Food and Drug Administration (FDA) postmarket reported side effects and adverse events associated with pulmonary hypertension therapy in pediatric patients.

Because most medications for pediatric pulmonary hypertension (PH) are used off label and based on adult trials, little information is available on pediatric-specific adverse events (AEs). Although drug manufacturers are required to submit postmarket AE reports to the Food and Drug Administration (FDA), this information is rarely transmitted to practitioners. In the setting of a recent FDA warning for sildenafil, the authors sought to give a better description of the AEs associated with current therapies in pediatric PH. In January 2010, a written request was made to the Food and Drug Administration for AE records of commonly used PH medications. Reports were screened for pediatric patients, analyzed in terms of AEs, and compared with the medical literature. Arbitrarily, AEs that could be attributed to concomitant medications were not attributed to the PH medication in question. Adverse events occurring in more than 5 % of events for each drug were assumed to be associated with the targeted PH medication. Between November 1997 and December 2009, 588 pediatric AE reports (death in 257 cases) were reported for the three most commonly used therapies: bosentan, epoprostenol, and sildenafil. Many of the AEs were similar to those reported previously. However, 27 AEs not previously reported in the literature (e.g., pulmonary hemorrhage, hemoptysis, and pneumonia) were found. The FDA postmarket records for PH medications in pediatric patients show a significant number of AEs. The discovery of AEs not previously reported will better inform those caring for these complex and critically ill children, and the large number of deaths suggest they may be underreported in current literature.

Validation of the Innocor device for noninvasive measurement of oxygen consumption in children and adults.

Outpatient measurements of oxygen consumption (VO2) and cardiac output (CO) are valuable in the management of pediatric cardiac disease. Current methods are inaccurate and cumbersome or require invasive procedures. New devices to measure these variables in adults have not been rigorously tested for children. The Innocor system uses a photoacoustic analyzer to measure gas content for noninvasive measurement of VO2 and CO. This study sought to validate Innocor-derived VO2 measurements in children and adults by comparing them against the gold standard Douglas bag method. Subjects were tested in an outpatient setting. Adaptations were made for pediatric patients based on weight. Resting VO2 measurements were obtained simultaneously by the Innocor system and Douglas bag during 3 min. The study enrolled 31 children (mean age, 12.2 years; range, 7-17 years, 17 girls) and 29 adults (mean age, 36.7 years; range, 19-57 years; 17 women). Strong correlation between the two techniques was seen for both the adults (R (2) = 0.88) and the children (R (2) = 0.82). The average discrepancy between the Innocor and Douglas bag measurements was 1.7 % (range, 0.6-19.1 %) for the adults, and 5.4 % (range, 0.1-32.2 %) for the children. The discrepancy was more than 15 % for 17 % of the adults and 22 % of the children, with the Innocor device tending to overestimate VO2 in children compared with the Douglas bag. This trend was not seen in adults. The Innocor system has excellent correlation with the Douglas bag and shows promise for noninvasive measurement of VO2 and CO in the school-age pediatric population.

Electrical and mechanical dyssynchrony in pediatric pulmonary hypertension.

BACKGROUND: Electrical and mechanical dyssynchrony are often seen in patients with left ventricular failure. In pediatric pulmonary hypertension (PH), right ventricular failure predominates; however, the prevalence of electrical and/or mechanical dyssynchrony in these patients is unknown. We examined the prevalence of electrical and mechanical dyssynchrony in pediatric PH patients. METHODS: Medical records (including, functional status, electrocardiograms and echocardiograms) of pediatric PH patients were reviewed. QRS duration z-scores were calculated to determine electrical dyssynchrony. Echo vector velocity imaging was used to calculate the mechanical dyssynchrony index (DI). RESULTS: Seventy-seven PH patients (idiopathic pulmonary arterial hypertension [IPAH]: n = 26; congenital heart disease: n = 41; other: n = 10) were studied. Electrical dyssynchrony was seen in 84% (p < 0.01 vs historic controls), with a mean z-score of 4.3 (95% CI 3.5 to 5.1). There was no difference between those with IPAH, z = 3.6 (95% CI 2.5 to 4.6), and those without, z = 4.7 (95% CI 3.6 to 5.8). Mechanical dyssynchrony was seen in 76% of patients (mean DI = 66 ± 47 vs 18 ± 8 milliseconds in historic controls, p < 0.01) in both IPAH and non-IPAH patients. Post-operative congenital heart disease patients had the largest dyssynchrony index. No correlation was found among electrical or mechanical dyssynchrony, hemodynamics or disease severity. CONCLUSIONS: Significant electrical and mechanical dyssynchrony is present in pediatric PH patients, regardless of etiology. The overall effect of electrical and mechanical dyssynchrony on outcomes in this patient population is still unknown. Select patients may benefit from resynchronization therapy.

Hypoplastic left heart syndrome: current considerations and expectations.

In the recent era, no congenital heart defect has undergone a more dramatic change in diagnostic approach, management, and outcomes than hypoplastic left heart syndrome (HLHS). During this time, survival to the age of 5 years (including Fontan) has ranged from 50% to 69%, but current expectations are that 70% of newborns born today with HLHS may reach adulthood. Although the 3-stage treatment approach to HLHS is now well founded, there is significant variation among centers. In this white paper, we present the current state of the art in our understanding and treatment of HLHS during the stages of care: 1) pre-Stage I: fetal and neonatal assessment and management; 2) Stage I: perioperative care, interstage monitoring, and management strategies; 3) Stage II: surgeries; 4) Stage III: Fontan surgery; and 5) long-term follow-up. Issues surrounding the genetics of HLHS, developmental outcomes, and quality of life are addressed in addition to the many other considerations for caring for this group of complex patients.