Permanent longitudinal strain damage of cardiotoxic drugs in childhood cancer: What is the safe level?

Objective: Anthracycline administration in children is associated with cardiac dysfunction. Speckle-tracking echocardiography (STE) can detect subclinical cardiac damage that may go undetected by conventional two-dimensional (2D) echocardiography. This study aims to investigate medium-term anthracycline cardiotoxicity using STE and determine a safer administrable level of anthracyclines (ACs). Methods: This observational case-control study enrolled 37 healthy controls and 78 pediatric cancer survivors who received chemotherapy. The patients were divided into two groups: cardiotoxic received (CR) and cardiotoxic free (CF). Data on segmental longitudinal strain (LS), global LS (GLS), and 2D echocardiographic parameters were collected after a drug-free period of at least one year. Results: A total of 115 children with a mean age of 108 ± 55 months, of whom 66% were males, were included in the study. Both the groups of cancer survivors exhibited significantly reduced GLS compared to healthy controls (CR vs. controls, P = 0.001; CF vs. controls, P = 0.013), but no significant difference in left ventricular ejection fraction (LVEF) was observed (P = 0.75). Overall, cancer survivors treated with ACs demonstrated a significant reduction in strain in 10 left ventricular segments, particularly in the basal segments (P < 0.05). Among CR patients, those with impaired GLS (n = 43, GLS worse than -21.9) had significantly higher mean age and cumulative anthracycline dose compared to CR patients with normal GLS (age, P = 0.024; anthracycline dosage, P = 0.036). Using an anthracycline cutoff of 223 mg/m2 resulted in a higher detection rate (49% vs. 25%) and fewer missed cases (51% vs. 74%) compared to the 360 mg/m2 anthracycline cutoff. Conclusion: Childhood cancer survivors demonstrate significantly reduced GLS while preserving a normal LVEF, which does not differ significantly from reference values of healthy children. The reduction in strain appears to be associated with higher anthracycline doses and older age. Lowering the anthracycline threshold to 223 mg/m2 may improve the predictability of a decline in cardiac function using strain imaging at medium-term follow-up.

Successful treatment of severe calcium channel blocker poisoning, new experience with the guidance of invasive hemodynamic monitoring in a 17-year-old girl: a case report.

BACKGROUND: Calcium channel blocker poisoning is one of the most lethal cardiac drugs overdoses. Calcium and high-dose insulin infusion are the first-line therapy for symptomatic patients, and Intralipid emulsion infusion is useful for refractory cases. CASE PRESENTATION: In this report, we describe a 17-year-old Iranian girl who took 250 mg of the drug for a suicidal attempt and presented with refractory hypotension and non-cardiogenic pulmonary edema treated successfully with the guidance of invasive hemodynamic parameters. CONCLUSION: For complicated cases, in addition to supportive care and adjuvant therapy such as high-dose insulin and Intralipid, it is mandatory to utilize advanced hemodynamic monitoring to treat hypotension in severe calcium channel blocker poisoning to guide the treatment.

Prevalence of congenital heart disease according to the echocardiography findings in 8145 neonates, multicenter study in southern Iran.

Introduction: Congenital heart disease (CHD), the lethal congenital anomaly in newborns, is multifactorial, with environmental and genetic factors contributing to its occurrence. Although some studies on the prevalence of CHD have been conducted throughout the country, this large-scale study aims to provide information on the prevalence of various types of CHDs in newborns according to the echocardiography findings. Patients and Methods: Over 3 years, 8145 neonates with suspected CHD who underwent echocardiography by a trained pediatric cardiologist were included in this multicenter, cross-sectional observational study. CHD was categorized into two major groups; cyanotic and acyanotic heart disease. The SPSS version 22 software was used to analyze the data with a significance level set at 0.05. Results: Of 8145 neonates who were referred to our centers with CHD symptoms, 6307 were indicated for echocardiography. The mean age of the studied population was 8.5 ± 9.3 days and the male-to-female ratio was 2.6, especially in the arterial septal defect (ASD), ventricular septal defect (VSD), and patent ductus arteriosus (PDA) groups. 77.2% of patients had acyanotic heart disease (100 in 1000 neonates) with ASD as the most common one and 9% were diagnosed with cyanotic heart disease (11 in 1000 neonates) with transposition of the great arteries as the most common form and the aortopulmonary window was the rarest form. Conclusion: This large prospective, multicenter screening study reported arterial septal defect (85%) and patents with ductus arteriosus (32%) as the most frequent type of CHD. Moreover, the prevalence of male patients was significantly higher. This information would be helpful for health policy makers, stakeholders, and general practitioners in regions where there are no trained pediatric cardiologist fellowships and limited access to echocardiography devices for better management of CHD.

