boersma.qxp 25/7/08 02:12 Page 87
Pulmonary Arterial Hypertension in Adults with Congenital Heart Disease
CONCOR patients with PAH is 38 years (range 18–81 years), and 60% of
Figure 1: Cardiac Magnetic Resonance Image of a Patient with
them are women.
2
PAH increases with age and is associated with a worse
Eisenmenger Syndrome Due to a Ventricular Septal Defect
functional class and greater risk of death, particularly among patients
with Eisenmenger syndrome.
7
Clinical Presentation
Clinical signs of PAH are variable and depend on the underlying congenital
heart disease, patient age, repair status and degree and direction of
shunting. Symptoms are related to reduced cardiac output, congestive
heart failure, arrhythmias and hypoxaemia and may affect quality of life,
morbidity and mortality. General symptoms suggestive of PAH are non-
specific and may include dyspnoea, chest pain, peripheral oedema and
syncope.
3
In patients with Eisenmenger syndrome, central cyanosis and
clubbing are the most visible clinical consequences. However, it should be
emphasised that not all Eisenmenger patients are cyanotic at rest.
In cyanotic patients, compensatory mechanisms to maintain adequate
tissue oxygenation take place. Chronic cyanosis results in elevated renal
production of erythropoietin, thus promoting erythropoiesis and
secondary erythrocytosis.
11
Repeated phlebotomies in cyanotic patients
with congenital heart disease and PAH induced iron deficiency and
should be abandoned. Iron deficiency has been associated with an
increased risk of cerebrovascular events in cyanotic adults.
12
Phlebotomy
is indicated only for symptomatic hyperviscosity syndrome and should be
performed with simultaneous isovolumic fluid replacement to avoid a
catastrophic collapse. In patients with Eisenmenger syndrome one or
more of the following non-cardiac complications may occur: bleeding,
thrombotic diathesis, endocarditis or cerebral abscess and impaired
The image is an oblique sagittal view, where the arrow indicates a right ventricular hypertrophy. Note the
hepatic and renal function.
13
Therefore, Eisenmenger syndrome can be dilated pulmonary artery (PA) with a small regurgitant jet.
considered as a multisystem disorder.
LV = left ventricle; RV = right ventricle.
In the last decade, new medical treatment strategies have been
Prognosis demonstrated to be beneficial in patients with PAH.
18–20
Recent studies
In patients with Eisenmenger syndrome, mortality is high: 21% died have shown short-term positive treatment effects of intravenous
during the five-year follow-up period of the EHS.
7
The general prognosis prostacyclin, endothelin receptor antagonist and phosphodiesterase-5
is related to both the severity of PAH and the underlying congenital heart (PDE5) inhibitors in patients with PAH associated with congenital heart
disease. Variables associated with poor long-term outcome are syncope, disease.
20–29
The different pathways for this medical treatment of PAH are
elevated right heart filling pressure, severe hypoxaemia and Down‘s shown in Figure 2. Prostacyclin, or epoprostenol, is a potent short-acting
syndrome.
4,14
PAH is a progressive condition and patients usually die vasodilator and inhibitor of platelet aggregation produced by the vascular
between the third and fifth decade of life. In patients with Eisenmenger endothelium. In patients with PAH, the synthesis of prostacyclin is
syndrome, median survival is reduced by approximately 20 years markedly diminished in the pulmonary endothelium. However,
compared with healthy individuals.
13
Around 55–63% of patients with prostacyclin therapy is complicated by the need for continuous
Eisenmenger syndrome die of sudden cardiac death. Other frequent intravenous infusion or frequent nebulisers.
21
Bosentan inhibits the
causes of death include congestive heart failure, haemoptysis, brain endothelin A and B receptors and competes with endothelin-1, which
abscess, thromboembolism and complications of pregnancy or non- usually binds to those receptors. Endothelin-1 is a potent vasoconstrictor
cardiac surgery.
15,16
However, survival in patients with Eisenmenger and a mitogen for vascular smooth-muscle cells and fibroblasts.
syndrome is far better than the median survival of 2.8 years in patients Overexpression of endothelin-1 has been demonstrated in the pulmonary
with idiopathic pulmonary arterial hypertension.
17,18
vasculature of patients with PAH. By blocking endothelin receptors type
A and B, bosentan may decrease endothelin-related vasoconstriction and
New Developments in Medical Treatment Strategies smooth cell proliferation and thus modify functional and structural
Once the Eisenmenger syndrome is present, surgical closure of the defect changes in the pulmonary vessels. PDE5 is abundantly expressed in the
is no longer an option. The right ventricle will be unable to generate lung, where it inactivates cyclic guanosine monophosphate (cGMP),
enough pressure to overcome the high pulmonary vascular resistance and thereby inhibiting the vasodilatory effects of nitric oxide and atrial
will decompensate. Until recently, treatment options for patients with natriuretic peptides. The PDE5 inhibitor sildenafil causes relaxation of
PAH associated with congenital heart disease were limited to the pulmonary vascular smooth muscles by activating large-conductance,
avoidance and treatment of complications. As natural survival prospects calcium-activated potassium channels.
30
are far better compared with idiopathic or other forms of PAH,
heart–lung transplantation is restricted to highly symptomatic patients New medical treatment strategies are promising; however, experience
and those in whom life expectancy is considered short. in adults with congenital heart disease is limited and no long-term
EUROPEAN CARDIOLOGY 87
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100 |
Page 101 |
Page 102 |
Page 103 |
Page 104 |
Page 105 |
Page 106 |
Page 107 |
Page 108 |
Page 109 |
Page 110 |
Page 111 |
Page 112 |
Page 113 |
Page 114 |
Page 115 |
Page 116