Left ventricular function assessment in Kawasaki disease by two-dimensional global longitudinal systolic strain with automated function imaging.

BACKGROUND: Kawasaki disease is an acute febrile vasculitis of childhood mainly affecting children under 4 years of age. In the acute stage of the disease, heart function decreases and gradually returns to normal after treatment. However, subendocardial involvement may persist, which cannot be assessed by M-mode echocardiography. Strain echocardiography is a recently developed technique to assess subendocardial involvement of myocardial deformation. We aimed to study the stratified strain of left ventricular function in a Kawasaki patient at least 6 months after the acute stage of the disease with special conditions for entering the study using two-dimensional speckle-tracking imaging. Between September 2020 and October 2022, 27 healthy children and 27 children with a history of Kawasaki disease more than 6 months ago were evaluated using two-dimensional global longitudinal peak systolic strain with automated function imaging technology. RESULTS: The mean age of patients was 5.6 years. With M-mode echocardiography, ejection fraction of each group was in the normal range. Mean (± standard deviation) global longitudinal peak strain in four-chamber view of girls with Kawasaki disease was - 23.74 ± 2.77, and that in boys with Kawasaki disease was - 20.93 ± 2.06 (P value = 0.008). GLPS (global longitudinal peak strain) was compared as an overall average and as in a separate segment, which showed significant difference in two comparisons. In our study, a decrease in the function of some cardiac segments is reported. Global longitudinal peak strain in four-chamber view was significantly lower in boys. Comparing different segments, a difference in global left ventricular long-axis strain was found between the two groups. On the other hand, there was a major difference between the two groups in the basal inferolateral, basal anterolateral, and mid-inferolateral, which receives blood from Left Circumflex artery. CONCLUSION: Using stain echocardiography to detect continued subendocardial involvement in asymptomatic children with a history of Kawasaki disease for a better understanding of the condition, effective management and follow-up is recommended.

Correlation between echocardiographic estimation of right atrial pressure and invasive measurement of central venous pressure in postoperative pediatric patients with congenital heart disease: a prospective observational study.

BACKGROUND: Right atrial pressure plays a critical role as a hemodynamic parameter in diagnosing pulmonary hypertension and other cardiac diseases, as well as guiding the treatment and prognosis of various cardiac disorders. If there is no obstruction between the inferior or superior vena cava (SVC) as central veins and the right atrium, the pressures in these veins could be considered equal to the right atrial pressure. This study aimed to examine the correlation between echocardiographic methods for estimating right atrial pressure and invasive measurements of central venous pressure (CVPi) in infants and children with congenital heart disease during the 48 h after cardiac surgery and to establish regression equations for echocardiographic estimation of central venous pressure (CVPe). RESULTS: We prospectively enrolled 43 infants and children, ranging in age from 6 months to 16 years, including 20 males and 23 females. We found a significant correlation between CVPi and the ratio of the maximal diameter of IVC to the maximal diameter of the descending aorta ratio (IVCmax/DAOmax) (r = 0.529, P < 0.001), SVCS/D velocity ratio (SVCS/D) (r = 0.462, P = 0.006), right atrial vertical diameter (RAVD) (r = 0.409, P = 0.01), area (r = 0.384, P = 0.014), and tricuspid valve A wave acceleration rate (TVAAR) (r = 0.315, P = 0.048). Multiple regression analysis yielded an equation for estimating central venous pressure using four parameters related to the IVC, SVC, tricuspid valve, and right atrium. The equation is as follows: estimated CVP = 4.36 + (2.35 × IVCmax/DAOmax) + (1.06 × SVCS/D) + (0.059 × RAVD) + (0.001 × TVAAR). This equation is strongly correlated with CVPi (Pearson r = 0.698, P = 0.002). CONCLUSIONS: The estimation of central venous pressure through a multi-parametric equation that included the ratio of the maximal diameter of the inferior vena cava to the maximal diameter of the descending aorta, the ratio of S to D velocity of the superior vena cava, the vertical diameter of the right atrium, and the acceleration rate of the A wave of the tricuspid valve demonstrated a robust correlation with invasively measured central venous pressure. To assess the accuracy of predicted pressures by this equation, further investigations are required to apply this innovative multi-parametric formula to a prospective population of pediatric patients with congenital heart disease.

