Chronic thromboembolic pulmonary hypertension (CTEPH) is a pulmonary vascular disease that results from fibrotic transformation of thromboemboli causing obstruction in the pulmonary vasculature. If left untreated, pulmonary artery pressure worsens, affecting right ventricular function and causing significant morbidity and mortality, with up to 68% 5-year survival. European registry data suggest that the annual incidence of CTEPH is about 5 per million adults per year, which is likely an underestimate due to underrecognition of the disease. This makes it one of the most common causes of pulmonary hypertension.
Up to 3% of patients with acute pulmonary embolism progress to develop CTEPH. In CTEPH, the pulmonary thromboemboli remain attached to the wall of the pulmonary vasculature, which can be distributed in the main, lobar, segmental, and/or subsegmental branches of the pulmonary vasculature. This then triggers an inflammatory process leading to organization and fibrosis of this thrombus into webs, luminal narrowing, and sometimes complete obstruction of the pulmonary vessels.
Clinical presentation
Patients with CTEPH present with dyspnea and/or signs of right-sided heart failure. CTEPH may be suspected when there are persistent symptoms after 3 months of anticoagulation after an acute pulmonary embolus. This disease can be suspected from the history, including risk factors for hypercoagulable states, signs, and symptoms, along with ancillary testing, which includes electrocardiography (showing right ventricular strain pattern), chest radiography, pulmonary function testing, and echocardiography. Clues from these can raise the suspicion of the presence of CTEPH and exclude other causes of dyspnea.
Diagnosis and testing
If CTEPH is suspected, the next step is to perform ventilation–perfusion lung scintigraphy (V/Q scan). This test has a high sensitivity of detecting perfusion defects and a high negative predictive value, so CTEPH can be excluded if normal.
If the V/Q scan reveals perfusion defects, the next step would be to perform confirmatory testing, which includes pulmonary computed tomography angiography (CTA) and right heart catheterization with pulmonary angiography. Pulmonary CTA is effective in detecting thromboembolic material in the main and lobar segments of the pulmonary vasculature; however, it is less sensitive in detecting segmental and subsegmental lesions.
Perfusion single photon emission computed tomography (SPECT)/CTA is a more recent modality that integrates anatomic and perfusion data and provides additional data for diagnosis and procedural planning ( Fig. 30.1 ). Right heart catheterization is needed to measure baseline pulmonary pressures and pulmonary vascular resistance and directly image the pulmonary arteries with pulmonary angiography. Pulmonary angiography is highly sensitive in detecting segmental and subsegmental thromboembolic material, which is important for decision-making in treating CTEPH.
How to perform pulmonary angiography
- 1.
Using a balloon wedge pressure catheter (Teleflex, Morrisville, NC) positioned in the right or left pulmonary artery, insert a regular 0.035″ guidewire and exchange the balloon wedge catheter for a 7F 145-cm pigtail.
- 2.
Position the pigtail in the main left or right pulmonary artery. Connect the pigtail to a power injector and inject 60 cc (±10 cc) of contrast into each pulmonary artery.
- 3.
In conventional biplane angiography, the left or right lung is placed in the isocenter with straight left ascending oblique (LAO) and anteroposterior (AP) projections at a 90-degree angle. Image acquisition is set to the digital subtraction angiography mode at a rate of four frames per second. The patient is asked to hold their breath, and contrast is injected. Cine acquisition should be set up to have a long enough duration to acquire the pulmonary flow in the arterial phase, followed by the levo-phase where pulmonary venous drainage flow can be assessed.
- 4.
As an alternative, rotational angiography can be performed using a C-arm that is equipped with the capability and software to perform rotational image acquisition and image reconstruction. The right or left lung is again positioned in the isocenter. Contrast is injected while cine acquisition is performed with the C-arm rotating around the isocenter, obtaining a series of x-ray images. With this modality, contrast is injected at 12 to 14 cc/second, and image acquisition is initiated 2 seconds after the initiation of contrast delivery to adequately opacify the vasculature. The images are then reconstructed using special software into a three-dimensional pulmonary tree. Rotational angiography permits a more thorough assessment of overlapping vasculature and may assist in procedural planning and camera positioning during subsequent interventions.
