Acquired Heart Disease Research Articles

Association of reduced peak left atrial strain with supraventricular arrhythmia in adults with congenital heart disease.

Atrial arrhythmias are an important cause of morbidity and mortality in adults with congenital heart disease (ACHD). In acquired heart disease, the left atrial (LA) strain has been shown to predict supraventricular tachyarrhythmias (SVT). This study aimed to investigate whether reduced LA strain is associated with SVT in ACHD patients. This retrospective, single-center cohort study collected baseline clinical and echocardiographic data of 206 ACHD patients (157 left heart defect, 49 right heart defect). Patients with sinus rhythm at baseline and a 5-year follow-up (median age 29, IQR 22-41 years) were included. Diagnosis of sustained SVT was determined from clinical reports during the follow-up period. New or recurrent sustained SVT occurred in 16 patients (7.8%, median follow-up of 6.2 years). Patients who developed SVT were older, more likely to have diastolic dysfunction, and had larger LA dimensions, left ventricular mass, and a lower peak LA longitudinal strain (PALS). Lower PALS was associated with higher risk of SVT in patients with left and right heart defects. Patients in the lowest quartile for PALS had a 15.9-fold higher hazard ratio of SVT (95% confidence interval, 4.5 to 56.0, p < 0.001) in comparison with the top three quartiles. PALS provides information about the occurrence of SVT in the ACHD population. Including measurement of LA strain in the follow-up of these patients may allow to better identify patients at risk of future atrial arrhythmias.

Bilateral facial nerve palsy complicating Kawasaki disease: A case report and literature review.

Kawasaki disease (KD) manifests as an acute, self-limited vasculitis disease that constitutes the primary cause of acquired heart disease in children under 5 years of age. Facial nerve palsy (FNP) is a rare complication associated with coronary artery lesions (CALs) in patients with KD. Patients with KD and FNP usually present atypically, leading to a delayed diagnosis and treatment of KD. A 4-month-old boy with fever, left FNP and bilateral conjunctival injection with spontaneous resolution, was admitted to the hospital, received a short course of intravenous dexamethasone, and experienced rapid FNP recovery on the first admission. The patient experienced a resurgence of fever, bilateral conjunctival injection, and right FNP, which led to readmission. Physical examination revealed redness at the site of Bacillus Calmette-Guérin inoculation, reddening of lips, and desquamation of the distal extremities. Echocardiography revealed right-sided CALs. The patient initially missed KD on the first admission, and was later diagnosed with complete KD with FNP on the second admission. After a short course of intravenous dexamethasone, the left FNP resolved quickly. However, right FNP recurred after corticosteroids withdrawal. Meanwhile, more typical symptoms were observed, and KD was diagnosed. Treatment ensued with intravenous immunoglobulin (IVIG), aspirin, and dexamethasone. The patient achieved rapid remission, without recurrence. Echocardiography continued to show normal findings during 1-year follow-up after discharge. The clinical symptoms of FNP complicating KD in children are atypical and can easily lead to delayed diagnosis and treatment. FNP in patients with KD may serve as a risk factor for CALs, which are more challenging to resolve than the FNP itself. Adding corticosteroids to IVIG may be recommended to reduce IVIG resistance, decrease the risk of developing CALs, and alleviate CALs.

Patient Reported Outcome Measures in Adults with Fontan Circulatory Failure.

