Chronic Thromboembolic Pulmonary Hypertension (Suspected)

cteph

Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

• Chronic thromboembolic pulmonary hypertension (CTEPH) is classified as group 4 pulmonary hypertension
• CTEPH is a serious but rare adverse sequela of acute pulmonary embolism (PE) that occurs in about 3% of PE survivors, 1 although up to 38% of patients with CTEPH have no documented history of venous thromboembolism 2
• A diagnosis of CTEPH was previously associated with a poor prognosis, however it is now potentially curable with surgery. 3 Improvements in medical and endovascular treatments have led to some improved survival in inoperable or refractory CTEPH 3
• Diagnosing CTEPH following PE is challenging because symptoms are generally non-specific; diagnosis is delayed on average for by over a year 4
  • Routine screening for CTEPH after PE is not currently recommended 5
  • Unfortunately guidelines are lacking for how long patients should be followed up after PE and when diagnostic tests for CTEPH should be performed 6
  • Patients with a higher burden of thrombus at time of diagnosis are at increased risk 7
  • CTEPH can be suspected in patients who remain symptomatic after 3 months of effective anticoagulation. 5 Risk factors for developing CTEPH include recurrent PE and unprovoked PE 4
  • CTEPH can also develop in the absence of previous diagnosed acute PE. 5 Patients with known clotting disorders and underlying connective tissue diseases such as scleroderma are at increased risk
• CTEPH is defined as: 8
  • Mean pulmonary artery pressure ≥25mmHg
  • Pulmonary capillary wedge pressure
  • Persistence of multiple organised thrombi in the lobar, segmental or sub-segmental pulmonary arteries after at least 3 months of effective anticoagulation
• CTEPH can also be a result of organised thrombus, e.g. vessel occlusion or stenosis. These can be present in the absence of residual thrombus
• However, not all patients with residual clot burden proceed to develop pulmonary hypertension and incidental clot may co-exist with other groups of pulmonary hypertension. Likewise, pulmonary hypertension may be multifactorial which would have implications for management, so early referral to a specialist centre is recommended in suspected pulmonary hypertension
• Sarcoid involving the pulmonary arteries mimics CTEPH and can only be identified following transplant or at autopsy. This can be suspected in patients with known sarcoidosis with symptoms and/or imaging features of CTEPH

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Lung Scintigraphy (V/Q or ventilation/perfusion scan)

• Lung scintigraphy (V/Q or ventilation/perfusion scan) is the first-imaging modality for CTEPH and can rule out a diagnosis of CTEPH with high certainty 5
• Originally found to have a significantly higher sensitivity than CTPA (96-97.4% compared to 51%) 9,10
  • More recent studies with later CT technology have demonstrated comparable sensitivity for V/Q scan and CTPA for CTEPH, 11 so there may be a growing role for CTPA in the future
• Radiolabelled compounds are inhaled for ventilation scanning, whilst perfusion scintigraphy is performed after intravenous injection of technetium-99m macroaggregated albumin. A PE characteristically appears as a pleural based segmental perfusion defect 12
• Patients with CTEPH show at least one segmental or larger perfusion defect unmatched by ventilation abnormalities 13
• Visualisation of the vascular bed with CTPA or MRA (or DSA) is still required for treatment decision making following V/Q scan 5
• Ventilation perfusion scans, compared to CTPA, are associated with lower radiation exposure but the extreme difference between the effective doses as existed previously has been reduced drastically with the new generation MDCT helical scanners that use low dose (using tube currents of 80kVp or 100kVp) 14-18

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Transthoracic Echocardiogram

• In patients presenting with dyspnoea following treated PE, echocardiography is recommended as a first-line on-invasive diagnostic investigation for the assessment of pulmonary artery pressures 5,13
  • TTE also gives information on the presence of structural cardiac abnormalities, valvular dysfunction and systolic or diastolic cardiac function that may contribute to symptoms. 13 Cardiac MRI is the gold standard for assessment of the right ventricle, however it is not widely available
• If TTE findings are compatible with a high or intermediate probability of pulmonary hypertension, a V/Q scan is recommended to exclude CTEPH. 5 However, a positive TTE is not required for diagnosis
• TTE alone is not sufficient to support a treatment decision or to rule out CTEPH in patients with risk factors. 5 If suspected, a V/Q scan should be performed irrespective of TTE
  • TTE relies on tricuspid regurgitation of pulmonary arterial hypertension (PAH) and can miss diagnoses. For example, if right heart failure is present, TTE may not demonstrate tricuspid regurgitation despite elevated pulmonary arterial pressures, resulting in false negatives
  • Alternatively, pulmonary artery pressures should still be confirmed with right heart catheter because TTE may over-diagnose pulmonary hypertension by up to three times 1
  • In asymptomatic patients with a high risk of CTEPH, V/Q scan may be the diagnostic test of choice to rule out CTEPH 13
• Some patients have chronic thromboembolic pulmonary disease without PAH. These patients may warrant monitoring as they may develop PAH, although there have been no studies to demonstrate this 13