Q wave in paediatric myocarditis: an underinvestigated, readily available prognostic factor.

BACKGROUND: Myocarditis is an uncommon disease in children with potentially fatal consequences. An electrocardiogram (ECG) change seen in myocarditis is pathological Q wave. Pathological Q wave is linked to permanent damage and myocardial death in several cardiac diseases. We investigated the significance of pathological Q waves in children with acute myocarditis (AM). METHODS: This retrospective observational study analysed the data of 59 children with AM admitted to our hospital between January 2016 and July 2021. They were divided into Q wave and non-Q wave myocarditis groups. Patients' laboratory data, echocardiography, treatment and hospital outcome were analysed. RESULTS: Patients were 64.4% male and had a median age of 6 years and 9 months. Pathological Q waves were found in 52.5% of the patients. Q wave myocarditis group had higher troponin I values (499 vs. 145 ng/L, p = 0.011) and longer hospital stays (13 vs. 9 days, p = 0.020) than the non-Q wave group. They also required higher doses of inotropic or vasoactive drugs. 61.3% of Q wave patients needed mechanical ventilation compared to 35.7% of non-Q wave patients (p = 0.069). All the patients who died or discharged with an LVEF < 30% belonged to the Q wave group. CONCLUSION: Q wave in AM warrants close monitoring and intensive treatment as it accompanies more severe complications and poorer outcomes. This readily available ECG finding can be a clue to prognoses of AM patients. Further research with larger populations is needed to better understand Q wave prognostic accuracy and its potential role in guiding more expensive treatments.

Mitral and aortic valve regurgitation following surgical and transcatheter perimembranous ventricular septal defect closure in children and adolescents: midterm outcomes.

BACKGROUND: Closure of perimembranous ventricular septal defects (pmVSD), either surgical or percutaneous, might improve or cause new-onset mitral regurgitation (MR) and aortic regurgitation (AR). We aimed to evaluate the changes in MR and AR after pmVSD closure by these two methods. MATERIAL AND METHOD: We performed a comparative retrospective data review of all pediatric patients with pmVSDs treated at our institution with surgical or antegrade percutaneous methods from 2014 to 2019 and 146 consecutive patients under 18 years were enrolled. We closely looked at the mitral and aortic valve function after repair. Included patients had no or lower than moderate aortic valve prolapse and baseline normal mitral or aortic valve function or less than moderate MR or AR. RESULTS: Out of 146 patients, 83 (57%) pmVSDs were closed percutaneously, and 63 (43%) pmVSDs were closed surgically. 80 and 62 patients were included for MR evaluation, and 81 and 62 patients for AR evaluation in percutaneous and surgical groups. The mean follow-up time was 40.48 ± 21.59 months in the surgery group and 20.44 ± 18.66 months in the transcatheter group. Mild to moderate degrees of MR and AR did not change or decreased in most patients. In detail, MR of 70% and AR of 50% of the valves were resolved or decreased in both groups. 13% of patients with no MR developed trivial to mild MR, and 10% of patients with no AR showed mild to moderate AR after pmVSD closure in both methods. There was no significant difference between the two methods regarding emerging new regurgitation or change in the severity of the previous regurgitation. CONCLUSION: pmVSD closure usually improves mild to moderate MR and AR to a nearly similar extent in both percutaneous and surgical methods among children and adolescents. It might lead to the onset of new MR or AR in cases with no regurgitation.

Pericardial effusion among children: Retrospective analysis of the etiology and short-term outcome in a referral center in the south of Iran.