Background: Patient reported outcomes (PROs) are important measures in acquired heart disease but have not been well defined in Adult Congenital Heart Disease (ACHD). Our aim was to explore the discriminatory capacity of PRO survey tools in Fontan circulatory failure (FCF). Methods: Consecutive adults were enrolled from our ambulatory clinics. Inclusion criteria were age ≥18 years, a Fontan circulation or a hemodynamically insignificant shunt lesion, and sufficient cognitive/language abilities to complete PROs. A comprehensive package of PRO measures, designed to assess perceived health-related quality of life (HRQOL) was administered (including the Kansas City Cardiomyopathy Questionnaire [KCCQ-12], EuroQol-5-dimension [EQ5D], Short Form Health Status Survey [SF-12], self-reported New York Heart Association [NYHA] Functional Class, and Specific Activity Scale [SAS]). Results: We compared 54 Fontan patients (35 ± 10 years) to 25 simple shunt lesion patients (34 ± 11 years). The KCCQ-12 score was lower in Fontan versus shunt lesion patients (87 [IQR 79, 95] versus 100 [IQR 97, 100], p-value < 0.001). The FCF subgroup was associated with lower KCCQ-12 scores as compared with the non-FCF subgroup (82 [IQR 56, 89] versus 93 [IQR 81, 98], p-value = 0.002). Although the KCCQ-12 had the best discriminatory capacity for determination of FCF of all PRO tools studied (c-statistic 0.75 [CI 0.62, 0.88]), superior FCF discrimination was achieved when the KCCQ-12 was combined with all PRO tools (c-statistic 0.82 [CI 0.71, 0.93]). Conclusions: The KCCQ-12 questionnaire demonstrated good discriminatory capacity for the identification of FCF, which was further improved through the addition of complementary PRO tools. Further research will establish the value of PRO tools to guide management strategies in ACHD.

Evaluation of Oral Health Status and Treatment Needs of Children with Congenital and Acquired Heart Disease.

Objective: To evaluate the oral health status and treatment needs of children with congenital and acquired heart disease. Methods: This descriptive study included 301 children aged 5-14 from June 2022 to June 2023. Heart conditions were classified by congenital/acquired status and severity. The children's sociodemographic characteristics, medical and dental history, tooth brushing habits, and non-nutritional habits (bruxism, nail-biting, thumb-sucking, etc.) were evaluated. Oral health assessments including caries, oral hygiene, enamel defects, and dental treatment needs-related indices were recorded. Results: The mean age was 8.95 ± 2.91 years, and 271 (90%) of the children had congenital heart disease. The children with moderate and severe heart disease had significantly higher decayed/missing/filled surfaces (dmfs) (p = 0.038) and pulp exposure (p = 0.015) compared to the children with mild heart disease. According to the International Caries Detection and Assessment System II (ICDAS II) index, which included initial caries lesions, there were no caries-free children and 75.7% had extensive caries. The mean plaque index and gingival index were found to be 1.18 ± 0.38 and 0.69 ± 0.53, respectively. Enamel defects were observed in 15.9%. The Treatment Needs Index (TNI) was 85.8% for the primary teeth and 88.9% for the permanent teeth. The Care Index (CI) was 12.4% for the primary teeth and 10.8% for the permanent teeth. Conclusions: Children with congenital and acquired heart disease exhibit a high prevalence of untreated dental caries, gingivitis, and plaque accumulation, with a high need for dental treatments. Dentists should prioritize addressing these issues to prevent the risk of infective endocarditis (IE) and improve oral health outcomes in this population.

Subtle myocardial effects of rheumatic heart disease in children are revealed earlier with two-dimensional speckle tracking echocardiography.

Rheumatic heart disease (RHD) is the most common cause of acquired heart disease in developing countries and remains a serious public health problem. In the subclinical course of carditis, the absence of typical symptoms and the normal range of classical echocardiographic measurements used to evaluate cardiac functions have required new echocardiographic methods and parameters. Previous studies regarding rheumatic heart disease in children and adults have shown that strain patterns obtained by speckle tracking echocardiography, are in fact affected although left ventricular systolic functions are preserved, yet some studies have suggested otherwise. The aim of our study is to compare the use of speckle tracking echocardiography with conventional methods in the evaluation of cardiac functions and myocardial involvement in children with subclinical RHD. The study group consisted of 24 patients with asymptomatic cardiovascular who had no history of acute rheumatic fever, but had definite or probable rheumatic valve disease. This study group was determined according to the World Heart Federation guidelines by an echocardiographic examination performed for different reasons, as well as the control group of 22 healthy children. In order to evaluate the left ventricular regional myocardial functions of the patients, tissue Doppler echocardiography (TDE) and speckle tracking echocardiographic parameters were compared with the control group. The mean ages of the patient and control groups were 14.1±2.7 years and 13.9±2.3 years, respectively. There was no statistically significant difference between the two groups in terms of conventional methods (p>0.05) but global longitudinal strain and strain rate values were found to be significantly lower in the patient group (p<0.01). These changes appeared to be relevant throughout the duration of the illness. In patients with subclinical rheumatic heart disease, conventional echocardiographic evaluations are likely negative, whereas two-dimensional speckle tracking echocardiography reveal systolic and diastolic dysfunctions of the disease.

