Balloon Dilation Atrial Septostomy and Potts Anastomosis for Severe Pulmonary Arterial Hypertension: Why, When, and How

Background and Rationale

There is both clinical and experimental evidence suggesting that, in the setting of PAH, an interatrial right-to-left shunt may be of benefit. From a clinical standpoint, we know that PAH patients with a patent foramen ovale survive longer than those without one.⁷ We also know that Eisenmenger patients with a comparable degree of pulmonary hypertension (PH) survive longer and do not develop severe RV dysfunction when compared to patients with PAH, reflecting better RV performance in Eisenmenger's physiology.^8,9 The first study exploring and supporting the role of interatrial shunts in PAH was published by Austen et al almost 50 years ago.¹⁰ This study is extraordinary, not only because it demonstrated that the surgical creation of an atrial septal defect (ASD) in the setting of experimental RV hypertension provided hemodynamic benefit at rest and during exercise, but also because it described most of the knowledge we now possess regarding the physiological changes caused by atrial septostomy in the setting of PAH. In his original publication, Austen proposed that the surgical creation of an ASD should be performed for the management of patients with “primary” pulmonary hypertension (PPH).¹⁰ Interestingly, this operation never took place in part because years later, nonsurgical creation of an ASD for the management of CHD (ie, transposition of the great arteries) was successfully achieved by Rashkind⁵ and Park.⁶

Continuous improvements in transcatheter techniques to create an ASD became an attractive alternative in the setting of human PAH. In 1983, Rich and Lam¹¹ were the first to perform this intervention. The rationale was that clinical deterioration and death in PPH were associated with obstruction to systemic flow and dilation and failure of the RV, thus creation of an ASD in this context would allow a right-to-left shunt to increase systemic output and allow for decompression of the right chambers, alleviating RVF. Initial case series published in the early 1990s^12–14 appeared to confirm this hypothesis and showed promising hemodynamic benefits for PAH patients, albeit with a high procedure-related mortality. Hence, recommendations to minimize procedure-related mortality were made at the World Symposium on PH in 1998,^15,16 and have remained since.

Procedure

The technique of atrial septostomy has evolved over time and has undergone minor modifications by performing centers. At present, balloon dilation atrial septostomy (BDAS) is the preferred technique.^14,17 It involves a standard right and left heart catheterization; baseline right and left heart pressures are recorded simultaneously and cardiac output is calculated by Fick method. Following baseline hemodynamic assessment, standard trans-septal puncture is performed using a Brockenbrough needle and a Mullins-type dilator. In recent years, the use of intracardiac echocardiography has been advocated to acquire better visualization of the atrial septum to guide trans-septal puncture.¹⁸ In addition, radiofrequency-assisted perforation of the atrial septum has been described as a safe and feasible alternative to conventional needle puncture.¹⁹ Once access into the left atrium is gained, the septostomy orifice is sequentially dilated using noncompliant peripheral balloons in a carefully graded step-by-step manner, beginning with a 4 mm diameter balloon, followed by dilation with an 8 mm, 12 mm, and 16 mm balloon if needed (Figure 1). Between each step and after a 3-minute waiting period allowing hemodynamic stabilization, left ventricular end-diastolic pressure (LVEDP) and arterial oxygen saturation (SaO₂) are obtained. The final diameter of the ASD is reached on an individual basis when any of the following criteria are met: 1) LVEDP increase to ≥18 mm Hg; 2) decrease in SaO₂ to 80% or below; or 3) a 10% SaO₂ decrease from baseline. Post-procedure care requires a stay in the intensive care unit for at least 48 hours, where continuous supplementary oxygen is delivered and appropriate anticoagulation is started. Upon hospital discharge, all patients are followed as outpatients, with particular attention to maintaining effective oral anticoagulation and appropriate hemoglobin levels.^14,17

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Worldwide Experience

Proper appreciation of the role of atrial septostomy in the management of PAH has been limited mainly by the lack of controlled clinical trials demonstrating its efficacy and safety. Most of our knowledge regarding the procedure comes from small series of patients or case reports. In addition, the relative success of current pharmacologic strategies, as well as the notion of a previously reported high procedure-related mortality^12,13,20 have prevented widespread use of this valuable intervention. Despite these limitations, experience with atrial septostomy has increased in the past few years.

In a recent worldwide experience review,²¹ 372 procedures performed in 324 patients were identified; 304 had been reported in case series and another 20 as case reports. This experience is further enriched by the recent report of 85 procedures performed in 63 patients reported in 4 series^22–25 and 3 more reported as case reports,^18,26,27 showing similar results. These studies demonstrate that atrial septostomy has largely been performed in young people (mean age 31 years), mostly women (∼70%), and in patients with idiopathic PAH (IPAH) in functional classes III and IV (∼77%). In a significant proportion, BDAS has been performed in patients with refractory CHF and recurrent syncope despite maximal medical treatment. In this context, BDAS is the procedure of choice, and the size of the defect usually varies from 8 to 18 mm, with a mean value of approximately 11 mm. A large majority of patients (∼86%) survive the procedure, with 90% of patients describing improvement in symptoms and functional capacity. Furthermore, approximately 13% of patients received a lung transplant at some point after the procedure.²¹

