Mild coronary artery dilatation developed in some children with mild COVID-19 but completely regressed within 3 months.

AIM: We studied the incidence and time course of any coronary artery changes in children up to 2 years of age who were hospitalised with mild COVID-19. METHODS: This was a single-centre prospective study of 29 children (19 males) with a median age of 3 months and interquartile range (IQR) of 1.6-4.3 months. They were admitted to a Greek University hospital for mild COVID-19 from 1 March to 30 December 2021. Three echocardiographic evaluations were performed at a median (IQR) of 19 (16-24) days, 82 (75-89) days and 172 (163-197) after the first symptoms. The prevalence of coronary artery dilation, regression, and changes was documented. RESULTS: Coronary artery dilation was present in 3 (10.3%) cases at the first evaluation, with complete regression at the second. Regression was observed in 18/24 (75%) cases with follow-up data and 9 (31%) demonstrated significant z-score changes of >2. Coronary artery changes in any segment at any time were documented in 18/29 (62%) of the patients. CONCLUSION: Cases of transient and very mild coronary artery dilatation following mild COVID-19 completely regressed within 3 months. Large-scale studies are needed to document the extent and time course of coronary artery dilation following paediatric COVID-19.

Pesticides and cardiotoxicity. Where do we stand?

Cardiovascular diseases are among the most significant causes of mortality in humans. Pesticides toxicity and risk for human health are controlled at a European level through a well-developed regulatory network, but cardiotoxicity is not described as a separate hazard class. Specific classification criteria should be developed within the frame of Regulation (EC) No 1272/2008 in order to classify chemicals as cardiotoxic, if applicable to avoid long-term cardiovascular complications. The aim of this study was to review the cardiac pathology and function impairment due to exposure to pesticides (i.e. organophosphates, organothiophisphates, organochlorines, carbamates, pyrethroids, dipyridyl herbicides, triazoles, triazines) based on both animal and human data. The majority of human data on cardiotoxicity of pesticides come from poisoning cases and epidemiological data. Several cardiovascular complications have been reported in animal models including electrocardiogram abnormalities, myocardial infarction, impaired systolic and diastolic performance, functional remodeling and histopathological findings, such as haemorrhage, vacuolisation, signs of apoptosis and degeneration.

Epidemiology of Pediatric Cardiomyopathy in a Mediterranean Population.

BACKGROUND: Our knowledge regarding the epidemiology of pediatric cardiomyopathy is based on large national population studies reporting an annual incidence of 1 case per 100,000 children, with a higher incidence observed in infancy and among selected populations. The aim here is to document the epidemiology of pediatric cardiomyopathy in a Mediterranean population. METHODS: Children younger than 18 years of age living on the Mediterranean island of Crete, Greece, who have been evaluated since the establishment of tertiary pediatric cardiology services (2002-2022) were included in this retrospective study. RESULTS: A total of 40 children were included, corresponding to an average annual incidence of pediatric cardiomyopathy of 1.59 cases (95% CI: 1.4-2.3) and a prevalence of 26 cases per 100,000 children. In decreasing order of frequency, most cases corresponded to dilated (50%), followed by hypertrophic (42.5%), arrhythmogenic (5%), and restrictive (2.5%) cardiomyopathy. An etiology was identified in 40%, including a genetic diagnosis in 22.5%. CONCLUSIONS: The incidence of pediatric cardiomyopathy in the Mediterranean island of Crete is higher compared with that reported previously for other Caucasian populations. Further study is needed to investigate the exact prevalence and specific genetic factors associated with the epidemiology of pediatric cardiomyopathy in Mediterranean populations.

Echocardiographic predictors of outcome in eisenmenger syndrome.

