevalence of 1:2500 live female births. The present study aims to identify a circulating microRNA (miRNA) signature for TS patients with and without congenital heart disease (CHD). Methods Microarray platform interrogating 2549 miRNAs were used to detect the miRNA abundance levels in the blood of 33 TS patients and 14 age-matched healthy volunteer controls (HVs). The differentially abundant miRNAs between the two groups were further validated by RT-qPCR. Results We identified 60 differentially abundant miRNA in the blood of TS patients compared to HVs, from which, 41 and 19 miRNAs showed a higher and a lower abundance levels in TS patients compared to HVs, respectively. RT-qPCR confirmed the significantly higher abundance levels of eight miRNAs namely miR-374b-5p, miR-199a-5p, miR-340-3p, miR-125b-5p, miR-30e-3p, miR-126-3p, miR-5695, and miR-26b-5p in TS patients as compared with the HVs. The abundance level of miR-5695 was higher in TS patients displaying CHD as compared to TS patients without CHD (p = 0.0265; log2-fold change 1.99); whereas, the abundance level of miR-126-3p was lower in TS patients with congenital aortic valve disease (AVD) compared to TS patients without BAV (p = 0.0139, log2-fold change 1.52). The clinical feature statistics revealed that miR-126-3p had a significant correlation with sinotubular junction Z-score (r = 0.42; p = 0.0154). Conclusion The identified circulating miRNAs signature for TS patients with manifestations associated with cardiovascular diseases provide new insights into the molecular mechanism of TS that may guide the development of novel diagnostic approaches

Nicht-invasive ultraschallgestützte Evaluation der kardiovaskulären Morbidität bei Patienten mit Ullrich-Turner-Syndrom

Einleitung: Das Ullrich-Turner-Syndrom ist eine chromosomale Erkrankung, die auf einen kompletten oder partiellen Verlust eines X-Chromosoms beruht. Das Ullrich-Turner-Syndrom geht mit einer erhöhten kardiovaskulären Morbidität und Mortalität einher. Das Ziel dieser kumulativen Dissertation bestand in der nicht-invasiven Evaluation der kardiovaskulären Morbidität bei Ullrich-Turner-Syndrom-Patienten mittels moderner ultraschallgestützter Techniken. Methodik: Insgesamt wurden zwischen 35 und 39 Ullrich-Turner-Syndrom-Patienten sowie 19 Vergleichsprobanden für die jeweiligen Studien rekrutiert. Die linksventrikuläre Funktion wurde echokardiographisch durch dreidimensionale Speckle Tracking Echokardiographie, nicht-invasiv generierter dreidimensionaler linksventrikulärer Druck-Volumen-Kurve und nicht-invasiv generierter linksventrikulärer Druck-Strain-Kurve beurteilt. Die Evaluierung der arteriellen Gefäßsteifigkeit erfolgte durch zweidimensionales Speckle Tracking der Aorta abdominalis. Ergebnisse: Verglichen mit den Vergleichsprobanden, wiesen die untersuchten Ullrich-Turner-Syndrom-Patienten signifikant niedrigere Werte im Longitudinal Strain und Area Strain auf. Die Arterial Elastance, die Cardiac Work sowie der Global Myocardial Work Index, jeweils bezogen auf die Körperoberfläche, waren in dem Ullrich-Turner-Syndrom-Kollektiv signifikant erhöht. Übergewichtige und adipöse Ullrich-Turner-Syndrom-Patienten zeigten, verglichen mit normalgewichtigen Ullrich-Turner-Syndrom-Patienten, eine signifikant niedrigere linksventrikuläre Effizienz auf. Der aortale Strain war, verglichen mit dem Kontrollkollektiv, bei Ullrich-Turner-Syndrom-Patienten signifikant erniedrigt. Schlussfolgerungen: Nach bestem Wissen wurden die oben beschriebenen Ultraschalltechniken im Rahmen dieser kumulativen Dissertation erstmalig in einem Ullrich-Turner-Syndrom-Kollektiv angewandt und analysiert. Dabei zeigten sich neuartige Einblicke in die kardiovaskuläre Morbidität dieses Patientenkollektivs: Die dreidimensionale Speckle Tracking Echokardiographie ließ auf eine signifikant niedrigere linksventrikuläre Deformation bei den untersuchten Ullrich-Turner-Syndrom-Patienten schließen. Durch die Generierung einer nicht-invasiven dreidimensionalen linksventrikulären Druck-Volumen-Kurve und einer nicht-invasiven linksventrikulären Druck-Strain-Kurve konnten Zeichen einer signifikant höheren linksventrikulären Nachlast und Arbeit im untersuchten Ullrich-Turner-Syndrom-Kollektiv aufgezeigt werden. Innerhalb des Ullrich-Turner-Syndrom-Kollektivs wiesen übergewichtige und adipöse Ullrich-Turner-Syndrom-Patienten eine signifikant niedrigere linksventrikuläre Effizienz auf. Durch das zweidimensionale Speckle Tracking der Aorta abdominalis konnten zudem Zeichen einer signifikant höheren Gefäßsteifigkeit bei Ullrich-Turner-Syndrom-Patienten nachgewiesen werden. Die Ergebnisse deuten auf den potenziellen Nutzen einer noch engeren kardiologischen Anbindung dieses Patientenkollektivs hin, um frühzeitige kardiovaskuläre Funktionsstörungen zu erkennen und zu behandeln.Non-invasive ultrasound-based evaluation of cardiovascular morbidity in patients with Turner Syndrome Background: Turner syndrome, an X chromosomal disease, is associated with increased cardiovascular morbidity and mortality. The primary objective of this doctoral thesis was to evaluate the cardiovascular morbidity of Turner syndrome patients using advanced ultrasound techniques. Methods: In total, between 35 and 39 Turner syndrome patients, and 19 healthy, age-matched controls were recruited for the respective studies. Left ventricular function was evaluated through three-dimensional speckle tracking echocardiography, non-invasive three-dimensional left ventricular pressure–volume loop analysis and non-invasive left ventricular pressure-strain loop analysis. Arterial stiffness was measured through two-dimensional speckle tracking of the abdominal aorta. Results: Compared to healthy, age-matched controls, Turner syndrome patients showed significantly lower values for longitudinal strain and area strain. Arterial elastance, cardiac work and global myocardial work index, each indexed to body surface area, were significantly increased in the examined Turner syndrome cohort. Overweight and obese Turner syndrome patients displayed, in comparison to normal weight Turner syndrome patients, a significantly lower left ventricular efficiency. Aortic strain was, compared to healthy, age-matched controls, significantly reduced in Turner syndrome patients. Conclusions: To the best of our knowledge, the above-mentioned ultrasound-based techniques have not been applied and analysed yet in Turner syndrome patients. Using these advanced techniques, novel insights in the cardiovascular morbidity of Turner syndrome patients were shown: The three-dimensional speckle tracking echocardiography demonstrated a significantly lower left ventricular deformation in the examined Turner syndrome patients. The non-invasive three-dimensional left ventricular pressure–volume loop analysis and the non-invasive left ventricular pressure-strain loop analysis displayed a significantly increased left ventricular afterload and workload in the examined Turner syndrome group. Within the Turner syndrome cohort, overweight and obese Turner syndrome patients demonstrated a significantly lower left ventricular efficiency. The two-dimensional speckle tracking of the abdominal aorta showed signs of a significantly increased arterial stiffness in the examined Turner syndrome patients, compared to healthy, age-matched controls. These results suggest that Turner syndrome patients might benefit from a more thorough cardiac care to facilitate early detection and treatment of cardiovascular dysfunctions

