CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 6, November/December 2010
AFRICA
337
type-5 inhibitors, none of these therapies are available in this
country.
Based on published evidence, all class 4 patients should
receive intravenous epoprostenol, since this is the only therapy
that has demonstrated a survival benefit in patients with PAH.
10
The choice of therapy in class 2 to 3 patients and the optimum
combination of drugs are as yet unclear. Also unknown is
whether therapy should be initiated in asymptomatic patients
with confirmed PAH. Apart from epoprostenol in class 4
patients, importantly, no therapy has shown significant survival
benefit and the nature and magnitude of an appropriate surrogate
endpoint are still debatable.
Patients refractory to medical therapy and with advanced
symptoms may be considered for balloon atrial septostomy or
lung transplantation. The rationale of creating a right-to-left
shunt percutaneously is based on the fact that patients with
Eisenmengers syndrome have a much better survival than other
groups of PAH, perhaps because of the possibility of unload-
ing the right ventricle and increasing systemic blood flow, even
though this may be at the expense of desaturated blood.
Does the future hold any promise for new
therapies for PAH?
The still-dismal outcome of patients with PAH has stimulated
intense and exciting avenues of research into new therapies that
would hopefully reverse the pulmonary hypertensive phenotype.
As we delve deeper into the pathobiology of PAH, we increas-
ingly realise the complexity of pathways involved in vascular
remodelling. While many new approaches have shown promise
at the bench side and in the monocrotaline-induced rat model of
PAH, these remain to be tested in the clinical arena.
Inhibition of TGF-
b
receptors with antibodies or losartan,
statins which increase BMPR2 gene promoter function, inhibi-
tion of tyrosine kinase, which is an important mediator of cellular
proliferation andmigration, with drugs such as imatinib, and alter-
ation of intracellular signalling via the SMAD pathway are but a
few examples of potential therapeutic targets. Since right ventric-
ular function may be an even more robust predictor of outcomes
than the actual level of pulmonary pressure, more detailed study
of right ventricular remodelling and the molecular determinants
of hypertrophy and failure of this chamber are also crucial.
Conclusion
In the not-too-distant future, we may be able to provide our
patients with PAH with a cure. Until such time, however, it
behoves us as clinicians to always consider the possibility of
PAH, institute a diligent workup to make a precise diagnosis and
assessment of severity and reversibility, and do all we can to make
available potential therapies to this desperate group of patients.
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