Correlating Severity of Pulmonary Hypertension by Echocardiogram with Mortality in Premature Infants with Bronchopulmonary Dysplasia.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth. Infants with BPD are at increased risk for pulmonary hypertension (PH). Cardiac catheterization is the gold standard for diagnosing PH, but cardiac catheterization is challenging to perform in small, sick, premature infants. The utility of echocardiography for diagnosing PH and predicting outcomes in extremely premature infants has not been clearly defined. Therefore, we sought to use predefined criteria to diagnose PH by echocardiogram and relate PH severity to mortality in extremely premature infants with BPD. STUDY DESIGN: Echocardiograms from 46 infants born ≤28 weeks' postmenstrual age with a diagnosis of BPD were assessed for PH by three pediatric cardiologists using predefined criteria, and survival times among categories of PH patients were compared. A total of 458 echocardiograms were reviewed, and 15 (33%) patients were found to have at least moderate PH. Patients with at least moderate PH had similar demographic characteristics to those with no/mild PH. RESULTS: Ninety percent of infants without moderate to severe PH survived to hospital discharge, compared with 67% of infants with at least moderate PH (p = 0.048). Patients with severe PH had decreased survival to hospital discharge (38%) compared with moderate (100%) and no/mild PH (90%) groups. Kaplan-Meier survival curves also differed among PH severity groups (Wilcoxon p < 0.001). CONCLUSION: Using predefined criteria for PH, premature infants with BPD can be stratified into PH severity categories. Patients diagnosed with severe PH by echocardiogram have significantly reduced survival. KEY POINTS: · A composite score definition of PH by echocardiogram showed high inter- and intrarater reliability.. · Infants with severe PH by echocardiogram had decreased survival rates.. · Early diagnosis of PH by echocardiogram dictates treatment which may improve outcomes..

Causes of Death in Infants and Children with Congenital Heart Disease.

With improved surgical outcomes, infants and children with congenital heart disease (CHD) may die from other causes of death (COD) other than CHD. We sought to describe the COD in youth with CHD in North Carolina (NC). Patients from birth to 20 years of age with a healthcare encounter between 2008 and 2013 in NC were identified by ICD-9 code. Patients who could be linked to a NC death certificate between 2008 and 2016 were included. Patients were divided by CHD subtypes (severe, shunt, valve, other). COD was compared between groups. Records of 35,542 patients < 20 years old were evaluated. There were 15,277 infants with an annual mortality rate of 3.5 deaths per 100 live births. The most frequent COD in infants (age < 1 year) were CHD (31.7%), lung disease (16.1%), and infection (11.4%). In 20,265 children (age 1 to < 20 years), there was annual mortality rate of 9.7 deaths per 1000 at risk. The most frequent COD in children were CHD (34.2%), neurologic disease (10.2%), and infection (9.5%). In the severe subtype, CHD was the most common COD. In infants with shunt-type CHD disease, lung disease (19.5%) was the most common COD. The mortality rate in infants was three times higher when compared to children. CHD is the most common underlying COD, but in those with shunt-type lesions, extra-cardiac COD is more common. A multidisciplinary approach in CHD patients, where development of best practice models regarding comorbid conditions such as lung disease and neurologic disease could improve outcomes in this patient population.

Overcoming underpowering: Trial simulations and a global rank end point to optimize clinical trials in children with heart disease.

BACKGROUND: Randomized controlled trials (RCTs) in children with heart disease are challenging and therefore infrequently performed. We sought to improve feasibility of perioperative RCTs for this patient cohort using data from a large, multicenter clinical registry. We evaluated potential enrollment and end point frequencies for various inclusion cohorts and developed a novel global rank trial end point. We then performed trial simulations to evaluate power gains with the global rank end point and with use of planned covariate adjustment as an analytic strategy. METHODS: Data from the Society of Thoracic Surgery-Congenital Heart Surgery Database (STS-CHSD, 2011-2016) were used to support development of a consensus-based global rank end point and for trial simulations. For Monte Carlo trial simulations (n = 50,000/outcome), we varied the odds of outcomes for treatment versus placebo and evaluated power based on the proportion of trial data sets with a significant outcome (P < .05). RESULTS: The STS-CHSD study cohort included 35,967 infant index cardiopulmonary bypass operations from 103 STS-CHSD centers, including 11,411 (32%) neonatal cases and 12,243 (34%) high-complexity (Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery mortality category ≥4) cases. In trial simulations, study power was 21% for a mortality-only end point, 47% for a morbidity and mortality composite, and 78% for the global rank end point. With covariate adjustment, power increased to 94%. Planned covariate adjustment was preferable to restricting to higher-risk cohorts despite higher event rates in these cohorts. CONCLUSIONS: Trial simulations can inform trial design. Our findings, including the newly developed global rank end point, may be informative for future perioperative trials in children with heart disease.