Physical Activity and Diet Quality: Effects on Cardiovascular Morbidity in Women with Turner Syndrome&mdash;Results from an Online Patient Survey

Turner syndrome (TS) is a rare chromosomal disease with increased cardiovascular morbidity and mortality. The aim of this study was to investigate the influence of physical activity and diet quality on cardiovascular morbidity in German TS women. An anonymous online questionnaire was established. The questionnaire was based on the 2020 WHO recommendations on physical activity and sedentary behaviour and included the 14-Item Mediterranean Diet Assessment Tool. In addition, TS patients were asked about existing cardiovascular conditions. In total, 83 TS women were included in the final analysis. The achievement of &lt;600 Metabolic Equivalent-minutes per week for recreational activities was significantly associated with the presence of arterial hypertension (p = 0.006). High adherence to the Mediterranean diet was achieved by only 20.5% of TS subjects and tended to be inversely associated with the presence of lipid metabolism disorders (p = 0.063). Only 37.3% of TS participants received nutritional counselling. Given the increased cardiovascular risk, specific counselling for lifestyle optimisation may play an important role in the management of TS. Further studies are required to evaluate the effects of regular aerobic physical training and different nutritional programs on cardiovascular morbidity in TS

Energy Drinks and Their Acute Effects on Heart Rhythm and Electrocardiographic Time Intervals in Healthy Children and Teenagers: A Randomized Trial

Beyond their effect on blood pressure, the effect of energy drinks on heart rate in children and teenagers has not been evaluated until now. Thus, this study aimed to investigate the acute cardiovascular effects of energy drinks in healthy children and teenagers. Twenty-six children and adolescents (mean age 14.49 years) received a commercially available energy drink (ED) and placebo on two consecutive days based on the maximum caffeine dosage as proposed by the European Food Safety Authority. Heart rhythm and electrocardiographic time intervals were assessed in a prospective, randomized, double-blind, placebo-controlled, crossover clinical study design. ED consumption resulted in a significantly increased number of supraventricular extrasystoles (SVES) compared to the placebo, whereas supraventricular tachycardia or malignant ventricular arrhythmias were not observed. The mean heart rate (HR) was significantly lower following consumption of EDs. In contrast, QTc intervals were not affected by EDs. Being the first of its kind, this trial demonstrates the cardiovascular and rhythmological effects of EDs in minors. Interestingly, EDs were associated with adverse effects on heart rhythm. Whether higher dosages or consumption in children with preexisting conditions may cause potentially harmful disorders was beyond the scope of this pilot study and remains to be determined in future trials. Trial Registration Number (DRKS-ID): DRKS00027580