Mechanical QT and JT intervals by M-mode echocardiography: An extrapolation from the concurrent electrocardiographic tracings.

Background: Congenital long QT syndrome (CLQTS) is a life-threatening ion channelopathy leading to syncope and sudden death. Early diagnosis during the prenatal period and timely intervention can prevent sudden cardiac death and catastrophic consequences of this genetic ion channelopathy. Fetal magnetocardiography and fetal electrocardiography (ECG) enable the measurement of fetal QT and JT intervals, but their inherently technically challenging and/or resource-intensiveness nature preclude their routine clinical application. On the other hand, the high-temporal resolution of M-mode echocardiography makes it a well-suited and widely available modality for the measurement of cardiac events. Aims and Objectives: We aimed to investigate the mechanical counterparts of the electrical QT and JT intervals on M-mode echocardiographic images of the tricuspid, mitral and aortic valves, and aortic wall. Methods: We performed a prospective study on consecutive children referred to the outpatient pediatric cardiology clinic at a tertiary children's hospital. We defined M-mode echocardiographic landmark points on tracings of tricuspid annular planar systolic excursion, mitral and aortic valves, and aortic wall with simultaneous electrocardiographic recording. We measured the mean±SD of the absolute time difference and RR-adjusted time difference in cases with non-coincident ECG events and echocardiographic landmarks. Results: Fifty healthy children were enrolled in the study. In 47 (94%) out of the 50 children, Q was coincident with the starting point of the tricuspid annular plane systolic excursion. In all children, the Q was coincident with the mid-point of the A-C line of the mitral valve. In 38 (76%) cases, there was a bump on the anterior wall of the aortic root immediately before the change in the slope of the aortic wall. This was coincident with the Q wave in 100% of cases. In all cases, the J point coincided with the point of acceleration of velocity on TAPSE. In all children, the J point coincided with the initial maximal opening of the aortic cusps. The end of the T wave occurred coincident with the peak of the tricuspid annular planar systolic excursion in 47 children (94%). In 48 children (96%), the end of the T wave coincided with the aortic cusps' closure point. Conclusions: Based on our findings, we propose to measure the averaged mechanical QT and JT intervals by using an angled M-mode tracing of the aortic and mitral valve in five consecutive beats in the parasternal long-axis view. This is the first study on mechanical QT and JT intervals in healthy children. The study opens the horizons into the in-utero diagnosis of congenital long QT syndrome by measuring fetal QT and JT intervals using the widely available M-mode echocardiography.

COVID-19: A New Horizon in Congenital Heart Diseases.

Objective: Previous studies have demonstrated that both children and adult patients with a history of congenital heart disease (CHD) are at high risk for coronavirus disease 2019 (COVID-19) infection. This study investigates the status of COVID-19 infection among children undergoing surgical repair within the past 2 years. Methods: All alive patients operated on in a tertiary referral center between March 2018 and March 2020 were recruited in the present study. Detailed demographics, past medical and surgical history, and physical examination were reviewed for each patient. During the COVID-19 pandemic, data regarding the patient's status were collected by telephone survey from April 15 to April 30, 2020. Results: A total number of 210 patients are analyzed in this study. Participants' median age was 21.59 months [interquartile range (IQR) = 12-54.67], and 125 (59.5%) were female. The median interval between surgery and COVID-19 assessment was 305 days (IQR = 215-400). In addition, 67 (32%) patients used angiotensin receptor blocker (ARB)/angiotensin-converting enzyme (ACE) inhibitor (spironolactone and/or captopril). Sixteen patients (7.6%) were symptomatic and had positive chest CT results and/or RT-PCR compared to the previously reported prevalence of COVID-19 among the pediatric population (2.4% of children with <18 years of age); the prevalence of COVID-19 among the patients operated on due to CHD in the present study was significantly higher (p = 0.00012). Two patients were admitted to the intensive care unit (ICU); one patient was discharged 2 weeks later with acceptable status, and one patient died 2 days after ICU admission due to cardiac and respiratory arrest and myocarditis. The complexity of the underlying cardiac disorders was not different between patients with low risk (p = 0.522), suspicious patients (p = 0.920), and patients positive for COVID-19 (p = 0.234). The ARB/ACE inhibitor consumption was not associated with the COVID-19 infection [p = 0.527, crude odds ratio (OR) = 1.407, 95% CI = 0.489-4.052]. Conclusion: Children with a history of previous CHD surgery are more susceptible to infections, especially those infections with pulmonary involvements, as the lung involvement could cause worsening of the patient's condition by aggravating pulmonary hypertension. The results of the current study indicate that these patients are more prone to COVID-19 infection compared to the healthy children population.