Rationale and design of the STeroids to REduce Systemic inflammation after infant heart Surgery (STRESS) trial.

For decades, physicians have administered corticosteroids in the perioperative period to infants undergoing heart surgery with cardiopulmonary bypass (CPB) to reduce the postoperative systemic inflammatory response to CPB. Some question this practice because steroid efficacy has not been conclusively demonstrated and because some studies indicate that steroids could have harmful effects. STRESS is a randomized, placebo-controlled, double-blind, multicenter trial designed to evaluate safety and efficacy of perioperative steroids in infants (age < 1 year) undergoing heart surgery with CPB. Participants (planned enrollment = 1,200) are randomized 1:1 to methylprednisolone (30 mg/kg) administered into the CPB pump prime versus placebo. The trial is nested within the existing infrastructure of the Society of Thoracic Surgeons Congenital Heart Surgery Database. The primary outcome is a global rank score of mortality, major morbidities, and hospital length of stay with components ranked commensurate with their clinical severity. Secondary outcomes include several measures of major postoperative morbidity, postoperative hospital length of stay, and steroid-related safety outcomes including prevalence of hyperglycemia and postoperative infectious complications. STRESS will be one of the largest trials ever conducted in children with heart disease and will answer a decades-old question related to safety and efficacy of perioperative steroids in infants undergoing heart surgery with CPB. The pragmatic "trial within a registry" design may provide a mechanism for conducting low-cost, high-efficiency trials in a heretofore-understudied patient population.

Agreement of an echocardiogram-based diagnosis of pulmonary hypertension in infants at risk for bronchopulmonary dysplasia among masked reviewers.

OBJECTIVE: To evaluate the agreement of an echocardiogram-based pulmonary hypertension diagnosis in premature infants at risk for bronchopulmonary dysplasia (BPD). STUDY DESIGN: Echocardiograms from infants born ≤28 weeks post menstrual age were retrospectively reviewed with a standardized reading protocol by three pediatric cardiologists masked to patient's clinical history to determine the presence of pulmonary hypertension. RESULTS: A total of 483 echocardiograms from 49 unique patients were each reviewed by three pediatric cardiologists. Overall there was an 82.9% agreement on the presence of pulmonary hypertension among the three readers (95% CI: 78.4%, 85.4%) with a modified Fleiss' kappa of 0.759 (95% CI: 0.711, 0.801). Percent agreement between rereads was 92.4%, and modified Fleiss' kappa was 0.847 (95% CI: 0.750, 0.931). CONCLUSIONS: Using a standardized reading protocol and echocardiogram-based definition of pulmonary hypertension, there is high inter- and intra-rater agreement for the diagnosis of pulmonary hypertension in at-risk premature infants, suggesting echocardiography can be successfully used for clinical and research monitoring of pulmonary hypertension in infants.

PRKAG2 mutations presenting in infancy.

PRKAG2 encodes the γ2 subunit of AMP-activated protein kinase (AMPK), which is an important regulator of cardiac metabolism. Mutations in PRKAG2 cause a cardiac syndrome comprising ventricular hypertrophy, pre-excitation, and progressive conduction-system disease, which is typically not diagnosed until adolescence or young adulthood. However, significant variability exists in the presentation and outcomes of patients with PRKAG2 mutations, with presentation in infancy being underrecognized. The diagnosis of PRKAG2 can be challenging in infants, and we describe our experience with three patients who were initially suspected to have Pompe disease yet ultimately diagnosed with mutations in PRKAG2. A disease-causing PRKAG2 mutation was identified in each case, with a novel missense mutation described in one patient. We highlight the potential for patients with PRKAG2 mutations to mimic Pompe disease in infancy and the need for confirmatory testing when diagnosing Pompe disease.

Pulmonary Arterial Hypertension in Glycogen Storage Disease Type I

Abstract Pulmonary arterial hypertension (PAH) is a rare and highly fatal disease that has been reported in 8 patients with glycogen storage disease type I (GSDI). We describe an additional case of an acute presentation of PAH in a 14-year-old patient with GSDI, which was successfully treated with inhaled nitric oxide and sildenafil. We investigated the incidence of PAH in 28 patients with GSDI on routine echocardiography and found no evidence of PAH and no significant cardiac abnormalities. This study highlights that PAH is a rare disease overall, but our case report and those previously described suggest an increased incidence in patients with GSDI. Should cardiopulmonary symptoms develop, clinicians caring for patients with GSDI should have a high degree of suspicion for acute PAH and recognize that prompt intervention can lead to survival in this otherwise highly fatal disease.

