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.

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.

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.

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.

Outcome of Antibody-Mediated Fetal Heart Disease With Standardized Anti-Inflammatory Transplacental Treatment.

Background Transplacental fetal treatment of immune-mediated fetal heart disease, including third-degree atrioventricular block (AVB III) and endocardial fibroelastosis, is controversial. Methods and Results To study the impact of routine transplacental fetal treatment, we reviewed 130 consecutive cases, including 108 with AVB III and 22 with other diagnoses (first-degree/second-degree atrioventricular block [n=10]; isolated endocardial fibroelastosis [n=9]; atrial bradycardia [n=3]). Dexamethasone was started at a median of 22.4 gestational weeks. Additional treatment for AVB III included the use of a ß-agonist (n=47) and intravenous immune globulin (n=34). Fetal, neonatal, and 1-year survival rates with AVB III were 95%, 93%, and 89%, respectively. Variables present at diagnosis that were associated with perinatal death included an atrial rate <90 beats per minute (odds ratio [OR], 258.4; 95% CI, 11.5-5798.9; P<0.001), endocardial fibroelastosis (OR, 28.9; 95% CI, 1.6-521.7; P<0.001), fetal hydrops (OR, 25.5; 95% CI, 4.4-145.3; P<0.001), ventricular dysfunction (OR, 7.6; 95% CI, 1.5-39.4; P=0.03), and a ventricular rate <45 beats per minute (OR, 12.9; 95% CI, 1.75-95.8; P=0.034). At a median follow-up of 5.9 years, 85 of 100 neonatal survivors were paced, and 1 required a heart transplant for dilated cardiomyopathy. Cotreatment with intravenous immune globulin was used in 16 of 22 fetuses with diagnoses other than AVB III. Neonatal and 1-year survival rates of this cohort were 100% and 95%, respectively. At a median age of 3.1 years, 5 of 21 children were paced, and all had normal ventricular function. Conclusions Our findings reveal a low risk of perinatal mortality and postnatal cardiomyopathy in fetuses that received transplacental dexamethasone±other treatment from the time of a new diagnosis of immune-mediated heart disease.

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.

A History of Heart Failure Is an Independent Risk Factor for Death in Patients Admitted with Coronavirus 19 Disease.

AIMS: The association between cardiovascular diseases, such as coronary artery disease and hypertension, and worse outcomes in COVID-19 patients has been previously demonstrated. However, the effect of a prior diagnosis of heart failure (HF) with reduced or preserved left ventricular ejection fraction on COVID-19 outcomes has not yet been established. METHODS AND RESULTS: We retrospectively studied all adult patients with COVID-19 admitted to our institution from March 1st to 2nd May 2020. Patients were grouped based on the presence or absence of HF. We used competing events survival models to examine the association between HF and death, need for intubation, or need for dialysis during hospitalization. Of 4043 patients admitted with COVID-19, 335 patients (8.3%) had a prior diagnosis of HF. Patients with HF were older, had lower body mass index, and a significantly higher burden of co-morbidities compared to patients without HF, yet the two groups presented to the hospital with similar clinical severity and similar markers of systemic inflammation. Patients with HF had a higher cumulative in-hospital mortality compared to patients without HF (49.0% vs. 27.2%, p < 0.001) that remained statistically significant (HR = 1.383, p = 0.001) after adjustment for age, body mass index, and comorbidities, as well as after propensity score matching (HR = 1.528, p = 0.001). Notably, no differences in mortality, need for mechanical ventilation, or renal replacement therapy were observed among HF patients with preserved or reduced ejection fraction. CONCLUSIONS: The presence of HF is a risk factor of death, substantially increasing in-hospital mortality in patients admitted with COVID-19.

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.

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.

Long-term outcomes of sinus node modification in patients with severely symptomatic drug-refractory inappropriate sinus tachycardia: a single-center experience.

BACKGROUND: The purpose of the study was to evaluate the long-term outcomes of sinus node modification (SNM) in treating patients with severely symptomatic drug-refractory inappropriate sinus tachycardia (IST). METHODS: The study included 39 patients with symptomatic drug-refractory IST who have undergone SNM at Saint Louis University Hospital. Data was reviewed retrospectively. Recurrence of symptoms was assessed at 3-6-month follow-up intervals. RESULTS: The mean age of our cohort was 31.5 ± 11. The mean HR at diagnosis was 135 ± 25.4 beats per minute (BPM). Thirty-seven of 39 (94.8%) patients had complete resolution of symptoms. Of these 37 patients, 16 required 1 SNM, 17 patients required 2 SNM, and 4 patients required 3 SNM in order to achieve complete symptom resolution. Mean HR post-procedure was 78.6 ± 12.3 BPM. Thirteen of 39 patients required rate control medication post-procedure, all of whom were prescribed beta-blockers. Patients were followed every 3 to 6 months with a mean follow-up duration of 62.3 ± 42.9 months from the patient's last SNM procedure. Thirteen of those 37 patients (35.1%) developed intermittent symptomatic bradycardia requiring permanent pacemaker implantation. Two of the 39 patients had phrenic nerve injury, and 6 patients had post-procedure pericarditis. CONCLUSIONS: This study provides additional information to the limited dataset available in the literature and shows that SNM might provide patients with long-term symptomatic relief bearing in mind the potential increased risk for the need for permanent pacing.

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.

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.

Adherence to Measuring What Matters: Description of an Inpatient Palliative Care Service of an Urban Teaching Hospital.

BACKGROUND: Benefits of palliative care have been extensively described; however, reports on adherence to national quality indicators are limited. OBJECTIVES: This study focuses on describing the characteristics of patients who were seen at an urban academic hospital and their care team's adherence to 5 out of 10 Measuring What Matters (MWM) quality indicators. DESIGN: Retrospective chart review Setting/Subjects: Patients seen by inpatient palliative care service from January 2014 to December 2015 in an urban academic hospital. MEASUREMENTS: Patient age, gender, ethnicity, disease category, discharge end point, life-sustaining preferences, surrogate decision-maker documentation, and initial palliative assessment were analyzed using descriptive, parametric, and nonparametric statistics. RESULTS: During two years, 1272 patients were seen by the inpatient palliative care service. Fifty-one percent of patients were male, with an average age of 68 years. The majority were Caucasian (57%) and African American (41%). Life-limiting illnesses included were cancer, complex chronic illnesses, and gastrointestinal illness. Adherence to comprehensive palliative care assessment was measured at 64%; initial visit assessment for physical symptoms was 38%; code status preference was 99%; care consistent with preference in vulnerable elders was 99%; and surrogate documentation was noted at 33%. Compared to hospital patients discharged without hospice, patients discharged with hospice care had consults with higher adherence to comprehensive assessment and surrogate documentation quality standards (p < 0.05). CONCLUSIONS: Adherence to MWM measures was variable. Subjects discharged with hospice services were more likely to receive comprehensive assessment within 5 days of admission and surrogate documentation compared to those subjects without hospice care.

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.

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.