Toward Eliminating Perinatal Comfort Care for Prenatally Diagnosed Severe Congenital Heart Defects: A Vision.

Over the past 40 years, the medical and surgical management of congenital heart disease has advanced considerably. However, substantial room for improvement remains for certain lesions that have high rates of morbidity and mortality. Although most congenital cardiac conditions are well tolerated during fetal development, certain abnormalities progress in severity over the course of gestation and impair the development of other organs, such as the lungs or airways. It follows that intervention during gestation could potentially slow or reverse elements of disease progression and improve prognosis for certain congenital heart defects. In this review, we detail specific congenital cardiac lesions that may benefit from fetal intervention, some of which already have documented improved outcomes with fetal interventions, and the state-of-the-science in each of these areas. This review includes the most relevant studies from a PubMed database search from 1970 to the present using key words such as fetal cardiac, fetal intervention, fetal surgery, and EXIT procedure. Fetal intervention in congenital cardiac surgery is an exciting frontier that promises further improvement in congenital heart disease outcomes. When fetuses who can benefit from fetal intervention are identified and appropriately referred to centers of excellence in this area, patient care will improve.

Bidirectional Cavopulmonary Shunt for Right Ventricular Unloading.

BACKGROUND: Right-sided heart failure remains a challenge in the care of congenital heart disease patients, both those with right ventricular dilation and dysfunction and those with right ventricular hypoplasia. Two strategies for treatment are atrial septal fenestration and bidirectional cavopulmonary shunt (BCPS). METHODS: This review details the strategies for right ventricular unloading, with summaries of pertinent data and commentaries on the subject. RESULTS: While atrial septal fenestration provides right ventricular unloading and can be appropriate in cases of moderate right ventricular dysfunction and dilation, this unloading is not as substantial as a BCPS. A BCPS more effectively unloads the right ventricle, provides preload to the left ventricle, and can significantly improve ventricular-ventricular interactions. A BCPS is often appropriate in cases of severe right ventricular dysfunction and dilation, if factors favorable for BCPS circulation are in place. Certain anatomic and physiologic factors assessed both preoperatively and intraoperatively help guide the decision regarding which patient may benefit from right ventricular unloading and which technique is optimal. CONCLUSIONS: When used strategically in select patients, BCPS and atrial-level fenestration are effective in managing right ventricular failure in congenital heart disease patients. Preoperative imaging and intraoperative anatomic and physiologic factors help guide the appropriate management for a given patient.

Safety and efficacy of (+)-epicatechin in subjects with Friedreich's ataxia: A phase II, open-label, prospective study.

BACKGROUND: (+)-Epicatechin (EPI) induces mitochondrial biogenesis and antioxidant metabolism in muscle fibers and neurons. We aimed to evaluate safety and efficacy of (+)-EPI in pediatric subjects with Friedreich's ataxia (FRDA). METHODS: This was a phase II, open-label, baseline-controlled single-center trial including 10 participants ages 10 to 22 with confirmed FA diagnosis. (+)-EPI was administered orally at 75 mg/d for 24 weeks, with escalation to 150 mg/d at 12 weeks for subjects not showing improvement of neuromuscular, neurological or cardiac endpoints. Neurological endpoints were change from baseline in Friedreich's Ataxia Rating Scale (FARS) and 8-m timed walk. Cardiac endpoints were changes from baseline in left ventricular (LV) structure and function by cardiac magnetic resonance imaging (MRI) and echocardiogram, changes in cardiac electrophysiology, and changes in biomarkers for heart failure and hypertrophy. RESULTS: Mean FARS/modified (m)FARS scores showed nonstatistically significant improvement by both group and individual analysis. FARS/mFARS scores improved in 5/9 subjects (56%), 8-m walk in 3/9 (33%), 9-peg hole test in 6/10 (60%). LV mass index by cardiac MRI was significantly reduced at 12 weeks (P = .045), and was improved in 7/10 (70%) subjects at 24 weeks. Mean LV ejection fraction was increased at 24 weeks (P = .008) compared to baseline. Mean maximal septal thickness by echocardiography was increased at 24 weeks (P = .031). There were no serious adverse events. CONCLUSION: (+)-EPI was well tolerated over 24 weeks at up to 150 mg/d. Improvement was observed in cardiac structure and function in subset of subjects with FRDA without statistically significant improvement in primary neurological outcomes. SYNOPSIS: A (+)-epicatechin showed improvement of cardiac function, nonsignificant reduction of FARS/mFARS scores, and sustained significant upregulation of muscle-regeneration biomarker follistatin.

Autologous stem cell therapy for hypoplastic left heart syndrome: Safety and feasibility of intraoperative intramyocardial injections.

