Awareness of cholesterol levels in 46,309 Italian children and adolescents unveils the tip of the iceberg.

BACKGROUND AND AIMS: Cardiovascular diseases (CVD) risk factors include high cholesterol. Children with total cholesterol (TC) levels ≥ 170 mg/dL are usually considered hypercholesterolemic. This study aimed at investigating the awareness of TC levels in a large Italian paediatric population and at looking for a possible correlation between their TC and TC in their parents' blood. METHODS AND RESULTS: A survey was carried out in 46,309 subjects (mean age 9.7 ± 2.3 years; age range 6-14 years) to check the awareness of their own TC levels by using a personal and family medical history questionnaire. In 95.67% of the sample TC value was unknown. In 2.69% TC was < 170 mg/dL, whereas 1.64% were hypercholesterolemic (TC ≥ 170 mg/dL). A statistically significant correlation was found between children with normal TC values and physiological TC values in both parents (p < 0.0001). Again, a significant association between children with high TC and their parents with high TC was detected when parents were analysed separately (i.e. children with TC ≥ 170 mg/dl vs maternal TC ≥ 200 mg/dL: OR 2.01 (95% CI 1.61-2.49, p < 0.001); children with TC ≥ 200 mg/dl vs maternal TC ≥ 240 mg/dL: OR 3.14 (95% CI 2.14-4.6, p < 0.001); children with TC ≥ 170 mg/dl vs paternal TC ≥ 200 mg/dL: OR 2.39 (95% CI 1.91-2.98, p < 0.001); children with TC ≥ 200 mg/dl vs paternal TC ≥ 240 mg/dL: OR 3.85 (95% CI 2.70-5,.50, p < 0.001). CONCLUSION: Just a minority of the investigated young patients knew their TC. This is worrisome. Children with normal TC values are more likely to be born from healthy parents with physiological TC. In addition, high TC in the enrolled subjects is significantly associated with high TC in their parents. Overall, these findings seem to highlight the importance of health education and genetics in TC pathogenesis.

Nailfold capillaroscopy reveals early peripheral microcirculation abnormalities in children affected by heterozygous familial hypercholesterolemia.

BACKGROUND: nailfold capillaroscopy (NCF) is a non-invasive imaging technique to seek peripheral microcirculation abnormalities in children and adults. Familial hypercholesterolemia is a genetic disorder caused by mutations capable of increasing blood levels of low-density lipoproteins cholesterol (LDL-C), thus triggering early atherosclerosis. The study aims at evaluating peripheral microcirculation in children with heterozygous familial hypercholesterolemia (HeFH) by means of NFC in comparison with healthy peers and at searching for possible correlations between these abnormalities and patients' lipid panel. METHODS: thirty-six HeFH patients were enrolled (13 males and 23 females. Mean age 8 ± 3 years; age range 3-13 years). They had increased levels of total cholesterol (237.9 ± 34.2 mg/dl) and LDL-C (154.2 ± 37.6 mg/dl). Both values were ≥95th gender and age specific centile. All the subjects in the study underwent NFC. RESULTS: In 69.4 % of HeFH children nailfold capillaries were tortuous (p < 0.00001 compared to healthy controls). In 41.6 % the number of capillaries was markedly reduced (<7 capillaries/mm). The mean number of capillaries was 8.4 ± 2.6/mm in HeFH and 12.2 ± 1.4/mm in healthy controls (p < 0.00001). In 100 % of the sample size capillary blood flow was slowed down (p < 0.00001). In 50 % of the sample size a blood "sludge" phenomenon was seen (p < 0.00001). No gender differences were detected. Sludge phenomenon was seen only in those with LDL-C over 99th centile (p < 0.00001). CONCLUSION: NCF allows the identification of an early peripheral microvascular dysfunction in HeFH children which is similar to that already seen in atherosclerotic disease. Prompt identification of these capillary abnormalities may be crucial in implementing early prevention measures.

Planning Transition of Care for Adolescents Affected by Congenital Heart Disease: The Irish National Pathway.