Pulmonary angiographic images are then reviewed to look for lesions that commonly present as ostial narrowing, total occlusions, and hypoperfused arteries with poor microvascular blush and delayed venous return.
Case selection
Location and severity of lesions identified on CTA (for central lesions) and pulmonary angiography (for peripheral lesions) is key for the management of CTEPH. As a rule of thumb, the more distal the involvement of thromboembolic material in the pulmonary tree, particularly in segmental and subsegmental branches, the more challenging, higher-risk, and less successful surgical thromboembolectomy becomes. Therefore thromboembolic material involving the central vasculature is a favorable anatomy for surgical thromboembolectomy, and this is the treatment of choice. However, if the thromboembolic material involves the distal branches, then surgical resection becomes very challenging and often not feasible.
Pulmonary balloon angioplasty is used in patients with thromboembolic lesions in the distal pulmonary vessels that are not amenable for surgical resection. Angioplasty can also be offered in a hybrid procedure for patients who have central and peripheral thromboembolic involvement, whereby they undergo surgical resection of the central lesions and then are brought back for balloon pulmonary angioplasty of residual disease in the segmental and subsegmental territories.
Medical therapy is the first step if the patient has distal involvement and is not found to be a surgical candidate. Currently the only pharmacologic agent approved for CTEPH is riociguat, a soluble guanylate cyclase stimulator. This promotes pulmonary artery dilatation. Patients are given a trial of 6 to 8 weeks followed by a repeat right heart catheterization along with additional objective reassessment of exercise limitation. If no improvement is observed with medical therapy, pulmonary balloon angioplasty would be the next step.
Procedural planning
Once the decision is made to proceed with pulmonary balloon angioplasty, careful procedural planning is performed. This is a critical step and enough time should be spent planning, given the complex three-dimensional anatomy of the pulmonary vasculature. Fundamental principles should be applied in planning each procedure:
- 1.
These procedures are to be divided into three to four sessions, given the risk of postangioplasty reperfusion pulmonary edema. Each session would target about three segmental arteries and are to be spaced out by a minimum of 3 to 5 days, depending on the patient’s reserve, complexity of the anatomy, and results of previous interventions. Staggering interventions by longer periods of 2 or more weeks may provide an additional margin of safety.
- 2.
These patients can be fairly ill at baseline and have low cardiopulmonary reserve; therefore the initial balloon angioplasty procedural sessions should target vessels that are in the distribution of the lowest perfusion territories on V/Q scan and can extract most benefit from angioplasty, at the same time targeting lesions with favorable anatomy, allowing for angioplasty to be done with the highest success rate and lowest complication rate. More complex lesions can be tolerated better in later sessions as the patient’s hemodynamics improve.
- 3.
Cardiopulmonary reserve is determined by the severity of baseline mean pulmonary artery pressure. Patients are less likely to tolerate even minor complications if they have higher mean pulmonary artery pressure. Moreover, the higher the mean pulmonary artery pressure, the higher the risk of procedural complications such as postrevascularization pulmonary edema or bleeding from an inadvertent wire perforation. Therefore a conservative approach is warranted for all patients, with closer attention to those with severely elevated mean pulmonary artery pressures.
Step-by-step planning
- 1.
Review the V/Q scan or the perfusion SPECT/CTA scan (if available: provides anatomic and physiologic correlation). Identify territories with the lowest perfusion.
- 2.
Review the pulmonary angiography and divide the pulmonary branches according to conventional nomenclature as shown in Fig. 30.2 .
Fig. 30.2
Conventional nomenclature for pulmonary branches.
- 3.
Select target vessels on pulmonary angiography that correlate with areas of lowest perfusion on V/Q scan or perfusion computed tomography (CT) scan.
- 4.
