69: ASD Repair after a 10-month treatment with Bosentan in a patient with severe pulmonary arterial hypertension: A Case Report. Hoetzenecker K, Ankersmit HJ, Bonderman D, Hoetzenecker W, Seitelberger R, Klepetko W, Lang IM. Journal of Thoracic and Cardiovascular Surgery.

Introduction
Congenital type II atrial septal defect (ASD II) is associated with precapillarypulmonary hypertension (PAH) in roughly 10% of cases. Principally, closure of the shunt lesion is recommended and large ASDs must be repaired in early childhood to prevent an Eisenmenger’s syndrome. Once severe pulmonary hypertension or Eisenmenger’s syndrome has developed, ASD closure is problematic due the increased risk of right ventricular failure and pulmonary hypertensive crisis. At this stage, heart-lung transplantation is the only surgical option. Non-surgical strategies include supplemental oxygen, digitalis, anticoagulation and vasodilator treatments. In contrast to the traditional rule of inoperability of an ASD with severe pulmonary hypertension, single case reports have demonstrated that a surgical correction of an ASD is feasible, but requires long-time pre- and post-operative treatment with vasodilators. Endothelin (ET) receptor antagonists are a new class of vasoactive substances, some of which (e.g. bosentan) are orally active. Bosentan has been shown to lower pulmonary artery pressure (PAP) and to induce reverse remodelling of the pulmonary arteries. We report the case of a patient with ASD II and severe pulmonary hypertension. Successful surgical closure of the ASD was possible with near-normalized PAPs after ten months of “conditioning” medication with bosentan.

Clinical Summary
A 71-year-old female was admitted to hospital because of exercise intolerance and cough. She presented in WHO functional class IV and was given permanent oxygen. Pneumonia was diagnosed and an antibiotic regimen was started. Electrocardiography showed a right bundle branch block (RBBB) with left axis deviation of -130°. Routine echocardiography revealed severe pulmonary hypertension with a systolic PAP of 89mmHg, and a large ASD II with a bidirectional shunt. The defect size was 15x36mm, thus too large for interventional closure. Cardiac catheterization confirmed the diagnosis of severe PAH with a pulmonary vascular resistance (PVR) over 400dynes.s.cm-5 which is the cut-off for shunt closures at our institution, and a nitric oxide (NO) non-responder status (Table 1). Surgical repair of the ASD II deemed impossible because of the degree of PAH with a mean PAP of 54, high B-Type natriuretic peptide (BNP) and the patient’s severe physical limitation. Bosentan therapy to condition the patient towards a later ASD closure was found to be an option by an interdisciplinary consent. Bosentan was started at a dosage of 125mg/day (2x62.5mg bid) and was increased to 250mg/day after one month. Laboratory parameters were controlled monthly, no significant elevation of liver enzymes occurred. 10 months after initiation of bosentan a repeat cardiac catheterization revealed significantly reduced pulmonary pressures (Table 1) stimulating a surgical closure of the ASD II with a Dacron patch. In addition the patient’s tricuspid valve insufficiency was repaired utilizing an Edwards Lifesience MC3 32mm ring was performed. The patient was extubated on the first postoperative day, norepinephrine and dobutamine given for cardiac support could be stopped two days later. During the further post-operative course recurrent right-sided pleural effusion and a sudden pericardial tamponade had to be tapped. The patient was discharged from the hospital on post-operative day 28 under bosentan treatment (250mg/d). 8 months thereafter the patient was in good clinical condition with mild pulmonary hypertension.

Discussion
In this case report we describe significant hemodynamic improvement under bosentan therapy, allowing surgical closure of an ASD II 10 months after bosentan induction, with good clinical outcome 8 months post-operatively. Treatment options for elderly patients suffering from pulmonary hypertension are limited. Medical treatment is the standard therapeutic option as surgical closure of the shunt is associated with an increased post-operative mortality. The main obstacle for surgical treatment is right ventricular dysfunction/failure in the presence of severe pulmonary hypertension after the surgical intervention. However, several recent case reports have demonstrated that post-operative reduction of PAP significantly reduces the risk of right heart failure, making surgical closure a possible treatment option.
Recently, Frost et al. reported a vasodilatative “conditioning” therapy in a patient suffering from Eisenmenger's syndrome that was initially considered inoperable. The ASD II in this case could be closed after 4 years of epoprostenol therapy. 8 years after surgical intervention the patient is clinically stable with near-normal pulmonary pressures.We now present a similar case treated with bosentan. Bosentan has several advantages compared to epoprostenol. Because it is an oral drug, there are no complications related to an intravenous delivery system which are common under prostaglandin therapy. Furthermore, adverse side effects of epoprostenol including headache, diarrhoea and rash are avoided. By contrast, the side effect profile of oral bosentan includes elevated liver enzymes in 7% of cases. Fortunately, no clinically relevant increases of transaminases occurred in the patient during 16 months of follow-up.
In the described case bosentan was continued because of the 8 months hemodynamic data together with the assumption that a pulmonary vascular disease is present. As the clinical outcome in this elderly patient is excellent further invasive diagnostic procedures re-evaluating bosentan therapy were abandoned. We conclude that bosentan treatment of a patient with ASD II and severe pulmonary hypertension results in an amelioration of pulmonary hypertension that may allow surgical correction according to standard operating procedures of pulmonary hypertension units.

a PDF of this paper can be provided upon request