Clinico-Laboratory Profile and Outcome of Kawasaki Disease in Children in a Tertiary Care Hospital in Kathmandu

Introduction: Kawasaki disease (KD) is one of the most common vasculitis of childhood. It contributes significantly to acquired heart disease in children and results in coronary artery abnormalities including aneurysm in 25% of untreated children. This study aims to retrospectively assess the clinical course, laboratory results, and presenting symptoms of patients with complete and incomplete KD treated at tertiary care hospital in Kathmandu.Method: This retrospective study was conducted in the Department of Pediatrics. Data from January 2020 to December 2020 were retrieved from medical records department of the hospital and analyzed using Microsoft excel.Result: The total number of cases evaluated in our study was 9. The median age at the time of the diagnosis of KD was 24 months (median age for incomplete KD-21 months, complete KD-37 months). Male to female ratio was 1.2:1. The peak season of KD occurrence was Spring (March – May). Mean duration of stay in the hospital was 7 days. All children presented with fever, with an mean fever duration of 7 days at the time of presentation. Fever was present in every case. The most common principal symptom was a polymorphous skin rash, observed in 88% of the cases. Elevated CRP levels (≥3 mg/dl) were noted in all 9 cases. Cardiovascular complications were present in 88% of the patients, with coronary artery aneurysm (CAA) detected in 11%, coronary artery dilation in 22%, and mild pericardial effusion documented in 66% of the cases. Eight patients (88%) received IVIG, all 9 patients (100%) received aspirin, and 2 patients received steroids. There were no fatalities.Conclusion: KD is a common vasculitis in children which do not have significant sex predilection in oppose to most of the studies. Majority of cases occurred in spring season. The most common symptom was polymorphous rash. A high level of suspicion for diagnosing KD is essential, and early treatment is crucial to prevent complications and reduce the future economic burden on families and the nation.

Intervention needs assessment in children with heart diseases presenting to Tibebe-Ghion Specialized Teaching Hospital, Bahir Dar, North West Ethiopia – Tip of the iceberg of the intervention gap in Low-and-middle-income Countries (LMICs)

BackgroundPediatric heart disease is becoming a major contributor to childhood mortality. Almost half of congenital heart defects require intervention, either surgical or trans-catheter. Rheumatic heart disease also remains a global health problem in Low-and-middle-income-countries (LMICs). Intervention timing depends on the natural course and hemodynamic significance of the lesion with an emphasis on earlier intervention to prevent the damage of volume or pressure load and hypoxia. Objectivedescribe the current unmet intervention need of children with heart diseases presenting to Bahir Dar University Tibebe-Ghion Specialized Teaching Hospital. MethodsThis is a descriptive cross-sectional study involving three-hundred-seventy-six children (376) who had echocardiography-confirmed cardiac diseases over fifteen months from August 01, 2022, to October 30, 2023. Variables were analysed using IBM SPSS version 27 software. ResultsOf the 376 children with heart diseases, 54% were boys. The mean (SD) age was 53 (58) months, the median (IQR) being 26 (5–96). Congenital heart defects (CHDs) account for 68% of pediatric heart diseases. 77% of CHDs were acyanotic. Isolated Ventricular septal defect (21%) is the most common acyanotic CHD followed by patent ductus arteriosus (13.2%). Tetralogy of Fallot is the most common cyanotic CHD (41%). Rheumatic heart disease is the most common acquired heart disease (76.9%). 89.4% (336) of children were eligible for intervention need assessment. 35.4% (119) of intervention-eligible children had delayed presentation. 79.8% (268) of intervention-eligible children need intervention at the current presentation. 61%(163) of children who need intervention had delayed intervention timing. 242/268 (90.3%) of children with intervention needs were candidates for surgery. Only 0.7% of children had intervention. ConclusionOur study illustrates the unmet intervention need for pediatric heart diseases our health facilities faced to achieve the 2030 Sustained-development-goal (SDG) target.

