Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Details

CTEPH is Group 4 pulmonary hypertension, defined by persistent organised thromboembolic obstructions within the pulmonary arteries causing pre-capillary PH (mPAP >20 mmHg, PAWP ≤15 mmHg, PVR >2 WU) for >3 months despite adequate anticoagulation, most commonly following acute pulmonary embolism (PE). CTEPH is under-diagnosed; registry data indicate a prevalence of 26–38 cases/million adults. The 2022 ESC/ERS guidelines introduced the term CTEPD (chronic thromboembolic pulmonary disease) for patients with persistent thromboembolic disease without meeting the haemodynamic PH threshold. Treatment is multimodal: surgical pulmonary endarterectomy (PEA) is the treatment of choice for accessible disease; balloon pulmonary angioplasty (BPA) was upgraded to Class I for inoperable cases in 2022; riociguat remains the only approved medical therapy.

Key Facts

Epidemiology

• Prevalence: 26–38 cases/million adults; incidence 2–6 cases/million adults. Increasing due to greater disease awareness and more active post-PE screening. (sources/PHT-ESC-2022, rating: very high)
• CTEPH after acute PE: Cumulative incidence 0.6% in all PE patients; 3.2% in survivors; 2.3% at 2 years in prospective data (FOCUS study). Up to 50% of patients have persistent perfusion defects after acute PE, but clinical relevance is unclear. (sources/PHT-ESC-2022, rating: very high)
• Misdiagnosis risk: Due to insufficient awareness, some CTEPH patients are initially misclassified as acute PE — delays diagnosis and treatment. (sources/PHT-ESC-2022, rating: very high)

CTEPD — New Entity (2022/2026)

• CTEPD (without PH): All patients with persistent perfusion defects attributable to post-thrombotic deposits, whether or not haemodynamic PH criteria are met. Newly formalised in ESC 2022. Prevalence unknown; requires further study. (sources/PHT-ESC-2022, rating: very high)
• CTEPD management: Long-term anticoagulation on individual basis (Class IIa); PEA or BPA in selected symptomatic patients (Class IIa). (sources/PHT-ESC-2022, rating: very high)
• AHA/ACC 2026 CTEPD definition: Encompasses patients with prior PE who have persistent symptoms, residual pulmonary vascular obstruction (RPVO), and pulmonary vascular disease-related exercise limitation — both with and without resting PH. Up to 50% of acute PE patients have persistent perfusion defects on imaging (RPVO), many asymptomatic. CTEPD with PH (CTEPH) occurs in ~3% of acute PE; CTEPD without PH is felt to be at least as prevalent. (sources/acute-pe-aha-2026, rating: very high)

CTED — the 2019 Predecessor Term

• ESC 2019 introduced this entity as CTED (chronic thromboembolic disease), not CTEPD: "some patients may present with normal pulmonary haemodynamics at rest despite symptomatic disease. If other causes of exercise limitation are excluded, these patients are considered as having chronic thromboembolic disease." The acronym was changed to CTEPD by the 2022 ESC/ERS PH guideline and carried into AHA/ACC 2026 — the entity is the same, and the wiki uses both terms across sources (sources/acute-pe-esc-2019, rating: very high)
• ESC 2019 explicitly states medical therapy is not indicated in CTED — patients with documented post-thrombotic obstructions but no PH at right heart catheterisation at rest (sources/acute-pe-esc-2019, rating: very high)
• ESC 2019 follow-up recommendations (the origin of the current pathway): routine clinical evaluation 3–6 months after acute PE (Class I/B); an integrated model of post-PE care involving hospital specialists, qualified nurses and primary care physicians (Class I); referral to a PH/CTEPH expert centre for symptomatic patients with mismatched perfusion defects on V/Q persisting beyond 3 months (Class I/C); further diagnostic evaluation should be considered for persistent or new-onset dyspnoea/exercise limitation (IIa/C); and may be considered in asymptomatic patients with CTEPH risk factors (Class IIb — upgraded from III in 2014). Dyspnoea severity standardised by the Medical Research Council scale or WHO functional class (sources/acute-pe-esc-2019, rating: very high)
• ESC 2019 also flags deconditioning as the usual explanation: in survivors with functional limitation, muscle deconditioning — particularly with excess body weight and cardiopulmonary comorbidity — is largely responsible, rather than residual thrombi or persistent PH. Consequently, when V/Q is normal and symptoms persist unexplained, alternative causes including deconditioning are pursued rather than escalating the CTEPH workup (sources/acute-pe-esc-2019, rating: very high)

