AJTCCM VOL. 29 NO. 3 2023 103
EDITORIAL
Chronic thromboembolic pulmonary hypertension (CTEPH) (World
Health Organization (WHO) group 4 pulmonary hypertension (PH))
is a rare complication of pulmonary embolism (PE), yet tantalisingly
oers the potential for eective interventions. e precise incidence
of CTEPH aer PE is not known, with reported estimates ranging
from 0.1% to 12% in the following 2 years. Furthermore, up to
50% of patients with CTEPH may not have a documented history
of PE, which alludes to a complicated pathogenesis involving both
obstruction of the pulmonary arteries by unresolved brotic clots
and secondary vasculopathy.[1]
Fortunately, there is both increasing local awareness of CTEPH
and increasing interventions and experience available, which
makes the article by Davies-van Es etal.[2] in this issue of AJTCCM
highly topical. e disease has traditionally been divided into four
anatomical levels, involving the proximal main artery (level I) or
the lobar (level II), segmental (level III) or subsegmental arteries
(levelIV), which are used as a guide to management. Surgery, in
the form of pulmonary endarterectomy (PEA), remains the best
therapeutic option for anatomically proximal disease (levels I - III),
while balloon pulmonary angioplasty (BPA) and medical therapy are
used for more distal disease and residual PH aer PEA.[3]
PEA is a technically demanding operation, but it oers patients
with CTEPH an opportunity for relief from this debilitating disease,
with impressive results in experienced centres. e most important
aspect of PEA is to perform as complete an endarterectomy as
possible with removal of all the distal lesion tail ends from the
pulmonary vascular tree. Perfect visualisation is essential, and the
procedure is performed with the use of cardiopulmonary bypass and
deep hypothermic circulatory arrest periods limited to 20 minutes
at a time.[4]
Until very recently BPA was not available in South Africa, but
fortunately it is now an option locally. BPA is reserved for the
treatment of patients who are not suitable candidates for PEA,[5]
which, depending on surgical expertise and the patient population,
may constitute up to one-third of all CTEPH patients.[6] e rst
reported cohort of BPA patients had unacceptably high complication
rates.[7] Subsequent renement of the original technique, using a
measured, conservative and step-wise approach along with improved
patient selection, has resulted in improved eort tolerance, reduced
pulmonary pressures and better quality of life with relatively low
complication rates. Arandomised controlled trial (Multicenter
Randomized controlled trial based on Balloon Pulmonary
Angioplasty (MR BPA))[8] conrmed that the outcomes in patients
undergoing BPA are better than in those receiving medical therapy
in the form of riociguat alone. Despite similarities in catheter
and coronary wire manipulation as well as percutaneous balloon
angioplasty, BPA is very different from coronary intervention.
The approach to BPA is much more conservative, forgoing the
immediate complete dilatation and stenting of stenotic lesions
seen in coronary intervention in favour of progressive dilatation of
lesions over multiple sessions. Stenting in BPA is very uncommon.
Operator experience is essential to improve outcomes and decrease
complications,[9] and for this reason it is recommended that BPA be
performed in a dedicated PH centre with a sucient volume of work
to ensure upskilling and skill retention. Ultimately the goal of a BPA
centre of excellence should be to perform >100 BPA procedures per
year or perform BPA on >30 patients per year.[5]
Medical therapy should be reserved for inoperable or residual
PH, and riociguat (an oral guanylate cyclase stimulator) and
subcutaneous treprostinil (a prostacyclin agonist) are approved
for patients with inoperable CTEPH abroad, but both therapies
are expensive and not licensed locally. Other PH medications are
used o-label in CTEPH; however, oral combination therapy is not
infrequent in patients with severe haemodynamic disease.[1]
Against this backdrop of expanding available interventions for
CTEPH, individual patient work-up becomes critical to determine
the anatomical nature and extent of disease, to evaluate the
haemodynamics in the context of a possible coexistent vasculopathy,
and to exclude other pathologies. All investigations used provide
important and often complementary information. Ventilation/
perfusion (V/Q) and increasingly V/Q single-photon emission
computed tomography (SPECT) scanning provide evidence of
disease in the subsegmental areas, frequently below the resolution
of most computed tomography (CT) scans, while CT scanning
provides detail of both the vasculature and the lung parenchyma,
including demonstration of lung regions that are unlikely to gain
benet from reperfusion (e.g. emphysematous or brotic areas).