Promotion of maturation of human pluripotent stem cell-derived cardiomyocytes via treatment with the peroxisome proliferator-activated receptor alpha agonist Fenofibrate.

As research on in vitro cardiotoxicity assessment and cardiac disease modeling becomes more important, the demand for human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is increasing. However, it has been reported that differentiated hPSC-CMs are in a physiologically immature state compared to in vivo adult CMs. Since immaturity of hPSC-CMs can lead to poor drug response and loss of acquired heart disease modeling, various approaches have been attempted to promote maturation of CMs. Here, we confirm that peroxisome proliferator-activated receptor alpha (PPARα), one of the representative mechanisms of CM metabolism and cardioprotective effect also affects maturation of CMs. To upregulate PPARα expression, we treated hPSC-CMs with fenofibrate (Feno), a PPARα agonist used in clinical hyperlipidemia treatment, and demonstrated that the structure, mitochondria-mediated metabolism, and electrophysiology-based functions of hPSC-CMs were all mature. Furthermore, as a result of multi electrode array (MEA)-based cardiotoxicity evaluation between control and Feno groups according to treatment with arrhythmia-inducing drugs, drug response was similar in a dose-dependent manner. However, main parameters such as field potential duration, beat period, and spike amplitude were different between the 2 groups. Overall, these results emphasize that applying matured hPSC-CMs to the field of preclinical cardiotoxicity evaluation, which has become an essential procedure for new drug development, is necessary.

Long-term cardiovascular inflammation and fibrosis in a murine model of vasculitis induced by Lactobacillus casei cell wall extract.

Kawasaki disease (KD), an acute febrile illness and systemic vasculitis, is the leading cause of acquired heart disease in children in industrialized countries. KD leads to the development of coronary artery aneurysms (CAA) in affected children, which may persist for months and even years after the acute phase of the disease. There is an unmet need to characterize the immune and pathological mechanisms of the long-term complications of KD. We examined cardiovascular complications in the Lactobacillus casei cell wall extract (LCWE) mouse model of KD-like vasculitis over 4 months. The long-term immune, pathological, and functional changes occurring in cardiovascular lesions were characterized by histological examination, flow cytometric analysis, immunofluorescent staining of cardiovascular tissues, and transthoracic echocardiogram. CAA and abdominal aorta dilations were detected up to 16 weeks following LCWE injection and initiation of acute vasculitis. We observed alterations in the composition of circulating immune cell profiles, such as increased monocyte frequencies in the acute phase of the disease and higher counts of neutrophils. We determined a positive correlation between circulating neutrophil and inflammatory monocyte counts and the severity of cardiovascular lesions early after LCWE injection. LCWE-induced KD-like vasculitis was associated with myocarditis and myocardial dysfunction, characterized by diminished ejection fraction and left ventricular remodeling, which worsened over time. We observed extensive fibrosis within the inflamed cardiac tissue early in the disease and myocardial fibrosis in later stages. Our findings indicate that increased circulating neutrophil counts in the acute phase are a reliable predictor of cardiovascular inflammation severity in LCWE-injected mice. Furthermore, long-term cardiac complications stemming from inflammatory cell infiltrations in the aortic root and coronary arteries, myocardial dysfunction, and myocardial fibrosis persist over long periods and are still detected up to 16 weeks after LCWE injection.