OBJECTIVES: Staged surgical palliation for hypoplastic left heart syndrome results in an increased workload on the right ventricle serving as the systemic ventricle. Concerns for cardiac dysfunction and long-term heart failure have generated interest in first-in-infant, cell-based therapies as an additional surgical treatment modality. METHODS: A phase 1 clinical trial was conducted to evaluate the safety and feasibility of direct intramyocardial injection of autologous umbilical cord blood-derived mononuclear cells in 10 infants with hypoplastic left heart syndrome at the time of stage II palliation. RESULTS: All 10 patients underwent successful stage II palliation and intramyocardial injection of umbilical cord blood-derived mononuclear cells. Operative mortality was 0%. There was a single adverse event related to cell delivery: An injection site epicardial bleed that required simple oversew. The cohort did not demonstrate any significant safety concerns over 6 months. Additionally, the treatment group did not demonstrate any reduction in cardiac function in the context of the study related intramyocardial injections of autologous cells. CONCLUSIONS: This phase 1 clinical trial showed that delivering autologous umbilical cord blood-derived mononuclear cells directly into the right ventricular myocardium during planned stage II surgical palliation for hypoplastic left heart syndrome was safe and feasible. Secondary findings of preservation of baseline right ventricular function throughout follow-up and normalized growth rates support the design of a phase 2b follow-up trial.

Hypoplastic Left Heart Syndrome: An Overview for Primary Care Providers.

Hypoplastic left heart syndrome is one of the most complex congenital heart diseases and requires several cardiac surgeries for survival. The diagnosis is usually established prenatally or shortly after birth. Each stage of surgery poses a unique hemodynamic situation that requires deeper understanding to manage common pediatric problems such as dehydration and respiratory infections. Careful multidisciplinary involvement in the care of these complex patients is improving their outcome; however, morbidity and mortality are still substantial. In this review, we focus on the hemodynamic aspects of various surgical stages that a primary care provider should know to manage these challenging patients.

Tricuspid Valve Imaging and Intervention in Pediatric and Adult Patients With Congenital Heart Disease.

Tricuspid valve abnormalities in congenital heart disease comprise a wide spectrum, with the most common being Ebstein anomaly and tricuspid valve dysplasia. Tricuspid valve dysfunction may also be secondary to other types of congenital heart disease, including functional tricuspid regurgitation seen in right heart volume overload conditions, such as atrial septal defect and repaired tetralogy of Fallot with severe pulmonary valve regurgitation. Congenitally corrected transposition and Mustard and Senning procedures maintain the right ventricle as the systemic ventricle, and the tricuspid valve is subject to unique hemodynamic stress not typically seen in normal circulation. Surgical treatment of tricuspid valve disease remains the mainstay of therapy; primary catheter-based interventions are uncommon. However, once a tricuspid valve has been replaced with a bioprosthesis, the patient may be a candidate for tricuspid valve-in-valve catheter-based replacement.

Innovative 2-Step Management Strategy Utilizing EXIT Procedure for a Fetus With Hypoplastic Left Heart Syndrome and Intact Atrial Septum.

Hypoplastic left heart syndrome (HLHS) with intact atrial septum (HLHS-IAS) carries a high risk of mortality and affects about 6% of all patients with HLHS. Fetal interventions, postnatal transcatheter interventions, and postnatal surgical resection have all been used, but the mortality risk continues to be high in this subgroup of patients. We describe a novel, sequential approach to manage HLHS-IAS and progressive fetal hydrops. A 28-year-old, gravida 4 para 2 mother was referred to Mayo Clinic for fetal HLHS. Fetal echocardiography at 28 weeks of gestation demonstrated HLHS-IAS with progressive fetal hydrops. The atrial septum was thick and muscular with no interatrial communication. Ultrasound-guided fetal atrial septostomy was performed with successful creation of a small atrial communication. However, fetal echocardiogram at 33 weeks of gestation showed recurrence of a pleural effusion and restriction of the atrial septum. We proceeded with an Ex uteroIntrapartum Treatment (EXIT) delivery and open atrial septectomy. This was performed successfully, and the infant was stabilized in the intensive care unit. The infant required venoarterial extracorporeal membrane oxygenator support on day of life 1. The patient later developed hemorrhagic complications, leading to his demise on day of life 9. This is the first reported case of an EXIT procedure and open atrial septectomy performed without cardiopulmonary bypass for an open-heart operation and provides a promising alternative strategy for the management of HLHS-IAS in select cases.

Cardiac imaging in Ebstein anomaly.

Ebstein anomaly is a congenital disorder of right ventricular myocardial development, which affects the tricuspid valve in addition to the right ventricular myocardium. Cardiac imaging by transthoracic echocardiography and cardiac magnetic resonance imaging are the key modalities used to assess timing and type of surgery. In this article, we review the current standards of echocardiographic and magnetic resonance imaging in Ebstein anomaly.

Lambl's excrescences in children: Improved detection via transthoracic echocardiography.