At some point in their life, adolescent patients with a congenital heart disease (CHD) transition from paediatric services to adult care facilities. The process is not without any risks, as it is often linked with a significantly progressive deterioration in adolescents' health and loss of follow-up. In fact, transition patients often encounter troubles in finding a care giver who is comfortable managing their condition, or in re-establishing trust with the new care provider. Planning the rules of transition is pivotal in preventing these risks. Unfortunately, the American and European guidelines on CHD provide just generic statements about transition. In a recently published worldwide inter-societies consensus document, a hybrid model of transition, which should be adapted for use in high- and low- resource settings, has been suggested. Currently, in literature there are a few models of transition for CHD patients, but they are by far local models and cannot be generalized to other regions or countries. This paper describes the Irish model for transition of care of CHD patients. Due to the peculiarity of the healthcare organization in the Republic of Ireland, which is centralized with one main referral centre for paediatric cardiology (in Dublin, with a few smaller satellite centres all around, according to the "hub and spoke" model) and one centre for adult with CHD (in Dublin), the model can be considered as a national one and the first to be released in the old continent.

Metabolomics in Pulmonary Hypertension-A Useful Tool to Provide Insights into the Dark Side of a Tricky Pathology.

Pulmonary hypertension (PH) is a multifaceted illness causing clinical manifestations like dyspnea, fatigue, and cyanosis. If left untreated, it often evolves into irreversible pulmonary arterial hypertension (PAH), leading to death. Metabolomics is a laboratory technique capable of providing insights into the metabolic pathways that are responsible for a number of physiologic or pathologic events through the analysis of a biological fluid (such as blood, urine, and sputum) using proton nuclear magnetic resonance spectroscopy or mass spectrometry. A systematic review was finalized according to the PRISMA scheme, with the goal of providing an overview of the research papers released up to now on the application of metabolomics to PH/PAH. So, eighty-five papers were identified, of which twenty-four concerning PH, and sixty-one regarding PAH. We found that, from a metabolic standpoint, the hallmarks of the disease onset and progression are an increase in glycolysis and impaired mitochondrial respiration. Oxidation is exacerbated as well. Specific metabolic fingerprints allow the characterization of some of the specific PH and PAH subtypes. Overall, metabolomics provides insights into the biological processes happening in the body of a subject suffering from PH/PAH. The disarranged metabolic pathways underpinning the disease may be the target of new therapeutic agents. Metabolomics will allow investigators to make a step forward towards personalized medicine.

Micra pacemaker in adult congenital heart disease patients: A case series.

INTRODUCTION: Implantation of transvenous endocardial or epicardial pacemakers presents specific challenges in adult congenital heart disease (ACHD) patients. Micra leadless permanent pacemakers (Micra PPM) may overcome some of these difficulties. METHODS: Fifteen ACHD patients who underwent Micra PPM insertion were retrospectively evaluated. RESULTS: Males 53.3%. Mean age at study: 37.5 ± 10.7 years. Mean age at Micra PPM insertion: 35.5 ± 11.0 years. Mean follow-up so far: 2.0 ± 0.3 years. Concerning the ACHD patients, 6.7% had a simple defect, 66.6% had a moderately complex defect, 26.7% were complex. Four patients (26.7%) had a previous PPM implantation. Three patients (20%) had a systemic right ventricle. Two patients (13.3%) had a single ventricle physiology. Five (33.3%) had Trisomy 21. The most commonly used Micra PPM modality was single chamber ventricular pacemaker (73.3%). Mean threshold post implantation was 0.48 V [range: 0.25-1.13 V], while mean threshold at 6 months control was 0.60 V [range: 0.38-1.13 V] (p = ns). Mean R wave postimplantation was 10.3 V [range: 3.25-19.4 V], whilst mean R wave at 6 months follow-up was 10.1 V [range: 3.5-19.0 V] (p = ns). No major peri and postprocedural complications were encountered. CONCLUSIONS: since ACHD patients are living longer and surviving into adulthood, the incidence of conduction disorders continues to increase, as part of the natural history of some lesions or as early or late complication of surgery. The Micra leadless PPM can be successfully implanted in ACHD patients and have significant theoretical advantages. They should be considered when transvenous and epicardial pacing are either contraindicated or represent an otherwise suboptimal approach.

Children's heart and COVID-19: Up-to-date evidence in the form of a systematic review.

