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Pulmonary Arterial Hypertension in Connective Tissue Diseases – A Devastating Complication
rather late in the course of the disease and are too unspecific to use as
Figure 1: Radiogram of the Chest of a Systemic Sclerosis Patient
a screening tool. With physical examination, signs of right heart failure
Revealing Enlargement of the Central Pulmonary Arteries
can be detected, as can an accentuated pulmonary component of the
second heart sound; however, these signs are absent in early PAH.
17
Chest radiography in PAH can demonstrate enlargement of the central
pulmonary arteries (see Figure 1), and an electrocardiogram (ECG) can
show right-axis deviation and RV hypertrophy.
16
Pulmonary function
testing can often detect a mild restriction, and Steen and co-workers
found that an isolated decrease in diffusing capacity for carbon
monoxide (DLCO) predicts PAH in SSc, even 4.5 years before clinically
evident PAH is diagnosed.
18
However, a decrease in DLCO can also be
caused by smoking and interstitial lung disease. The most widely used
screening method is Doppler echocardiography estimation of the
systolic and diastolic PAP by measuring the tricuspid regurgitation
velocity and right atrial pressure. The sensitivity of echocardiography is
approximately 75%, using a threshold of an estimated systolic PAP
>35mmHg. However, echocardiography is flawed by both false-
positive and false-negative results, as well as by overestimation of PAP,
and may lead to unnecessary right heart catheterisations.
19
The
accuracy of echocardiography could be enhanced by the addition of
Figure 2: Analysis of Pulmonary Hypertension
other markers, such as the RV Tei index,
19
tissue Doppler imaging
20
or
biomarkers such as N-terminal pro-hormone brain natriuretic peptide
Detection
(NT-proBNP);
21
however, the value of these markers is yet to be
confirmed. In theory, evaluation during exercise – for example a cycle
History Chest X-ray
Physical examination Echocardiogram
ergometer and echocardiography during exercise – could provide Pulmonary function testing Arterial blood gas analysis
valuable information in early PAH patients, but the invasive nature of
Cardiopulmonary function testing Complete bloodcount, creatinine
Electrocardiogram and liver function tests
the first and practical issues to do with the latter are major obstacles
to their use as screening tools. Characterisation
Test: If positive perform:
In conclusion, the optimal screening tool to date is an annual
Right heart catheterisation
Vasoreactivity testing
6-minute walk test
echocardiography combined with a thorough history and, when
feasible, pulmonary function testing.
1
However, a clinical history of
Antinuclear antibodies
Antiextractable nuclear antigens,
immunoblotting
declining exercise capacity should be regarded as a potential sign of
pulmonary hypertension regardless of the findings of pulmonary
Echo abdomen and Doppler splenic vein
Consultation with gastroenterologist
function testing and echocardiography,
22
and should prompt a right
Serology for hepatitis B and C
heart catheterisation, the gold standard for the assessment of
pulmonary hypertension. According to the guidelines, once the
HIV serology
Consultation with HIV specialist
diagnosis of PAH is confirmed at right heart catheterisation, a
V/Q lung scan
vasoreactive study should be performed. In our experience, and also in
Pulmonary artery angiogram
Anticardiolipin antibody activity
Computed tomography (CT) angiography
that of others, vasoreactivity is absent in CTD patients and could be
Lupus anticoagulant activity
left out of the evaluation. For classification of a patient with
History suspected of sleep-disordered
Overnight oximetry
pulmonary hypertension, a complete evaluation is indispensable; this is
breathing
also the case in known CTD patients. The complete evaluation consists
of, among others, an echographic study of the abdomen with Doppler
High resolution CT scan of lungs
of the splenic vein, perfusion scintigraphy and HIV serology
23
(see
Figure 2). In cases in which no other cause is found for the pulmonary
hypertension besides the CTD, the diagnosis of PAH associated with threatening bleeding when combined with anticoagulation therapy. In
CTD can be established. In order to apply the appropriate treatment cases of RV failure, diuretics and possibly digoxin should be applied.
options, the next step is to determine the functional class of the
patient according to the NYHA scale (see Table 2). Specific Treatment
Specific treatment of patients with PAH is targeted to produce
Treatment of Pulmonary Hypertension vasodilatation and vascular growth inhibition; since acute vasoreactivity is
Treatment of PAH consists of general therapeutic options and specific absent in CTD patients, remodelling of the pulmonary vasculature is
treatment. Oxygen therapy is indicated in patients with hypoxemia. regarded as the mechanism of action in these patients. The treatment
Anticoagulation therapy, which is used in patients with idiopathic PAH, is arsenal for PAH consists of the endothelin receptor antagonists, the
often contraindicated in CTD patients. In patients with SSc and MCTD, prostacyclin analogues and phosphodiesterase-5 inhibition. Current
oesophageal dysmotility frequently leads to occult blood loss, and the treatment algorithms for PAH recommend first-line treatment with oral
regularly present angiodysplasias in the intestinal tract may cause life- medication such as bosentan
24
and sitaxsentan,
25
both endothelin
EUROPEAN MUSCULOSKELETAL REVIEW 2007 45
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