From Other Journals: A Review of Recent Articles by Our Editorial Team.

In this review, we provide a brief description of recently published articles addressing topics relevant to pediatric cardiologists. Our hope is to provide a summary of the latest articles published recently in other journals in our field. The articles address (1) A new index for prenatal diagnosis of total anomalous pulmonary venous return, (2) Outcomes of patients with Tetralogy of Fallot after pulmonary valve replacement (PVR), and (3) Short-term outcomes of the self expanding Harmony valve for transcatheter PVR.

Review of cardiac safety in onasemnogene abeparvovec gene replacement therapy: translation from preclinical to clinical findings.

Human gene replacement therapies such as onasemnogene abeparvovec (OA) use recombinant adeno-associated virus (rAAV) vectors to treat monogenic disorders. The heart and liver are known target organs of toxicity in animals; with cardiac and hepatic monitoring recommended in humans after OA dosing. This manuscript provides a comprehensive description of cardiac data from preclinical studies and clinical sources including clinical trials, managed access programs and the post-marketing setting following intravenous OA administration through 23 May 2022. Single dose mouse GLP-Toxicology studies revealed dose-dependent cardiac findings including thrombi, myocardial inflammation and degeneration/regeneration, which were associated with early mortality (4-7 weeks) in the high dose groups. No such findings were documented in non-human primates (NHP) after 6 weeks or 6 months post-dose. No electrocardiogram or echocardiogram abnormalities were noted in NHP or humans. After OA dosing, some patients developed isolated elevations in troponin without associated signs/symptoms; the reported cardiac adverse events in patients were considered of secondary etiology (e.g. respiratory dysfunction or sepsis leading to cardiac events). Clinical data indicate cardiac toxicity observed in mice does not translate to humans. Cardiac abnormalities have been associated with SMA. Healthcare professionals should use medical judgment when evaluating the etiology and assessment of cardiac events post OA dosing so as to consider all possibilities and manage the patient accordingly.

From Other Journals: A Review of Recent Articles by Our Editorial Team.

In this review, we provide a brief description of recently published articles addressing topics relevant to pediatric cardiologists. This review includes (1) Fetal diagnosis, associated anomalies, and factors affecting outcomes in fetal congenitally corrected transposition of the great arteries (ccTGA), (2) The impact of Fontan-associated liver disease on heart and heart/liver transplant, (3) 1-year outcomes of the Harmony transcatheter pulmonary valve, (4) Risk factors associated with major adverse cardiac events in patients with pulmonary atresia and intact ventricular septum undergoing intervention, and (5) Benefits of pulmonary valve replacement in tetralogy of Fallot patients.

Topsy-Turvy Heart with Aortopulmonary Window and Severe Airway Malacia: Prenatal Diagnosis and Review of the Literature.

The topsy-turvy heart is a very rare cardiac malformation that involves a global 90° clockwise rotation of the heart along its long axis. This rotation results in the displacement of the great arteries and severe elongation and stretching of the brachiocephalic arteries and the bronchi. We present an unusual case of topsy-turvy heart diagnosed prenatally with a large aorto-pulmonary window and. This case gives an insight into the morphological details and clinical presentation of this rare malformation and its associated complications. We also present a review of the literature of this rare anomaly showing only 15 live cases that have been published with only three cases diagnosed prenatally.

COVID-19 related multisystem inflammatory syndrome in children (MIS-C): a case series from a tertiary care pediatric hospital in Qatar.