BACKGROUND: Eisenmenger syndrome differs significantly from other types of pulmonary arterial hypertension in its physiology and prognosis. We sought to assess the relationship between the echocardiographic characteristics of patients with Eisenmenger syndrome and mortality. METHODS AND RESULTS: Clinical and echocardiographic variables were assessed in 181 consecutive patients with Eisenmenger syndrome, excluding those with complex congenital heart disease. Patients' mean age was 39.1 ± 12.8 years, 59 (32.6%) were male, 122 (67.4%) were in functional class III or higher, and 74 (40.9%) were on advanced therapies. Mean oxygen saturation at rest was 85.1 ± 7.8%, and median B-type natriuretic peptide was 55.4 ng/L. Over a median follow-up of 16.4 months, 19 patients died; the strongest predictors of mortality were tricuspid annular plane systolic excursion and peak systolic velocity, myocardial performance (expressed as total isovolumic time and ratio of systolic to diastolic duration), and elevated central venous pressure (expressed as right atrial [RA] area, RA pressure, and ratio of RA to left atrial area), even after we accounted for advanced therapies. A composite score based on the strongest echocardiographic predictors of outcome, including 1 point for each of the following: tricuspid annular plane systolic excursion <15 mm, ratio of right ventricular effective systolic to diastolic duration ≥ 1.5, RA area ≥ 25 cm², ratio of RA to left atrial area ≥ 1.5, was highly predictive of clinical outcome (area under the curve 0.90 ± 0.01), with no improvement when B-type natriuretic peptide and resting saturations were added into the model. CONCLUSIONS: Echocardiographic parameters of right ventricular function and RA area predict mortality in Eisenmenger patients. A new composite echocardiographic score, described herewith, may be incorporated into the noninvasive, periodic assessment of these patients.

Skills of primary healthcare physicians in paediatric cardiac auscultation.

AIM: To evaluate the performance of primary healthcare physicians in paediatric cardiac auscultation and the impact of a multimedia-based teaching intervention. METHODS: A total of 106 primary healthcare physicians (77 paediatricians, 14 general practitioners and 15 medical graduates) attended four paediatric cardiac auscultation teaching courses based on virtual patients' presentation (digital phonocardiography). Their auscultatory performance was documented at the beginning of each course and at the end of two of the courses. RESULTS: Participants initially detected 73% of abnormal murmurs and 17% of additional sounds, while 22% of innocent murmurs were interpreted as abnormal. Overall cardiac auscultation performance, assessed by a combined auscultation score, was low and independent of training level (graduates: 39.5/trainees: 42.8/board certified: 42.6, p = 0.89) or specialty (paediatricians: 42.7/general practitioners: 43.1, p = 0.89). Multimedia-based teaching was associated with a significant improvement in abnormal murmur (92.5%) and additional sound (40%) detection (p < 0.001), while 25% of innocent murmurs were still interpreted as abnormal (p = 0.127). CONCLUSION: Clinical skills of primary healthcare physicians in paediatric cardiac auscultation, independent of training level or specialty, still leave potential for improvement. Multimedia-based teaching interventions represent an effective means of improving paediatric cardiac auscultatory skills.

Abnormal origin of right pulmonary artery from the ascending aorta in an infant ("Hemitruncus").

Key Clinical Message: Anomalous origin of right pulmonary artery from the ascending aorta is a rare congenital malformation and it needs surgical management. Consequences of this condition affect lead to pulmonary hypertension and severe pulmonary vascular disease. Abstract: Anomalous origin of right pulmonary artery from the ascending aorta is a rare congenital heart malformation that results in early infant mortality affecting the right pulmonary artery more than the left. These patients are at risk for the early development of significant pulmonary hypertension. The surgical management during the early period of life is imperative.

Cardiomyopathies in children: An overview.

Paediatric cardiomyopathies form a heterogeneous group of disorders characterized by structural and electrical abnormalities of the heart muscle, commonly due to a gene variant of the myocardial cell structure. Mostly inherited as a dominant or occasionally recessive trait, they might be part of a syndromic disorder of underlying metabolic or neuromuscular defects or combine early developing extracardiac abnormalities (i.e., Naxos disease). The annual incidence of 1 per 100,000 children appears higher during the first two years of life. Dilated and hypertrophic cardiomyopathy phenotypes share an incidence of 60% and 25%, respectively. Arrhythmogenic right ventricular cardiomyopathy (ARVC), restrictive cardiomyopathy, and left ventricular noncompaction are less commonly diagnosed. Adverse events such as severe heart failure, heart transplantation, or death usually appear early after the initial presentation. In ARVC patients, high-intensity aerobic exercise has been associated with worse clinical outcomes and increased penetrance in at-risk genotype-positive relatives. Acute myocarditis in children has an incidence of 1.4-2.1 cases/per 100,000 children per year, with a 6-14% mortality rate during the acute phase. A genetic defect is considered responsible for the progression to dilated cardiomyopathy phenotype. Similarly, a dilated or arrhythmogenic cardiomyopathy phenotype might emerge with an episode of acute myocarditis in childhood or adolescence. This review provides an overview of childhood cardiomyopathies focusing on clinical presentation, outcome, and pathology.