Little Hearts Are Affected by COVID19: Importance of the Myocardial Systolic Evaluation.

Background: Identifying the cardiac changes could help design measures to recover the cardiovascular system and lessen the mortality and morbidity rate. Accordingly, this cross-sectional study was performed to evaluate the echocardiography indices which are indicators of the cardiac alterations of the children with COVID19 infection. Methods: This study was performed as a cross-sectional study evaluating echocardiography indices in children infected with COVID19. Fifteen children, known cases of the COVID19, and 14 healthy children were enrolled. Evaluated parameters include left ventricle ejection fraction (LVEF), left ventricle end-diastolic diameter (LVED), mitral valve Sa (MV Sa), Tricuspid annular plane systolic excursion (TAPSE), and laboratory parameters. Results: The participants' mean age and weight were 62.8 (±48.0) months and 19.95 (±15.67) kg, respectively. None of the laboratory and echocardiography parameters differed between males and females, between patients with and without positive past medical history, between the patients with and without respiratory tract symptoms, and between patients with and without GI tract symptoms (P.0.05). Patients had significantly higher TAPSE (p = 0.027), although MV Sa (p = 0.01) was significantly higher among healthy children. LV EF (p = 0.425) and LVED diameter (p = 0.603) were not different significantly. None of the patients had pericardial effusion, pleural effusion, and cardiac tamponade. Conclusion: The heart can be involved during the disease course in children, even at the level of echocardiography indices. This could contribute to a worse prognosis, higher morbidity, and mortality rate, especially in patients with overt myocardial involvement. Non-classic indicators, including LVEF, may not be conclusive for cardiac involvement in non-symptomatic patients.

A Pathogenic Homozygous Mutation in The Pleckstrin Homology Domain of RASA1 Is Responsible for Familial Tricuspid Atresia in An Iranian Consanguineous Family.

OBJECTIVE: Tricuspid atresia (TA) is a rare life-threatening form of congenital heart defect (CHD). The genetic mechanisms underlying TA are not clearly understood. According to previous studies, the endocardial cushioning event, as the primary sign of cardiac valvulogenesis, is governed by several overlapping signaling pathways including Ras/ ERK pathway. RASA1, a regulator of cardiovascular development, is involved in this pathway and its haploinsufficiency (due to heterozygous mutations) has been identified as the underlying etiology of the autosomal dominant capillary malformation/arteriovenous malformation (CM/AVM). MATERIALS AND METHODS: In this prospective study, we used whole exome sequencing (WES) followed by serial bioinformatics filtering steps for two siblings with TA and early onset CM. Their parents were consanguineous which had a history of recurrent abortions. Patients were carefully assessed to exclude extra-cardiac anomalies. RESULTS: We identified a homozygous RASA1 germline mutation, c.1583A>G (p.Tyr528Cys) in the family. This mutation lies in the pleckstrin homology (PH) domain of the gene. The parents who were heterozygous for this variant displayed CM. CONCLUSION: This is the first study reporting an adverse phenotypic outcome of a RASA1 homozygous mutation. Here, we propose that the phenotypic consequence of the homozygous RASA1 p.Tyr528Cys mutation is more serious than the heterozygous type. This could be responsible for the TA pathogenesis in our patients. We strongly suggest that parents with CM/AVM should be investigated for RASA1 heterozygous mutations. Prenatal diagnosis and fetal echocardiography should also be carried out in the event of pregnancy in heterozygous parents.

A novel splicing variant in FLNC gene responsible for a highly penetrant familial dilated cardiomyopathy in an extended Iranian family.

