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doi:10.1378/chest.06-1227
(Chest. 2007; 131:977-983)
© 2007 American College of Chest Physicians
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Atrial Septostomy in Treatment of End-Stage Right Heart Failure in Patients With Pulmonary Hypertension*

Marcin Kurzyna, MD, PhD; Marek Dabrowski, MD, PhD; Dariusz Bielecki, MD; Anna Fijalkowska, MD, PhD; Piotr Pruszczyk, MD, PhD; Grzegorz Opolski, MD, PhD; Janusz Burakowski, MD, PhD; Michal Florczyk, MD; Witold Z. Tomkowski, MD, PhD, FCCP; Liliana Wawrzynska, MD, PhD; Monika Szturmowicz, MD, PhD, FCCP and Adam Torbicki, MD, PhD

* From the Department of Chest Medicine (Drs. Kurzyna, Fijalkowska, Florczyk, Wawrzynska, Szturmowicz, and Torbicki), and Intensive Care Unit (Drs. Burakowski and Tomkowski), National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland; the Department of Cardiology (Drs. Dabrowski and Bielecki), Bielanski Hospital, Warsaw, Poland; and the Department of Internal Medicine, Hypertension, and Angiology (Dr. Pruszczyk), and the First Department of Cardiology (Dr. Opolski), Medical University of Warsaw, Warsaw, Poland.

Correspondence to: Marcin Kurzyna, MD, PhD, Department of Chest Medicine, National Tuberculosis and Lung Diseases Research Institute, Plocka 26, 01–138 Warsaw, Poland; e-mail: m.kurzyna{at}igichp.edu.pl

Abstract

Background: Right ventricular (RV) failure is the main cause of death in patients with pulmonary hypertension (PH). Balloon atrial septostomy (BAS) is believed to relieve symptoms of PH by increasing systemic flow and reducing RV preload.

Methods: Fourteen BAS procedures were performed in 11 patients (5 men and 6 women; mean [± SD] age, 33 ± 12 years) with RV failure in the course of PH that was refractory to conventional treatment. BAS consisted of a puncture of the interatrial septum and subsequent dilatations with balloons of increasing diameter in a step-by-step manner.

Results: After BAS, the mean oxygen saturation of aortic blood decreased (before, 93 ± 4%; after, 84 ± 4%; p = 0.001), while mean cardiac index increased (before, 1.54 ± 0.34 L/min/m2; after, 1.78 ± 0.35 L/min/m2; p = 0.001), resulting in a positive trend for mean systemic oxygen transport (before, 270 ± 64 mL/min; after, 286 ± 81 mL/min; p = 0.08). Pulmonary vascular resistance (PVR) slightly increased immediately after the procedure, and this rise inversely correlated with mixed venous blood partial oxygen pressure both before BAS (r = –0.69; p = 0.009) and after BAS (r = –0.64; p = 0.018). Mean functional class improved from 3.2 ± 0.4 to 2.6 ± 0.7 (p = 0.03) after 1 month. At follow-up (mean time to follow-up, 8.1 ± 6.2 months; range, 0.8 to 20.2 months), seven patients died and two underwent lung transplantation. There was no difference in the survival rate compared to that obtained from National Institutes of Health equation. A significant size reduction in the created defect was observed in six patients, requiring repeat BAS procedures in three cases.

Conclusions: The current BAS technique improves cardiac index and functional class without significant periprocedural complications, except for a transient increase in PVR related to acute desaturation of mixed venous blood. At long-term follow-up, a high incidence of spontaneous decrease in orifice size has been observed.

Key Words: atrial septostomy • interventional cardiology • pulmonary hypertension • survival • treatment

Balloon atrial septostomy (BAS) has emerged as a potential therapeutic option in patients with severe pulmonary arterial hypertension (PAH), which is a progressive disease predominantly affecting young adults and usually leading to fatal right ventricular (RV) failure.1 BAS is a transcutaneous intervention consisting of a puncture of the interatrial septum followed by repetitive balloon dilatation of the created atrial septal defect to a diameter leading to hemodynamically predefined right-to-left shunt. BAS aims at creating a "safety valve" by unloading the right heart, and increasing left ventricular preload and output, peripheral perfusion, net oxygen tissue delivery, exercise tolerance, and prognosis. Though it is a palliative procedure, BAS is becoming an element of therapy for PAH patients as a bridge to lung transplantation or as a main therapeutic option, if pharmacologic and surgical treatment are not feasible.23 Following an earlier preliminary report,4 we now share our experience with this method to help in better understanding the physiopathology and clinical implications of acutely created right-to-left shunt at the atrial level in patients with severe pulmonary hypertension (PH).