CTEPD Surveillance After Acute PE (AHA/ACC 2026)

• Symptom screening every visit for ≥1 year post-PE (COR 1/C-LD): ask about dyspnea and functional limitations at every follow-up visit to screen for CTEPD. (sources/acute-pe-aha-2026, rating: very high)
• Evaluation for persistent symptoms ≥3 months: recommended diagnostic evaluation with TTE + lung perfusion scan (V/Q or SPECT/CT) (COR 1/B-NR); CPET reasonable to exclude CTEPD (COR 2a/B-NR). (sources/acute-pe-aha-2026, rating: very high)
• TTE alone is insufficient: one-third of confirmed CTEPD with PH patients had normal TTEs in retrospective series; 40% of CTEPD patients had no echocardiographic PH signs but had CPET evidence of impaired pulmonary perfusion. (sources/acute-pe-aha-2026, rating: very high)
• V/Q negative predictive value: approaches 100% for excluding CTEPD. (sources/acute-pe-aha-2026, rating: very high)
• Timing: vascular obstruction does not change after 3 months post-PE; waiting longer only delays diagnosis. Median time to CTEPD with PH diagnosis: 129 days (FOCUS study). (sources/acute-pe-aha-2026, rating: very high)
• Continue anticoagulation during CTEPD evaluation to prevent recurrent VTE/CTEPD progression (COR 1/B-NR). (sources/acute-pe-aha-2026, rating: very high)
• Routine imaging in asymptomatic patients with resolved symptoms: NOT beneficial (COR 3:NB/B-NR). (sources/acute-pe-aha-2026, rating: very high)
• Pulmonary rehabilitation: reasonable for persistent impairment when CTEPD is excluded (COR 1/B-R). (sources/acute-pe-aha-2026, rating: very high)
• Referral: CTEPD with PH → expert centre (COR 1/C-LD); CTEPD without PH → consider expert centre (COR 2a/C-LD). (sources/acute-pe-aha-2026, rating: very high)

Diagnosis

• V/Q scintigraphy: Recommended for screening for CTEPH in unexplained PH (Class I/C); mismatched perfusion defects distinguish CTEPH from PAH. (sources/PHT-ESC-2022, rating: very high)
• CT pulmonary angiography: Recommended in suspected CTEPH (Class I/C); intravascular filling defects, mosaic perfusion, enlarged bronchial arteries on imaging. (sources/PHT-ESC-2022, rating: very high)
• Digital subtraction angiography: Should be considered in the CTEPH work-up (Class IIa). (sources/PHT-ESC-2022, rating: very high)
• Echocardiography: Preferred first-line non-invasive test in suspected CTEPH (pre-capillary PH pattern: RV/RA enlargement). (sources/PHT-ESC-2022, rating: very high)
• RHC: Required to confirm pre-capillary haemodynamic profile and exclude PAH. (sources/PHT-ESC-2022, rating: very high)
• ESC 2019 imaging performance (sources/acute-pe-esc-2019, rating: very high):
  • Planar V/Q lung scan is the suitable first-line modality — 96–97% sensitivity and 90–95% specificity for CTEPH. SPECT appears less sensitive than planar V/Q when assessed at a level, which is why the 2019 guideline kept planar as first-line while the 2026 acute-PE guideline prefers V/Q SPECT
  • CTPA should not be used as a stand-alone test to exclude CTEPH, though it is gaining ground as a diagnostic modality. Newer options include dual-energy CT, which allows simultaneous assessment of morphology and perfusion
• Antiphospholipid syndrome testing: Class I — recommended in all CTEPH patients. VKA anticoagulation recommended if antiphospholipid syndrome confirmed (Class I). (sources/PHT-ESC-2022, rating: very high)