Panorama da mortalidade por cardiopatia reumática crônica entre 2017 e 2021, no Rio Grande do Sul

Introduction: Chronic rheumatic heart disease is a complication of rheumatic fever (RF), a disease that results from pharyngotonsillitis, causing acquired heart disease in young people and can lead to valvular sequelae and death. The objective of the study is to evaluate mortality from rheumatic heart disease in Rio Grande do Sul, with emphasis on voluntary involvement, and to analyze a possible association between age group and sex. Material and Methods: This research consists of a cross-sectional study using the database of the Department of Information Technology’s Unified Health System (DataSUS). Deaths from rheumatic heart diseases were included, divided by sex and age, during the period from 2017 to 2021 in Rio Grande do Sul. For statistical analysis, the Chi-Square test (χ²) was used, using the software SPSS. Results: 321 deaths from rheumatic valve disease were found between 2017 and 2021, the majority of which were caused by mitral valve disease. Women had a higher number of deaths from mitral valve disease and men from other heart diseases. Regarding the age group, deaths due to mitral valve disease were more prevalent among those aged 40 to 49 years, while in tricuspid valve disease, there was a greater association with individuals aged 80 years or older. In other diseases, no association was demonstrated. Conclusion: From this, an association was established between sex and age group in the incidence of rheumatic heart disease among the studied population. Therefore, a more comprehensive therapeutic approach is needed, associated with the development of campaigns that publicize the importance of correct treatment in order to reduce mortality rates.

Platelets in Kawasaki disease: mediators of vascular inflammation.

Kawasaki disease, a systemic vasculitis that affects young children and can result in coronary artery aneurysms, is the leading cause of acquired heart disease among children. A hallmark of Kawasaki disease is increased blood platelet counts and platelet activation, which is associated with an increased risk of developing resistance to intravenous immunoglobulin and coronary artery aneurysms. Platelets and their releasate, including granules, microparticles, microRNAs and transcription factors, can influence innate immunity, enhance inflammation and contribute to vascular remodelling. Growing evidence indicates that platelets also interact with immune and non-immune cells to regulate inflammation. Platelets boost NLRP3 inflammasome activation and IL-1β production by human immune cells by releasing soluble mediators. Activated platelets form aggregates with leukocytes, such as monocytes and neutrophils, enhancing numerous functions of these cells and promoting thrombosis and inflammation. Leukocyte-platelet aggregates are increased in children with Kawasaki disease during the acute phase of the disease and can be used as biomarkers for disease severity. Here we review the role of platelets in Kawasaki disease and discuss progress in understanding the immune-effector role of platelets in amplifying inflammation related to Kawasaki disease vasculitis and therapeutic strategies targeting platelets or platelet-derived molecules.

Secular trend of Kawasaki disease and its correlation with viral activity in Taiwan: a nationwide population-based study

BackgroundKawasaki disease (KD) is the most important acquired heart disease in children. This study investigated annual incidence, seasonality, secular trend and the correlation of KD incidence with viral activity in Taiwan.MethodsThrough the national health insurance database, we identified KD during 2001–2020. The viral activity was obtained from nationwide surveillance database. We analyzed KD age-specific annual incidence, secular trends, seasonality and the correlation between KD incidence and common enteric or respiratory viral activity.ResultsThe KD incidence of subjects younger than 18 years significantly increased from 2001 to 2020 (11.78 and 22.40 per 100,000 person-years, respectively), and substantially decreased with age. Infants younger than 1 year presented the highest KD annual incidence at 105.82 to 164.34 per 100,000 person-years from 2001 to 2020. For all KD patients, the most frequently occurring season was summer followed by autumn. The KD incidence of infants younger than 1 year had significantly positive correlation with enteric (r = 0.14) and respiratory (r = 0.18) viral activity.ConclusionsThis study demonstrates the increasing trend of KD annual incidence and seasonality (more in summer and autumn) in Taiwan. The activity of common respiratory and enteric viruses was significantly correlated with KD incidence in infants.

Maternal Cardiac Disease and Perinatal Outcomes in a Single Tertiary Care Center.

