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.

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.

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.

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.

Update on shunt closure in neonates and infants.

Introduction: Cardiac defects that result in shunting are the most common types of congenital heart anomalies. Although these lesions can be simple, they can cause significant hemodynamic changes and can be challenging to manage in neonates and infants. Over the recent decades, the development of new transcatheter techniques and devices has made it safe and feasible to manage such defects when indicated, even in the smallest of patients. Understanding these interventional procedures is essential in order to manage those patients.Areas covered: In this article, we review the techniques and experience for closure of atrial septal defects, ventricular septal defects, patent ductus aarteriosus,as well as coronary arteriovenous malformations and fistulas in neonates and infants. Literature review of PubMed articles was performed through January 2021, with focus on the latest data and results of the usage of interventional techniques in treating these lesions specifically in this age-group.Expert opinion: Significant shunting lesions can be particularly challenging to manage in neonates and infants. Newer lower profile devices will likely continue to be developed in the future, allowing their use for transcatheter interventions in even smaller patients and those with more complex anatomy.

The Emergency Department Crash Cart: A systematic review and suggested contents.

BACKGROUND: As the field of Emergency Medicine grows worldwide, the importance of an Emergency Department Crash Cart (EDCC) has long been recognized. Yet, there is paucity of relevant peer-reviewed literature specifically discussing EDCCs or proposing detailed features for an EDCC suitable for both adult and pediatric patients. METHODS: The authors performed a systematic review of EDCC-specific literature indexed in Pubmed and Embase on December 20, 2016. In addition, the authors reviewed the 2015 American Heart Association (AHA) guidelines for cardiopulmonary resuscitation and emergency cardiovascular care, the 2015 European Resuscitation Council (ERC) guidelines for resuscitation, and the 2013 American College of Surgeons (ACS) Advanced Trauma Life Support (ATLS) 9th edition. RESULTS: There were a total of 277 results, with 192 unique results and 85 duplicates. After careful review by two independent reviewers, all but four references were excluded. None of the four included articles described comprehensive contents of equipment and medications for both the adult and pediatric populations. This article describes in detail the final four articles specific to EDCC, and proposes a set of suggested contents for the EDCC. CONCLUSION: Our systematic review shows the striking paucity of such a high impact indispensable item in the ED. We hope that our EDCC content suggestions help enhance the level of response of EDs in the resuscitation of adult and pediatric populations, and encourage the implementation of and adherence to the latest evidence-based resuscitation guidelines.

Development of quality metrics for ambulatory care in pediatric patients with tetralogy of Fallot.

OBJECTIVE: The objective of this study was to develop quality metrics (QMs) relating to the ambulatory care of children after complete repair of tetralogy of Fallot (TOF). DESIGN: A workgroup team (WT) of pediatric cardiologists with expertise in all aspects of ambulatory cardiac management was formed at the request of the American College of Cardiology (ACC) and the Adult Congenital and Pediatric Cardiology Council (ACPC), to review published guidelines and consensus data relating to the ambulatory care of repaired TOF patients under the age of 18 years. A set of quality metrics (QMs) was proposed by the WT. The metrics went through a two-step evaluation process. In the first step, the RAND-UCLA modified Delphi methodology was employed and the metrics were voted on feasibility and validity by an expert panel. In the second step, QMs were put through an "open comments" process where feedback was provided by the ACPC members. The final QMs were approved by the ACPC council. RESULTS: The TOF WT formulated 9 QMs of which only 6 were submitted to the expert panel; 3 QMs passed the modified RAND-UCLA and went through the "open comments" process. Based on the feedback through the open comment process, only 1 metric was finally approved by the ACPC council. CONCLUSIONS: The ACPC Council was able to develop QM for ambulatory care of children with repaired TOF. These patients should have documented genetic testing for 22q11.2 deletion. However, lack of evidence in the literature made it a challenge to formulate other evidence-based QMs.

Development of Quality Metrics in Ambulatory Pediatric Cardiology.

The American College of Cardiology Adult Congenital and Pediatric Cardiology (ACPC) Section had attempted to create quality metrics (QM) for ambulatory pediatric practice, but limited evidence made the process difficult. The ACPC sought to develop QMs for ambulatory pediatric cardiology practice. Five areas of interest were identified, and QMs were developed in a 2-step review process. In the first step, an expert panel, using the modified RAND-UCLA methodology, rated each QM for feasibility and validity. The second step sought input from ACPC Section members; final approval was by a vote of the ACPC Council. Work groups proposed a total of 44 QMs. Thirty-one metrics passed the RAND process and, after the open comment period, the ACPC council approved 18 metrics. The project resulted in successful development of QMs in ambulatory pediatric cardiology for a range of ambulatory domains.

Device closure of congenital ventricular septal defects.

Ventricular septal defect is the most common congenital heart malformation. Surgical closure, when indicated, has been practiced for over 50 years with good results; however, surgical closure is still associated with significant morbidity and mortality. Over the past decade, several occluding devices have been developed that made catheter device closure an attractive alternative to surgery with widely satisfactory results. In this article, a comprehensive review of percutaneous and perventricular (hybrid) device closure of each type of ventricular septal defect is presented.

Device closure of muscular ventricular septal defects in infants less than one year of age using the Amplatzer devices: feasibility and outcome.

OBJECTIVES: In this study, we evaluated the feasibility, safety, and outcome of device closure of muscular ventricular septal defects (mVSD) in infants less than 1 year of age using the Amplatzer devices. BACKGROUND: Closure of mVSDs continues to represent a surgical challenge with significant morbidity. Hence, device closure is becoming an attractive and reliable alternative. However, little is known about the feasibility of this procedure in small infants. METHODS: Between July 1999 and September 2006, device closure of mVSD was attempted in 20 infants ranging in age from 3 days to 12 months (median +/- SD; 4.6 +/- 3.8) and in weight from 3.2 to 8.9 kg (4.6 +/- 1.9) under TEE guidance by percutaneous or hybrid (perventricular) techniques. The size of the VSD as assessed by TEE ranged from 3 to 11 mm (6.0 +/- 2.2) and the Qp:Qs ratio ranged from 0.7 to 8.8 (2.8 +/- 2.3). RESULTS: The device was successfully placed in 19/20 infants and it ranged in size from 4 to 14 mm (8.0 +/- 2.6). It was percutaneously deployed in 11/19 and by the hybrid approach in 8/19. There were 30 devices placed in 19 infants with multiple devices placed in 5/19 infants. Fluoroscopy times ranged from 11 to 136 min (41 +/- 28) and procedure times ranged from 57 to 291 min (178 +/- 68). The success rate as defined by complete closure or a trivial shunt was 84% immediately and 100% at 1-year follow-up. Major complications occurred in 4/20 patients: wire perforation and hemopericardium (n = 1), device migration (n = 1), transient electromechanical dissociation (n = 1), and mediastinitis (n = 1). At a median follow-up of 3.8 years, all patients improved and had no hemodynamically significant VSDs. No major complications were encountered in patients with multiple devices. CONCLUSION: In infants less than 1 year of age, percutaneous and perventricular device closure of mVSDs is technically feasible and highly effective with low morbidity. Long term safety and efficacy needs to be assessed.