G Protein-coupled Receptor Biased Agonism.

G protein-coupled receptors are the largest family of targets for current therapeutics. The classic model of their activation was binary, where agonist binding induced an active conformation and subsequent downstream signaling. Subsequently, the revised concept of biased agonism emerged, where different ligands at the same G protein-coupled receptor selectively activate one downstream pathway versus another. Advances in understanding the mechanism of biased agonism have led to the development of novel ligands, which have the potential for improved therapeutic and safety profiles. In this review, we summarize the theory and most recent breakthroughs in understanding biased signaling, examine recent laboratory investigations concerning biased ligands across different organ systems, and discuss the promising clinical applications of biased agonism.

Transcatheter pulmonary embolectomy after fontan.

Pulmonary embolism (PE) is a significant cause of morbidity and mortality among hospitalized patients, and thrombolytics are the mainstay of treatment. However, for patients who fail or have contraindications to thrombolytic therapy, catheter-based therapies, such as the AngioVac aspiration system, have emerged as an alternative to surgical embolectomy. Here, we present the novel case of a 22 year-old woman with Fontan circulation who developed severe postpartum cardiomyopathy and a saddle PE. She failed thrombolytic therapy but underwent successful pulmonary embolectomy by AngioVac aspiration. Patients with Fontan circulation have an increased incidence of thromboembolic events, and AngioVac thrombectomy is a valuable treatment option in these complex patients.

Coarctation of the aorta: Management from infancy to adulthood.

Coarctation of the aorta is a relatively common form of congenital heart disease, with an estimated incidence of approximately 3 cases per 10000 births. Coarctation is a heterogeneous lesion which may present across all age ranges, with varying clinical symptoms, in isolation, or in association with other cardiac defects. The first surgical repair of aortic coarctation was described in 1944, and since that time, several other surgical techniques have been developed and modified. Additionally, transcatheter balloon angioplasty and endovascular stent placement offer less invasive approaches for the treatment of coarctation of the aorta for some patients. While overall morbidity and mortality rates are low for patients undergoing intervention for coarctation, both surgical and transcatheter interventions are not free from adverse outcomes. Therefore, patients must be followed closely over their lifetime for complications such as recoarctation, aortic aneurysm, persistent hypertension, and changes in any associated cardiac defects. Considerable effort has been expended investigating the utility and outcomes of various treatment approaches for aortic coarctation, which are heavily influenced by a patient's anatomy, size, age, and clinical course. Here we review indications for intervention, describe and compare surgical and transcatheter techniques for management of coarctation, and explore the associated outcomes in both children and adults.

Thoracoscopic resection of the left atrial appendage after failed focal atrial tachycardia ablation.

BACKGROUND: This case series describes 3 patients with the unusual location of focal atrial tachycardia in the left atrial appendage who failed catheter ablation but were successfully treated by left atrial appendage resection by a totally thoracoscopic surgical technique. METHODS: In all 3 cases, left atrial appendage resection was carried out by video-assisted thoracoscopic surgery using only 3 5- to 10-mm incisions, eliminating the need for median sternotomy or thoracotomy. An endoscopic stapler was used to resect the left atrial appendage at its base, successfully eliminating the source of the patients' focal atrial tachycardia. RESULTS: The mean operative time was 84 minutes. All 3 patients tolerated the procedure without any complications and were discharged on postoperative day 3. At an average follow-up of 4.5 years, all patients remained asymptomatic and with normal ambulatory rhythm monitoring off all antiarrhythmic medications. CONCLUSIONS: Surgical resection of the left atrial appendage using a totally thoracoscopic approach is a safe and successful treatment option for patients who have failed endocardial catheter ablation. This novel approach utilizes smaller incisions and shorter operative times than the more invasive surgical techniques previously described in the literature.

Tinea capitis mimicking dissecting cellulitis.

Tinea capitis is a common disease of childhood that typically follows one of several clinical patterns. Our patient and several previously reported cases demonstrate the existence of a dissecting cellulitis-like presentation of tinea capitis. This variant should be recognized to prevent misdiagnosis of dissecting cellulitis and allow proper treatment to prevent scarring alopecia.