This study aims to compare the perinatal outcomes of pregnant women with heart disease and a healthy pregnant control group, as well as the maternal and newborn outcomes of pregnant women with congenital heart disease and acquired heart disease. Pregnant women with heart disease and healthy control pregnant women were included in this retrospective study. Sociodemographic data of all patients included in the study were obtained from electronic records. Perinatal outcomes of all patients were compared. A total of 258 pregnant women were included in the study. While 129 pregnant women were diagnosed with heart disease, 129 patients were low-risk pregnant women. Preeclampsia (p=0.004) and cesarean section (p=0.01) rates were higher in pregnant women with heart disease compared to healthy pregnant women. Compared with healthy pregnant women, pregnant women with heart disease had a lower birth weight (p=0.003), a higher fetal growth restriction (FGR) rate (p=0.036), lower birth percentiles (p=0.002), a lower 5-minute APGAR (p=0.0001), a higher neonatal intensive care unit (NICU) admission rate (p=0.001), and a longer NICU stay rate (p=0.001). The mean gestational age at birth of pregnant women with congenital heart disease was higher than that of those with acquired heart disease (p=0.017). It was observed that all maternal heart diseases were associated with adverse perinatal outcomes compared to healthy pregnant women. In this series, perinatal adverse outcomes of pregnant women with congenital and acquired heart disease did not differ.

The Appraisal of Adults with Congenital Heart Disease: Lesson from Comparison of Surgical Outcomes.

The population of adults with congenital heart disease (ACHD) is constantly growing. There seems to be a consensus that these patients are difficult to manage especially if compared to patients with acquired heart disease. The aim of this study is to compare outcomes and results of cardiac surgery in ACHD patients with a reference population of adults with acquired cardiac disease. Retrospective study of 5053 consecutive patients older than 18years hospitalized for cardiac surgery during a 5-years period in our Institution. Two groups of patients were identified. Group I: 419 patients operated for congenital heart disease; Group II: 4634 patients operated for acquired heart disease. In each Group were identified low, medium, and high-risk patients, according to validated scores. Right ventricular outflow tract surgery was the most frequent procedure in Group I, while coronary artery by-pass grafting was the most common in Group II. Patients with ACHD were younger (37.8 vs. 67.7years), with higher number of previous operations (32.1% vs. 6.9%), had longer post-ICU hospital stay (11 vs. 8days) but had lower ICU stay (1 vs. 2days), shorter assisted mechanical ventilation (12 vs. 14h) and lower surgical mortality (1 vs. 3.7%) (all p < 0.001). No differences were found in term of post-operative complications (12.4 vs. 15%). The surgical treatment of ACHD patients can be done with excellent results and if compared with acquired cardiac disease patients they have better results with shorter ICU stay and lower mortality.

Rheumatic Heart Disease in East of Bali Indonesia

Background: Rheumatic heart disease remains to be the most acquired heart disease among people aged &lt;25 years. Despite improvements in high sociodemographic countries, low and low-middle sociodemographic countries have been less successful in lowering the burden of RHD.1 However, data of patient with RHD is still lacking in Indonesia, especially in Bali. Karangasem is a rural area, one of the regencies in the eastern part of Bali. Methods: This retrospective study was performed between January 2023 and January 2024 at two hospitals in Karangasem Regency, Karangasem Regional General Hospital and BaliMed Karangasem Hospital. These two hospitals were the only hospital in Karangasem regency. The study population comprised all patients who were diagnosed with RHD. Patient characteristics and echocardiographic parameters were collected retrospectively from medical records. Results: Data from 101 patients with RHD were collected. They were predominantly female (73.3%) young adults (mean ages 41.97 years), graduated from primary school (58.4%), unemployed (26.7%), and mostly from the Karangasem subdistrict (34.7%). Mitral stenosis and mitral regurgitation were the same counts (65.3%), with mixed valve lesions (mitral and aortic) as the most common lesion (45.5%). Fifty-eight patients (57.4%) had secondary tricuspid regurgitation, with 6 patients with TR V-Max &gt;3.4m/s. Atrial fibrillation was a common complication (47.5%). Most patient with RHD had preserved Left Ventricular Ejection Fraction (LVEF &gt;50%). Only a quarter of patients had reduced RV contractility (TAPSE &lt;17mm). All of the patients with AF were given warfarin. All under 40-year-old patients were given a benzathine penicillin G injection. Only 7 patients had a history of valve surgery. Conclusion: Mixed valve lesion (mitral and aortic) was the most observed condition of valve lesion in RHD with the same count of mitral stenosis and mitral regurgitation. Characteristic of patients in this study were predominantly female, young adult, graduated from primary school, unemployed, had preserved LV function, normal RV contractility, high prevalence of AF with all prescribed warfarin, all of under 40 years were given antibiotics prophylaxis.

