May 23, 2023
Katharine Clapham, MD is an Assistant Professor in the Division of Cardiovascular Medicine at University of Utah Health. @UofUHealth
Dr. Clapham discusses methamphetamine-associated pulmonary arterial hypertension.
I
am Katie Clapham. I'm an assistant professor of cardiology at the
University of Utah. I'm a cardiologist that has done additional
training in pulmonary hypertension, and I see patients together
with pulmonologists in our group here at the University of
Utah.
Today, I want to talk about methamphetamine-associated pulmonary
arterial hypertension, which is a type of pulmonary hypertension
that the medical community has grown increasingly aware of and for
which there are some new emerging treatments.
As many of you know, pulmonary hypertension can have multiple
different causes. We think about it in terms of the WHO groups as
causes for pulmonary hypertension, but within Group I, pulmonary
arterial hypertension, methamphetamine use is becoming an
increasingly recognized cause of pulmonary arterial
hypertension.
Some of the work that's demonstrated that has come out of Dr. Roham
Zamanian's group at Stanford University. Our group at the
University of Utah recently published a paper looking at the causes
of pulmonary arterial hypertension that we see. It turns out that
about one-third of our patients with associated pulmonary arterial
hypertension have toxin-induced pulmonary arterial hypertension. In
the majority of those patients, the toxin is methamphetamine
use.
Patients will present to us a variety of ways. Some individuals
have been hospitalized and found to have pulmonary hypertension
when they're in the hospital. Some individuals are referred to us
by providers in states like Utah, Wyoming, Nevada. Some
individuals, they come to us for shortness of breath, and then we
find that they have pulmonary hypertension. Then in our evaluation
of the causes of pulmonary hypertension, we identify
methamphetamine as the provoking cause.
I did most of my training on the East Coast in Boston, and
methamphetamine use isn't as common there or at least not as
commonly recognized a problem there. Methamphetamine use is more
common in the Western United States and Midwest, although more
recent research that we saw presented, for example, at the
Drug-induced Pulmonary
Hypertension Symposium at Stanford, showed that it is more
prevalent in the East Coast than maybe people screen for or are
aware of.
So moving out here to Utah, when I took this job at University of
Utah, it was eye-opening for me to realize how common
methamphetamine use is in this part of the United States and how
common a cause of pulmonary hypertension in the patients that we
see it is.
People are still late to be identified with pulmonary hypertension
in the course of the disease, and we'd like to find people earlier.
I think that is part of why it's important to raise awareness about
the disease so both providers and patients know that this is a
possibility.
The way that the majority of our patients get identified as
potentially having pulmonary hypertension is after they have an
echocardiogram performed, which is an ultrasound of the heart. The
echocardiogram may indicate some signs of pulmonary hypertension,
like right ventricular enlargement, right ventricular dysfunction,
or we can estimate the pulmonary artery pressures from the
echocardiogram. If those are very elevated, that raises suspicion
for pulmonary hypertension. That often prompts a referral to our
group.
The mechanism by which methamphetamine use causes pulmonary
arterial hypertension is not that well understood. But we know that
methamphetamine is pretty chemically similar to the anorexigens.
I'm talking about Aminorex, the drug that was used for weight loss
that was later found to cause pulmonary arterial hypertension. So
methamphetamine looks chemically similar to that.
There have been some studies in the lab that show that
methamphetamine can cause the formation of reactive oxygen species,
which can damage the vasculature. It causes release of substances
like dopamine, norepinephrine, and serotonin. Animal studies in
mice, for example, show amphetamine exposure results in suppression
of this factor called HIF-1-alpha, which in turn disrupts the
response to mitochondrial oxidative stress. This leads to DNA
damage and that leads to injury of the vasculature.
I don't think there's good data about whether people can reverse
PAH with stopping methamphetamine use, but I would say anecdotally
talking to physicians who take care of these patients and in our
experience, we do see people with significant improvement in their
pulmonary arterial hypertension and right ventricular function
after stopping the drug. I think that's an area that needs more
investigation. But we do know that these people also respond to
pulmonary vasodilators just like other patients with different
forms of PAH do. So I think it's really important that people who
have methamphetamine PAH get into our care so that we can work with
them, both to help them stop the use of methamphetamine as well as
to treat the pulmonary arterial hypertension.
I think there is a lot of stigma around substance use disorders,
but we've learned that substance use disorders affect people from
all walks of life, both genders, many ages, different socioeconomic
strata. That's why it's so important to include asking about
methamphetamine use or screening for its use in a comprehensive
evaluation of the patients that we see. I think because of that
stigma that is associated with substance use, it's really important
to communicate that we as the medical team are really on the side
of the patient and want what's best for them and to help them. Not
everyone is ready to stop using substances, but if they are, we
really want to give our best effort to help them to achieve that
goal. We've been working closely with our addiction medicine
colleagues to figure out how to best support our patients. We have
a lot of really wonderful resources available to us for people that
are interested in them.
There is data, for example, from Dr. Roham Zamanian's paper
published in 2018 that patients who have methamphetamine-associated
pulmonary arterial hypertension are less frequently treated with
parenteral therapies. That comes partly out of concern that having
an indwelling line, for example, while engaging in drug use may
present more of a risk for infection or harm. That does definitely
impact the way our patients are treated. It's a tough problem
because sometimes parenteral therapy might be the best therapy for
our patients who have meth-associated pulmonary arterial
hypertension, but because of the safety concerns, it isn't always
possible to treat people with the therapies we would most like
to.
We're working on trying to understand the disease better. There's a
lot of variables at play here in terms of how much methamphetamine
use can lead to pulmonary arterial hypertension. There's variation
in the composition of methamphetamine that people use because it's
a street drug and not regulated by any governmental agency. We
don't always know what's in methamphetamine, and sometimes it
contains dangerous substances like fentanyl, for example, and that
also presents a challenge.
There are efforts to understand more about
methamphetamine-associated PAH, including an NIH-sponsored registry
called Expose PAH that we're participating in along with Stanford
and other universities across the country, so hopefully that will
be helpful in understanding more.
We also know, for example, through Dr. Vinicio de Jesus Perez’s
work that some people may be more predisposed to develop
methamphetamine-induced PAH. They may have mutations in their DNA
that put them at higher risk of developing this problem so we're
trying to understand that more. I think there's ongoing work too to
understand the best way to support patients with methamphetamine
substance use disorders. There's some literature about using
VIVITROL for methamphetamine use disorder, or there's a behavioral
intervention called contingency management that's had some success.
Also, it might be that we may be able to use prescription
stimulants to treat methamphetamine use disorders. That is also an
area of ongoing investigation and learning. Then not only learning
what interventions are most effective, but how to best integrate
them into our PH practice is also an area that we're working
on.
I think it's important both for patients and providers to know that
this is an issue and it's probably more of an issue than we even
realize. I want people to know that there's treatment out there for
substance use disorders, and I want them to know there's treatment
for methamphetamine-related PAH. While we're still learning, there
are things we can do right now to help people.
My name is Katie Clapham, and I'm aware that my patients are
rare.
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