Background and Aims: We reinvestigated the causes, symptoms, and management of childhood pericardial effusion (PE) and its gradual changes during recent years in a referral pediatric cardiology center in the south of Iran. Methods: We retrospectively analyzed the profile of PE patients who were under 18 years old from 2015 to 2020. The patient's demographic, clinical, and paraclinical information was extracted and analyzed using SPSS software. Result: In general, 150 out of 63,736 admitted patients (0.23% of the total pediatric admissions) were diagnosed with PE (male/female 1:1.17). The median age was 3.25 years (range:\ 2 days to 18 years; interquartile range: 9.5), and 50% of them were under 3 years of age. 32.6% had moderate to severe PE. Most patients presented with acute symptoms (68%) and respiratory problems, as the most common symptoms (30.6%). Tamponade signs were presented in 2% (n = 3) of the patients, and 80.7% (n = 121) were in a stable hemodynamic condition. In total, renal failure (22%) and parapneumonic effusion were the leading etiologies. Viral (7%) and bacterial (5%) pericarditis were the seventh and eighth causes; however, in severe cases, renal failure (22%) and bacterial pericarditis (14%) were dominant. In total, 14.1% (n = 21) of the patients needed pericardiocentesis that increased to 78.3% (n = 18) in severe cases. Only 6% had persistent PE for more than 3 months. Conclusion: Childhood PE is mostly a result of renal failure and noninfectious causes. True pericarditis cases are not common, except in severe cases. It is more common in less than 3-year-old patients, and chronicity is rare. Severe cases had a high chance of pericardiocentesis, but other cases were mainly managed by treatment of the underlying causes.

Effect of coarctation of aorta anatomy and balloon profile on the outcome of balloon angioplasty in infantile coarctation.

OBJECTIVE: Coarctation of the Aorta (CoA) is a relatively common cardiovascular disorder. The present study aimed to evaluate the effect of COA anatomy and high versus low-pressure balloons on the outcome of balloon angioplasty among neonates and infants. METHODS: In this retrospective study, the neonates and infants undergoing balloon angioplasty at Namazi hospital were enrolled. After balloon angioplasty, immediate data results were promptly recorded.Moreover, midterm echocardiographic information was collected via electronic cardiac records of pediatric wards and clinical and echocardiographic data at least 12 months after balloon angioplasty. Finally, data were analyzed using SPSS-20. RESULTS: In this study, 42 infants were included. The median age at the time of balloon angioplasty was 1.55 (range 0.1-12) months and 66.7% of the patients were male. The mean pressure gradient of coarctation was 38.49 ± 24.97 mmHg, which decreased to 7.61 ± 8.00 mmHg (P < 0.001). A high-pressure balloon was used in 27, and a low-pressure balloon was used in 15 patients. COA's pressure gradient changed 30.89 ± 18.06 in the high-pressure group and 24.53 ± 20.79 in the low-pressure balloon group (P = 0.282). In the high-pressure balloon group, 14.81% and in the low-pressure group, 33.33% had recoarctation and need second balloon angioplasty (p < 0.021). The infant with discrete coarctation had a higher decrease in gradient and lower recoarctation. CONCLUSION: Recoarctation rate was lower in the high-pressure balloon. The infant with discrete COA had a better response to the balloon with more decrease in gradient and lower recoarctation rate. Therefore, the stenotic segment anatomy needs to be considered in the selection of treatment methods.

Age-adjusted Reference Values and Z-scores of the Coronary Sinus Diameter among Healthy Children and Adolescents in Southern Iran.

BACKGROUND: Coronary sinus dimension is an important factor for diagnosing some types of cyanosis as well as congenital heart diseases and insertion of some devices into the coronary sinus if required. This study was designed to access the diameter and Z-score of the coronary sinus among children under 18 years of age. METHODS: In this cross-sectional study on 95 individuals, the coronary sinus diameter was measured by transthoracic echocardiography in the four-chamber view at the connection to the right atrium, middle part, and distal end. The linear regression equation was utilized to determine age-adjust reference values, Z-scores, and the relationship between the individuals' coronary sinus diameter age, height, and body surface area. The study was conducted from March to July 2020 in Namazi hospital clinic of Shiraz University of Medical Sciences, Shiraz, Iran. RESULTS: The mean age of the persons who entered this study was 5.87±4.25 years. The mean coronary sinus diameter was 4.91±1.29 mm at the site of connection to the right atrium, 4.50±1.44 mm at the middle part, and 3.74±1.32 mm at the distal end. Coronary sinus diameter correlates positively with the participants' age, weight, height, and body surface area (P<0.001). CONCLUSION: Coronary sinus diameter significantly correlates with the age, height, and body surface area of the cases. These features are useful in diagnosing some congenital heart diseases and insertion of suitable devices through it.