BACKGROUND: Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of coronavirus disease 2019 (COVID-19) in children, which is increasingly being reported worldwide. Here we report the first case series of 7 children diagnosed with MIS-C in Qatar. METHODS: Clinical features and outcomes of COVID-19 positive patients admitted to Sidra Medicine, Qatar from June to October 2020, who met the WHO case definition for MIS-C were reviewed. RESULTS: The mean age in our case series was 5.6 years, of which 71.4% were males. All patients were previously healthy but had a history of COVID-19 infection. Fever, rash, vomiting and abdominal pain were the most common symptoms (70-100%). The average hospitalization was 12.9 days with no case fatalities. Laboratory findings included lymphopenia and thrombocytopenia in most patients, as well as evidence of coagulopathy and elevated inflammatory markers such as C-reactive protein, ferritin and procalcitonin. Many patients (71.4%) required inotropic support in intensive care, while only one required respiratory support. Although all patients had elevated cardiac biomarkers, cardiovascular involvement was observed in 42.9% of patients with one patient developing a giant coronary aneurysm. All patients received intravenous immunoglobulin (IVIG) and 86% of patients received corticosteroids, with two patients requiring treatment with IL-1 inhibitors. CONCLUSIONS: Our report is one of the first reports on MIS-C from Asia. Although clinical features and outcomes are not significantly different from those reported elsewhere, lack of case fatalities in our cohort may indicate that early recognition and prompt medical attention is necessary for a favorable outcome in MIS-C.

Preclinical comparative assessment of a dedicated pediatric poly-L-lactic-acid-based bioresorbable scaffold with a low-profile bare metal stent.

BACKGROUND: Polymer-based bioresorbable scaffolds (PBBS) have been assessed for coronary revascularization with mixed outcomes. Few studies have targeted pediatric-specific scaffolds. We sought to assess safety, efficacy, and short-term performance of a dedicated drug-free PBBS pediatric scaffold compared to a standard low-profile bare metal stent (BMS) in central and peripheral arteries of weaned piglets. METHODS: Forty-two devices (22 Elixir poly-L-lactic-acid-based pediatric bioresorbable scaffolds [BRS] [6 × 18 mm] and 20 control BMS Cook Formula 418 [6 × 20 mm]) were implanted in the descending aorta and pulmonary arteries (PAs) of 14 female Yucatan piglets. Quantitative measurements were collected on the day of device deployment and 30 and 90 days postimplantation to compare device patency and integrity. RESULTS: The BRS has a comparable safety profile to the BMS in the acute setting. Late lumen loss (LLL) and percent diameter stenosis (%DS) were not significantly different between BRS and BMS in the PA at 30 days. LLL and %DS were greater for BRS versus BMS in the aorta at 30 days postimplantation (LLL difference: 0.96 ± 0.26; %DS difference: 16.15 ± 4.51; p < .05). At 90 days, %DS in the aortic BRS was less, and PA BRS LLL was also less than BMS. Histomorphometric data showed greater intimal proliferation and area stenosis in the BRS at all time points and in all vessels. CONCLUSIONS: A dedicated PBBS pediatric BRS has a favorable safety profile in the acute/subacute setting and demonstrates characteristics that are consistent with adult BRSs.

Prenatal Diagnosis of Isolated Atrioventricular Discordance and Ventriculoarterial Concordance and Double-Outlet Right Ventricle in Situs Inversus: Case Report and Review of the Literature.

Atrioventricular (AV) discordance and ventriculoarterial (VA) concordance in the setting of visceral situs inversus are one of the rarest forms of cardiac malformations. To our knowledge, this is the first reported case of prenatal diagnosis of such rare cardiac anatomy in association with double-outlet right ventricle on fetal echocardiography. The physiology of this cardiac anomaly is similar to that of transposition of the great arteries, and the best surgical option is the atrial switch operation.

Hepatitis C-Positive Donors in Cardiac Transplantation: Problems and Opportunities.

PURPOSE OF REVIEW: With the growing need for donor hearts and longer transplant waiting lists, there is a growing interest in expanding the donor pool by reconsidering previously excluded donor candidates. There has been an increase in solid organ availability due to drug overdose deaths in the setting of the recent opioid epidemic. However, these donors often have transmissible infections such as hepatitis C. In this review, we discuss the challenges associated with heart transplantation from hepatitis C-infected donors as well as the recent advancements that are making the use of these organs possible. RECENT FINDINGS: With the introduction and widespread use of nucleic acid testing (NAT), the ability to distinguish viremic donors and those that have cleared the virus has become a reality. In addition, with the emergence of direct antiviral agents, there is an increase in data showing the short-term outcomes and success of hepatitis C treatment for recipients of viremic donor hearts. As techniques to distinguish donor hepatitis C infection status and successful treatments emerge, the percentage of accepted hepatitis C donor hearts is increasing. A number of studies showing success with hepatitis C organ transplants present a promising new avenue for organ procurement essential to meet the increasing demand for donor hearts.