Risk Factors for CTEPH

• History of PE (prior symptomatic PE in ~75%; may occur without recognized PE history)
• Antiphospholipid syndrome
• Permanent intravascular devices (pacemaker leads, central venous catheters)
• Inflammatory bowel disease
• Essential thrombocythaemia, splenectomy
• High-dose thyroid hormone replacement
• Malignancy
• ESC 2019 (Table 13) organises these by timing and adds several (sources/acute-pe-esc-2019, rating: very high):
  • Findings related to the acute PE event, obtained at diagnosis: previous episodes of PE or DVT; large pulmonary arterial thrombi on CTPA; echocardiographic signs of PH/RV dysfunction; CTPA findings suggesting pre-existing chronic thromboembolic disease
  • Concomitant chronic diseases/conditions, documented at PE diagnosis or at 3–6-month follow-up: ventriculo-atrial shunts; infected chronic i.v. lines or pacemakers; history of splenectomy; thrombophilic disorders, particularly APS and high coagulation factor VIII; non-O blood group; hypothyroidism treated with thyroid hormones; history of cancer; myeloproliferative disorders; inflammatory bowel disease; chronic osteomyelitis
• A history of acute PE was reported by 75% of patients in an international CTEPH registry (sources/acute-pe-esc-2019, rating: very high)