Recent achievements in the genetic diagnosis of Dilated Cardiomyopathy (DCM) have disclosed rare variants in numerous genes encoding different types of myocardial proteins. However, the causative gene underlying the pathogenesis of about 60% of familial cases with DCM has not been identified. One novel gene introduced in 2016 for cardiac-restricted DCM is FLNC. In this study, we applied Whole Exome Sequencing (WES) and bioinformatics-based methods to a member of an extended non-consanguineous family with DCM history accompanied with fatal arrhythmia in at least four consecutive generations. We found a novel splice-site mutation in FLNC gene (c.2389+1G>A) which cosegregated with all symptomatic individuals in the family. Computational prediction software tools as well as RT-PCR method were used to evaluate the impact of the FLNC splice site mutation. This substitution leads to exon 15th donor-site disruption and exon skipping, which would result in a premature stop codon three aminocids downstream of the mutation site. The aberrantly mRNA transcript can induce nonsense-mediated mRNA decay. Although carrier individuals show remarkable variable expression regarding the severity of DCM as well as the disease age of onset, a highly penetrant fatal arrhythmia was found to be shared between them. We strongly suggest that the involvement of FLNC gene, due to haploinsufficiency, should be considered in familial cases with DCM, especially if accompanied with arrhythmia and increased incidence of sudden cardiac death.

Effectiveness of Coenzyme Q10 on echocardiographic parameters of patients with Duchenne muscular dystrophy.

BACKGROUND: Myocardial damage is a common complication in patients with Duchenne muscular dystrophy (DMD) that occurs due to myocardial replacement by fat and fibrosis. In recent years, efforts have been made toward finding new pharmacological agents with fewer complications which can be used as prophylactic before the symptoms. Coenzyme Q10 plays a central role in production of bioenergy in heart muscle and antioxidant in reperfusion condition of myocardial damaged muscle and leads to membrane stability and prevents cell death. OBJECTIVE: This study aimed at comparing the Effectiveness of coenzyme Q10 on echocardiographic parameters of pediatric patients with Duchenne muscular dystrophy. METHODS: This randomized clinical trial study (RCT) was carried out on 25 pediatric patients with pre-diagnosed DMD who attended the Children's Medical Center (CMC), Tehran, Iran from February 2013 to 2015. The patients were randomly divided into two groups. Group-1; (n=12) was treated with coenzyme Q10 for six months and group-2 ;(n=13) received placebo for the same time. The primary aim was to compare the myocardial performance index (MPI), between the two groups at the end of six months. Data were analyzed by SPSS software (ver-16) and using T-Test. RESULTS: Twenty-five patients under study were divided into two groups of (Q10=12) and (placebo=13). Mean ages were 8.9±1.7 and 8.6±1.4 in Q10 and placebo groups (P=0.66). No significant difference was detected in MPI at all three views of mitral and tricuspid and septum respectively in two groups after the end of treatment (0.41±0.13, and 0.43±0.6; P=0.59), (0.45±0.12, and 0.46±0.1; P=0.05), and (0.45±0.06, and 0.45±0.1; P=0.31). CONCLUSION: According to the results obtained from this study, coenzyme Q10 had no significant effect on improving the performance of echocardiographic parameters in patients with DMD. TRIAL REGISTRATION: The trial is registered at the Iranian Clinical Trial Registry (IRCT.ir) with the IRCT identification number IRCT2015070223018N1. FUNDING: This research has been financially supported by the Research Council of Tehran University of Medical Sciences.

A novel method for quantification of left ventricular noncompaction using two-dimensional echocardiography in children.

OBJECTIVE: Although there are several echocardiographic criteria, there is not yet a general consensus about the diagnosis of left ventricular noncompaction. The current criteria are mostly based on the areas with maximal noncompaction in the heart. The echocardiographer may miss this maximal point leading to a misdiagnosis. Accordingly, we suggested a new method to measure the percentage of myocardial noncompaction using two-dimensional echocardiography. METHODS: In this study, the new method was examined on 4 noncompaction and 26 dilated cardiomyopathies, and 25 normal subjects. The percentage of noncompaction was measured at 3 levels (apical, papillary muscle and mitral valve) and averaged. FINDINGS: The mean percentages of myocardial noncompaction were 3.59±2.27, 8.86±5.52 and 34.7±26.1 in the control, dilated cardiomyopathy and noncompaction groups, respectively. A value of 17% or greater could distinguish left ventricular noncompaction from dilated cardiomyopathy with 92% specificity and 100% sensitivity and from normal subjects with 100% specificity and sensitivity. This percentage had a statistically significant association with noncompacted to compacted myocardial thickness ratio (P<0.001). CONCLUSION: This method showed good correlations with the existing echocardiographic and magnetic resonance criteria. However, it is not dependent on finding the area of maximal involvement. Being comparable to magnetic resonance imaging in accuracy, it is easier to perform and more available.