Materials and Methods

Study Population
We performed 14 BAS procedures in 11 patients (5 men and 6 women; mean [± SD] age, 33 ± 12 years) with refractory right heart failure in the course of idiopathic PAH (9 patients). One patient had PAH associated with corrected aortopulmonary window, and another patient had chronic distal thromboembolic PH that was unsuitable for surgical treatment because of the distal location of the thrombi. A differential diagnosis of PH subclasses was established according to European Society of Cardiology guidelines on the diagnosis and treatment of PAH.2 Indications for BAS were syncope at exercise, fluid retention, and progressive cachexia despite the maximal medical therapy available in Poland at the time of the BAS procedure. In most cases, pharmacologic treatment could be offered only in the framework of open extensions of randomized controlled trials assessing the clinical efficacy of treprostinil, bosentan, and beraprost. Epoprostenol has not been approved in Poland for the long-term treatment of PAH. Two patients underwent BAS while receiving only supportive therapy, because pharmacotherapy was not immediately available. Three patients were in World Health Organization (WHO) functional class IV, while the others were in WHO functional class III. Baseline hemodynamic data were applied to assess the probability of survival at 6 and 12 months using the regression equation obtained from the primary PH registry of the US National Institutes of Health.5 The clinical characteristics and background therapy received by individual patients are shown in Table 1 . All patients consented to participate in the study. The procedures we followed were in accordance with the ethical standards of the Institutional Ethics Committee and with the Helsinki Declaration.


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  		Table 1. Patients Status Before BAS, Predicted Survival Probability at 6 and 12 Months, and Clinical Follow-up*

 
Description of the Procedure
BAS procedures were performed according to a protocol previously described by Sandoval et al6 using our own modification. After local analgesia, the right femoral artery and the femoral vein were punctured, and vascular sheaths were introduced. Initially, transthoracic echocardiography was used to monitor the procedure. In the last three patients, an intracardiac echocardiographic probe (AcuNaV; Siemens Medical Solutions USA; Malvern, PA) was introduced into the right atrium through the right jugular vein, allowing better visualization of the interatrial septum and precise continuous echocardiographic monitoring during the procedure. Left heart catheterization was performed with a 5F pigtail catheter for monitoring pressures and oxygen saturation. Complete right-sided hemodynamic data, including oxygen saturation levels, were obtained from a catheter that was forwarded into the pulmonary artery. The catheter was removed from the pulmonary artery, and a transseptal puncture was made with a Brockenbrough needle, through which an Inoue guidewire with a circular end was passed into the left atrium.

The first dilatation of the interatrial septum was performed with an Inoue dilator, which was subsequently exchanged for a Mansfield balloon with a diameter of 5 mm. Before the balloon was inflated, its position was controlled with echocardiography. After each step, the oxygen saturation of aortic blood was measured, and the size of the defect and the importance of the shunt were estimated using echocardiography. Progressively larger balloons were used until the systemic saturation decreased to 85%. After the BAS was completed, right and left hemodynamic measurements were performed. Blood for oxygen saturation assessment was sampled from the aorta, pulmonary veins, pulmonary artery, and both caval veins. The values of pulmonary and systemic flows were calculated separately using the Fick method, allowing the assessment of shunt volume and systemic oxygen transport (SOT). Pulmonary vascular resistance (PVR) was calculated as a transpulmonary gradient divided by pulmonary flow. The oxygen uptake that was directly measured before the BAS procedure was considered to be constant throughout the procedure. Oxygen therapy was started immediately after the BAS procedure.

Statistical Analysis
The data are expressed as the mean ± SD or 95% confidence intervals (CIs). Values obtained before and after the BAS were compared with a paired t test. The association between variables was assessed by the Pearson coefficient of correlation. Hypothetical and observed survival was compared at 6 and 12 months after the BAS procedure. All tests of hypothesis were carried out using 0.05 as the level of statistical significance

Results

Procedure and Periprocedural Period
No serious complications were observed during the BAS, and all patients survived the procedure. The most common problem was transient ventricular or supraventricular tachyarrhythmia, which was related to mechanical irritation by catheters. In one case, atrial fibrillation occurred, which was successfully treated.

