Extracorporeal Membrane Oxygenation as a Novel Bridging Strategy for Acute Right Heart Failure in Group 1 Pulmonary Arterial Hypertension

Abstract

Patients with group 1 pulmonary arterial hypertension (PAH) and decompensated right heart failure (RHF) were not previously considered for extracorporeal membrane oxygenation (ECMO) as bridge to transplantation (BTT) or bridge to recovery (BTR) because options were limited by long transplantation wait times and perceived inability to wean ECMO. In a retrospective review, we describe our center’s multidisciplinary mechanical–medical approach to ECMO as a bridging therapy for PAH (2009–2012). Suitability for ECMO was determined using a defined algorithm. Six patients (age, 32 ± 11 years) underwent mechanical–medical bridging. Two transplant-eligible patients underwent successful BTT. The four patients ineligible for transplantation underwent BTR with escalation of targeted medical therapies before weaning off ECMO. Three of four BTR patients survived to ECMO decannulation (duration, 12 ± 7; range, 7–23 days). In this single-institution experience, mechanical–medical BTT and BTR with ECMO and targeted PAH therapies were used as a novel treatment strategy to successfully manage acute RHF in PAH.

Historically, World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH) patients with refractory right heart failure (RHF) were not offered extracorporeal membrane oxygenation (ECMO) as a bridging therapy because of the notion that PAH patients would not be able to wean off ECMO as a bridge to recovery (BTR) from an acute decompensation. Furthermore, with long lung transplantation waiting times, particularly for PAH patients with RHF, using ECMO as bridge to transplantation (BTT) did not seem feasible. However, in the context of recent advances in targeted medical therapies and ECMO technology, there may be an emerging role of ECMO as a bridging therapy for acute decompensation in chronic group 1 PAH patients. We report our single-center experience using ECMO and a multidisciplinary team approach to bridge group 1 PAH patients to either lung transplantation or recovery.

Methods

This is a retrospective case series of consecutive group 1 PAH patients who underwent ECMO as BTR or BTT at the New York-Presbyterian Hospital/Columbia University College of Physicians and Surgeons between 2009 and 2012. Demographic data, including medical therapies, ECMO configurations, ECMO duration, and outcomes, are reported. Our local institutional review board approved this work (IRB Exp, approval #: IRB-AAAF3940).

Results

Six patients with group 1 PAH (all are females; age, 34 ± 9 years; range, 21–48 years) underwent mechanical–medical bridging with ECMO between 2009 and 2012. Venoarterial ECMO was used in four patients. In two patients with large congenital atrial septal defects (ASDs), venovenous ECMO was feasible and initiated via a bicaval dual-lumen cannula (Maquet Cardiovascular, Wayne, NJ), with the reinfusion jet directed across the ASD, effectively creating an oxygenated right-to-left shunt providing “physiologic V-A ECMO,” without the need for arterial cannulation.¹ Suitability for ECMO, including eligibility for an extubated, nonsedated, ambulatory strategy with an upper-body configuration, was determined using a clinical algorithm (Figure 1). Lung transplantation–eligible patients, who were actively listed, received ECMO as BTT and those not eligible were treated as BTR.

Figure 1: Algorithmic approach to mechanical–medical bridging therapy in pulmonary arterial hypertension (PAH). ASD, atrial septal defect; BTR, bridge to recovery; BTT, bridge to transplant; ECMO, extracorporeal membrane oxygenation; HD, hemodynamic; IV, intravenous; PH, pulmonary hypertension; RHF, right heart failure; VA, venoarterial; VV, venovenous.

Two patients underwent BTT (Table 1; patients 1 and 3). Patient 1 had PAH associated with an unrepaired secundum ASD and was on maximal medical therapy when she developed massive hemoptysis. She underwent urgent coil embolization of aorto-pulmonary collaterals but remained severely cyanotic with suprasystemic pulmonary arterial pressures before ECMO initiation. Patient 3 had idiopathic PAH with severe RHF and ensuing renal failure, which would have led to removal from the lung transplantation list. She was placed on ECMO and renal function rapidly improved. We used an extubated, upper-body venoarterial ECMO approach to permit active physical therapy, including ambulation, while awaiting lung transplantation.² Physical conditioning in this setting is essential to maintaining transplant candidacy.

Table 1: Baseline Demographics, Pulmonary Hypertension Management, and Outcomes

Targeted PAH therapies including ambrisentan, intravenous epoprostenol, intravenous treprostinil, and sildenafil were weaned off cautiously during the ECMO course after an initial downtitration of intravenous prostanoid dosages upon ECMO initiation. The initial prostanoid downtitration of at least 10% of the original dosage was performed to avoid systemic hypotension with initiation of venoarterial ECMO and systemic delivery of the drug. Both BTT patients successfully underwent bilateral lung transplantation (ECMO day 7 and day 19).

Four PAH patients received ECMO as BTR, all of whom had an identifiable trigger for an acute decompensation (pneumonia, n = 2; hemoptysis, n = 1; acute RHF leading to cardiac arrest, n = 1), including one patient who was not previously medically optimized. Three patients were placed on ECMO during cardiac arrest; two within our institution and one at an outside hospital by our ECMO transport team. As opposed to ECMO for BTT, where targeted PAH therapies were weaned off, during BTR, targeted medical therapies including IV prostanoids were escalated and optimized before weaning off of ECMO (Table 1).

