natriuretic-peptide--brain and Protein-Losing-Enteropathies

Post-Fontan protein-losing enteropathy (PLE) is associated with significant morbidity and mortality. Although heart transplantation (HTx) can be curative, PLE may increase the risk of morbidity before and after HTx. This study analyzed the influence of PLE influence on waiting list and post-HTx outcomes in a pediatric cohort.. Fontan patients listed for HTx and enrolled in the Pediatric Heart Transplant Study from 1999 to 2012 were stratified by a diagnosis of PLE, and the association of PLE with waiting list and post-HTx mortality, rejection, and infection was analyzed.. Compared with non-PLE Fontan patients (n = 260), PLE patients listed for HTx (n = 96) were older (11.9 years vs 7.6 years; p = 0.003), had a larger body surface area (1.1 m(2) vs 0.9 m(2); p = 0.0001), had lower serum bilirubin (0.5 vs 0.9 mg/dl; p = 0.01), lower B-type natriuretic peptide (59 vs 227 pg/ml; p = 0.006), and were less likely to be on a ventilator (3% vs 13%; p = 0.006). PLE patients had lower waiting list mortality than non-PLE Fontan patients (p < 0.0001). There were no intergroup differences for post-HTx survival or times to the first infection or rejection. PLE was not independently associated with increased post-HTx mortality at any time point.. In this multicenter cohort, the diagnosis of PLE alone was not associated with increased waiting list mortality or post-HTx morbidity or mortality. Given the limitations of our data, this analysis suggests that PLE patients in the pediatric age group have outcomes similar to their non-PLE counterparts. Additional multicenter studies of PLE patients with targeted collection of PLE-specific information will be necessary to fully delineate the risks conferred by PLE for HTx.

Topics: Age Factors; Bilirubin; Body Surface Area; Child; Child, Preschool; Cohort Studies; Female; Fontan Procedure; Graft Rejection; Heart Transplantation; Humans; Male; Natriuretic Peptide, Brain; Postoperative Complications; Protein-Losing Enteropathies; Treatment Outcome; Ventilators, Mechanical

Protein-losing enteropathy (PLE) is an enigmatic disease with significant morbidity and mortality seen after the Fontan operation. The pathophysiology is poorly understood. The purpose of this study is to investigate the association between PLE after the Fontan operation and candidate pathophysiologic mechanisms of the disease by searching for abnormalities of the following: (1) mesenteric blood flow; (2) systemic inflammation; (3) neurohormonal activation; (4) protein glycosylation.. A cross-sectional analysis of 62 patients after the Fontan operation was performed. Twenty-four hour stool sample was collected for alpha-1-antitrypsin (A1AT) clearance, to determine the presence of abnormal enteric protein loss (AEPL) defined as either an abnormal fecal A1AT clearance of greater than 27 mL/24 hours, or an abnormal fecal A1AT concentration of greater than 54 mg/dL. Subjects underwent ultrasonography of the mesenteric and celiac artery blood flow and blood draw for tumor necrosis factor-alpha (TNF-a), high sensitivity C reactive protein (CRP), brain natriuretic peptide (BNP), angiotensin II, coagulation factors protein S, protein C, and antithrombin III (AT III), and serum transferrin for determination of glycosylation defect.. Age at study was 10.9 +/- 3.4 years; 8.6 +/- 3.9 years after the Fontan operation. Seven subjects had AEPL. Mesenteric-to-celiac artery flow ratio was lower for the AEPL group, than for the non-AEPL group (p < 0.05). The TNF-a, CRP, BNP, and angiotensin II levels were elevated; however, there was no correlation with AEPL. Abnormalities in coagulation factors were present but did not correlate with AEPL. No glycosylation defects were identified.. Potential candidate mechanisms for elucidation of the pathophysiology of PLE include abnormal mesenteric vascular resistance and inflammation, conditions uniquely present after the Fontan operation. Targeted investigations of these parameters may provide clues as to the mechanism of onset of PLE after Fontan operation.

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Blood Coagulation; C-Reactive Protein; Child; Child, Preschool; Cross-Sectional Studies; Fontan Procedure; Glycosylation; Humans; Liver; Natriuretic Peptide, Brain; Protein-Losing Enteropathies; Proteins; Splanchnic Circulation; Tumor Necrosis Factor-alpha