At catheterization, the mean right atrial pressure (RAP) for the whole group was significantly elevated and contrasted with the low mean left atrial pressure (LAP), which could be directly measured after septal puncture (Table 2 ). After the BAS procedure, cardiac index significantly increased, while the oxygen saturation of aortic and mixed venous blood decreased. SOT tended to increase. Pulmonary artery pressures (PAPs), RAP, and LAP did not change after BAS. Interestingly, PVR measured directly after the procedure increased significantly, and that change inversely correlated with the value of mixed venous blood PO2 both before BAS (r = –0.69; p = 0.009) and after BAS (r = –0.64; p = 0.018), and with mixed venous blood oxygen saturation achieved after BAS (r = –0.56; p = 0.048) [Fig 1 ]; but it did not correlate with either the oxygen saturation of aortic blood or its drop after BAS.


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  		Table 2. Summary of Hemodynamic Parameters Before and Immediately After BAS Procedures (n = 14)*

 

Figure 1
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  		Figure 1. Correlation between changes in PVR and mixed venous oxygen saturation measured after BAS (data obtained during 13 procedures; the value for patient 2 is unknown).

 
The maximal size of the balloon used during the procedures varied from 5 to 8 mm (mean size, 6.6 ± 1.6 mm). This resulted in right-to-left shunts ranging from 0.31 to 1.16 L/min (mean, 0.65 ± 0.27 L/min) [Table 3 ]. In patient 8, the BAS repeat procedure failed because of the inability to puncture the interatrial septum.


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  		Table 3. Maximal Diameter of Created Septostomy, Volume of Right-to-Left Shunt, and Hemodynamic Changes Immediately After BAS*

 
All patients received oxygen immediately after BAS through a nasal cannula or a face mask to maintain arterial oxygen saturation at > 85%. However, despite initial stabilization in the catheterization laboratory, progressive refractory hypoxemia was observed in four patients over the next few hours (Table 4 ). They received rescue therapy with inhaled iloprost (Ventavis; Schering AG; Berlin, Germany), after which they experienced a rapid increase in the oxygenation of arterial blood and clinical stabilization. This additional therapy could be gradually withdrawn over the next 3 to 5 days without the recurrence of progressive systemic hypoxemia. Patient 2 received mechanical ventilation and required the infusion of catecholamines. Before BAS, the patient had presented with symptoms of severe RV dysfunction with elevated RAP up to 30 mm Hg, and despite the use of a small balloon (6 mm) a high interatrial pressure gradient caused extensive shunting with profound and refractory hypoxemia. This patient died 24 days after undergoing the BAS procedure.


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  		Table 4. Values of Oxygen Saturation and PO2 in Aortic and Mixed Venous Blood, SOT, and PVR Before and After BAS*

 
Long-term Follow-up
The 30-day mortality rate was 9%, with one death (patient 2) as described above. The cumulative survival rate at 6 and 12 months for the patients studied was 64% (95% CI, 34 to 94%) and did not differ from the mean survival rates predicted from the National Institutes of Health equation of 63% (95% CI, 55 to 71%) and 53% (95% CI, 44 to 62%), respectively.

In addition to one death, which occurred 24 days after the BAS, three patients died during the 12 months of follow-up. Patients 9 and 10 died because of progressive right heart failure that was resistant to medical therapy, and sudden death occurred in patient 11, who had been scheduled for the second BAS.

At the 1-month follow-up, five patients had improved their WHO functional class from III to II, and one patient had changed from class IV to class III. Three patients remained in class III, and one patient was still in class IV (Fig 2 ). The mean functional class improved from 3.2 ± 0.4 to 2.6 ± 0.7 (p = 0.03) at 1 month after the BAS procedure. After 12 months of follow-up, five patients presented in WHO functional class III, one in class II, and one patient (patient 4) underwent successful lung transplantation (9 months after BAS).


Figure 2
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  		Figure 2. Number of individuals in respective WHO functional classes before, 4 weeks and 12 months after BAS. LTx = lung transplantation.

 
At follow-up (mean time to follow-up, 13.8 ± 11.9 months; range, 0.8 to 42 months), spontaneous closure with the recurrence of symptoms of right heart failure and increase in oxygen saturation confirmed on echocardiography occurred in six patients (54%). In three patients, repeat procedures were performed. In addition, one patient refused to undergo a second BAS.

