AimsAn endothelin-1 receptor blocker, shown to be effective in patients with pulmonary arterial hypertension, might decrease pulmonary vascular resistance to increase cardiac filling and consequently improve exercise capacity in Fontan patients. Methods and resultsThis was a prospective, multicentre randomized open label trial in Fontan patients. One group received bosentan for 6 months. The other group did not receive study medication for the first 3 months, followed by bosentan for 6 months. The primary endpoint was exercise capacity, and secondary endpoints were NT-proBNP level, cardiac output, SF-36 (Short Form-36) quality of life (QoL), and NYHA class. Forty-two adults (median age 29 (range 18 -56) years, 52% male, 88% NYHA class I-II) from five tertiary referral centres participated in the study. Ten patients were on diuretics. Ten patients were not motivated to finish the study. Analysis of all 32 patients who finished the study at 6 months of treatment showed that mean peak V'O 2 (24 vs. 25 mL/kg/min), median SQUASH score (6614 vs. 6390), median NT-proBNP (314 vs. 274 ng/L), and mental QoL (50 vs. 51) remained unchanged as compared with baseline (P ¼ NS, for all). After treatment, NYHA class had improved in 6 (19%), was unchanged in 24 (75%), and declined in 2 (6%) patients. Subgroup analysis on age, ventricular morphology, type of Fontan circulation, or baseline NT-proBNP level did not reveal efficacy of bosentan. Six transient adverse effects were reported. ConclusionAn increased NT-proBNP level was present in the majority of Fontan patients. Six months of bosentan treatment was not beneficial. Trial registration

No abstract

Pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) due to systemic to pulmonary shunting is associated with a high risk of morbidity and mortality. In this study we evaluated 4 years treatment effect of bosentan on exercise capacity and quality of life and survival rates in 64 adult patients with PAH associated with CHD, including patients with Down syndrome (DS). All patients were evaluated at baseline and during follow-up with laboratory tests, 6-minute walk test, quality of life questionnaires, and Doppler echocardiography. In total, 13 patients (20%) died during 4-years of follow-up; 4 patients with DS and 9 patients without DS. Mean follow-up of all patients treated with bosentan was 3.5 ± 1.2 year. We analyzed treatment efficacy separately within patients without DS (n=34) and patients with DS (n=30). Mean 6-minute walking distance (6 MWD) in patients without DS significantly increased at 6 months from 417 ± 108 to 458 ± 104 m (+41 m; p=0.002) and significant improvement continued to exist during at least 2.5 years of follow-up (p=0.003). Moreover, stroke volume increased significantly (p=0.02). In the patients with DS, 6-MWD, stroke volume and quality of life remained stable during treatment. In this study we demonstrate a prolonged beneficial effect of bosentan treatment on exercise capacity, stroke volume and quality of life in patients without DS. However the mortality rate of 20% of patients after 4 years of follow-up remains high.

Right ventricular function (RVF) is often selectively declined after coronary artery bypass graft surgery. In adult patients with congenital heart disease (CHD) the incidence and persistence of declined RVF after cardiac surgery is unknown. The current study aimed to describe RVF after cardiac surgery in these patients. Adult CHD patients operated between January 2008 and December 2009 in the Academic Medical Centre in Amsterdam were studied. Clinical characteristics, laboratory tests, surgical data and intensive care unit outcome were obtained from medical records. RVF was measured by trans-thoracic echocardiography (TTE) and expressed by tricuspid annular plane systolic excursion (TAPSE), tissue Doppler imaging (RV S’) and myocardial performance index (MPI) pre-operatively and direct, at intermediate and late follow up. Of a total of 185 operated, 86 patients (mean age 39 ± 13 years, 54% male) had echo data available. There was a significant fall in RVF after cardiac surgery. TAPSE and RV S’ were significantly higher and MPI was significantly lower pre-operatively compared to direct post-operative values (TAPSE 22 ± 5 versus 13 ± 3 mm (P < 0.01), RV S’ 11 ± 4 versus 8 ± 2 cm/s (P < 0.01) and MPI 0.36 ± 0.14 vs 0.62 ± 0.25; P < 0.01). There were no significant differences in left ventricular function pre-operatively compared to post-operative values. Right-sided surgery was performed in 33, left-sided surgery in 37 and both sided surgery in 16 patients. Decline in RVF was equal for those groups. Patients with severe decline in RVF, were patients who underwent tricuspid valve surgery. Decline in RVF was associated with post-operative myocardial creatine kinase level and maximal troponin T level. There was no association between decline in RVF and clinical outcome on the intensive care unit. 18 months post-operatively, most RVF parameters had recovered to pre-operative values, but TAPSE which remained still lower (P < 0.01). CHD patients have a decline in RVF directly after cardiac surgery, regardless the side of surgery. Although a gradual improvement was observed, complete recovery was not seen 18 months post-operatively.

No abstract