The Effects of Aspirin dose in Children with Congenital and Acquired Heart Disease. Results from the Paediatric Study of Aspirin Efficacy using Diagnostic and Monitoring Tools (PAED-M).

The optimal dose of aspirin required in children with congenital and acquired heart disease is not known. The primary aim of this prospective observational study was to evaluate the effects of aspirin dose on platelet inhibition. The secondary aim was to determine the prevalence and clinical predictors of aspirin non-responsiveness. Measurements were by Thromboelastography with Platelet Mapping (TEGPM) only in children less than 2years (y) of age with particular emphasis on the parameter known as maximum amplitude with arachidonic acid (MAAA) and using both TEGPM, and light transmission aggregometry (LTA) in children greater than 2y. We prospectively studied 101 patients with congenital and acquired cardiac disease who were receiving empirical doses of aspirin for a minimum of 4weeks but no other antiplatelet agents. Patients were stratified according to dose concentration and age. There was a trend toward lower age in patients with no response or semi-response to aspirin. All patients were considered responsive to aspirin in the higher-dose quartile (Q4) with a median dose of 4.72 (4.18-6.05) mg/kg/day suggesting that patients in this age group may require 5mg/kg/day as an empirical dose. In children > 2y, there was no significant difference in inhibition found in patients dosed at higher doses in Q3 versus Q4 suggesting that patients in this cohort are responsive with 3mg/kg/day dose. The current practices may lead to reduced platelet inhibition in some children due to under-dosing or overdosing in others. In conclusion, younger children require higher doses of aspirin. Laboratory assessment is warranted in this population to mitigate against under and overdosing.

Normal Values for Echocardiographic Myocardial Work in a Large Pediatric Population.

Echocardiographic myocardial work is a new load-independent echocardiographic technique to quantify left ventricle (LV) systolic performance. Our aim was to establish normal values for echocardiographic myocardial work in a large population of healthy children. For all the subjects 4-, 2-, and 3-chamber-view videos were stored. The following parameters were obtained by offline analysis: the global myocardial work (GMW), the global myocardial constructive work (GCW), the global myocardial wasted work (GWW), and the global myocardial work efficiency (GWE). Age, weight, height, heart rate, and body surface area (BSA) were used as independent variables in the statistical analysis. In all, 516 healthy subjects (age range, 1 day-18 years; median age, 8.2 ± 5.3 years; 55.8% male; body surface area (BSA) range, 0.16 to 2.12 m2) were included. GWI, GCW, and GWW increased with weight, height, and BSA (ρ ranging from 0.635 to 0.226, p all < 0.01); GWI and GCW positively correlated with age (ρ 0.653 and 0.507). After adjusting for BSA differences, females showed higher mean GWI (p = 0.002) and GCW values (p < 0.001), thus Z-score equations for gender have been presented. We provided MW values in a large population of healthy pediatric subjects including lower ages. MW values increased with age and body size and, interestingly, were higher in females than in men. These data cover a gap in current nomograms and may serve as a baseline for the evaluation of MW analysis in children with congenital and acquired heart diseases.

Sudan's rheumatic fever and rheumatic heart disease guidelines: a simplified approach in an endemic country.