Fetal and Postnatal Echocardiographic Diagnosis of Ebstein Anomaly of the Mitral Valve.

Ebstein anomaly of mitral valve (MV) is an extremely rare congenital heart disease. In the current report, we present a case of Ebstein of MV that was diagnosed prenatally. Fetal echocardiogram showed that the posterior leaflet of MV was tethered to the lateral wall of left ventricle (LV) with downward displacement into LV cavity. Postnatal transthoracic and transesophageal echocardiograms confirmed the diagnosis with apical displacement of the level of coaptation MV into the LV cavity. To the best of our knowledge, fetal diagnosis of Ebstein anomaly of MV has not yet been reported in the medical literature.

Routine Cardiac Catheterization Prior to Fontan Operation: Is It a Necessity?

Prior to the Fontan procedure, patients with single ventricle physiology with Glenn shunt are typically referred for cardiac catheterization to assess hemodynamics and potentially provide interventional measures. Currently, echocardiography provides detailed information which together with other non-invasive imaging such as CT scan and MRI may obviate the need for routine cardiac catheterization prior to the Fontan procedure. In this study, we examine the findings in cardiac catheterization in this population to determine: (a) the accuracy of echocardiography in providing adequate information prior to the Fontan procedure, particularly in identifying those in need of per-catheter intervention, and (b) the percentage of patients requiring interventional procedures during cardiac catheterization. We performed a retrospective chart review of echocardiographic and cardiac catheterization data for patients who underwent pre-Fontan cardiac catheterization at our center in the period from 02/01/2008 to 02/28/2017. We aimed to re-examine the necessity of routine cardiac catheterization in all single ventricle patients. This was performed through examining pre-catheterization echocardiography reports and comparing them to findings of the subsequent cardiac catheterization reports. Echocardiography reports were evaluated for accuracy in identifying significant anatomical or hemodynamic findings, which may impact success of Fontan procedure as well as the ability of echocardiography to predict findings important to know prior to the Fontan procedure. In this cohort of 40 children, 3 patients were found to have significant hemodynamic findings through cardiac catheterization which were not previously known by echocardiography. In addition, 28 out of 40 patients (70%) required interventional procedures to address significant abnormalities (systemic to pulmonary arterial collaterals, pulmonary artery stenosis, aortic arch stenosis, etc.). All cases of aortic arch stenosis were detected by echocardiography, however, all patients who required systemic to pulmonary arterial or left SVC embolization were not detected by echocardiography. Furthermore, echocardiography did not detect the need for branch pulmonary artery stenosis in 50% of cases. Cardiac catheterization appears to be an essential part of patient assessment prior to Fontan completion in patients with single ventricle physiology. This current practice may change in the future if a non-invasive screening tool is found to have high positive and negative predictive values in identifying the subset of patients who require potential intervention in pre-Fontan cardiac catheterization.

Use of Speckle Tracking Echocardiography to Assess Left Ventricular Systolic Function in Patients with Surgically Repaired Tetralogy of Fallot: Global and Segmental Assessment.