Review the characteristics of each target vessel carefully with particular attention to the lesion morphology and length. Classify these angiographic lesions using this novel classification system suggested by Kawakami et al. :
Type A: Ring stenosis
Type B: Webbed stenosis
Type C: Subtotal occlusion
Type D: Total occlusion
Type E: Tortuous, distal stenosis with cotton-wool stains of capillary arteries
The success rate and complication rate are associated with lesion type. Type A and B lesions have up to 94% success rate with less than 3% risk of complication, whereas the success rate decreases and the complication rate increases with the other types of lesion morphologies, with up to 52% rate of success and up to 15.5% risk of complications in types D and E.
This classification will help serve as a guide when choosing target lesions for initial sessions, where the focus should be on selecting favorable anatomy associated with the highest success rate and the lowest risk in the hopes of improving the pulmonary reserve of the patient so they tolerate angioplasty of more complex lesions at later sessions.
- 1.
Lastly, before the procedure, baseline data should be recorded, including loudness of P2 on physical examination; blood work, particularly NT proBNP, the level of which is directly associated with the risk of postrevascularization pulmonary edema; and a 6-minute walk test.
- 2.
Warfarin is stopped 5 days before the procedure, and direct oral anticoagulants (DOACs) are held 48 hours before the procedure and bridging with low-molecular-weight heparin is performed.
- 3.
Aspirin and clopidogrel are not required for the procedure. Previous anticoagulants are reinitiated after the procedure, with bridging anticoagulation being used for warfarin.
Procedural steps
Figs. 30.3 to 30.10 present the steps necessary for this procedure.
- 1.
The patient is prepped in the usual sterile fashion, and careful moderate sedation is initiated.
- 2.
Access is obtained in the femoral vein using a 7F sheath placed using sterile technique. If an inferior vena cava (IVC) filter is present, the procedure can still be carried out through the filter. The right internal jugular vein is a potential option to use, but is technically more challenging and exposes the proceduralist to higher levels of radiation.
- 3.
Right heart catheterization is performed using a balloon wedge catheter. Pressures and cardiac output using the Fick method are recorded.
- 4.
The balloon wedge catheter is placed in the left or right pulmonary artery depending on the site of intervention.
- 5.
An exchange-length, extra-stiff wire is then inserted into the balloon wedge catheter.
- 6.
The balloon wedge catheter is then exchanged over the stiff wire for an 8F shuttle sheath, which is advanced with the dilator into the main left or right pulmonary artery.
- 7.
The dilator and the exchange length wire are then removed and a 7F guiding catheter is then inserted over a regular 0.0350 wire into the shuttle sheath with continuous flush. Guide catheters of choice include a JR4 or JL4 for most of the interventions. In the lower lobe branches, a multipurpose guiding catheter can occasionally help with better engagement and reach.
- 8.
Unfractionated heparin is given with a target activated clotting time (ACT) of 250 to 300 seconds.
- 9.
The manifold is connected and pressure is monitored while the shuttle sheath and guiding catheter are carefully manipulated to engage the target vessel branch. Pressure tracing is continuously checked to ensure no damping occurs before and after any injection. This is a critical step in vessel injury complication avoidance, especially if the mean pulmonary artery pressure is high. With the variation in the pulmonary artery tree anatomy, catheters can abut the vessel wall, causing damping, and contrast injection into the thinner pulmonary vessel wall with high mean pulmonary artery pressure can be catastrophic.
- 10.
Perform selective angiography, carefully documenting antegrade flow, lesion location and morphology, and levo-phase, looking at venous drainage flow. A grading system has been suggested to systematically classify pulmonary flow angiographically, called the pulmonary flow grade ( Table 30.1 ). Using this grading score, classify the flow according to the pulmonary flow grading system. Lesion stenosis severity is most frequently determined angiographically. Physiology of indeterminate-severity lesions can be assessed by a pressure wire placed across the lesion, just like the fractional flow reserve counterpart in coronary artery disease assessment, with a cutoff value of less than 0.80 being a physiologically significant stenosis. The pressure wire can be exchanged with the working wire through a microcatheter or over-the-wire balloon.
