Chronic thromboembolic pulmonary hypertension (CTEPH) arises from total or partial occlusion of the pulmonary vascular bed from non-resolving thromboemboli. Although pulmonary embolism (PE) is one of the more common cardiovascular diseases, CTEPH remains an under-diagnosed condition. CTEPH is defined as precapillary pulmonary hypertension with mean pulmonary artery pressure (mPAP) of more than 25 mmHg, pulmonary capillary wedge pressure (PCWP) of less than 15 mmHg and pulmonary vascular resistance (PVR) of more than 2 Wood units.
CTEPH is a relatively rare but important sequela of deep venous thrombosis (DVT) and PE, where in up to 4% of patients, the acute embolic material fails to resolve. Given that DVT and PE is as common as 1/1000 population per year, the annual incidence of CTEPH may be of the order of 8–40 cases/million population. However, because some patients diagnosed with chronic thromboembolic disease have no preceding history of acute embolism, the true incidence of this disorder could be much higher.
The majority of DVT and acute PE are managed medically with anticoagulation. Cardiothoracic surgeons rarely become involved in management of acute PE, unless it is in a hospitalised patient who survives a massive embolism that causes life-threatening acute right heart failure and shock. Conversely, the majority of CTEPH cases are amenable to surgical treatment by pulmonary endarterectomy (PEA). PEA is the definitive, and in most cases the curative, treatment for CTEPH. The objective of the surgery is the normalisation of pulmonary artery pressure with resultant significant symptomatic and prognostic benefit. Medical management is only palliative, and lung transplantation has an inferior outcome compared with PEA and is only relevant for very selected patients with distal disease and extreme pulmonary hypertension (PH).
It is uncertain why some patients have unresolved emboli, but a variety of factors play a role, alone or in combination. Initially, thrombus resolution probably results from a combination of thrombus fragmentation and endogenous fibrinolysis. In the majority of patients this leads to complete clot resolution. Further resolution relies on clot organisation and neovascularisation, during which the obstructed vessel becomes recanalised and vessel patency is partially restored.
After the clot becomes wedged in the pulmonary artery, one of two processes occurs:
1. The organisation of the clot proceeds to canalisation, producing multiple small endothelialised channels separated by fibrous septa (i.e. bands and webs).
2. Complete fibrous organisation of the fibrin clot without canalisation may result, leading to a solid mass of dense fibrous connective tissue totally obstructing the arterial lumen.
The generation of PH in CTEPH is not just the result of simple obstruction of the pulmonary arterial bed; indeed, there is little rise in pulmonary artery pressure following a pneumonectomy. The increased pressure as a result of redirected pulmonary blood flow in the unobstructed pulmonary vascular bed can create an arteriopathy in the small precapillary blood vessels similar to that seen in idiopathic pulmonary arterial hypertension. Hence, the pathogenesis of chronic thromboembolic occlusion in CTEPH with resultant raised PVR is thought to be secondary to obstruction by thromboemboli and remodelling of the previously normal pulmonary vascular bed.
Clinical Presentation and Diagnosis
There are no symptoms specific for chronic thromboembolism. The most common symptom associated with thromboembolic pulmonary hypertension, as with all other causes of pulmonary hypertension, is exertional dyspnoea. This dyspnoea is out of proportion to any abnormalities found on clinical examination. Syncope, or presyncope, is another common symptom in severe pulmonary hypertension.
The physical signs of pulmonary hypertension are the same no matter what the underlying pathophysiology. Initially the jugular venous pulse is characterised by a large ‘A’ wave. As the right heart fails, the ‘V’ wave becomes predominant. The right ventricle is usually palpable near the lower left sternal border. The second heart sound is often narrowly split and varies normally with respiration. In the later stages of the disease, signs of right heart failure predominate with oedema and ascites. Tricuspid regurgitation can be severe, with a pansystolic murmur and an enlarged pulsatile liver.
High index of suspicion and awareness of the disease is crucial. The chest radiograph may be entirely normal. Pulmonary function tests reveal minimal changes in lung volume and ventilation. Diffusion capacity is often reduced and may be the only abnormality on pulmonary function testing. Most patients are hypoxic. Dead space ventilation is increased.
The ventilation-perfusion lung scan is the essential test for establishing the diagnosis. An entirely normal lung scan excludes the diagnosis of both acute and chronic thromboembolism.
Transthoracic echocardiogram (TTE) is usually the test that gives the first indication of the presence of PH. Systolic pulmonary artery pressure is significantly raised. Features that may be seen on TTE depend on the chronicity and degree of right ventricular failure; raised right ventricular dimension, impaired right ventricular function and right ventricular hypertrophy.
Currently, pulmonary angiography is said to be the gold standard imaging test for evaluation of operability in CTEPH, but experience is essential for the proper interpretation of pulmonary angiograms. Organised thrombi appear as filling defects, webs or bands, or as completely thrombosed vessels ‘missing’ (Figure 39.1). Distal vessels demonstrate the rapid tapering and pruning characteristic of pulmonary hypertension. Other modalities of imaging, including multislice CT pulmonary angiogram and magnetic resonance angiography, are gaining acceptance and are now favoured over conventional angiography in some centres.
Figure 39.1 Right pulmonary angiography of a patient with CTEPH demonstrating a web in the trifurcation of the lower lobe vessels with complete occlusion of two segments of the lower lobe and both segments of the middle lobe.
Right heart catheterisation is crucial for the diagnosis of pulmonary hypertension, defined as a mPAP >25 mmHg at rest. Right atrial pressure, right ventricular end-diastolic pressure, pulmonary artery pressure and mixed venous O2 saturation are measured directly. Cardiac output and PVR can then be calculated. Coronary angiography and other cardiac investigations are recommended for patients over 40–45 years being considered for surgery.
