Adjunct Targeted Biologic Inhibition Agents to Treat Aggressive Multivessel Intraluminal Pediatric Pulmonary Vein Stenosis.

OBJECTIVE: To evaluate the use of imatinib mesylate with or without bevacizumab targeting neoproliferative myofibroblast-like cells with tyrosine kinase receptor expression, as adjuncts to modern interventional therapies for the treatment of multivessel intraluminal pulmonary vein stenosis (PVS). We describe the 48- and 72-week outcomes among patients receiving imatinib mesylate with or without bevacizumab for multivessel intraluminal PVS. STUDY DESIGN: This single-arm, prospective, open-label US Food and Drug Administration approved trial enrolled patients with ≥2 affected pulmonary veins after surgical or catheter-based relief of obstruction between March 2009 and December 2014. Drug therapy was discontinued at 48 weeks, or after 24 weeks of stabilization, whichever occurred later. RESULTS: Among 48 enrolled patients, 5 had isolated PVS, 26 congenital heart disease, 5 lung disease, and 12 both. After the 72-week follow-up, 16 patients had stabilized, 27 had recurred locally without stabilization, and 5 had progressed. Stabilization was associated with the absence of lung disease (P = .03), a higher percentage of eligible drug doses received (P = .03), and was not associated with age, diagnosis, disease laterality, or number of veins involved. Survival to 72 weeks was 77% (37 of 48). Adverse events were common (n = 1489 total), but only 16 were definitely related to drug treatment, none of which were serious. CONCLUSION: Survival to 72 weeks was 77% in a referral population with multivessel intraluminal PVS undergoing multimodal treatment, including antiproliferative tyrosine kinase blockade. Toxicity specific to tyrosine kinase blockade was minimal.

Decreased exercise performance with age in children with hypoplastic left heart syndrome.

OBJECTIVE: Children born with hypoplastic left heart syndrome (HLHS) may experience cardiac dysfunction after staged surgery or transplantation, which may worsen with age. We examined the hypothesis that exercise testing can address cardiovascular capacity and suggest interventions to improve quality of life. STUDY DESIGN: Children with HLHS > or = 8 years old performed treadmill or bicycle ergometric testing at 4 centers. Results were compared with norms for age and sex. RESULTS: Of the 42 participants, the mean age was 12.9 years (range, 8.5-17.0 years), 64% were boys, 20 had staged surgery, and 34 completed metabolic assessment. The percent of predicted maximal oxygen uptake (mVO2) was higher in younger children. Children aged 8 to 12 years achieved 70% of predicted mVO2; children aged 13 to 17 years achieved 60% of predicted mVO2 (P = .02). The percent of predicted peak heart rate trended higher in younger patients (83% versus 75%, P = .07). Electrocardiographic changes were more common in older children. In treadmill testing, patients who had a transplant had better exercise performance than patients who underwent staged surgery in percent of predicted exercise time (82% versus 54%, P < .0001) and peak rate-pressure product (241 x 10(3) versus 195 x 10(3), P = .02). The percent of predicted mVO2 did not differ between patients who had a transplant (66%) and patients who underwent staged surgery (61%, P = .25). CONCLUSION: Children with HLHS showed considerable age-related decline in exercise performance, regardless of surgical strategy.

Improvement in congenital heart surgery in a developing country: the Guatemalan experience.

BACKGROUND: In 1997, an effort was made to disseminate US pediatric cardiac surgical practices to create a new comprehensive program in Guatemala. The objective of this study was to describe the improvement of the program by exploring the reduction in risk-adjusted in-hospital mortality. METHODS AND RESULTS: A retrospective cohort study of surgical procedures performed in Guatemala from February 1997 to July 2004 was conducted. Data were divided into 3 time periods (1997 to 1999, 2000 to 2002, and 2003 to 2004) and compared with a US benchmark (2000 Kids' Inpatient Database of 27 states and 313 institutions). The risk adjustment for congenital heart surgery (RACHS-1) method was used to adjust for case mix. Mortality rates, standardized mortality ratios, and 95% confidence intervals were calculated. A total of 1215 surgical procedures were included. Median age was 3.1 years (range, 1 day to 17.9 years). The overall mortality was 10.7% (n=130). The RACHS-1 method showed better discrimination than in prior reports (area under receiver operating characteristic curve=0.854). A decreasing trend in mortality rate was observed in every RACHS-1 risk category over the 3 time periods. When compared against the US benchmark, the reduction in risk-adjusted mortality was noted by a decrease of standardized mortality ratio from 10.0 (95% confidence interval, 7.2 to 13.7) in 1997-1999, to 7.8 (95% confidence interval, 5.9 to 10.0) in 2000-2002, and to 5.7 (95% confidence interval, 3.8 to 8.3) in 2003-2004. CONCLUSIONS: In a short time period, mortality after congenital heart surgery has been reduced substantially in Guatemala. Measurement of risk-adjusted mortality is a useful method to assess pediatric cardiac program improvement in the developing world.