Cardiovascular Care of Turner Syndrome Women in Germany: Where Do We Stand?&mdash;Results from an Online Patient Survey

Background: This study aimed to investigate whether the cardiovascular care of Turner Syndrome (TS) women in Germany is in accordance with the latest clinical practice guidelines established by the 2016 Cincinnati international TS meeting. Methods: An anonymous online questionnaire was created to ask TS subjects about existing cardiovascular conditions and cardiovascular care received. Depending on cardiovascular morbidity and type of medical care received, the fulfillment of the latest clinical practice guidelines for the care of TS women was assessed. Results: 120 TS patients were included in this study. The mean age of TS subjects was 36.79 years. Only 80% of subjects received annual blood pressure measurements within the TS cohort, and only 60% received cardiac imaging according to international clinical practice guidelines. More than 55% of TS women did not feel well informed about TS-specific cardiovascular risk factors by their treating physician. Conclusions: A potential lack of cardiovascular care might be present in TS women in Germany as the results of this online patient survey suggest. The cardiovascular care of TS patients, particularly cardiac imaging and patient education, needs to receive more attention

Energy Drinks Decrease Left Ventricular Efficiency in Healthy Children and Teenagers: A Randomized Trial

Background: Minors are considered the main consumer group of energy drinks (EDs). The aim of this study was to investigate the acute effects of ED consumption on left ventricular (LV) hemodynamics and efficiency in healthy children and teenagers. Methods: This study was a randomized, single-blind, placebo-controlled, crossover clinical trial. Study participants consumed a weight-adjusted amount of an ED or a placebo on two consecutive days. LV hemodynamics and efficiency parameters were evaluated non-invasively by generating LV pressure&ndash;volume loops (PVLs) through simultaneous echocardiography and blood pressure measurement. Results: A total of 24 children and teenagers (14.90 &plusmn; 2.27 years, 13 male) were included in the present study. Conventional echocardiographic parameters of LV function did not show significant differences between both beverage groups. The non-invasive generation of LV PVLs revealed a significantly lower cardiac efficiency 240 min after the ED consumption compared to the placebo intake (140.72 (133.21&ndash;149.73) mmHg vs. 135.60 (124.78&ndash;140.33) mmHg, p &lt; 0.01). Conclusions: Acute ED consumption is associated with a significantly lower cardiac efficiency in healthy minors. The generation of non-invasive LV PVLs might be beneficial in the assessment of subtle changes in LV efficiency. Further studies need to investigate the influence of chronic ED consumption on LV function and morphology

Step by Step: Evaluation of Cardiorespiratory Fitness in Healthy Children, Young Adults, and Patients with Congenital Heart Disease Using a Simple Standardized Stair Climbing Test

(1) Background: Cardiorespiratory fitness (CRF) is known to be a prognostic factor regarding long-term morbidity and mortality. This study aimed to develop a standardized Stair Climbing Test (SCT) with a reliable correlation to spiroergometry and the 6MWT which can be used in healthy children as well as patients with congenital heart disease (CHD) and a restricted exercise capacity. (2) Methods: A total of 28 healthy participants aged 10–18 years were included. We tested the individuals’ CRF by cardiopulmonary exercise testing (CPET) on a treadmill, the 6MWT, and a newly developed Stair Climbing Test (SCT). For the SCT, we defined a standardized SCT protocol with a total height of 13.14 m to achieve maximal exercise effects while recording time and vital parameters. To compare the SCT, the 6 Min Walking Test, and CPET, we introduced an SCT-Index that included patient data (weight, height) and time. To assess the SCT’s feasibility for clinical practice, we also tested our protocol with five adolescents with complex congenital heart disease (i.e., Fontan circulation). (3) Results: A strong correlation was observed between SCT-Index and O2 pulse (r = 0.921; p 2max (mL/min/kg) and VO2max (mL/min), strong correlations were found (r = −0.672; p p 2max (mL/min) (r = 0.927; p = p = 0.003). It appears to be feasible in patients with Fontan circulation. (4) Conclusions: We were able to demonstrate that there is a significant correlation between our standardized SCT and treadmill CPET. Therefore, we can say that the SCT can be used as an easy supplement to CPET and in certain contexts, it can also be used as a screening tool when CPET is not available. The advantages would be that the SCT is a simple, quick, cost-effective, and reliable standardized (sub)maximal exercise test to evaluate CRF in healthy children on a routine basis. We can even assume that it can be used in patients with congenital heart disease