Five of the six patients (83%) survived to ECMO decannulation (duration 12 ± 7 days; range, 7–23). Both BTT patients underwent successful lung transplantation and were discharged to home. Three of the four BTR patients (75%) survived to ECMO decannulation, with two patients (50%) surviving to discharge. One patient experienced severe anoxic brain injury during cardiac arrest just before cannulation, ultimately leading to withdrawal of life support. Two patients died from complications of pneumonia; one who remained in the hospital awaiting lung transplantation and the other 2 months after discharge. In one BTR patient, epoprostenol was weaned off after full recovery before hospital discharge, and she remains functionally independent. Complications of ECMO included right arm neuropathy in two patients, with resolution in one. One patient required tracheostomy.

Discussion

Patients with group 1 PAH often die of acute RHF while waiting for lung transplantation or during an acute respiratory illness. However, with advances in targeted PAH therapies and ECMO technology, there seems to be an emerging role of ECMO in bridging group 1 PAH patients to recovery or transplantation.^3–7 In this single-center experience, medical–mechanical bridging was considered for patients with group 1 PAH and decompensated RHF as BTT or BTR. If patients were actively listed for lung transplantation and the likelihood of near-term survival without it was poor, they were considered for BTT by a multidisciplinary team consisting of both medical and surgical specialists. The use of an extubated, nonsedated, upper-body ambulatory ECMO in these patients facilitated physical conditioning, which further optimized their transplant candidacy.^2,8–10 An additional, unanticipated benefit for PAH patients is that ECMO support may reduce the time on the lung transplantation waiting list.³

In all of these cases, “physiologic V-A ECMO” was selected, either by conventional V-A configuration or by using a V-V ECMO configuration in the presence of a large congenital ASD. There is no role for straight conventional V-V ECMO in patients with severe PAH in the absence of a large congenital systemic to pulmonary shunt/communication. Two patients in this report had congenital ASDs enabling use of V-V ECMO with a single dual-lumen Avalon Elite catheter and directed oxygenated return across the interatrial communication. None had intentional creation of atrial septostomy at the time of ECMO initiation. Although atrial septostomy might be feasible in a patient who is bridging to lung transplantation from ECMO, it would pose a significant risk for profound hypoxemia in a PAH patient who is on ECMO as BTR as they weaned from ECMO; the atrial septostomy would have to be at least 2 cm diameter to accommodate venous return adequately from the Avalon cannula. Upon decannulation from ECMO, a patient with baseline severe PAH would then develop severe hypoxemia because of right-to-left shunting which would not be well tolerated. For patients bridging to lung transplantation, the creation of an atrial septostomy large enough (2 cm) to accommodate venous return would be technically challenging even with a cutting balloon but could be done. In this scenario however, a single cannula with an iatrogenic atrial septostomy would add more risk than benefit with a decompensating PAH patient who requires ECMO, making V-A ECMO the physiologically preferred method of support. Therefore, we have only included patients with large congenital ASDs in the algorithm for this approach (Table 2).

Table 2: ECMO Configurations, Duration, and Settings

Establishing whether a patient would be suitable for BTR versus BTT is a critical part of the initial decision process before ECMO cannulation. Our team’s strategy was to use BTT for patients who had decompensated RHF associated with PAH, and who were already actively listed for lung transplantation at our institution. The criteria for BTR were not previously established, so a multidisciplinary team approach was used for patient selection. The team included a thoracic surgeon, pulmonary hypertension specialist, and medical-ECMO/critical care specialist. A neurologist was consulted if there was a concern about compromised neurologic status. Together, the multidisciplinary team decided whether the PAH patient had 1) an acute insult that could be reversed while on ECMO or 2) inadequate management of PAH before the acute decompensation where ECMO would afford the opportunity to escalate targeted PAH therapy and recovery from the acute illness. If a patient decompensated from chronic worsening RHF, and was not a candidate for immediate lung transplantation listing, they were not considered as a BTR candidate. Three out of four patients survived BTR short-term. The one long-term survivor of BTR approach (patient 2) was a patient who was highly functional with WHO functional class II symptoms at baseline. The patient had a history of complex congenital heart surgery as a young child but was an ideal candidate for BTR as the patient was not recovered during cardiac arrest and was not deconditioned from severe RHF before BTR for acute pneumonia.

In BTR patients, ECMO can enable temporary cardiopulmonary support during an intercurrent illness, or even after cardiac arrest, enabling time to both treat the underlying trigger and optimize the targeted PAH medical regimen before weaning ECMO support. The medical strategy for managing these patients while on ECMO and during transition off must be individualized. For BTT patients, the targeted PAH therapies were weaned while on ECMO, whereas for the BTR patients, the targeted PAH therapies were temporarily decreased while on ECMO and then escalated and optimized before weaning off ECMO (Table 1). The decision-making process for these patients requires swift multidisciplinary collaboration as it may occur during a sudden cardiac arrest. The medical and surgical teams must determine whether there is a reversible process superimposed on the underlying chronic PAH. In cases when a patient presents with severe PAH that has not been maximally treated (example, patient 4), there may also be a role of ECMO as BTR while the PAH-targeted therapy is optimized. For any unstable patient being considered for BTT or BTR at a transferring hospital, an ECMO transport team with expertise in ECMO, pulmonary hypertension, and lung transplantation may be required to safely transport the patient to a center.¹¹ Patient selection for a strategy of BTR is critical and, as experience grows, it will be important to develop evidence-based guidelines on patient selection.

Conclusions

In this single-institution experience, ECMO, in combination with targeted PAH therapies, was successfully used as BTT or BTR for acute RHF in group 1 PAH patients. ECMO as BTT and BTR leads to a significant improvement in gas exchange and end-organ function. This novel approach for group 1 PAH patients requires further study and should only be undertaken in pulmonary hypertension centers with a combined medical and surgical team with extensive experience in the management of both PAH and ECMO. As experience grows, we may anticipate earlier institution of ECMO in suitable group 1 PAH patients.