Assessment of fetal myocardial deformation using speckle tracking techniques.

OBJECTIVE: To report the current status of speckle tracking techniques in evaluation of fetal myocardial deformation. METHODS: A variety of non-Doppler ultrasound methods are available using offline analysis of standard four-chamber and short axis views of the heart. RESULTS: Most reports have used techniques developed for the measurement of strain and strain rate in the adult heart and produced conflicting descriptions of gestational changes in strain. Myocardial velocities usually reflect mean modal velocities and are lower than the peak velocities obtained using Doppler techniques. CONCLUSIONS: In the fetus, most current methods of acquisition result in frame rates that are too low, and the fetal heart size is too small to achieve reliable measures of fetal myocardial deformation.

Fetal longitudinal myocardial function assessment by anatomic M-mode.

AIM: To evaluate the feasibility of offline anatomic M-mode (AMM) to study fetal atrioventricular annulus long-axis displacement (LAD) and compare its performance against real-time conventional M-mode (MM). MATERIAL AND METHODS: Paired AMM and MM LAD studies were recorded prospectively in 54 fetuses, and performance was compared. Insonation angles were less than 30° in all but 4 cases. The overall feasibility of AMM was tested in a composite total sample of 91 normal singleton pregnancies (median gestational age 23⁺6 weeks, range 12-36). AMM LAD was measured by placement of a virtual M-mode line on digitally stored raw data of fetal 4-chamber video loops. We studied annulus LAD at the lateral mitral (left ventricle; LV), proximal mitral (intraventricular septum; IVS), and lateral tricuspid (right ventricle; RV) myocardial segments. We compared LAD and its regression with gestational age measured using both methods in paired studies and AMM in the whole cohort. RESULTS: Annulus LAD was measured using AMM, in all cases and segments, irrespective of cardiac axis alignment to the ultrasound beam. Good correlation existed between AMM and MM (RV r = 0.901, LV r = 0.899, IVS r = 0.815, p < 0.001). AMM recorded higher LAD values than MM in RV [mean 6.17 (SD 1.46) vs. 5.82 (SD 1.74) mm, p = 0.002] and LV [mean 4.18 (SD 1.11) vs. 3.98 (SD 1.12), p = 0.007]. Both methods showed LAD in RV > LV > IVS and a significant gestational increase in LAD values in all segments (p < 0.001) CONCLUSIONS: AMM permits offline evaluation of fetal longitudinal myocardial function in routinely obtained 2D fetal heart images with similar values to conventional MM in paired studies recorded <30°.

Myocardial strain abnormalities in fetal congenital heart disease assessed by speckle tracking echocardiography.

OBJECTIVES: To compare myocardial deformation patterns in fetuses with congenital heart disease (CHD) with our reference range using speckle tracking echocardiography. METHODS: We prospectively stored and analyzed 4-chamber loops of 28 fetuses with CHD (median gestation 27 weeks, range 20.9-37.0). The peak longitudinal left (LVs) and right (RVs) ventricular free wall Lagrangian strain and LV/RV strain ratio were measured from Syngo VVI software- (Siemens) derived original coordinates. Strain values from the first examination were compared with normative data from the same population using ANOVA with post hoc tests and serial examinations described in 14 fetuses. RESULTS: Simple shunt lesions (0.82) and shunts with pulmonary stenosis or atresia (0.93) had reduced mean LV/RV strain ratios compared to normal fetuses (1.01; 95% CI 0.97-1.05). Fetuses with hypoplastic left heart had the lowest (0.29), and those with Ebstein the highest (1.55), LV:RV ratio. Serial measurements showed increased LVs in aortic coarctation and aortic stenosis, but not in one developing important mitral regurgitation. Increased right ventricular loading in a fetus developing pulmonary regurgitation was associated with increasing RVs. CONCLUSIONS: Myocardial strain reflects the changing physiology of fetal CHD. Speckle tracking might be a useful tool to study the progress of myocardial function in affected fetuses.