Patients with repaired Tetralogy of Fallot (rToF) can have significant right and left ventricular dysfunction which can impact clinical outcome. Conventional echocardiographic evaluation using ejection fraction can be limited in detecting early stages of deteriorating left ventricular (LV) systolic function. Speckle-tracking echocardiography (STE) provides a promising emerging tool for early detection of LV systolic dysfunction. The aim of this cross-sectional study is to evaluate the left ventricular global and regional function using STE in rToF patients with preserved left ventricular ejection fraction to detect early signs of LV dysfunction. The study is a retrospective review of the medical records and transthoracic echocardiograms of rTOF patients who were seen in the pediatric cardiology clinic at our institution from August 2016 till May 2018. The rTOF group was compared with a matched healthy control group. Offline strain analysis of TTE studies was completed in each subject according to mode set by the American Society of Echocardiography. Twenty-two patients with rTOF and 22 age-matched controls (rTOF 18.7 ± 6 years and control 14.6 ± 9.6 years, P value 0.19) were included during the study period. The rTOF group consisted of 12 males and 10 females, whereas the control group consisted of 15 males and 7 females. There was no significant difference in terms of LV ejection fraction using both 2-chamber as well as 4-chamber views. Global LV longitudinal strain was significantly lower in the rTOF group compared with the control group (rTOF - 15.92 ± 3.16 vs control - 22.79 ± 2.45, P value 0.00). All 17 segments showed significantly lower longitudinal strains in rTOF group compared with the control group. Global circumferential left ventricle strain was significantly lower in the rTOF patients compared with the control group (- 17.24 ± 5.86 vs - 22.74 ± 3.99, P value 0.001). 13 out of 16 segments had lower circumferential strains in the rTOF patients compared with controls. Asymptomatic surgically repaired TOF patients exhibited abnormal segmental and global left ventricle longitudinal and circumferential strains despite having normal left ventricle ejection fraction. Our findings suggest subclinical damage to the left ventricle systolic function post-surgical repair of TOF. 2-D speckle-tracking echocardiography may be used as a valuable method in the early recognition of left myocardial systolic function impairment in patients after TOF repair. The application of this method to guide clinical decision and management of rTOF patients such as earlier pulmonary valve replacement or risk stratification for sudden cardiac death needs further investigation.

Determination of the Frequency of Right and Left Internal Mammary Artery Embolization in Single Ventricle Patients: A Two-Center Study.

Embolization of systemic to pulmonary artery collaterals to regulate pulmonary arterial flow or pressure of the cavopulmonary circulation in patients with single ventricle is a common practice. The relative incidence and impact of this practice on future interventions like coronary artery bypass grafting is poorly understood. This study aims to evaluate the frequency and implications of internal mammary artery (IMA) embolization in the single ventricle (SV) population. A retrospective chart review was performed of SV patients who underwent cardiac catheterization before and after Fontan procedure between February 2007 and 2017. Data were collected from two tertiary care centers in the Midwest. Of the 304 SV patients, 62 (20.4%) underwent embolization of one or more IMAs, whereas 242 (79.6%) did not. The rate of embolization of IMA was 40.5% in one center and 14.5% in the second center. Among patients who received IMA embolization, left internal mammary artery (LIMA) embolization was seen in 6 (9.7%) patients. Majority of patients underwent either right internal mammary artery (RIMA) embolization (n = 25; 40.3%) or RIMA and LIMA embolization (n = 27; 43.5%). IMA embolization in SV patients is common. Embolizing IMAs early in life will likely eliminate a valuable graft option for coronary artery bypass grafting should it be required in the future care of these patients. Multi-center, prospective, nation-wide studies are warranted to examine coronary artery disease in the SV population and true frequency of IMA embolization. Delineation of which IMAs were embolized is a necessary in surgical and cardiac intervention national data, such as Society of Thoracic Surgeons (STS) database. All measures should be taken to preserve IMAs patency, if deemed feasible and safe.

Hybrid pulmonary artery plication followed by transcatheter pulmonary valve replacement: Comparison with surgical PVR.