Midterm follow up of transcatheter closure of coronary artery fistula with Nit-Occlud® patent ductus arteriosus coil.

BACKGROUND: Coronary artery fistula (CAF) is a rare congenital anomaly with a challenging scenario in children. This study reports our experience in transcatheter closure of CAF with Nit-Occlude PDA coil and midterm clinical and imaging follow-up. METHODS: Twelve children with congenital CAF between 2009 and 2019, mean age 2.05 ± 2.05 years (4 days to 7.2 years), mean weight 8.8 ± 4.83 (2.8-17 kg), who underwent transcatheter closure with PFM coil at the Namazi hospital, Shiraz, Iran, were reported. Echocardiography and electrocardiogram were done before and after the procedure (early, 3, and 6 months after), and Multi-slice computerized tomography or conventional coronary angiography was performed at least one year after closure. RESULTS: In a median follow-up of 5.5 years (range 13 months to 8 years), retrogradely closed fistula had no residual, and the fistula tract was wholly occluded, but in most anterogradely closed fistula, had a small residual, which made the fistula tract open and need additional coil closure. CONCLUSIONS: Transcatheter closure of CAF with PFM coil is feasible and effective with low mortality and morbidity, although antegrade closure with this device may be accompanied by residual shunt and need for multiple coil insertion.

Hidden pulmonary arteries in tetralogy of Fallot and pulmonary artery pressure in patients operated with a pulmonary artery.

INTRODUCTION: The absence of a pulmonary artery is a rare congenital anomaly that occurs isolated or with other congenital cardiac disorders, particularly tetralogy of Fallot (TOF); meanwhile, a hidden pulmonary artery might exist and originate from a closed ductus arteriosus (DA), which can be stented to reach the artery. MATERIAL AND METHODS: This prospective study describes cardiac catheterization of nine TOF patients diagnosed with the absence of the left pulmonary artery before the operation. The patients were stratified into three groups: group one, whose closed DA was found and connected to the hidden pulmonary artery with a stent; group two, whose hidden pulmonary arteries were found via the pulmonary vein angiography; and group three, for whom we could not find the remnant of the DA, or our attempt to stent the DA to the hidden pulmonary artery was not successful. We also evaluated outcomes of six other surgically-corrected TOF patients who were operated with the absent left pulmonary artery. RESULTS: The first group included the patients aged 1, 24, and 30 months, whose CT angiography 6-9 months after stenting showed acceptable left pulmonary artery diameter for surgical correction, and the pulmonary vein angiography of the second group showed a hidden left pulmonary artery with a suitable diameter for surgical correction. However, we were unable to find or stent the DA of group three patients, aged 12, 38, 60, and 63 months. Earlier Angiography might have increased the chance of access to the hidden vessel. Apart from these three groups, follow-ups of six other patients previously corrected with only the right pulmonary artery revealed pulmonary artery hypertension in all patients. CONCLUSION: The concealed pulmonary artery might be found, and stenting of the closed DA to it might be performed to improve the diameter of the diminutive pulmonary artery. This procedure may allow TOF total surgical correction with two pulmonary arteries. Besides, pulmonary vein angiography can reveal the hidden pulmonary artery.

Hemolysis and its outcome following percutaneous closure of cardiac defects among children and adolescents: a prospective study.