BACKGROUND: Lambl's excrescences (LE) are fibrous extensions that can be found along the lines of closure of the aortic valve. Due to improvements in ultrasound technology, LE are frequently imaged during transthoracic echocardiography (TTE) in adults. OBJECTIVE: The purpose of this study was to determine the prevalence of LE among children from two eras (2004-2006 and 2011-2012) and the effect of technological advancements on LE detection. METHODS: TTE from 700 subjects (age 18 years old or younger) were reviewed. All parasternal long and short axis images of the aortic valve were reviewed by a board certified echocardiographer, and the positive studies were then reviewed by two additional observers to confirm the presence of LE. A two-sample t test with 95% significance was used to analyze the presence of LE in the cohorts. Median follow-up duration was 66 months. RESULTS: Of the 700 subjects, 12 (1.7%) children were found to have LE. No significant difference in prevalence was found between the two eras (.9% vs. 2.6%, P = .08) and the presence of LE was not related to age (P = .36). The youngest subject with an LE was 5 months old. During long-term follow-up there were no clinical events in the 12 children identified with a LE. CONCLUSIONS: The prevalence of LE in children is lower than that reported in adults, this supports the age-related "wear and tear" process that has been described in previous studies. LE do not require intervention or more aggressive invasive imaging in children.

Two-dimensional measurement of tricuspid annular plane systolic excursion in children: can it substitute for an m-mode assessment?

BACKGROUND: Tricuspid annular plane systolic excursion measured by M-mode (MM-TAPSE) has been validated as a marker of right ventricular systolic performance. A similar measurement by 2D imaging (2D-TAPSE) can be obtained. We sought to determine the correlation and strength of agreement between MM-TAPSE and 2D-TAPSE in children. METHODS: Echocardiographic studies performed for clinical indications were reviewed retrospectively. All consecutive subjects ≤18 years of age were included. The cohort was divided into those with normal echocardiographic findings and those with disorders affecting the right ventricle. Digitally recorded images were analyzed for both MM-TAPSE and 2D-TAPSE. Measurements of 2D-TAPSE were made in an apical four-chamber view, from the tricuspid valve annulus to a consistent point at the apex of the imaging sector at end-diastole and end-systole, with the difference representing the 2D-TAPSE value. RESULTS: A total of 329 subjects (mean age 9.0 ± 6.1 years) met entry criteria. Correlation coefficient between MM-TAPSE and 2D-TAPSE was 0.90. Bland-Altman analysis showed agreement between the two methods to be within 1.2 ± 2.6 mm (mean percentage difference of 6.5%). About 1 mm difference between MM-TAPSE and 2D-TAPSE was consistently observed in all diagnostic subgroups, and across all age categories. CONCLUSION: MM-TAPSE and 2D-TAPSE correlate strongly, with 2D-TAPSE being consistently about 1 mm less than values obtained by the M-mode technique. We conclude that 2D-TAPSE can provide a reliable alternative to MM-TAPSE to quantitatively measure right ventricular systolic function and may be especially useful in situations where retrospective comparisons are sought.

Importance of absent ductus arteriosus in tetralogy of Fallot with absent pulmonary valve syndrome.

Tetralogy of Fallot without pulmonary valve syndrome is almost always associated with an absent ductus arteriosus. Patients with right aortic arch and retroesophageal left subclavian artery have a vascular ring if the left ductus arteriosus or its remnant and the Kommerell diverticulum are present. We report the cases of 2 infants in whom the role of an absent ductus arteriosus or its remnant is noteworthy. Both patients had a combination of tetralogy of Fallot with absent pulmonary valve syndrome and right aortic arch with retroesophageal left subclavian artery without a vascular ring. The absence of the ductus arteriosus has a role in the pathogenesis of tetralogy of Fallot with absent pulmonary valve syndrome. The absence of a ductus arteriosus in the right aortic arch with retroesophageal left subclavian artery precludes a vascular ring.

Biventricular repair after stage II univentricular surgery: palliation is not a one-way path.

Surgical decision in mild forms of hypoplastic left heart syndrome can be challenging. Once a univentricular pathway has been chosen, it can be difficult to reconsider a biventricular repair. A commitment to a palliative pathway is usually considered irreversible after initial univentricular repair. We present this case as an example in which the primary surgical palliation pathway was altered, and eventually a successful biventricular repair was performed in a mild variant of hypoplastic left heart syndrome, despite the fact that maneuvers to promote left ventricular growth were not recruited at the time of initial surgery.

Can the consequences of universal cholesterol screening during childhood prevent cardiovascular disease and thus reduce long-term health care costs?

The National Heart, Lung, and Blood Institute (NHLBI) Expert Panel in the United States (US) recently published its report, Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. The Panel's goals were to develop comprehensive, evidence-based strategies for use by general practitioners in the primary and primordial prevention of cardiovascular disease (CVD). These Guidelines have been endorsed by the American Academy of Pediatrics. Many of the recommendations restate existing lifestyle guidance similar to those proposed by the Committee on Nutrition in 2008. However a debate has emerged because for the first time, universal and comprehensive childhood dyslipidemia screening and treatment is now recommended by these new Guidelines. Because of universal screening, dyslipidemia attributed to both lifestyle and genetic factors could potentially be ascertained. The recommendations to screen for serum lipids and glucose have stimulated heated discussions among pediatricians, subspecialists, and policy-makers. This commentary discusses the medical, psychosocial and economic benefits and risks of universal cholesterol screening in children.

Enhancing our view of the doubly committed ventricular septal defect.

A case of a doubly committed ventricular septal defect is presented that highlights the value of 3-dimensional echocardiography in the preoperative planning of surgical closure.