Management

• Lifelong anticoagulation: Class I/C — for all CTEPH patients regardless of VTE history. VKA preferred in antiphospholipid syndrome. (sources/PHT-ESC-2022, rating: very high)
• Multidisciplinary CTEPH team review: Class I — all CTEPH patients must be reviewed for multimodality management (surgery, BPA, medical therapy). (sources/PHT-ESC-2022, rating: very high)
• PEA (pulmonary endarterectomy): Class I — treatment of choice for patients with accessible fibrous obstructions in the main, lobar, or segmental pulmonary arteries; performed under deep hypothermia circulatory arrest. (sources/PHT-ESC-2022, rating: very high)
• PEA operative detail (ESC 2019) — unlike surgical embolectomy for acute PE, PEA requires a true bilateral endarterectomy through the medial layer of the pulmonary arteries, under deep hypothermia and intermittent circulatory arrest without cerebral perfusion. Post-operative ECMO is standard of care in PEA centres: early reperfusion oedema may require veno-arterial ECMO, and severe persistent PH may need bridging to emergency lung transplantation. Combining ECMO with surgical embolectomy is supported in high-risk PE with or without CPR (sources/acute-pe-esc-2019, rating: very high)
• Natural history without surgery: in two historical trials before surgical treatment was available, mean PAP >30 mmHg was related to poor survival, similar to idiopathic pulmonary arterial hypertension. This is the reference point against which the benefit of PEA and BPA is judged (sources/acute-pe-esc-2019, rating: very high)
• BPA registry data (ESC 2019): the largest published registry at the time — 249 patients, mean age 61.5 years, treated 2004–2013 across seven Japanese centres — showed mean PAP falling from 43 to 24 mmHg after completion of treatment. BPA requires particular expertise because the complexity and individual variability of the pulmonary arterial tree greatly exceeds that of other vascular beds; complications include wire- and balloon-induced injury. It has also been used sequentially for PH persisting after PEA, and rarely as "rescue" in unstable patients (sources/acute-pe-esc-2019, rating: very high)
• Anticoagulation in CTEPH (ESC 2019): lifelong oral anticoagulation with VKAs is recommended, including after successful PEA or BPA. Optimal medical treatment otherwise consists of anticoagulants plus diuretics and oxygen for heart failure or hypoxaemia (sources/acute-pe-esc-2019, rating: very high)
• BPA (balloon pulmonary angioplasty): Class I (upgraded from IIb in 2015) — recommended for technically inoperable patients or those with residual PH after PEA with distal obstructions amenable to BPA. Medical therapy should be considered prior to BPA (Class IIa). (sources/PHT-ESC-2022, rating: very high)
• BPA procedural standard: Disease-level classification guides PEA vs BPA selection: levels 1–3 (main/lobar/segmental) → PEA preferred; level 4 (subsegmental) → BPA Class I. Lesion types (ring/web = standard risk; subtotal/total occlusion = higher risk; tortuous vessels = highest risk, >40% vascular complications, avoid BPA). Pd:Pa >0.80 is empirical adequacy threshold. 4–8 sessions typically required for complete revascularisation. (sources/BPA-AHA-2024, rating: very high)
• BPA safety trends (2013–2022): Meta-analysis (1675 patients, 7603 procedures): hemoptysis/vascular injury halved (14.1% → 7.7%); lung injury fell sharply (11.3% → 1.4%); invasive MV (0.7% → 0.1%); mortality (2.0% → 0.8%). Improvement attributed to technical refinement, better patient/lesion selection, and adjunctive vasodilator therapy. (sources/BPA-AHA-2024, rating: very high)
• RACE trial: BPA vs riociguat in non-operable CTEPH (PVR >4 WU) — BPA achieved significantly greater PVR reduction; riociguat pretreatment before BPA supported. (sources/BPA-AHA-2024, rating: very high)
• MR BPA trial: Japanese multicentre RCT confirming BPA superiority over riociguat in inoperable CTEPH. (sources/BPA-AHA-2024, rating: very high)
• Expert centre requirements (AHA/ESC): ≥30 BPA patients/year or >100 BPA procedures and >50 PEA surgeries/year; must offer both PEA and BPA; multidisciplinary team including PEA surgeon, BPA interventionalist, imaging expertise, PH physician, ECMO on-site. (sources/BPA-AHA-2024, rating: very high)
• See concepts/Balloon-Pulmonary-Angioplasty for comprehensive BPA procedural framework.
• Riociguat (sGC stimulator): Class I — for symptomatic inoperable CTEPH or persistent/recurrent PH after PEA. Only guideline-approved medical therapy for CTEPH. (sources/PHT-ESC-2022, rating: very high)
• Multimodality approach (sGC/PDE5i + ERA + prostacyclin): Class IIa — for persistent PH after PEA or inoperable CTEPH; combination strategies under evaluation. (sources/PHT-ESC-2022, rating: very high)
• Off-label PAH drugs in inoperable CTEPH: Class IIb. (sources/PHT-ESC-2022, rating: very high)
• Treprostinil s.c.: Class IIb — for WHO-FC III–IV inoperable or residual/recurrent CTEPH. (sources/PHT-ESC-2022, rating: very high)
• Long-term follow-up: Class I — after PEA and BPA, and for CTEPH patients on medical therapy. (sources/PHT-ESC-2022, rating: very high)

Contradictions / Open Questions

• BPA upgraded to Class I with low-quality evidence: GRADE assessment rates BPA evidence as Very Low quality (primarily Japanese single-centre registry data); external validity in non-specialised centres and non-Japanese populations remains uncertain. (sources/PHT-ESC-2022, rating: very high)

• BPA vs. riociguat vs. combined approaches: RACE and MR BPA RCTs show BPA superior to riociguat for PVR reduction in inoperable CTEPH with PVR >4 WU; RACE supports riociguat pretreatment before BPA. No data for BPA vs medical therapy in surgically inaccessible disease with mild or no haemodynamic impairment. (sources/PHT-ESC-2022, rating: very high; sources/BPA-AHA-2024, rating: very high)

• Post-PEA BPA: Class I recommendation is based only on observational case series data; hemoptysis and vessel injury rates appear higher post-PEA than in de novo distal CTEPH. Shared decision-making recommended. (sources/BPA-AHA-2024, rating: very high)

