CTEPH is rare, hard to diagnose and can be fatal. But if discovered in time, it is probably the only type of pulmonary hypertension that is curable with surgery.
By Asst Prof Alicia Chia, Consultant, Department of Cardiothoracic Surgery
Toss out the words “Chronic Thromboembolic Pulmonary Hypertension (CTEPH)’ and you are likely to get a collection of blank stares.
CTEPH is a condition caused by the long-term accumulation of clots in the blood vessels of the lung, called the pulmonary artery. In some people, their bodies are unable to naturally break down these clots. Over time, the clot gets incorporated into the wall of the blood vessels, causing them to scar and narrow. The resultant pulmonary hypertension or high blood pressure in the lungs places so much strain on the heart that it can be life-threatening.
Patients with untreated CTEPH encounter a higher risk of death. Once the mean pulmonary pressure reaches 50 mmHg, 90% of these patients do not survive beyond three years1 .
Nonetheless, the diagnosis of CTEPH can be difficult and is often missed due to numerous reasons:
Characteristic symptoms of CTEPH include shortness of breath on exertion or at rest and a progressive decrease in exercise tolerance, which can also be caused by several other health conditions. In the later course of the disease, exertional chest pain, haemoptysis (coughing up blood) and syncope (blackout) may occur due to massive pulmonary hypertension and right heart failure.
Majority of patients have no history of venous thrombosis (clots elsewhere in the body) or acute pulmonary embolism (PE).
There is still a general lack of awareness of this clinical entity and the option of successful therapy. Hence, many cases either remain undiagnosed or are not referred to specialised pulmonary hypertension/ CTEPH centres.
NHCS CTEPH Clinical Service
Started in 2016, NHCS CTEPH clinical service is the first in Singapore to offer comprehensive treatment options for patients with CTEPH including Pulmonary Thromboendarterectomy, Balloon Pulmonary Angioplasty (BPA) and medical therapy. To date, more than 70 patients have been treated at NHCS. The service is managed by a multi-disciplinary team working hand-in-hand to provide a full spectrum of care comprising diagnostic investigations, customised treatment options and follow-up care for these patients.
The Razor’s Edge – Pulmonary Thromboendarterectomy
Pulmonary Thromboendarterectomy (PTE), another tongue-twisting name, is a technically demanding yet highly successful operation known to remove life-threatening clots from the blood vessels in the lung.
PTE is the guideline-recommended treatment for operable CTEPH. Data from both the First International CTEPH Registry and the United Kingdom ASPIRE Registry showed a superior survival in patients who underwent PTE surgery compared to those who declined surgery (5-year survival of 83% versus 55%)2-3.
Clots removed from pulmonary artery during PTE.
A PTE is a typically 7- to 8-hour procedure that requires the patient to be attached to a heart-lung bypass machine. The procedure begins with the surgeons opening the sternum (breastbone). During the operation, the body temperature is cooled to 20°C before the blood circulation is stopped and the heart-lung machine then completely drains the patient’s body of blood. From this point on, the surgeons will need to be quick and accurate at removing the clots, as they have to work within a 20-minute interval before blood circulation is restored to the body. These measures are necessary to protect the brain and other vital organs from damage. A surgeon would then use a sharp blade to delicately scrape away the clots embedded in the wall of the pulmonary artery. The process is highly intensive and requires precision skills to perform well. The most important thing is to identify where the clot begins and ends and make sure not to remove too little, or too much. Success or failure balances on the razor’s edge.
Balloon Pulmonary Angioplasty and Medical Therapy
Balloon Pulmonary Angioplasty (BPA) has become an established treatment for selected patients with inoperable CTEPH or where the clots are in the smaller blood vessels for which surgeons may not be able to reach directly. BPA uses a catheter with a balloon device to push the clots against the side of the blood vessels to restore blood flow.
Patients who are unsuitable for PTE and BPA will be offered medical therapy to lower the pressures in the lung.
FOR THE PHYSICIANS
The primary problem remains that this is an under-recognised condition. Despite the advent of therapies and effective interventions for CTEPH, the time of symptom onset to the diagnosis of CTEPH remains at more than two years, with most patients presenting with advanced stage of the disease. The latest European Society of Cardiology and European Respiratory Society (ESC/ERS) Guidelines, published in August 2022, proposed a new algorithm aiming at earlier detection of this condition in the community4.
In patients with persistent or new-onset dyspnoea or exercise limitation following pulmonary embolism (PE), further diagnostic evaluation to assess for CTEPH/ chronic thromboembolic pulmonary disease is recommended. [Class I recommendation]
For symptomatic patients with mismatched perfusion lung defects beyond three months of anticoagulation for acute PE, referral to a pulmonary hypertension/ CTEPH centre is recommended after considering the results of echocardiography, BNP/ NT pro-BNP and/or cardiopulmonary exercise testing (CPET). [Class I recommendation]
Risk factors for CTEPH include a history of PE, inherited hypercoagulable states (lupus anticoagulant, antiphospholipid antibodies, anti-thrombin III/ protein C/ protein S deficiency), permanent intravascular devices, inflammatory bowel diseases, essential thrombocythaemia, splenectomy, high-dose thyroid hormone replacement.
New modality includes alternative perfusion imaging techniques such as iodine subtraction mapping and dualenergy CT.
DSA = Digital subtraction angiography; CPET = Cardiopulmonary Exercise Test; RHC = Right Heart Catheterisation; MDT = Multidisciplinary Team
In conclusion, an increase in awareness of this condition and the possibility of an effective treatment would hopefully avail more patients of the opportunity for relief from this debilitating and ultimately fatal disease.
1. Trendelenberg F. Uber die operative behandlung der embolie der lungarterie. Arch Klin Chir 1908; 86: 686-700.
2. Delcroix M, Lang I, Pepke-Zaba J, et al. Long-Term Outcome of Patients With Chronic Thromboembolic Pulmonary Hypertension – Results From an International Prospective Registry. Circulation 2016;133:859-71
3. Quadery SR, Swift AJ, Billings CG, et al. The impact of patient choice on survival in chronic thromboembolic pulmonary hypertension. Eur Respir J 2018;52:1800589
4. Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J 2022; 00: 1-114
This article is from Murmurs Issue 44 (September – December 2022). Click here to read other articles or issues.