Noninvasive Screening for Pulmonary Hypertension by Exercise Testing in Congenital Heart Disease.

BACKGROUND: Patients with congenital heart disease and native or palliated conditions are at risk to develop pulmonary hypertension (PH) in later life. Screening for PH is currently performed by regular echocardiographic follow-up, which appears to be difficult in several congenital conditions. This study evaluated the screening for PH in congenital heart disease by cardiopulmonary exercise testing (CPET). METHODS: We analyzed our database including all patients with congenital heart disease referred for CPET in our institution from June 2001 to September 2013 and identified 683 patients who had an accompanied heart catheterization less than 6 month after CPET. Those 130 patients with proven PH were compared with the other 563 patients with congenital heart disease but without PH. RESULTS: Peak oxygen uptake was the most discriminative variable, showing two thresholds at 16.3 mL/min per kg and 25.2 mL/min per kg. The highest specificity of 95% for PH was found in patients with a peak oxygen uptake of 16.3 mL/min per kg or less and a breathing reserve of 37.4% or less. In patients with a peak oxygen uptake exceeding 16.3 mL/min per kg, there was a high specificity of 86.3% but a low sensitivity of 53.1%. With 25.2 mL/min per kg as the threshold, the sensitivity for PH was only 10.0%. CONCLUSIONS: Detection of PH in patients with congenital heart disease by CPET is difficult because of many falsely positive tests. However, a peak oxygen uptake higher than 25.2 mL/min per kg makes the diagnosis of PH unlikely.

Value of N-terminal pro brain natriuretic peptide levels in different types of Fontan circulation.

AIMS: N-terminal pro brain natriuretic peptide (NT-proBNP) is an important biomarker in congestive heart failure. This has also been confirmed in congenital heart disease. However, its clinical value in patients with different types of Fontan circulation remains questionable. METHODS AND RESULTS: We prospectively analysed 124 patients with various types of Fontan surgery between October 2006 and February 2011. We included 49 patients with older Fontan modification [atriopulmonary connection (APC) and atrioventricular connection (AVC)] and 75 patients with total cavopulmonary connection (TCPC). The NT-proBNP levels of patients with APC/AVC were significantly higher than in patients with TCPC (P < 0.001), even after accounting for sex, age, ventricular function, atrioventricular regurgitation, ventricular morphology, and arrhythmia (P = 0.035). Levels of NT-proBNP positively correlated with atrioventricular valve regurgitation (r = 0.29, P = 0.013) and ventricular dysfunction (r = 0.23, P = 0.052) only in patients with TCPC, but not in patients with APC or AVC (r = 0.01, P = 0.509 and r = 0.10, P = 0.493, respectively). CONCLUSION: Levels of NT-pro BNP are related to the type of Fontan circulation. The older types (APC/AVC) that involve more atrial tissue in the systemic venous pathway show higher NT-proBNP levels independently of their cardiac status. Their NT-proBNP levels should be interpreted with care.

Fukutin mutations in non-Japanese patients with congenital muscular dystrophy: less severe mutations predominate in patients with a non-Walker-Warburg phenotype.

Six genes including POMT1, POMT2, POMGNT1, FKRP, Fukutin (FKTN) and LARGE encode proteins involved in the glycosylation of α-dystroglycan (α-DG). Abnormal glycosylation of α-DG is a common finding in Walker-Warburg syndrome (WWS), muscle-eye-brain disease (MEB), Fukuyama congenital muscular dystrophy (FCMD), congenital muscular dystrophy types 1C and 1D and some forms of autosomal recessive limb-girdle muscular dystrophy (LGMD2I, LGMD2K, LGMD2M), and is associated with mutations in the above genes. FCMD, caused by mutations in Fukutin (FKTN), is most frequent in Japan, but an increasing number of FKTN mutations are being reported outside of Japan. We describe four new patients with FKTN mutations and phenotypes ranging from: severe WWS in a Greek-Croatian patient, to congenital muscular dystrophy and cobblestone lissencephaly resembling MEB-FCMD in two Turkish patients, and limb-girdle muscular dystrophy and no mental retardation in a German patient. Four of the five different FKTN mutations have not been previously described.