Overall procedure-related mortality is 14%, with 8% occurring within the first 24 hours due to refractory hypoxemia and an additional 6% occurring within the first month post-intervention. Baseline right atrial pressure (RAP), in particular RAP >20 mm Hg, remains the most significant risk factor for procedure-related mortality.²⁸ Low SaO₂ following intervention, perhaps in relation to an oversized septostomy, has also been associated with higher risk of death.²¹ Technical expertise and experience with the procedure also contribute to mortality, as reflected by lower mortality reported in recent series.^22,23,29

The hemodynamic effects of an atrial septostomy depend highly on the baseline RAP. Table 1 shows how a higher baseline RAP will result in a more pronounced hemodynamic effect, particularly when RAP is >20 mm Hg (ie, severe RVF). However, as previously mentioned, patients with RAP >20 mm Hg will also have a significantly higher risk of death during the procedure as a result of refractory hypoxemia. Thus, it appears that the best risk-benefit ratio corresponds to the group with RAP between 10 and 20 mm Hg. Nevertheless, it should be noted that even when RAP is <10 mm Hg (predominantly patients presenting with syncope), there is a significant increase in CI as well as an improvement in functional class, suggesting that septostomy at an earlier stage of disease could be beneficial.²¹ It is also important to note that most of the hemodynamic variables reported have been obtained during the resting state and that the hemodynamic impact might be different and better during exercise, when the septostomy could be functioning as a “safety pop-off valve.” This concept of better function in patients having an ASD during exercise in the setting of RV hypertension was demonstrated by Austen many years ago,¹⁰ and may in part explain the improvement in exercise tolerance reported by patients in some series.^14,30–32

Table 1. Hemodynamic effects of atrial septostomy according to baseline right atrial pressure

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With regard to the long-term effects on RV function after septostomy, information is scarce, but there appears to be sustained improvement. Kerstein¹³ and Law³³ have shown improvement in long-term hemodynamics: approximately 2 years after septostomy. Likewise, Espínola-Zavaleta³⁴ showed that, 3 to 6 months after septostomy, there was a decrease in right atrial area and in end-systolic and end-diastolic RV areas, a finding compatible with decompression of the right-sided chambers. In agreement with this decompression phenomenon and the relief of failure is the report from O'Byrne et al,³⁵ demonstrating a significant decrease in b-type natriuretic peptide (BNP) after septostomy. Atrial septostomy may also have additional beneficial effects on RV function. Ciarka and coworkers³⁶ showed a significant decrease in muscle sympathetic nerve activity after the procedure; of interest, sympathetic overdrive in PAH may be one mechanism involved in RVF.³⁷

Spontaneous closure of the septostomy is not an infrequent finding during follow-up. This situation can be overcome by repeating the procedure.¹⁴ In addition, alternative interventions such as deployment of a fenestrated device (ie, Amplatzer septal occluder),^38–42 concomitant use of a butterfly stent (flared at both extremes),^32,43,44 and cryo-ablation of the septostomy borders¹⁸ have been described. However, the safety and long-term efficacy of these additional interventions remains to be determined.

There is no definitive answer regarding the optimal size of the defect, and the size of the septostomy should be performed on an individual basis. One should aim to increase cardiac output and decompress the RV, but refractory hypoxemia should be avoided. Based on recent experimental data, it would appear that increasing cardiac output no more than 15% to 20% from baseline would provide the greatest benefits and results.^45–47

Although atrial septostomy improves hemodynamic variables that correlate with clinical improvement and survival, true impact of septostomy on survival of patients with PAH is difficult to assess due to lack of controlled long-term studies (something that is also true for most of the current pharmacological options). However, the survival rates for patients with long-term follow-up in different case series appear to be better when compared with either historical controls or predicted survival.^{13,22,29,32,33} Unfortunately, during follow-up there is a significant drop of cumulative survival in time, reflecting the palliative nature of the procedure. In other words, atrial septostomy does not cure or reverse PAH and the beneficial effects of the procedure erode over time. The short- or median-term impact on survival, however, provides valuable time for the application of other noteworthy interventions (ie, PAH-specific drugs and/or transplantation).

In summary, based on the review of the worldwide collective experience, atrial septostomy stands as an additional strategy in the treatment of severe RVF from PAH. In the majority of cases, the procedure has been performed at an advanced stage of the disease in patients already burdened with a significantly higher risk of death; yet, despite progression of disease in these patients, BDAS frequently leads to clinical and hemodynamic improvement. Analysis of the worldwide clinical experience suggests that procedure-related mortality is decreasing. In this regard, the following guidelines are important: 1) do not perform septostomy in moribund patients (those with RAP >20 mm Hg); 2) always perform BDAS using a step-by-step approach; 3) employ constant monitoring of hemodynamic variables (RAP, LVEDP, CI, and SaO₂; 4) limit the size of the defect to aim for a decrease in baseline SaO₂ of no more than 10% and an increase in baseline CI of no more than 15% to 20%; 5) BDAS should only be performed in centers widely experienced in both interventional cardiology and PH. The “ideal” candidate for the procedure remains a patient in functional class III, with RAP between 10 and 18 mm Hg and a baseline SaO₂ >90%, with history of syncope or persistent RVF despite maximal medical therapy as part of a goal-oriented strategy.³ The procedure may also be considered either as a bridge to lung transplant or as the sole treatment modality when other therapeutic options are not available.