Closure of interatrial defects by immediate-release patch.

The Immediate-Release Patch is the newest version of the Transcatheter Patch, which is a bioabsorbable device for the closure of cardiac defects. Closure of 12 atrial septal defects and 1 fenestration was attempted using this device. Of the 13 devices used, 12 were implanted successfully (including that for the fenestration), whereas 1 device moved from the original position and was retrieved percutaneously. No other major adverse events occurred. After a median follow-up period of 11 months, trivial (≤ 2-mm) residual shunts remained in two patients, and a significant residual defect (7 mm) remained in 1 patient. The major advantages of this device include its wirelessness, its bioabsorbablity, potential application for defects up to 30 mm using only three sizes, its easier retrieval, and its ability to occlude defects with a deficient rim and some ostium primum and sinus venosus type defects. In contrast to the metal devices, it is bulkier and has a different application method requiring operator familiarity, and it sometimes leaves residual shunts.

Transcatheter embolization of congenital hepatic arteriovenous malformation using ethylene-vinyl alcohol copolymer (Onyx).

A male infant with high-output heart failure who had been found to have a hepatic arteriovenous malformation by ultrasound imaging was referred to our center (Department of Diagnostic and Interventional Radiology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Islamic Republic of Iran) for further evaluation. Computed tomography angiography revealed a large hepatic arteriovenous malformation with feeders originating from enlarged hepatic arteries and draining to enlarged hepatic veins. We performed a transcatheter embolization of the anomaly using ethylene vinyl alcohol copolymer (Onyx) during a single session. The cardiac function of the infant rapidly improved after the procedure. Over the 19 months of follow-up, his cardiac output remained stable and within the normal limits, and no complications were detected.

Transcatheter patch occlusion of ventricular septal defect in Down syndrome.

Closure of perimembranous ventricular septal defects in patients with Down syndrome, either surgically or by Amplatzer occluders, carries a high risk of complete heart block. We report 5 closures using the transcatheter patch, a wireless bioabsorbable device without any reported heart block to date. The median defect size was 11 mm. Small devices were used in 4 patients and a medium size in 1. The patch was released after 48 hours in 3 patients and immediately in the other 2. Of the 5 patients, 3 were followed up for >5 years and 2 for 1 year. None of these patients had atrioventricular block during their follow-up. In conclusion, the transcatheter patch might be superior in terms of cardiac conduction system protection in patients with Down syndrome after ventricular septal defect closure.

Intracoronary administration of autologous mesenchymal stem cells in a critically ill patient with dilated cardiomyopathy.

Relatively high prevalence of dilated cardiomyopathy in children, unfavorable response to traditional drug therapy, and limitations in heart transplantation call for new therapeutic options. Stem cell therapy can be promising in children suffering from this disease. The presented case documents that intracoronary injection of autologous bone marrow-derived mesenchymal stem cells in a boy with progressive dilated cardiomyopathy is feasible and safe. Furthermore, it may positively influence functional class, quality of life, and echocardiographic indices of cardiac function.

Transcatheter Atrial Septal Defect Closure under Transthorasic Echocardiography in Children.

OBJECTIVE: Atrial septal defect (ASD) device closure is routinely done under the guide of transesophageal or intracardiac echocardiography which are expensive techniques and not easily affordable in developing countries. METHODS: Using metallic devices, we attempted 32 ASD device closures under transthoracic echocardiography. FINDINGS: Of those, 30 procedures were successful (94 %). In two patients with relatively large ASD we encountered difficulty in positioning the device. These patients were referred for surgical closure. CONCLUSION: ASD device closure can be carried out successfully in most patients under transthoracic echocardiography in situations where transesophageal or intravenous echocardiographies are not available or affordable.