Electronic versus conventional spatiotemporal image correlation (STIC) fetal echocardiography: a direct comparison.

OBJECTIVES: Recent advances in Spatial Temporal Image Correlation (STIC) 4 D fetal echocardiography include the application of eSTIC based on electronic probe image acquisition. We aimed to directly compare the performance of conventional STIC versus eSTIC technique (B-Mode and color Doppler imaging) during off-line reconstruction of STIC/eSTIC fetal heart volume pairs. METHODS: Pairs of B-Mode and Color Doppler STIC volumes were acquired sequentially by firstly conventional (STIC) followed by electronic (eSTIC) probes during 33 consecutive obstetric scans at median 23 (range 13-31) gestational weeks. The resulting 66 fetal heart volume pairs were assessed blindly off-line by a fetal cardiologist who documented feasibility of reconstruction, presence of motion artifacts, subjective image quality on a 4-level scale: 1-best to 4-non-diagnostic and morphological diagnosis, to enable a paired comparison of STIC and eSTIC in the same fetus under similar scanning conditions. RESULTS: eSTIC volumes had higher temporal resolution (37 vs. 24 frames per second, p < .001), less motion during acquisition (12 vs. 20 cases, O.R. 7.0, p = .002) and better average image quality (1.9 vs. 2.2, p = .006) compared to STIC volumes. More diagnostic reconstructions were achieved by eSTIC (n = 55, 86%) than STIC (n = 52, 78.8%), p = .001), in a comparable analysis time (mean 4.96 vs. 4.94 min). During a comparison of image quality of the original acquisition (A) and reconstructed planes (B and C planes) e STIC was superior in 22 (33%), 39 (59%) and 21 (38%) volumes, respectively, with the remaining cases being of similar quality (<10% in each plane in favor of STIC). Imaging mode and gestational age had a similar impact on both eSTIC and STIC performance: diagnostically acceptable studies in 49 (75.8%) vs. 48 (72.2%) by B-Mode, 60 (90.9%) vs. 56 (84.8%) by Color Doppler Mode, 8 (62.5%) vs. 10 (50%) in early scans, 38 (95%) vs. 38 (95%) in mid-gestation scans, and 7 (70%) vs. 6 (60%) in third trimester scans. Eight obstetric scans identified a fetus with a cardiac variant or structural abnormality. Diagnostic concordance of the two STIC approaches was comparable (40/48 concordant interpretations, kappa 0.657) all confirmed by fetal and/or postnatal echocardiography. CONCLUSIONS: eSTIC was associated with more effective 4 D fetal heart reconstruction due to reduced motion artifacts and superior image quality in all planes, when compared to STIC. Early gestation reconstructions were not generally successful using either technology. Further study is needed to define the cost-effectiveness and diagnostic impact of eSTIC over conventional STIC and their role over, or in addition to, screening 2 D fetal echocardiography by appropriately trained sonographers.

Mesenteric Lymphadenitis Presenting as Acute Abdomen in a Child with Multisystem Inflammatory Syndrome.

Multisystem inflammatory syndrome in children (MIS-C) may develop as a rare complication following COVID-19. MIS-C presentation varies substantially, but fever and gastrointestinal symptoms are the most prominent. Indeed, gastrointestinal involvement may be severe enough to present as acute abdomen, posing challenges to clinicians. We present herein the case of a healthy five-year-old male who presented with fever, vomiting, and abdominal pain, resembling acute abdomen. The patient had no history of SARS-CoV-2 infection or exposure, and MIS-C diagnosis was initially surpassed unnoticed. The patient underwent exploratory laparotomy that only revealed mesenteric lymphadenitis. Postoperatively, the patient met the clinical and laboratory diagnostic criteria of MIS-C. SARS-CoV-2 exposure was serologically confirmed and MIS-C treatment was commenced, resulting in defervescence and a satisfactory outcome. In young patients presenting with acute abdomen, surgeons should be aware of MIS-C, so that earlier diagnosis and appropriate treatment are made prior to surgical interventions.

Mexiletine Treatment for Neonatal LQT3 Syndrome: Case Report and Literature Review.

