Pulmonary hypertension in sarcoidosis: optimizing the diagnostic approach

Sarcoidosis is a systemic inflammatory syndrome of unknown aetiology
characterized by formation of non-caseating granulomas in affected tissues,
particulary the lung and lymphatic system. Pulmonary hypertension (PH) is a
serious complication of sarcoidosis with a suggested prevalence between 5 and
74% in patients with pulmonary involvement. PH is associated with an increased
morbidity and mortality in affected patients. Different pathophysiologic
mechanisms involved in PH associated sarcoidosis are: extrinsic compression of
the pulmonary vessels by lymphadenopathy or fibrosis, pulmonary veno-occlusive
disease, left ventricular dysfunction, portopulmonary hypertension, hypoxemia,
and intrinsic sarcoid vasculopathy. The management of PH associated sarcoidosis
depends on the underlying mechanism. The cornerstone in the diagnosis of PH is
the right heart catheterisation (RHC). Treatment decision should be made on a
case by case basis.

The first objective of the study is to predict the prevalence of PH in
sarcoidosis with pulmonary involvement, and to optimize the diagnostic approach
in screening for PH associated sarcoidosis using the RHC as gold standard
(Galie, 2009). The presence of disease is set by the multidisciplinary PH/ILD
team using all available diagnostics (including chest CT, pulmonary function
test, exercise test), but excluding the IVUS and flow measurements in the
pulmonary artery.

The second objective is to predict the mechanism and cause of PH associated
sarcoidosis. The mechanism of PH in pulmonary sarcoidosis is often unclear.
Other investigations will be performed if *out of proportion* findings are
present as discussed within the multidisciplinary PH/ILD team. The IVUS and
pressure and flow wire will be used to evaluate the mechanism of disease by
describing the characteristics of the vascular wall and local differences in
pressure and flow. This might be helpful in patients suffering *out of
proportion* PH in the presence of pulmonary sarcoidosis. This means worse
hemodynamics than expected by the distribution or severity of the pulmonary
fibrosis.

All patients will be screened for the presence of PH by a standardized
diagnostic approach including: transthoracic echocardiography with right
ventricle measurement using the Ventripoint system, electrocardiogram and
biomarkers related to PH (NT * pro BNP, troponin and uric acid). In a subgroup
of patients with the diagnosis *PH possible* based on the diagnostic approach
(as suggested by the international guidelines for PH), a RHC will be performed
for measuring the pulmonary hemodynamics. This will also include an
intra-vascular ultrasound (IVUS) and the measurements of flow in the pulmonary
arteries using a specific wire.

There are no immediate benefits for participating patients. They will serve
scientific research to clarify mechanisms and aetiology of PH in Sarcoidosis
patients. The additional risks are kept to a minimum, since the extra invasive
procedures (IVUS and ComboWire) will be executed in the same procedure as the
RHC, which is not a study intervention but part of the standardized work up.
Adverse events are described in the brochure of the company. They state that
major risks of peripheral angiography or angioplasty (as in RHC) are:
-dissection of the blood vessel
-Abrupt closure of the blood vessel
-Perforation
-Embolization or local thrombus
-Spasm or the artery
Minor side effects are:
-bleeding at the entry puncture site
-Local or systemic infection