Rheumatic heart disease (RHD) is a preventable sequelae of group A beta hemolytic streptococcal infection leading to an immune reaction: acute rheumatic fever (ARF) and progressive heart valve dysfunction. RHD is the leading cause of acquired heart disease in children and young adults in Sudan and many low/middle-income countries. In 2018, the World Health Organization (WHO) issued a resolution for RHD mandating that each country adopt updated guidelines for ARF and RHD management. These current guidelines are mainly directed to primary healthcare workers. Sudan's Federal Ministry of Health (FMOH) in collaboration with the WHO East Mediterranean Regional Office (EMRO) assembled a committee for updating RHD guidelines. We conducted a systematic literature search from 2000 to 2022 in National Institute of Health Database (PubMed) under the following titles: streptococcal pharyngitis, acute rheumatic fever, rheumatic heart disease, benzathine penicillin. Best available, evidence-based practices for diagnosis and management of ARF/RHD were selected and adapted to Sudan's situation. The guidelines were critically appraised by the committee then endorsed to the FMOH and WHO EMRO Noncommunicable Disease Departments in January 2023. This paper describes the updated guidelines. Simplified algorithms are provided for diagnosis of bacterial pharyngitis including two clinical criteria: sore throat and the absence of viral symptoms in the target age group. A simplified algorithm for diagnosis and management of ARF is adopted using two levels of diagnosis: suspected case at primary level where penicillin prophylaxis is started and secondary/tertiary care where echocardiography is performed and diagnosis confirmed or excluded. Echocardiography screening is recognized as the standard method for early diagnosis of RHD; however, due to the anticipated limitations, its implementation was not adopted at this time. Streptococcal skin infection is included as a precursor of ARF and a detailed protocol for benzathine penicillin administration is described. The Sudan guidelines for ARF/RHD management were updated. Endorsement of these guidelines to FMOH and WHO EMRO is expected to improve control of RHD in the region.

Precision Medicine in Congenital Heart Disease, Rheumatic Heart Disease, and Kawasaki Disease of Children: An Overview of Literature

Congenital heart disease and common acquired heart diseases like Kawasaki disease and rheumatic heart disease are prevalent cardiovascular conditions in children worldwide. Despite the availability of treatment options, they continue to be significant contributors to morbidity and mortality. Advancements in early diagnosis, improvements in treatment approaches, and overcoming resistance to available treatments are crucial to reduce morbidity. Researchers have turned to precision medicine to tackle these challenges. We aimed to analyze the existing literature concerning the utilization of precision medicine in congenital heart disease, rheumatic heart disease, and Kawasaki disease. The emphasis is placed on comprehending the key themes explored in these studies and evaluating the present state of their clinical integration. The central theme of most studies revolves around the examination of genetic factors. Despite promising research outcomes, limitations in these studies indicate that the clinical implementation of precision medicine in these conditions remains a distant prospect, necessitating additional exploration and attention to confounding factors.

Targeting the SIRT1 pathway to modulate inflammation in a murine model of Kawasaki Disease vasculitis

Abstract Kawasaki Disease (KD) is an acute febrile systemic vasculitis and the leading cause of acquired heart disease among children. Overactivation of the NLRP3 inflammasome and IL-1b production are critical for the development of cardiovascular lesions during KD. Sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase, is crucial for responding to cellular stress, and regulates NLRP3 activation as well as clearance of damaged mitochondria in cardiovascular diseases. However, its role in KD pathophysiology remains unknown. Here, we used the Lactobacillus casei cell wall extract (LCWE) murine model of KD to determine the role of SIRT1 on the development of cardiovascular lesions. We show that Sirt1 expression is downregulated in LCWE-injected mice with a significant reduction of nicotinamide, a product resulting from NAD+ degradation by SIRT1. In addition, supplementation of mice with NAD+ precursors significantly reduced the development of LCWE-induced cardiovascular lesions. Furthermore, KD development was less severe in SIRT1 overexpressing mice but was exacerbated with the specific deletion of Sirt1 in vascular smooth muscle cells. Treatment of LCWE-stimulated coronary smooth muscle cells with a SIRT1 activator favored mitophagy by inhibiting ribosomal S6 phosphorylation. These results indicate an impaired NAD+/SIRT1 axis during LCWE-induced KD vasculitis, which could potentially be targeted to reduce cardiovascular lesions in KD.