Background: Early diagnosis of long QT type 3 (LQT3) syndrome during the neonatal period is of paramount clinical importance. LQT3 syndrome results in increased mortality and a mutation-specific response to treatment compared to other more common types of LQT syndrome. Mexiletine, a sodium channel blocker, demonstrates a mutation-specific QTc shortening effect in LQT3 syndrome patients. Case Presentation: A neonate manifested marked QTc prolongation after birth. An electrocardiogram (ECG) recording was performed due to positive family history of genetically confirmed LQT3 syndrome (SCN5A gene missense mutation Tyr1795Cys), and an association with sudden cardiac death was found in family members. The mexiletine QTc normalizing effect (QTc shortening from 537 to 443 ms), practical issues related to oral mexiletine treatment of our young patient, along with a literature review regarding identification and mexiletine treatment in infants with LQT3 syndrome are presented. Conclusions: Mexiletine could be considered in the treatment of high-risk LQT3 patients already in the neonatal period in addition to b-blocker therapy. Availability of standardized commercial mexiletine pediatric formulas, serum mexiletine level analyses, and future prospective studies are needed to evaluate the potential beneficial effect of early mexiletine treatment on the incidence of future acute cardiac events in these high-risk LQT syndrome patients.

Case Report: Α Case of Endocarditis and Embolic Stroke in a Child, Suggestive of Acute Q Fever Infection.

Acute Q fever is usually asymptomatic or is associated with a mild self-limited course and a favorable outcome. The occurrence of endocarditis during acute infection by Coxiella burnetii is an emerging clinical entity observed in adults that has been attributed to an autoimmune complication of early infection. Herein, we report the first case of a previously healthy 2-year-old child with endocarditis complicated by septic embolic stroke, in which the identified microbiological evidence was suggestive of acute rather than chronic C. burnetii infection. The development of endocarditis in this case occurred in the absence of any autoimmune reaction, but in the context of a very mild form of congenital heart disease, a small ventricular septal defect, which might serve as a predisposing factor for endocarditis. This case suggests that acute Q fever endocarditis may affect children as well and can be attributed not only to autoimmune mechanisms but also to a potential effect of the infectious agent per se on the cardiac endothelium in patients with underlying heart defects, regardless of their severity.

Antenatal and postnatal evidence of periventricular leukomalacia as a further indication of vascular disruption in Adams-Oliver syndrome.

We describe a new family with Adams-Oliver syndrome (AOS). The propositus is a 14-month-old boy presenting with aplasia cutis congenita, distal limb transverse defects, growth retardation, and a wide atrial septal defect. Central nervous system abnormalities included central hypotonia, and magnetic resonance imaging (MRI) findings consistent with periventricular leukomalacia (PVL). Fetal MRI at 26 weeks' gestation had shown bilateral dilatation of lateral ventricles and periventricular cysts at the site of postnatal lesions. The patient's father and paternal grandfather also had manifestations indicative of AOS. Antenatal and postnatal MRI findings suggest that our patient's PVL represents an unusual congenital feature of AOS, possibly due to vascular disruption and decreased perfusion during critical periods of fetal brain development.

Troponins and natriuretic peptides in the monitoring of anthracycline cardiotoxicity.

Anthracycline-related cardiotoxicity has a substantial negative impact on long-term survivors of childhood cancer. The detection of cardiotoxicity is currently based on echocardiography or radionuclide angiography. However, as they depict only the final outcome of myocardial injury in terms of reduced heart contractility, heart specific biomarkers of myocardial destruction or dysfunction could be advantageous by allowing for an earlier detection of cardiotoxicity. In the present study, the usefulness of cardiac troponins and natriuretic peptides, the most commonly used biomarkers of myocardial destruction and ventricular dysfunction respectively, to detect and to predict the development of anthracycline cardiotoxicity has been reviewed.

A study of time-frequency features for CNN-based automatic heart sound classification for pathology detection.

This study concerns the task of automatic structural heart abnormality risk detection from digital phonocardiogram (PCG) signals aiming at pediatric heart disease screening applications. Recently, various systems based on convolutional neural networks trained on time-frequency representations of segmental PCG frames have been presented that outperform systems using hand-crafted features. This study focuses on the segmentation and time-frequency representation components of the CNN-based designs. We consider the most commonly used features (MFCC and Mel-Spectrogram) used in state-of-the-art systems and a time-frequency representation influenced by domain-knowledge, namely sub-band envelopes as an alternative feature. Via tests carried on two high quality databases with a large set of possible settings, we show that sub-band envelopes are preferable to the most commonly used features and period synchronous windowing is preferable over asynchronous windowing.