Objective/Background Historically, the sole option for patients with a dysfunctional native right ventricular outflow tract (RVOT) requiring re-establishment of pulmonary competence has been surgical PVR. We sought to compare early outcomes of hybrid pulmonary valve replacement (PVR) combining surgical plication of the main pulmonary artery followed by transcatheter PVR, with a contemporary cohort of surgical PVR patients. Methods Retrospective chart analysis of all patients with a dilated native RVOT eligible for surgical PVR over 36 months was performed. The cohorts included patients with previous tetralogy of Fallot repair (n = 14), and previous intervention for congenital abnormality of the pulmonary valve (n = 7). Results Twenty-one patients with a dysfunctional native RVOT met criteria for PVR; 8 using the hybrid procedure (group 1: age, 31.5 +/- 17.4 years) and 13 with cardiopulmonary bypass (CPB) (group 2: age, 31 +/- 18.4 years). Valve delivery was successful in all patients with no procedural mortality. Group 1 had a lesser requirement for blood products (P =< 0.001) and a trend toward shorter hospital stay and higher post-operative hemoglobin. No patients in group 1 received inotropic support post-operatively compared to 54% of patients in group 2. Mean follow-up was 3.4 months for group 1 and 13.6 months for group 2 with the average peak gradient across the RVOT of 20.1 and 15.1 mm Hg respectively (P = 0.12), all with no more than mild PI. Conclusions Transcatheter hybrid PVR following RVOT plication provides a reasonable alternative to surgical PVR particularly in higher risk cohorts, reducing possible longer-term consequences of repeated runs of CPB. © 2016 Wiley Periodicals, Inc.

Surgical repair of left ventricular pseudoaneurysm following perventricular device closure of muscular ventricular septal defect.

Left ventricular pseudoaneurysm formation following perventricular device closure of a muscular ventricular septal defect is a rare complication. We describe a case of left ventricular pseudoaneurysm in an infant with Swiss-cheese ventricular septal defects who initially underwent closure with an Amplatzer device using a hybrid approach. The pseudoaneurysm was successfully resected surgically.

The Use of Speckle Tracking Echocardiography for Early Detection of Myocardial Dysfunction in Patients with Duchenne Muscular Dystrophy.

Cardiac complications are the leading cause of death in patients with Duchenne muscular dystrophy (DMD). Two-dimensional echocardiography is the current standard for monitoring of LV systolic function in these patients, but it might not detect early systolic dysfunction. The current study examined the use of speckle tracking echocardiography (STE) to detect early signs of cardiac dysfunction in DMD patients. A retrospective review of charts and offline strain analysis of transthoracic echocardiographic studies of DMD patients at our institution from April 2014 to January 2015 were performed and compared to age-matched healthy male subjects. Nineteen DMD patients (age range 12.6 ± 3.1 years) with normal ejection fraction and shortening fraction were compared with sixteen controls. The global circumferential strain was lower in DMD patients compared with controls (-14.7 ± 4.7 vs. -23.1 ± 2.9 %, respectively, p value: 0.001). Circumferential strain measured at basal, mid-ventricular and apical parasternal short-axis views was lower in DMD patients compared with controls. Segmental circumferential strain was lower in DMD patients in most segments compared with controls. The global longitudinal strain was lower in DMD patients compared with controls (-13.6 ± 5 vs. -18.8 ± 3 %, respectively, p value: 0.001). Segmental longitudinal strain measured in various segments was lower in DMD patients compared with controls. DMD patients can have occult cardiovascular dysfunction as shown by reduction in circumferential and longitudinal strain measurements with STE despite normal standard echocardiographic parameters. The clinical significance of early detection of cardiac dysfunction in these patients warrants further studies.

Extended Application of the Hybrid Procedure in Neonates with Left-Sided Obstructive Lesions in an Evolving Cardiac Program.