The main treatment of CTEPH is surgical and all patients with suspected CTEPH should be referred to an experienced unit able to perform PEA. Untreated, the prognosis of CTEPH is very poor with severe debilitation and premature death from right heart failure. In historical case series, the mean survival is 6.8 years, and when the mPAP of patients with thromboembolic disease reaches 50mmHg or more, the 3-year mortality is about 90%.
Chronic anticoagulation represents the mainstay of the medical regimen. Anticoagulation is primarily used to prevent future embolic episodes, but it also serves to limit the development of thrombus in regions of low flow within the pulmonary vasculature. Historically, inferior vena caval filters were used routinely to prevent recurrent embolisation but this is now not recommended, as there are few data to support this indication.
Data from clinical drug trials in CTEPH are limited. Specific disease targeted drug therapy is therefore not licensed for CTEPH patients, but drugs used for the treatment of idiopathic pulmonary arterial hypertension such as Bosentan and Sildenafil are sometimes used and may provide symptomatic improvement in some patients.
The basis of the operation is the removal of the obstruction of the pulmonary vascular bed by endarterectomy within the superficial media of the arterial wall. Therefore, the reduction in the PVR after pulmonary endarterectomy is dependent on the burden of ‘clearable’ disease as defined on preoperative imaging. The correlation between the degree of ‘clearable’ disease in imaging studies and PVR is the main determinant of operability. The absolute preoperative and resultant postoperative PVR are also the main factors that determine outcome after endarterectomy. Mortality following endarterectomy may be five- to ten-fold higher in patients with a preoperative PVR > 1200 dyne s/cm5. Similarly, a postoperative residual PVR of > 500 dyne s/cm5 is a risk factor for in-hospital mortality.
Although preoperative imaging helps to determine operability, the true extent of the disease can only be determined intraoperatively and has been classified in four types:
Type 1: Central disease where major vessel clots (fresh and/or mature) are present.
Type 2: Lobar and segmental disease where thickened intima is present with webs in the lobar and segmental branches.
Type 3: Subsegmental disease where the disease begins distally at the subsegmental branches.
Type 4: Distal disease where small vessel disease is present and represents inoperable disease.
Surgery is more successful in patients with types 1 and 2 disease, with a greater reduction in PVR and lowest mortality. Surgery in patients with the more distal type 3 disease is more challenging with a smaller reduction in PVR and higher risk. Patients with predominant type 4 disease are considered ‘non-operable’ or to have ‘non-surgical’ disease.
This must be weighed against the amount of ‘clearable’ disease based on imaging and correlated to the pulmonary vascular resistance measured preoperatively.
Other patient comorbidities that will be significant in a prolonged cardiopulmonary bypass time such as age, known cerebrovascular condition, renal impairment and intrinsic lung parenchymal disease should also be considered.
The approach is via a median sternotomy with cardiopulmonary bypass (CPB). The patient is cooled systemically to 20oC and right and left pulmonary arteriotomies are performed within the pericardium. Adequate visualisation for distal dissection necessitates reduction in bronchial arterial collateral return to the pulmonary arteries. This is achieved by periods of complete deep hypothermic circulatory arrest for up to 20 minutes at a time with an intervening period of 10 minutes of re-perfusion on CPB. A cast of the inner layer of the pulmonary arterial tree is then dissected free (Figure 39.2).
Figure 39.2 Endarterectomy casts from both pulmonary arteries of the same patient in Figure 39.1, demonstrating long tapering ‘tails’ which is a hallmark of good clearance.
After completion of the endarterectomies, the patient is rewarmed slowly on full CPB. The procedure time is long because of the time necessary to cool and warm on bypass.
The aim is to achieve an immediate fall in mean PA pressure by approximately 50%, and reduction in PVR to approximately one third of the preoperative level in the majority of patients.
Most of the general principles of postoperative cardiac surgical care apply, but these principles centre around the management of the left ventricle. The management of patients following PEA involves these two principles:
Careful management of the right ventricle;
Minimising the pulmonary vascular resistance.
Most patients with CTEPH have a normal functioning left ventricle in the absence of coronary atherosclerosis and ‘left-sided’ heart valvular disease. Therefore left ventricular cardiac output and ultimately end-organ perfusion is usually dependent on the contractile reserve of the right ventricle and pulmonary vascular resistance in the post-PEA patients.
The contractile reserve of the right ventricle in the post-PEA patients depends on the following:
The varying degree of right ventricular impairment secondary to CTEPH in the preoperative period;
The post-PEA pulmonary vascular resistance that is dependent on the amount of disease cleared during PEA with resultant fall in pulmonary artery pressure. High PVR in the postoperative period can be due to technical failure to clear ‘surgical’ disease and/or presence of type 4 distal disease (inoperable):
Prolonged cardiopulmonary bypass, prolonged myocardial ischaemic time and inadequate right ventricular myocardial protection during PEA which impacts on right ventricular performance upon weaning from cardiopulmonary bypass.
Pulmonary vascular resistance in the post-PEA patient can be affected by the following:
Right ventricular function, hence inexplicably linked;
Hypoxia secondary to poor perfusion matching, intrinsic lung parenchymal disease, fluid overload, lung sepsis and mechanical complications such as pneumothorax;
Vasoconstrictor agents such as noradrenaline;
High peak airway pressures.
Considering the above factors when receiving a patient onto the Critical Care Area (CCA) following PEA surgery will help plan for potential problems that may be encountered during the postoperative period.