Lung Transplantation in Pulmonary Arterial Hypertension

Definition

Lung transplantation remains an important treatment option for patients with refractory PAH or PH who fail to achieve adequate risk reduction on optimised medical therapy. It addresses the underlying pulmonary vasculopathy directly and allows RV recovery. The modern era (post-2000) has seen major improvements in outcomes driven by: ECMO-based perioperative support, better understanding of post-transplant LV physiology, and patient selection refinement. In expert centres, 1-year survival now exceeds 90%.

Key Concepts

When to Refer

Referral to a transplant centre ≠ immediate listing. Early referral allows full evaluation, preparation, and optimal timing for listing. Patients often arrive too late, precluding careful evaluation.

Referral criteria — any of the following: (sources/PHT-RVsupport-WSPH-2019, rating: high)

• ESC/ERS intermediate or high risk on appropriate PAH medication
• REVEAL risk score >7 on appropriate PAH medication
• Progressive disease or recent hospitalisation for worsening of PAH
• Need for IV or SC prostacyclin therapy
• Known or suspected high-risk disease variants: PVOD, PCH, scleroderma-PAH, large/progressive pulmonary artery aneurysms
• Signs of secondary liver or kidney dysfunction due to PAH
• Recurrent haemoptysis

When to List

Listing criteria — all of the following should be considered: (sources/PHT-RVsupport-WSPH-2019, rating: high)

• Patient has been fully evaluated and prepared for transplantation
• ESC/ERS high risk on appropriate PAH medication (usually including IV/SC prostacyclin analogues)
• OR REVEAL risk score ≥10 on optimised medical therapy
• Expected 1-year mortality on medical therapy (>20%) exceeds expected 1-year post-transplant mortality (~10% in expert centres) → survival benefit is clear
• Local waiting time must inform listing timing

Additional listing considerations:

• Progressive hypoxaemia (especially in PVOD or PCH)
• Progressive (not end-stage) liver or kidney dysfunction due to PAH
• Life-threatening haemoptysis

Lung Allocation Score (LAS) limitations:

• LAS does not always reflect disease severity in PAH
• Modified LAS (released Feb 2015) adds: RAP ≥14 mmHg and 6MWD ≤300 m as independent mortality predictors beyond original LAS; also adds total bilirubin and CI
• Some countries have "exceptional LAS" or high-priority programmes for severe PH

Pre-Transplant Management

• Pre-transplant rehabilitation programmes benefit listed patients
• Ideal recipient is an ambulant outpatient — not all patients listed in ICU with ECLS can achieve comparable outcomes
• ECLS (VA-ECMO or PA-LA approach) as bridge to transplant is established when medical therapy fails — see concepts/ECLS-in-PH

Transplant Procedure

Type of Transplant

• Bilateral lung transplantation: method of choice for most patients with PAH (sources/PHT-RVsupport-WSPH-2019, rating: high)
• Combined heart-lung transplantation: historically used for patients with severe PH where "unconditioned" LV was thought unable to handle increased preload; largely replaced by bilateral Tx + post-operative ECMO strategy
• No degree of RV dysfunction precludes bilateral lung transplantation in PAH — almost any RV recovers within weeks post-transplant regardless of pre-transplant dilatation, dysfunction, or severity of TR

Intraoperative Support

• Intraoperative VA-ECMO has almost completely replaced conventional cardiopulmonary bypass
• ECMO advantages over CPB: fewer peri-operative complications (renal failure, transfusions), potentially better survival
• Pre-anaesthesia VA-ECMO established in patients with severe PH + RV failure to prevent haemodynamic collapse during induction

Post-Transplant Management

Why Extended ECMO is Needed

• The "unconditioned" LV: in severe PH, chronically reduced LV preload leads to a small, stiff, diastolic-dysfunctional LV
• After transplantation, the LV is suddenly exposed to normal/high preload → diastolic dysfunction → elevated filling pressures → pulmonary oedema (worse when patient is awake and agitated)
• This mechanism (LV failure, not residual PH) is the main cause of primary graft dysfunction in PAH transplantation
• Historical consequence: inability to wean from ventilator → prolonged ICU → death (sources/PHT-RVsupport-WSPH-2019, rating: high)

Post-Transplant ECMO Strategies

• Strategy 1 (Hannover approach): Extubation first, then continue VA-ECMO support 3–7 days while LV remodels; 1-year survival >90%
• Strategy 2: Brief post-operative ECMO in intubated patient until haemodynamic stabilisation + fluid balance normalisation + a few days of ventilation; 1-year survival >90%
• Both strategies prevent primary graft dysfunction and achieve comparable outcomes (sources/PHT-RVsupport-WSPH-2019, rating: high)
• A negative fluid balance (including haemofiltration when necessary) and extended ECMO support have substantially reduced early graft dysfunction

Outcomes in Expert Centres

• 1-year survival after lung transplantation for PH: >90% in experienced centres (1-year mortality ~10%)
• Historical 1-year mortality was higher for PAH than most other lung diseases due to early graft dysfunction — now dramatically improved with current perioperative strategy
• RV recovery after transplantation: almost universal within weeks, independent of pre-transplant severity
• Low-volume/high-risk procedure: should be concentrated in specialised centres

Ethical Considerations

• If transplantation and recovery are not realistic goals, advanced ICU care and ECLS are futile
• Best supportive care is appropriate when all treatment goals are unachievable
• Patient preferences should be explored early and proactively; perspectives may change when facing imminent death

Contradictions / Open Questions

• No RCT data exist for any aspect of lung transplantation strategy in PH: All recommendations are expert consensus from small series (sources/PHT-RVsupport-WSPH-2019, rating: high)
• Post-transplant ECMO strategy (extubation first vs intubated): Two approaches achieve similar 1-year survival but no head-to-head comparison exists; individual centre expertise is likely decisive
• LAS adequacy for PAH: Despite 2015 modifications, LAS may still inadequately reflect PAH severity in many health systems, particularly outside the US
• Combined heart-lung vs bilateral lung transplantation: Bilateral Tx + extended ECMO has largely replaced heart-lung Tx, but comparative evidence is limited and some centres continue heart-lung Tx for selected patients

Connections

• Related to concepts/Pulmonary-Hypertension — transplantation as treatment option for refractory PAH
• Related to concepts/Right-Ventricular-Failure — RV recovery post-transplant
• Related to concepts/ECLS-in-PH — ECMO as bridge to transplant and perioperative support
• Related to concepts/PAH-Risk-Stratification — REVEAL score and ESC/ERS risk strata drive referral/listing decisions

Sources

• sources/PHT-RVsupport-WSPH-2019 (high)