The hybrid approach to management of hypoplastic left heart syndrome (HLHS) was developed as an alternative to neonatal Norwood surgery, providing a less invasive initial palliation for HLHS. We describe our experience in extending the concept of the hybrid procedure to palliate neonates with anatomically compromised systemic arterial blood flow in a variety of congenital cardiac anomalies and supporting its application as first-line palliation in centers developing their HLHS programs. Retrospective review of patients undergoing therapy for HLHS at a single institution from June 2008 to December 2014 was performed. Subject demographics, clinical and procedural data, along with follow-up, were collected. Thirteen patients had initial hybrid palliation for HLHS during the time frame indicated at a median age of 8 days (range 1-29 days) and median weight of 3.4 kg (range 2.4-4.6 kg). Diagnoses included typical HLHS (n = 6), right-dominant unbalanced atrioventricular septal defect with arch hypoplasia (n = 4), double outlet right ventricle [subpulmonic VSD (n = 1) and intact ventricular septum (n = 1)] with hypoplastic transverse aortic arch and borderline left ventricular dimensions. Standard approach with bilateral pulmonary artery banding and ductal stenting was carried out in all thirteen patients. Two patients required two ductal stents at the time of index procedure. There were no intraprocedural complications. Median intubation length post-procedure was 4 days (range 1-74 days). Median hospital stay post-procedure was 47 days (range 15-270 days). The overall mortality rate on follow-up through comprehensive stage 2 over the 6-year experience was 38 % (5 out of 13). Of note, the mortality rate was significantly lower in the latter 3 years of the study period when the procedure was adopted as a primary palliation for HLHS (14 % or 1 out of 7) compared to the initial 3-year period when it was reserved for higher risk cohorts (67 % or 4 out of 6). Median time to subsequent surgery was 3 months (range 1-4 months). One patient required further ductal stenting on follow-up and developed subsequently airway compression. On median follow-up of 24 months, two patients required pulmonary artery arterioplasty. The hybrid procedure may be used for palliation for a variety of cardiac lesions to avoid high-risk surgery in the neonatal period. This approach may be also an alternative in centers performing lower number of Norwood surgery, which has been associated with higher mortality.

Research in congenital heart disease: a comparative bibliometric analysis between developing and developed countries.

Congenital heart disease (CHD) is the most common congenital anomaly, affecting 1 % of live births. The field of pediatric cardiology has witnessed major advances over the past 25 years triggered by research initiatives focusing on CHD. However, large disparities exist in research capabilities between Arab developing nations and the developed nations. This study used bibliometric analysis to assess the contribution of the Arab countries to CHD research. To identify articles on CHD published in the Arab countries, the United States, and Europe, a systematic search was run on MEDLINE, PubMed, and Scopus. The Arab countries, with an estimated population of 362 million, published 530 research articles addressing CHD in the last 25 years (average, 1.5 articles/10(6) population). This compares with 12,936 research articles published in the United States (average, 41 articles/10(6) population) and 12,260 published in Europe (average, 24.3 articles/10(6) population). Basic research relating to genetics and animal models of CHD is emerging sparsely in the Arab world, with few articles published in high-impact-factor journals. The Arab world research output in the field of CHD per capita is substantially low, estimated to be 29 times less than in developed countries. Despite the minimal increase in published research articles in global periodicals, most of the research relating to CHD continues to be far from innovative. Regional collaborations with international linkage are starting to evolve. The research facilities in the Arab countries need to increase substantially in research and infrastructure funding to keep up with the pace of research in developing countries.

Rupture of sinus of Valsalva aneurysm with aorto-biventricular fistulas and right-ventricular outflow tract obstruction: a unique association.

Sinus of Valsalva aneurysms are a rare entity. Rupture of such aneurysms is a major cause of aortocardiac fistulas usually occurring between the right sinus of Valsalva and right cardiac chambers. We report an exceptional case of a ruptured congenital sinus of Valsalva aneurysm with fistulas involving both the right- and left-ventricular outflow tracts and causing RVOT obstruction. We also demonstrate the utility of computed tomography angiography and transesophageal echocardiography in diagnosing these fistulas.

Pulmonary hypertension in pregnancy and its effects on the fetus.

Pulmonary hypertension (PH) is an important and potentially lethal diagnosis for pregnant patients. Although pregnancy is usually contraindicated in this condition and there is no standard algorithm for the treatment of pregnant patients with PH, studies in recent years have shown improvement in maternal outcomes for those with PH. Many factors have likely contributed to the improved outcomes, including earlier treatment by multidisciplinary teams. Pregnant patients with PH require specialized management throughout pregnancy, especially in the early post-partum period. Echocardiography is an important diagnostic tool to follow cardiac function in these patients. PH and its treatment during pregnancy has significant implications on maternal as well as fetal outcomes. In this review, PH management during pregnancy and the fetal implications are summarized.