BACKGROUND: Transcatheter closure of intracardiac defects might be complicated by intravascular hemolysis. We evaluated hemolysis and its outcome after transcatheter closure of these defects. METHODS AND PATIENTS: All patients who underwent transcatheter closure of patent ductus arteriosus, ventricular septal defect and atrial septal defect were included in this prospective study. Clinical data were obtained before and after the catheterization. RESULTS: One hundred and thirty-eight patients were enrolled; and four (3%) patients developed intravascular hemolysis; while two cases had residual shunt and two other cases had not residual flow. Although residual shunt occurred in ten patients, only 2 of these cases developed hemolysis. Patent ductus arteriosus closure was done for one of these cases and the other one, underwent perimembranous ventricular septal defect closure. Moreover, hemolysis occurred after device closure of patent ductus arteriosus in 2 of the other patients with no residual shunt. In this study the hemolysis was eliminated by conservative management within 2 weeks although residual shunt continued in this time. We observed a decline in lactate dehydrogenase value after catheterization in comparison with precatheterization, which was mainly among ventricular septal defect patients that might be due to mild chronic hemolysis in these patients. CONCLUSION: Incidence of hemolysis after device closure was low, and occurred with and without residual flow and was eliminated by conservative management in 2 weeks, without the need for surgery, although the residual shunt was continued.

Effect of Hemodialysis on Global and Regional Cardiac Function in Children With End-stage Renal Disease.

INTRODUCTION: Changes in cardiac structure and function are common among patients with end-stage renal disease. The aim of this study was to evaluate the effect of hemodialysis on global and segmental cardiac function in children with end-stage renal disease. MATERIALS AND METHODS: Fifty-two children with ESRD who were on long-term hemodialysis at Nemazee Hospital, Shiraz, were enrolled. They underwent echocardiography (M-mode, 2-dimensional, Doppler, and speckle echocardiography) 30 minutes prior to and after hemodialysis, and the values were compared. RESULTS: The mean age of the patients was 13.00 ± 3.53 years. There was a significant reduction in left ventricular systolic and diastolic dimensions and volume (P < .001) and the E:A ratio after dialysis (P = .03). Global and longitudinal strain and strain rate showed no significant changes before and after hemodialysis. CONCLUSIONS: Hemodialysis with volume reduction decreases left ventricular volume but not regional strain and strain rate significantly in children. This study showed preload independency of speckle echocardiography in children.

Noninvasive Assessment of Pulmonary Artery Pressure in Patients with Extracardiac Conduit Total Cavopulmonary Connection.

To assess quantitative measurement of mean pulmonary artery pressure (PAP) in extracardiac total cavopulmonary connection (TCPC) patients by noninvasive echocardiographic inferior vena cava collapsibility index (IVC-CI) and also correlation between the peripheral vein pressure and mean PAP. In 19 TCPC patients with at least 1-year follow-up after completion of TCPC, complete echocardiography including IVC-CI was recorded. All patients underwent cardiac catheterization for mean PAP pressure, peripheral vein pressure (PVP) and contrast study. Different cutoff points of mean PAP were analyzed, and based on the highest cutoff point, patients were categorized into two groups: mean PAP < 17 mmHg (acceptable) and > = 17 mmHg (high) for comparison analysis. Between 2006 and 2015, from 43 patients who had undergone TCPC, nineteen patients with a mean age 12.9 ± 6.6 years and mean follow-up time of 3.4 ± 1.9 years were included in this study. Mean PAP was 14.6 ± 3.97 (range 8-22 mmHg). Thirteen (68 %) patients had PAP < 17 mmHg. No significant statistical difference was detected with respect to age, sex, type of congenital heart disease and fenestration between these two groups. But, right ventricular dominancy was more prevalent in the high PAP group (50 % vs. 7.7 % P value 0.03). IVC-CI had a correlation with mean PAP (r 0.67, P < 0.001). IVC-CI < 21.8 % can predict PAP > = 17 mmHg with 83 % sensitivity and 100 % specificity. Regression analysis proposed an equation for PAP measurement: PAP (mmHg) = 20.2097-0.1796 × (IVC-CI), (r2 = 0.56). Peripheral vein pressure measurement also showed a good correlation with mean PAP and may be used to estimate PAP with the following equation: PAP (mmHg) = 0. 8675 × PVP, (r 0.90, P < 0.0001). In conclusion, IVC-CI as noninvasive and peripheral vein pressure measurement as a minimal invasive method may be useful for quantitative estimation of PAP in patients with extracardiac TCPC.