#pulmonary-hypertension #CTEPH #right-heart-failure #pulmonary-embolism

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)

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)
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

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)
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)

Connections

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