Incidence of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) in VTE Patients
The cumulative incidence of CTEPH after symptomatic pulmonary embolism is reported to be between 0.1% and 9.1% within the first two years after the event, with more recent data suggesting approximately 2-4% of patients develop this complication. 1
Epidemiology and Incidence
- CTEPH is a rare but serious complication of VTE, occurring in approximately 3% of patients after acute pulmonary embolism according to recent estimates 2
- The wide range in reported incidence (0.1-9.1%) is likely due to referral bias, absence of early symptoms, and difficulty differentiating acute PE from an acute episode superimposed on pre-existing CTEPH 1
- In a recent Japanese registry (COMMAND VTE Registry-2), the cumulative diagnosis of CTEPH after acute PE was 2.3% at 3 years in the direct oral anticoagulant era 3
- Most cases of CTEPH develop within the first two years after the index PE event, with no patients developing CTEPH later than 2 years after the index PE in some studies 1
- Importantly, a significant number of CTEPH cases (approximately 60%) develop in patients with no antecedent history of acute VTE 1
Risk Factors for CTEPH Development
- Female gender (HR 2.09) 3
- Longer interval from symptom onset to diagnosis of PE 3
- Hypoxemia at PE diagnosis (HR 2.52) 3
- Right heart load/dysfunction (HR 9.28) 3
- Unprovoked PE (HR 2.77) 3
- Other risk factors include:
- Inadequate anticoagulation 1
- Large thrombus mass and residual thrombi 1
- Recurrence of VTE 1
- Presence of lupus anticoagulant or antiphospholipid antibodies 1
- Elevated levels of coagulation factor VIII 1
- History of splenectomy, ventriculoatrial shunt, inflammatory bowel disease, and chronic osteomyelitis 1
Diagnostic Considerations
- Routine screening for CTEPH after PE is not supported by current evidence 1
- An echocardiogram performed approximately 6 weeks after acute PE might help predict subsequent CTEPH development 1
- V/Q scintigraphy is the best screening test for CTEPH, as a normal V/Q scan effectively excludes the diagnosis 1, 2
- A relatively normal CT angiogram can be observed in CTEPH despite substantial V/Q scan abnormalities 1
- Definitive diagnosis requires:
- Mean pulmonary arterial pressure ≥25 mmHg at rest
- Pulmonary capillary wedge pressure ≤15 mmHg
- Evidence of thrombotic pulmonary artery obstruction after at least 3 months of effective anticoagulation 1
Clinical Implications
- CTEPH is a debilitating disease with poor prognosis if left untreated 1
- In untreated patients, mortality rates of 70% have been reported among those with mean pulmonary artery pressure >40 mmHg, increasing to 90% at >50 mmHg 1
- Early recognition is challenging due to the non-specific nature of symptoms and the median time from symptom onset to diagnosis is 14 months 1
- Pulmonary thromboendarterectomy is potentially curative with mortality rates of approximately 2% at expert centers 2
Pathophysiology
- CTEPH results from incomplete resolution of pulmonary emboli with subsequent vascular remodeling 1
- Residual thrombus remains despite adequate anticoagulation at 1 year in as many as half of all patients 1
- Beyond major pulmonary vascular obstruction, CTEPH also involves pulmonary microvascular disease, which may contribute to disease progression 1
Understanding the relatively low but significant incidence of CTEPH following VTE is important for clinicians to maintain appropriate vigilance, particularly in patients with risk factors or persistent dyspnea after PE.