Electronic health record with computerized decision support tools for the purposes of a pediatric cardiovascular heart disease screening program in Crete.

BACKGROUND AND OBJECTIVE: Early detection of cardiovascular (CV) disease or associated risk factors during childhood is of paramount importance, allowing for early treatment or lifestyle modifications, respectively. The objective of this study was to describe the development of an electronic health record (EHR), with integrated computerized decision support system (CDSS), specifically designed for supporting the needs of a pilot pediatric CV disease screening program applied on primary school students of a Mediterranean island. METHODS: Evidence-based knowledge, national and international practice guidelines regarding sport preparticipation CV screening of children and young athletes has been used for the design of the designated EHR. A CDSS, capable for providing alerts for further cardiology evaluation need, has been incorporated into the EHR, based on normative anthropometric and electrocardiographic data as well as predefined positive history responses. RESULTS: We developed a designated EHR with integrated CDSS supporting pediatric CV disease screening, capable for documenting CV-related personal and family history responses, physical evaluation data (weight, height, blood pressure), allowing for entering electrocardiogam (ECG) measurements and for uploading of multimedia files (including ECG images and digital phonocardiogram audio files). The EHR incorporates clinical calculators and referral alerts for the presence (and degree) of adiposity, hypertension, ECG abnormalities and positive history responses indicative of high CV disease risk. In a preliminary EHR validation, performed by entering data from 53 previously available paper-based health records, the EHR was proven to be fully functional. CONCLUSIONS: The pediatric cardiology EHR with CDSS features which we developed might serve as a model for EHR for primary health care purposes, capable to document and early detect CV disease and associated risk factors in pediatric populations.

Stroke following Glenn anastomosis in a child with inherited thrombophilia.

The optimal anticoagulation following Fontan operation and its modifications remain controversial and it is even less well defined as regards patients with inherited thrombophilia. We present a case of a child with bidirectional Glenn anastomosis for double inlet left ventricle that suffered a stroke despite aspirin prophylaxis; the patient was combined homozygous for prothrombin G20210A mutation and for methylenetetrahydrofolate reductase C677T mutation as well. The family history was positive for fetal loss and premature cardiovascular disease. Large-scale studies are needed to evaluate whether carriers of thrombophilia mutations need more intense thromboprophylaxis.

Correlation of plasma N-terminal pro-brain natriuretic peptide levels with left ventricle mass in children treated with anthracyclines.

BACKGROUND: The incidence of subclinical cardiotoxicity following anthracycline treatment for childhood cancer varies according to the method used for its detection. The aim of the study was to document the prevalence of left ventricular myocardial mass (LVM) reduction and its possible association with plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in asymptomatic children treated with anthracyclines. PATIENTS AND METHODS: Nineteen asymptomatic children who had received anthracyclines during their treatment for cancer were evaluated. They had received an equivalent of doxorubicin dose 240 mg/m2 (22-1200 mg/m2) on average 3.9 years (0.6-8.3) before (median age at diagnosis 3.8 years). The LVM was determined by M-Mode echocardiography and compared to the expected value, obtained from the regression equation of LVM on height of a group of 160 healthy children. Additionally the patients' plasma NT-pro BNP levels were determined. RESULTS: A high prevalence of reduced LVM associated with increased NT-proBNP levels was found. The average LVM value was -14.4% (+/-4.9) lower than expected whereas fourteen patients (73%) had a lower LVM than predicted. The NT-pro BNP levels in patients with reduced LVM were significantly higher than those measured in patients without LVM reduction (0.316+/-0.02 versus 0.17+/-0.01 pmol/ml respectively, p=0.009). A cut off NT-pro BNP level of 0.2 pmol/ml could differentiate patients with LVM reduction from those with normal or greater than expected LVM. CONCLUSION: The association of higher NT-proBNP levels with reduced LVM in asymptomatic children after anthracycline administration could be an early indication of subclinical cardiotoxicity.