Protocol C: Microcirculatory response to phlebotomy in adult patients with Eisenmenger syndrome.

Eisenmenger syndrome is a congenital anomaly of the heart. In this syndrome, an
initial left-to-right central shunt subsequently reverses due to the
development of pulmonary hypertension. The hypoxaemia resulting from a
right-to-left shunt is compensated by an increase in haemoglobin concentration
(Ned Tijdschr Geneeskd 1999;143(10):501-5). Most patients have a compensated
erythropoiesis with stable haemoglobin that requires no intervention. However,
polycythaemia can lead to symptoms associated with hyperviscosity of the blood,
like headache and gout. These symptoms may be relieved by removal of one unit
of blood (phlebotomy), always with an equal volume replacement. This treatment
is recommended in patients with haematocrit >0.65 with signs of hyperviscosity
(Eur Heart J 2003;24;1035-1084). However, therapeutic phlebotomy in cyanotic
heart disease is controversial. Data suggest that phlebotomy has the potential
to increase exercise capacity, reduce the symptoms of hyperviscosity, and
reduce the potential risk of vaso-occlusive disease in selected patients.
However, removing blood may stimulate the bone marrow to produce even more red
cells. Furthermore, repeated phlebotomy depletes the iron stores and may result
in the production of iron-deficient red cells. These microcytic erythrocytes
are less deformable than normocytic erythrocytes and increase the risk of
stroke by increasing blood viscosity (Cardiol Rev 2007;15(1):31-4).
Recently, a two-dimensional imaging technique (called sidestream dark-field
(SDF) imaging) was developed and validated to assess microcirculatory blood
flow.

Aim of the proposed study will be to investigate whether microvascular blood
flow at baseline is impaired in Eisenmenger patients who experience symptoms of
the *hyperviscosity syndrome*. Furthermore, in view of the controversy whether
to perform phlebotomy or not, the effect of phlebotomy and successive volume
replacement on the microcirculation will be studied.

Observational study.
The imaging technique has been described in detail in protocol A, which already
was approved by the medical ethical committee of Erasmus MC (MEC-2006-352).
Sublingual SDF imaging will be performed three times:
1. Before phlebotomy (T0 = baseline).
2. Ten minutes after removal of 500 ml of blood (T1).
3. Ten minutes after 500 cc saline replacement. (T2).

Together with SDF imaging, the following data will be collected:
Length, weight, cardiac risk profile (diabetes mellitus, hypertension,
dyslipidemia, smoking), current medication use, body temperature, heart rate
and rhythm, arterial blood pressure, haemoglobin, haematocrit.

Hemoglobin concentration and hematocrit will be measured in routinely taken
blood samples.

Not applicable.