The new coronavirus disease outbreak in 2019 (COVID-19) represents a dramatic challenge for healthcare systems worldwide. As to viral tropism, lungs are not the only COVID-19 target but also the heart may be involved in a not negligible percentage of the infected patients. Myocarditis-related cardiac dysfunction and potentially life-threatening arrhythmias are the main aftermaths. A few studies showed that myocardial injury in adult patients is often linked with a fatal outcome. Conversely, scientific evidence in children is sparse, although several reports were published with the description of a cardiac involvement in COVID-19 paediatric patients. In these young subjects, a background of surgically treated congenital heart disease seems to be a predisposing factor.Conclusion: This systematic review is aimed at summarizing all COVID-19 cases with a cardiac involvement published in paediatric age and trying to explain the underlying mechanisms responsible for COVID-19-related myocardial damage.What is Known:• Coronaviruses proved to be able to jump from animals to humans.• The outbreak of COVID-19 started from China (Dec 2019) and became pandemic.What is New:• Even in childhood, COVID-19 is not without the risk of cardiac involvement.• Myocarditis, heart failure, and arrhythmias are among the possible manifestations.

A brief bout of exercise in hypoxia reduces ventricular filling rate and stroke volume response during muscle metaboreflex activation.

PURPOSE: The hemodynamic consequences of exercise in hypoxia have not been completely investigated. The present investigation aimed at studying the hemodynamic effects of contemporary normobaric hypoxia and metaboreflex activation. METHODS: Eleven physically active, healthy males (age 32.7 ± 7.2 years) completed a cardiopulmonary test on an electromagnetically braked cycle-ergometer to determine their maximum workload (Wmax). On separate days, participants performed two randomly assigned exercise sessions (3 minutes pedalling at 30% of Wmax): (1) one in normoxia (NORMO), and (2) one in normobaric hypoxia with FiO2 set to 13.5% (HYPO). After each session, the following protocol was randomly assigned: either (1) post-exercise muscle ischemia (PEMI) to study the metaboreflex, or (2) a control exercise recovery session, i.e., without metaboreflex activation. Hemodynamics were assessed with impedance cardiography. RESULTS: The main result was that the HYPO session impaired the ventricular filling rate (measured as stroke volume/diastolic time) response during PEMI versus control condition in comparison to the NORMO test (31.33 ± 68.03 vs. 81.52 ± 49.23 ml·s-1,respectively, p = 0.003). This caused a reduction in the stroke volume response (1.45 ± 9.49 vs. 10.68 ± 8.21 ml, p = 0.020). As a consequence, cardiac output response was impaired during the HYPO test. CONCLUSIONS: The present investigation suggests that a brief exercise bout in hypoxia is capable of impairing cardiac filling rate as well as stroke volume during the metaboreflex. These results are in good accordance with recent findings showing that among hemodynamic modulators, ventricular filling is the most sensible variable to hypoxic stimuli.

Learning from the past in the COVID-19 era: rediscovery of quarantine, previous pandemics, origin of hospitals and national healthcare systems, and ethics in medicine.

After the dramatic coronavirus outbreak at the end of 2019 in Wuhan, Hubei province, China, on 11 March 2020, a pandemic was declared by the WHO. Most countries worldwide imposed a quarantine or lockdown to their citizens, in an attempt to prevent uncontrolled infection from spreading. Historically, quarantine is the 40-day period of forced isolation to prevent the spread of an infectious disease. In this educational paper, a historical overview from the sacred temples of ancient Greece-the cradle of medicine-to modern hospitals, along with the conceive of healthcare systems, is provided. A few foods for thought as to the conflict between ethics in medicine and shortage of personnel and financial resources in the coronavirus disease 2019 era are offered as well.

Semiautomated analysis of carotid artery wall thickness in MRI.

PURPOSE: To develop a semiautomatic method based on level set method (LSM) for carotid arterial wall thickness (CAWT) measurement. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) of diseased carotid arteries was acquired from 10 patients. Ground truth (GT) data for arterial wall segmentation was collected from three experienced vascular clinicians. The semiautomatic variational LSM was employed to segment lumen and arterial wall outer boundaries on 102 MR images. Two computer-based measurements, arterial wall thickness (WT) and arterial wall area (AWA), were computed and compared with GT. Linear regression, Bland-Altman, and bias correlation analysis on WT and AWA were applied for evaluating the performance of the semiautomatic method. RESULTS: Arterial wall thickness measured by radial distance measure (RDM) and polyline distance measure (PDM) correlated well between GT and variational LSM (r = 0.83 for RDM and r = 0.64 for PDM, P < 0.05). The absolute arterial wall area bias between LSM and three observers is less than 10%, suggesting LSM can segment arterial wall well compared with manual tracings. The Jaccard Similarity (Js ) analysis showed a good agreement for the segmentation results between proposed method and GT (Js 0.71 ± 0.08), the mean curve distance for lumen boundary is 0.34 ± 0.2 mm between the proposed method and GT, and 0.47 ± 0.2 mm for outer wall boundary. CONCLUSION: The proposed LSM can generate reasonably accurate lumen and outer wall boundaries compared to manual segmentation, and can work similar to a human reader. However, it tends to overestimate CAWT and AWA compared to the manual segmentation for arterial wall with small area.