• BPA vs PEA in level 3 (mid-distal segmental) disease: No randomised data; expert disagreement on optimal treatment; local BPA availability may influence recommendations toward BPA even in patients who might benefit from PEA. (sources/BPA-AHA-2024, rating: very high)

• Pd:Pa >0.80 adequacy threshold: Empirical, not validated — adequate revascularisation endpoint remains unstandardised across centres. (sources/BPA-AHA-2024, rating: very high)

• CTEPD prevalence and natural history unknown: The newly formalised CTEPD entity has no validated prevalence data, and which CTEPD patients will progress to CTEPH or benefit from invasive intervention remains undefined. (sources/PHT-ESC-2022, rating: very high; sources/acute-pe-aha-2026, rating: very high)

• CTEPD without PH: optimal intervention strategy undefined: AHA/ACC 2026 notes CTEPD without PH is likely at least as prevalent as CTEPD with PH, but optimal diagnostic pathway (CPET vs perfusion scan vs RHC) and indications for PEA/BPA in these patients remain undefined. (sources/acute-pe-aha-2026, rating: very high)

• Advanced therapies for acute PE and long-term CTEPD prevention: It is unknown whether CDL or MT for intermediate-to-high risk acute PE reduces the subsequent incidence of CTEPD compared to anticoagulation alone — long-term outcome data beyond 30–90 days are lacking for all advanced therapies. (sources/acute-pe-aha-2026, rating: very high)

• The CTEPH haemodynamic threshold is inconsistent within the ESC's own output. The 2019 PE guideline requires mean PAP ≥25 mmHg for CTEPH; the 2022 ESC/ERS pulmonary hypertension guideline lowered it to >20 mmHg — the threshold this page uses elsewhere. A patient with mPAP 21–24 mmHg after PE is therefore CTEPH by the 2022 definition and not by the 2019 one, so the two documents would classify the same patient differently. (sources/acute-pe-esc-2019, rating: very high; sources/PHT-ESC-2022, rating: very high)

• Screening asymptomatic survivors looks contradictory across guidelines but is not. ESC 2019 recommends further diagnostic evaluation may be considered in asymptomatic patients with CTEPH risk factors (Class IIb, upgraded from III in 2014); AHA/ACC 2026 states routine imaging in asymptomatic patients with resolved symptoms is not beneficial (COR 3:NB). These are compatible once the qualifier is preserved: the 2026 recommendation applies to patients with resolution of symptoms and low suspicion, while the 2019 IIb is confined to asymptomatic patients who carry a risk factor from Table 13. The practical rule is that risk factors, not symptoms alone, drive the decision to investigate — but the two statements read as opposing if the qualifiers are dropped, which is a live risk when citing either in isolation. (sources/acute-pe-esc-2019, rating: very high; sources/acute-pe-aha-2026, rating: very high)

• Which imaging modality is first-line depends on the question being asked. ESC 2019 keeps planar V/Q as first-line for CTEPH diagnosis on 96–97% sensitivity (and notes SPECT appears less sensitive at a level), whereas AHA/ACC 2026 prefers V/Q SPECT for post-PE CTEPD surveillance. The recommendations point in opposite directions on the same test, arising from different endpoints — diagnostic sensitivity for established CTEPH versus practical surveillance after acute PE. (sources/acute-pe-esc-2019, rating: very high; sources/acute-pe-aha-2026, rating: very high)

Connections

• Related to entities/Pulmonary-Embolism
• Related to concepts/Pulmonary-Hypertension
• Related to concepts/Acute-PE-Clinical-Categories
• Related to concepts/PAH-Risk-Stratification
• Related to concepts/Balloon-Pulmonary-Angioplasty

Sources

• sources/BPA-AHA-2024
• sources/PHT-ESC-2022
• sources/acute-pe-aha-2026
• sources/acute-pe-esc-2019