Echocardiography is important not only as the initial screening
tool for diagnosing CTEPH, but also to assess functioning of both
the right and le ventricles; however, it cannot replace right heart
catheterisation in the measurement of important haemodynamic
parameters. Invasive digital subtraction pulmonary angiography,
performed at the same procedure as right heart catheterisation,
is important because it arms the PH team with a tool that can
accurately distinguish between primarily proximal disease, best
managed surgically, and inoperable distal disease, better suited to
BPA or medical therapy. It also assists in the identication of patients
likely to have signicant microvascular disease and therefore best
treated medically.[5,10] In order to extract this anatomical information,
high-quality angiographic images are required, but the acquisition
of such images itself requires time and experience, and is one of
the learning curves that must be overcome in the evolution of a PH
service, particularly where BPA is available.[10]
e experience of Davies-van Es etal.[2] from a single centre is
an important article and highlights the lack of standardisation of
work-up for CTEPH patients, even within an institution. is lack
of standardisation probably also reects changing practice over the
16-year study period. It is interesting to note that over that study
period, the majority of patients did not have V/Q imaging (29%) or
right heart catheterisation (24%), and no patients had pulmonary
Chronic thromboembolic pulmonary hypertension: More options,
more awareness
104 AJTCCM VOL. 29 NO. 3 2023
EDITORIAL
angiography, with the authors calling for a more standardised and
protocolised approach to work-up in their institution.
ere are additional important take-home messages from this
article. Firstly, ~10% of the authors’ original cohort did not have
CTEPH, but pulmonary angiosarcoma. It is important for clinicians
to appreciate that there are CTEPH mimics, which almost uniformly
will have poor outcomes if not recognised prior to surgery. Secondly,
the severity of disease presented for surgery appears worse than at
other centres internationally, with 80% of the patients in WHO
functional class III or IV, and almost half in clinical right heart
failure. is is likely to be an indication of an underappreciation
of CTEPH in the general community of physicians, with referral
only aer severe right ventricular failure occurs. is is an important
nding in and of itself, as early diagnosis and early intervention are
associated with improved outcomes, and is likely to be an important
contributing reason for the high morbidity and mortality in this
population compared with reported global norms. It serves as an
important reminder to us, the pulmonology community, to advocate
for increased awareness of the disease entity, follow-up aer PE, and
early referral for assessment and work-up.
Finally, despite the severe and late disease presentations in this
study, many patients had life-changing outcomes aer PEA, with
notable improvement in WHO functional class. This finding
emphasises that CTEPH is a condition that is potentially treatable.
Unfortunately, loss to follow-up in this particular retrospective
cohort limits accurate assessment of these outcomes, as only 75% of
the patients were assessed aer hospital discharge.
In summary, the future for patients with CTEPH is hopeful,
with both PEA for proximal disease, and now BPA for more distal
and residual disease, available locally. However, patients need to
be identied as early as possible, and routine post-PE follow-up is
advised for most patients aer 3 - 6 months of anticoagulation. Work-
up for CTEPH is advised in an experienced centre to ensure the best
individualised management strategies and to improve outcomes.
B W Allwood, MB BCh, FCP (SA), MPH, Cert Pulmonology (SA),
PhD
Division of Pulmonology, Department of Medicine, Faculty of Medicine and Health
Sciences, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa
brianallwood@sun.ac.za
L Joubert, MB ChB, MMed (Int Med), FCP (SA) MPhil (Cardiol),
Cert Cardiology (SA)
Division of Cardiology, Department of Medicine, Faculty of Medicine and
Health Sciences, Stellenbosch University and Tygerberg Hospital, Cape Town,
South Africa
J Janson, MB ChB, MMed (or), FCS (Cardio) (SA), PhD
Division of Cardiothoracic Surgery, Department of Surgical Sciences, Faculty of
Medicine and Health Sciences, Stellenbosch University and Tygerberg Hospital,
Cape Town, South Africa
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https://doi.org/10.1177/20458940211007372
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