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Chest Computed Tomography (CT)

• Non-contrast CT chest can be useful in the work up of pulmonary hypertension to assess the lung parenchyma, which may reveal a cause for PAH or separate cause for symptoms. 5 Can also rule out extrinsic pulmonary vascular compression from other causes such as neoplasm or fibrosis 13
• Multislice CT (or multidetector CT, MDCT) can be reconstructed into thin slices to assess parenchymal and bronchial detail, and continuous thick slices to assess for small nodules. Multislice CT has a fast acquisition time and high resolution when reconstructed in different planes

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Right Heart Catheterisation

• Invasive assessment of pulmonary haemodynamics is still required to confirm the diagnosis and to evaluate operability, as TTE may over- or underestimate pulmonary artery pressures 5
• There is a low associated risk of adverse events, with 1.1% associated morbidity and 0.05% mortality 19
• Pulmonary hypertension is defined as mean pulmonary artery pressure ≥25mmHg and pulmonary capillary wedge pressure 8
• Symptomatic patients with imaging findings consistent with CTEPH but normal pressures may be considered to have chronic thromboembolic pulmonary vascular disease (CTED). These patients may warrant monitoring for the development of PAH, although the natural history of CTED is unknown and there have been no studies to show that CTED evolves into CTEPH 13

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Catheter Pulmonary Angiography (Digital Subtraction Angiography)

• Invasive investigation that demonstrates the extent and location of disease; indicated to assess whether CTEPH may be amenable to surgical treatment. Also allows for endovascular intervention
• The chance of success with surgery is greatest when vascular obstruction is present in the main pulmonary arteries or lobar arteries 20
• Balloon pulmonary angioplasty can be used to treat peripheral obstructions in segmental or subsegmental pulmonary branches, and can be undertaken in conjunction with medical therapy. There is growing evidence for BPA as a promising treatment for patients who are unsuitable for surgery 21-23

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CT Pulmonary Angiography (CTPA)

• May be useful to demonstrate evidence of acute or chronic thromboembolic disease in patients without known history of PE and an indeterminate V/Q scan
• Role of CTPA is well established for the diagnosis of acute PE
• However, CTPA is not recommended to rule out CTEPH due to the high rate of false negatives. CTPA has a significantly lower sensitivity than V/Q scan (51% compared to 96-97.4%) 9
• Signs of CTEPH on CTPA include direct vascular signs of chronic PE as well as secondary signs including:
  • Eccentric, reorganised thrombus
  • Webs in pulmonary arteries
  • Pulmonary artery stenosis, which can be loss of normal tapering or focal overt stenosis. This is difficult to perceive via CT but is one of the commonest findings
  • Pulmonary artery occlusions
  • Paucity of distal vessels despite normal parenchyma. This is the cause for mosaic attenuation
  • Dilated systemic collaterals
  • Evidence of pulmonary hypertension, i.e. central pulmonary artery dilation, right heart dilation and right ventricular hypertrophy with flattening/bowing of the septum to the left, reflux of contrast into hepatic veins

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Magnetic Resonance Imaging: Pulmonary Angiography (MRPA or MRA), Pulmonary Perfusion and Cardiac MRI

• MRA is an excellent non-invasive test to whether CTEPH may be amenable to surgical or endovascular treatment
• MRA can demonstrate flow artefact caused by webs and stenoses which are not detectable on CT
• MR is also able to demonstrate perfusion deficits which correspond to abnormal vessels and defects seen on V/Q scan
• Cardiac MRI is the gold standard for the assessment of right ventricular function 24 and can also assess the myocardium and valve disease 18
• Gadolinium contrast-enhanced MRA has shown promise for the diagnosis of CTEPH with one study reporting sensitivity and specificity of 98 and 94% respectively 25
• MRI is especially useful as a baseline for follow-up and monitoring response to treatment 26
• Unlike CTPA and V/Q scan, there is no exposure to ionising radiation
• Disadvantages: 18
  • Limited availability. MR can be misleading or non-diagnostic if not performed in a high-volume, experienced cardiothoracic imaging centre
  • Cost
  • Long acquisition time – dyspnoeic patients may not be able to achieve breath hold
  • Claustrophobic
  • Contraindicated with some ferromagnetic prostheses

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