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Connective Tissue Disease
Table 1: Revised World Health Organization Clinical
catheterisation. In CTD patients, this evaluation must be individualised,
Classification of Pulmonary Hypertension (Venice 2003)
7
since the majority of patients are impaired in condition and motility due
to the CTD itself. Also, 6MWT results in CTD patients are in general lower
1. Pulmonary Arterial Hypertension
than the score achieved by the general PAH population.
Idiopathic
Familial
In all treatment studies in PAH the proportion of CTD patients is small and
Associated with:
the observation time is short, in general between 12 and 18 weeks.
• Collagen vascular disease
• Congenital systemic to pulmonary shunts
Therefore, the results should be interpreted with care. Denton performed
• Portal hypertension
a subanalysis of CTD patients treated in the bosentan pivotal trial and
• HIV infection found 64 evaluable patients, with a mean follow-up of 1.8 years. 6MWT
• Drugs/toxins
distance improved by 14.7m and 25% of the patients improved in terms
• Other
of NYHA class.
31
Survival after two years was 73.4% compared with 13.6%
Associated with significant venous or capillary involvement
in Kawut’s study, which was before endothelin receptor antagonists had
• Pulmonary veno-occlusive disease
become available.
32
In the Sitaxsentan To Relieve Impaired Exercise
• Pulmonary capillary haemangiomatosis
Persistent pulmonary hypertension of the newborn
(STRIDE-1) study only 24 CTD patients were included. In all patients treated
2. Pulmonary Hypertension with Left Heart Disease
with sitaxsentan, improvement of NYHA class was achieved in 13% and
Left-sided atrial or ventricular heart disease
6MWT distance improved by 24.9m.
25
In the Sildenafil Use in Pulmonary
Left-sided valvular heart disease Arterial Hypertension (SUPER) study, a subanalysis of 62 patients with CTD
3. Pulmonary Hypertension Associated with Lung Diseases and/or Hypoxemia
showed a 46m improvement of 6MWT distance; however, no decline in
Chronic obstructive lung disease
time to clinical worsening was determined.
26
In the study by Barst et al.
Interstitial lung disease
with epoprostanol, only patients with idiopathic PAH were included. Active
Sleep-disordered breathing
Alveolar hypoventilation disorders
treatment resulted in improved survival, improved quality of life and an
Chronic exposure to high altitude
increase of 44m in the 6MWT.
28
In a subanalysis of the 90 CTD patients
Developmental abnormalities
included in the two placebo-controlled studies of subcutaneous
4. Pulmonary Hypertension due to Chronic Thrombotic and/or Embolic Disease treprostinil, a 25m improvement in the 6MWT was reported, as well as
Thromboembolic obstruction of proximal pulmonary arteries
improvement of symptoms of PAH and haemodynamics.
33
Since the
Thromboembolic obstruction of distal pulmonary arteries
literature does not provide treatment guidelines in PAH associated with
Non-thrombotic pulmonary embolism (tumour, parasites, foreign material)
CTD, most information is gathered by observing daily practice.
5. Miscellaneous
Sarcoidosis, histiocytosis X, lymphangiomatosis, compression of pulmonary vessels
(adenopathy, tumour, fibrosing mediastinitis)
Daily Clinical Care of Pulmonary Arterial Hypertension–
Connective Tissue Disease Patients in Nijmegen
Table 2: Modified New York Heart Association
The pulmonary hypertension team in the Radboud University Nijmegen
Functional Classification
1 Medical Centre in The Netherlands consists of rheumatologists, chest
physicians, cardiologists, radiologists, pathologists and nurses. Working in
Class I: Patients with pulmonary hypertension in whom there is no limitation to usual
a tertiary referral hospital for SSc, our team specialises in PAH associated
physical activity. Ordinary physical activity does not cause increased dyspnoea, fatigue,
with CTD, which is diagnosed in almost 50% of our PAH patients. After a
chest pain or near syncope.
thorough evaluation of each patient, as described above and shown in
Class II: Patients with pulmonary hypertension who have mild limitation of physical
Figure 2, we initiate treatment with bosentan 125mg twice daily in NYHA
activity. There is no discomfort at rest, but normal physical activity causes increased
dyspnoea, fatigue, chest pain or near syncope.
class III patients, together with oxygen when applicable. Our experience
Class III: Patients with pulmonary hypertension who have a marked limitation of physical
with sitaxsentan is limited, since the registration and reimbursement of
activity. There is no discomfort at rest, but less than ordinary physical activity causes sitaxsentan in The Netherlands was completed only very recently, but it
increased dyspnoea, fatigue, chest pain or near syncope. could be an alternative treatment option in CTD patients. When evaluation
Class IV: Patients with pulmonary hypertension who are unable to perform any physical
of treatment after three months shows an improvement in terms of
activity without symptoms and who may have symptoms of right heart failure. Dyspnoea
complaints and exercise capacity as measured by 6MWT and NYHA
and/or fatigue may be present at rest and symptoms are increased by almost any
classification, together with a stabilisation or improvement of pulmonary
physical activity.
function tests and echocardiography, the treatment is continued and
evaluations are repeated every three months. When treatment goals are
receptor antagonists, and sildenafil,
26
a phosphodiesterase-5 inhibitor, not achieved, or no longer achieved, add-on therapy with sildenafil 20mg
for class III patients; and treprostinil
27
and epoprostanol,
28
both thrice daily is applied. If this is not effective, add-on therapy with
prostacyclin analogues, for class III and class IV patients. Up-to-date subcutaneous treprostinil is employed. Dosage is built up over three days
treatment is ‘goal-orientated’ – i.e. a 6-minute walking test (6MWT) to the effective dose of 20ng/kg/min, with weekly evaluations using
distance >380m, a peak oxygen uptake >10.4ml/min/kg, a peak systolic telephone interviews and a complete evaluation after eight weeks. In
blood pressure during exercise >120mmHg,
29
NYHA functional class I patients presenting with NYHA class IV, treatment is initiated with either
and a decrease in plasma brain natriuretic peptide (BNP) levels.
30
In order subcutaneous treprostinil or intravenous epoprostanol. When applicable,
to achieve an optimal treatment result, all initiated treatments should be these patients are registered as lung transplantation candidates. Patients
evaluated regularly – at least once every three months. This evaluation who deteriorate to NYHA class IV and right heart failure are initiated on
may consist of a careful history, 6MWT, plasma BNP levels, either intravenous epoprostanol or inhaled iloprost 100µg daily – divided
echocardiography, pulmonary function tests and right heart into six doses – using an ultrasonic nebuliser, combined with continuous
46 EUROPEAN MUSCULOSKELETAL REVIEW 2007
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