Discussion

Despite similar levels of PAP, patients with Eisenmenger syndrome survive much longer than patients with primary PH.7 Interestingly, right-to-left shunt through a patent foramen ovale was reported to indicate better prognosis in patients with primary PH.8 Atrial septostomy was first performed in 1983 in the hope of providing similar benefits to remaining patients with primary PH.9 An artificially created right-to-left shunt across the interatrial septum improves left ventricular filling and output, and, despite shunt-induced systemic hypoxemia, leads to a net increase in oxygen tissue delivery.10 At the same time, RV filling pressures decrease, resulting in a lower tendency toward progressive dilatation and facilitating the control of peripheral venostasis. The beneficial effects of BAS are even more apparent during exercise, and lead to improved functional class and distance covered during a 6-min walk test. Most importantly, BAS seems to improve survival, increasing the chances of patients with PAH who are waiting for transplantation, and in some cases serving as its alternative.6

Potential complications include severe hypoxemia and acute left ventricular failure. Both are related to excessive right-to-left shunt through an oversized defect created at the atrial level. This occurred more frequently with the technique initially applied (blade balloon septostomy), which was similar to the Rashkind procedure that is used in the treatment of congenital heart disease in children.11 In patients with severe RV failure leading to a high pressure gradient between the right and the left atrium, the uncontrolled shunt was immediately life threatening, most probably explaining the unacceptably high mortality rate (25%) of patients undergoing balloon blade septostomy. In contrast, controlled balloon dilatation is considered to be safer due to a stepwise increase in the diameter of the defect.12 However, in patient 2, despite the use of a small balloon with a diameter of 6 mm, BAS resulted in severe shunt and uncontrolled systemic hypoxemia. Whether this was due to a very high right-to-left driving pressure across the interatrial septum or to an uncontrolled septal tear resulting in an oversized orifice remains unanswered. Importantly, it is crucial to make all efforts to decrease RAP and to control systemic pressure prior to attempted BAS.

Selection of the optimal time for BAS still remains controversial. This procedure is generally recommended only for patients with advanced disease. This is especially reasonable in patients whose conditions are deteriorating despite targeted IV, subcutaneous, and oral therapy with agents such as prostanoids or endothelin blockers. However, hypothetically, right-to-left drug shunting might decrease the expected pulmonary vascular effects while increasing systemic side effects. Reported series have indicated a high mortality rate among patients with end-stage disease who have been referred for BAS. This was also our experience, suggesting that elective and not rescue BAS should be the preferred approach in patients with PAH. It should be emphasized that no procedure-related complications occurred and that early results were encouraging. However, larger groups and longer observations of patients would be required to more precisely assess whether persistent clinical improvement can be achieved with BAS if the orifice remains open.

Considering more recently published data13141516 as well as our own initial experience, it seems that elective BAS offers treatment that is invasive and palliative but is apparently effective in providing functional improvement in patients with severe PH who are experiencing limited pulmonary flow that results in insufficient left ventricular filling and systemic output. This is not a negligible benefit in this predominantly young population with a severely limited life expectancy. Correct qualification, the timing of the procedure, as well as controlled stepwise balloon dilatation is important for achieving final success. However, there might be different indications for BAS according to local resources. In patients who have access to modern pharmacotherapy, BAS should probably not be attempted until combination therapy, including parenteral prostacyclin analogues, had failed to stabilize the patient’s condition. In most such cases, performing BAS would also mean a concomitant listing for transplantation. However, restricted economic resources and health-care strategies in some countries may temporarily block access to pharmacotherapy in a significant proportion of the global PAH population. Clinical teams in such countries might choose to attempt "early" BAS, at an earlier stage of PH, trying to recreate the physiology of Eisenmenger syndrome with little or no prior pharmacotherapy. Experience derived from those attempts may bring additional information about the safety and efficacy of BAS, and may allow for a more evidence-based definition of its the future role in the management of patients with PAH.

In the current series, in addition to the recognized risk for undergoing the procedure, our data suggest that some cases of progressive hypoxemia developing shortly after optimally performed BAS may not be due to an oversized septostomy opening. Pulmonary arteriolar vasospasm can be sometimes observed after BAS and seems to be related to a rapid mixed venous blood desaturation.17 To our knowledge, this potentially life-threatening complication has not been reported before. Importantly, it can be averted by the timely administration of pulmonary vasodilators, in our case inhaled iloprost, which can be gradually withdrawn. The described phenomenon might be particularly important when BAS is attempted as a sole therapeutic option and not on top of long-term treatment with potent pulmonary vasodilators. We hope that our observations not only permit a better understanding of the hemodynamic and respiratory consequences of BAS in patients with PH, but also help to reduce potentially preventable adverse outcomes, thus improving the safety profile of BAS.

Footnotes

Abbreviations: BAS = balloon atrial septostomy; CI = confidence interval; LAP = left atrial pressure; PAH = pulmonary arterial hypertension; PAP = pulmonary arterial pressure; PH = pulmonary hypertension; PVR = pulmonary vascular resistance; RAP = right atrial pressure; RV = right ventricle; SOT = systemic oxygen transport; WHO = World Health Organization

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Received for publication May 15, 2006. Accepted for publication October 2, 2006.

References

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