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The ACCP recommendation for treatment of PAH patients
with WHO class IV symptoms are as follows: Patients with
PAH in functional class IV who are not candidates for,
or who have failed, CCB therapy are candidates for long-term
therapy with intravenous epoprostenol (treatment of choice).
Level of evidence: good; benefit: substantial; grade of
recommendation: A. Other treatments available for patients
with PAH and functional class IV include, in no hierarchical
order: Endothelin-receptor antagonists (bosentan). Level
of evidence: fair; benefit: intermediate; grade of recommendation:
B. Subcutaneous treprostinil. Level of evidence: fair;
benefit: intermediate; grade of recommendation: B. Inhaled
iloprost. Level of evidence: low; benefit: small; grade
of recommendation: C.
Dr. Klinger, how do you decide the approach for
the class IV patient with PAH? Is your general approach
the same as the above recommendations?
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 James
R. Klinger, MD
Associate Professor of Medicine
Division of Pulmonary, Sleep, and Critical Care
Medicine
Brown University School of Medicine
Medical Director
Respiratory Care Unit
Rhode Island Hospital
Providence, Rhode Island
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For the most part, I adhere to the guidelines that recommend
continuous intravenous infusion of epoprostenol for class
IV PAH patients. The most important finding in this group
is compromised right ventricular function. Patients with
poor functional status secondary to impaired right ventricular
function are a perilous group with significant nearterm
mortality. Prostacyclin derivatives are unique in that
they have a significant inotropic effect in addition to
being potent pulmonary vasodilators. Hemodynamics can
be misleading. Some patients have impressive pulmonary
arterial pressures, but maintain adequate cardiac output.
I‘m not likely to favor prostacyclins in class III
patients just because of high pulmonary artery pressures,
but patients with clinical evidence of decompensated right-heart
failure, ascites, severe peripheral edema, or severe pressure
overload or hypokinesis on echocardiography always have
me a little worried. We were recently referred a patient
by the cardiologist reading echocardiograms. He had come
across an echo that revealed severe right ventricular
dilation and hypokinesis. The peak pulmonary artery pressure
was estimated to be 80 mm Hg, but they just didn’t
like the way the right ventricle moved. Interestingly,
the patient complained of only moderate dyspnea on exertion,
but her right-heart catheterization findings confirmed
severely impaired right ventricular function with a cardiac
index less than 1.8. In general, I like to see these patients
treated with epoprostenol as soon as possible. The approach
should be to stabilize their condition and then consider
transition to oral therapy if they respond better than
anticipated.
The recommendations (algorithm and its footnotes)
indicate that epoprostenol is generally the first-line
therapy. Are there settings in which you’d consider
another drug?
Some patients just aren’t good candidates
for intravenous infusion therapy. For example, patients
at high risk for central line infection or those who struggle
with aseptic technique. Under these circumstances, I do
consider alternative therapies. Theoretically, treprostinil
should be as effective as epoprostenol if dosed aggressively.
Although the data from controlled trials in terms of functional
response and survival have not been as impressive, I have
had class IV patients do well with treprostinil.
Some patients simply refuse or are incapable of managing
continuous infusion therapy. In this situation, oral therapy
may be the only option. I’ve been slightly more impressed
with the response to sildenafil than with endothelin-receptor
antagonists in the few class IV patients I’ve treated
this way. This may be because of the lack of an immediate
hemodynamic effect with the latter drugs.
Finally, there is the occasional patient who may be
better suited for an alternative therapy. One of my patients
progressed from WHO class III to class IV while receiving
calcium-channel blockers and an endothelin-receptor antagonist.
She developed progressive hypoxemia and became difficult
to oxygenate despite continuous high flow oxygen. On repeat
catheterization, she had a similar vasodilator response
to epoprostenol and to inhaled nitric oxide, but her oxygenation
was considerably worse with epoprostenol. We participate
in a long-term home inhaled nitric oxide program and were
able to offer this option to the patient. She did remarkably
well for over a year on inhaled nitric oxide and an endothelin
antagonist.
So, there are certain situations in which I find treatments
other than epoprostenol to be appropriate for initial
therapy in class IV patients. However, these are the exceptions
to the rule and for the great majority of my patients
I still recommend
doing everything possible to get them to undergo intravenous
infusion therapy first.
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