Ankle-brachial index and its link to automated carotid ultrasound measurement of intima-media thickness variability in 500 Japanese coronary artery disease patients.

The purpose of this study was to evaluate whether the carotid intima-media thickness (cIMT) and intima-media thickness variability (IMTV) along the artery are correlated to the ankle-brachial index (ABI) in Japanese coronary artery disease patients. Five hundred consecutive patients (312 males; median age 69 ± 11 years) who underwent carotid ultrasonography and first coronary angiography were prospectively analyzed. By using automated software (AtheroEdge™, AtheroPoint, Roseville, CA, USA), we obtained the cIMT and IMTV. Pearson correlation analysis was performed to calculate the association between ABI, automatically measured cIMT, automatically measured IMTV, and the SYNTAX score. The mean cIMT was 0.881 ± 0.334 mm and the mean IMTV was 0.141 ± 0.112. IMTV was negatively and significantly correlated to ABI (ρ = -0.147; p = 0.001), whereas cIMT was not (ρ = -0.075; p = 0.097). IMTV and cIMT had the same significant correlation with the SYNTAX score. When we considered patients with a higher risk factor (ABI ≤ 0.9), we found higher values of IMTV and the SYNTAX score, but not higher values of cIMT. Logistic regression analysis showed that IMTV was independently associated with the complexity of the coronary artery disease (as assessed by the SYNTAX score). In conclusion, we show that IMTV automatically measured using AtheroEdge™ was correlated with ABI, whereas cIMT was not. IMTV could be integrated with cIMT measurement to improve the assessment of cardiovascular disease.

The Association between Mid-Upper Arm Circumference and Blood Pressure in an Italian Population of School-Aged Children and Adolescents with Lipid Disorders.

Background: Many anthropometric measurements have been investigated concerning their association with blood pressure (BP) in paediatric age groups. This study aims to find a relationship between mid-upper arm circumference (MUAC) and BP in a population of children and adolescents aged 1-18 years. Methods: 5853 subjects (2977 females and 2876 males) were studied. MUAC, body mass index (BMI), and BP were measured. The individuals in the study were subdivided and grouped by gender and type of school attended in Italy: 1-5 years (pre-school), 6-10 years (primary school), 11-13 years (secondary school), 14-18 years (high school). Results: In the age range of 6-13 years, all the subjects with MUAC > 50th percentile had systolic and diastolic BP significantly higher than children with MUAC below 50th percentile (p < 0.0001). In the age range 14-18 years, the relationship persisted only in females (p < 0.001 and p < 0.05 for diastolic and systolic BP, respectively). A linear relationship was found between MUAC and BMI. Conclusions: In Italian children of both genders aged 6-13, arm distribution of body fat is strongly associated with increased systolic and diastolic BP. As such, a simple anthropometric measurement like MUAC might represent a tool to identify young subjects who are at risk for HTN.

Appraisal of partial anomalous pulmonary venous drainage through a lumped-parameter mathematical model: a new pathophysiological proof of concept.

OBJECTIVES: Haemodynamic determinants of the ratio between pulmonary and systemic flow (Qp/Qs) in partial anomalous pulmonary venous return (PAPVR) are still not fully understood. Indeed, among patients with the same number of lung segments draining anomalously, a great variability is observed in terms of right ventricular overload. The aim of this study was to test the hypothesis that the anatomic site of drainage, affecting the total circuit impedance, independently influences the magnitude of shunt estimated by Qp/Qs. A zero-dimensional (0D) lumped parameter mathematical model was developed and validated on a sample of patients. METHODS: We developed a 0D lumped parameter model, using time varying elastances for heart chambers, RLC Windkessel circuits for the systemic and pulmonary circulations. Patients, were categorized into vena cava (VC) type (including left drainage to anomimous vein) and right atrium type (RA). The mathematical model is a system of ordinary differential equations that are numerically solved by means of the ode15s solver in the Matlab environment. RESULTS: The model showed an increase of Qp/Qs with the increase of the number of anomalous veins. With the same number of anomalous veins, Qp/Qs was lower in patients with anomalous drainage to the vena cava (VC) as compared with right atrium (RA) The validation sample consisted of 49 patients (27, 55% females). As predicted by the model, patients with PAPVR with VC type displayed a lower invasive and CMR Qp/Qs as compared with drainage to RA: 1.4 (1.2-1.7) and 1.45 (1.25-1.6) versus 2 (1.75-2.1) and 1.9 (1.6-2) p < 0.05. After stratifying for number of lung territories a lower Qp/Qs was measured in patients with VC PAPVR as compared with RA. CONCLUSIONS: In patients with PAPVR, the site of anomalous drainage modulates the Qp/Qs. According to the model, this effect is mediated by the post-capillary impedance of the circuit and significantly decreases with the increase of pulmonary vascular resistances.

Electrocardiography in Children Hospitalized for COVID-19 and Not Suffering from Multisystem Inflammatory Syndrome in Children (MIS-C): An Observational Study.

The risk of cardiac involvement with electrophysiological abnormalities during COVID-19 infection has been reported in adults but remains poorly studied in children. Our aim was to determine the frequency of cardiac involvement and the necessity of routine cardiac evaluation in children hospitalized for COVID-19. This observational study included 127 children, with a median (IQR) age of 2 (0.83-6.0) years, who were hospitalized for COVID-19 between 1 January 2021 and 31 August 2022, 62 (48.8%) of whom were males. Each patient underwent an ECG on admission and discharge as well as a laboratory assessment. A comparison between patients with COVID-19 and healthy controls showed significantly higher HR (p < 0.0001) and lower PR values (p = 0.02) in the first group. No arrhythmias or other electrocardiographic abnormalities were detected during hospitalization. The median levels of troponin, NT-proBNP, ferritin, and D-dimer were significantly higher in children aged <2 years, but they fell within the normal range for their age. Our results indicate that a detectable cardiac involvement is very rare in children hospitalized for COVID-19 and not suffering from Multisystem Inflammatory Syndrome in Children (MIS-C) and suggest that routine electrocardiographic assessment is not mandatory in these patients in the absence of cardiac symptoms/signs.

Pediatric Hypertension: A Condition That Matters.

Systemic hypertension has been considered mainly as an adult health issue for a long time, but it is now being increasingly acknowledged as a significant problem also among pediatric patients. The frequency of pediatric hypertension has grown mostly because of increases in childhood obesity and sedentary lifestyles, but secondary forms of hypertension play a role as well. Considering that unaddressed hypertension during childhood can result in enduring cardiovascular complications, timely identification and intervention are essential. Strategies for addressing this disease encompass not only lifestyle adjustments, but also the use of medications when needed. Lifestyle modifications entail encouraging a nutritious diet, consistent physical activity, and the maintenance of a healthy weight. Moreover, educating both children and their caregivers about monitoring blood pressure at home can aid in long-term management. Thus, the aim of this review is to discuss the etiologies, classification, and principles of the treatment of hypertension in pediatric patients.

Modern tools in congenital heart disease imaging and procedure planning: a European survey.

AIMS: Congenital heart diseases (CHDs) often show a complex 3D anatomy that must be well understood to assess the pathophysiological consequences and to guide therapy. Three-dimensional imaging technologies have the potential to enhance the physician's comprehension of such spatially complex anatomies. Unfortunately, due to the new introduction in clinical practice, there is no evidence on the current applications. We conducted a survey to examine how 3D technologies are currently used among CHD European centres. METHODS: Data were collected using an online self-administered survey via SurveyMonkey. The questionnaire was sent via e-mail and the responses were collected between January and June 2022. RESULTS: Ninety-eight centres correctly completed the survey. Of these, 22 regularly perform 3D rotational angiography, 43 have the availability to print in-silico models, and 22 have the possibility to visualize holographic imaging/virtual reality. The costs were mostly covered by the hospital or the department of financial resources. CONCLUSION: From our survey, it emerges that these technologies are quite spread across Europe, despite not being part of a routine practice. In addition, there are still not enough data supporting the improvement of clinical management for CHD patients. For this reason, further studies are needed to develop clinical recommendations for the use of 3D imaging technologies in medical practice.