Vinicio de Jesus Perez, MD - phaware® interview 539

The Hidden Epidemic: Meth and PH
Meth-Associated PAH is on the rise across the United States, yet many patients are not receiving the treatment they need. Dr. Vinicio de Jesus Perez discusses the shifting demographics of meth users, the challenges of treating addiction in cardiopulmonary care, and the need for compassionate, stigma-free screening.

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My name is Vinicio de Jesus Perez. I am a Professor of Medicine at Stanford University. I work with patients with pulmonary hypertension. In particular, I treat a sub-group of patients that have pulmonary hypertension that is caused by methamphetamine. Methamphetamine is an illicit drug that is being used over the last century in many ways. It was initially used as a stimulant for soldiers on both sides of the war, Americans, Japanese, Germans, as a way to keep the soldiers awake and ready for battle. Subsequent to the end of World War II, the drug found another life in the popular culture. It became a sought-after drug by artists, politicians, and other figures as a way to cope with pressures and indulge in creative bursts. Finally, the addictive potential of the drug was identified leading to its ban from pharmacies. 

Now, we have been seeing over the last three decades an epidemic of illicit drugs. Initially, in the '90s, we used to hear about cooks who will build meth labs in trailer parks, motels, and in their garages. But since then, this has now been replaced by a well-organized operation coming from Mexico where the drug is produced in large quantities, excellent quality, and shipped to the United States, where it enters through California. That's where I work.

When I started my career back in 2004, myself and my partner, Dr. Roham Zamanian, who is the Director now of our PH program at Stanford. We were trainees and we were working with one senior physician, Dr. Ramona Doyle. Among the patients that were being referred to us as we were going through the drug history, and at that time the most common drug that we had linked PH with, of course, was weight loss agents like aminorex, fen-phen. Part of the history that we take will always include the use of both prescription and illicit substances.

Time and time again, we heard that patients were either actively using meth or had used meth in the past. It was really hard not to see that there was a connection there. But whether it was causative or simply an association or risk factor, if you will, it was unclear. So, my career from that point as well as that of Roham, we began collecting information about these cases. In 2017, we were finally able to put our single center experience together. I think ours was not the first report of meth linked to PAH, but I think it comprehensively took patients who were well phenotyped. We had over 200 patients. We also had pathological samples and ultimately also outcomes. What we ended up finding was astounding. We found a very strong link between methamphetamine and pulmonary hypertension. But most importantly, we found that the clinical progression and outcome of these patients despite therapy was worse compared to the idiopathic patients.

What that signals is that these patients have a different clinical syndrome compared to other forms of pulmonary hypertension. What that means for me as a clinician is that these are patients that require a different level of care than the one that we offer our other patients. In addition, this is a patient population, particularly those that are actively using that need to be convinced and assisted. This is not a straightforward task, something that we as cardiopulmonologists are not trained to do. So multidisciplinary care has become the mainstay of management of Meth-PAH, work with social workers, cardiologists, if patients have other complications associated with meth like dilated cardiomyopathy, coronary artery disease, arrhythmias, et cetera, as well as addiction specialists. Of course, it's critical also to look at random urine testing, because this is a very complex addiction. It's not unusual for patients to stop taking methamphetamine and then going back to it. It can be a few weeks, it can be a few months, it can be a few years. So even if a patient stops using the drug, we will still continue to do these random checks.

It's important because the use of methamphetamine can trigger some acute effects on the pulmonary circulation that may translate into worsening of the condition. In the case of a patient with pulmonary hypertension, if I see somebody who is actually developing a progression, their functional classes getting worse or they're just losing steam in their six-minute walk, one thing is well, their disease is progressing. Or it could be that the acute use of methamphetamine again is triggering a worsening, which if the patient stops the medication it can be improved. These are some of the complexities that we deal with cases. I think as a group we have learned over decades of treating a large number of these patients how to approach it.

But of course, as the methamphetamine epidemic has evolved, we have now seen that in an unpublished study we currently have that has looked at a claims database between 2018 and 2022, looking at the trends in the diagnosis and treatment of Meth-PAH across the United States. What we have found is that the map has been evolved during that period of time where you see very clearly that in 2018, most of the cases will be in the West, Southwest and the South of the United States. But with time you're seeing a clear trend in increase of diagnosed cases in the East and Southeast portions of the United States.

What our study finds out, which I think is very concerning and certainly triggers a call to action, is that if you look at the treatment of Meth-PAH patients, not surprisingly, if you are a patient with Meth-PAH in the West, Southwest and South of the United States, you are getting treated for your condition. But as you look into the East, the Southeast, if you're a patient with Meth, you're not getting treated maybe. That is a cause of concern, because what we're seeing is that there's a clear trend of an increase in diagnosed cases. But what we're also seeing is that even those cases that are diagnosed are not getting the appropriate therapy. That's signals a disparity in the care of pulmonary hypertension for this particular phenotype. I think for us as a community, this is important.

Why this is the case, there's a lot to speculate. We can speculate that there's a lack of awareness, there's a lack of screening. There may be bias in terms of how patients respond to recommendations about care, or how physicians feel that a patient may be compliant with care. Many things we can speculate, but ultimately, I do feel that the data clearly points to an area that needs to be properly addressed because as I mentioned previously, these patients do have a much worse prognosis compared to idiopathic even when treated appropriately. I do feel like as a community we need to be aware and we need to advocate for these patients.

I think the first step is you need to ask point-blank about a history of active or previous use of methamphetamine. This is something that should be standard in the history taking of any patient with pulmonary hypertension. As we're looking to rule out potential causes, asking about former or active meth use should be a standard question. What we do in our center is that we routinely screen any new referral. As part of their workup, we screen them for drugs of abuse, not just methamphetamine but all drugs of abuse. We have been surprised to see that few patients that you will not have thought will be meth users. When we come back to discuss the results, they do admit to the use.

We're talking about patients who are functional, people who have families, work. They're otherwise standout citizens, so not what you will think will be the typical phenotype of a meth user that you will see in TV shows or in the newspaper. What that tells you is that you can really not trust your own bias regarding what a meth PH patient looks like. So, I will argue if you have a patient that tells you that they've used meth in the distant past or actively using, you should definitely consider methamphetamine use. You should screen that patient and you should also ask that patient, even those who are not active users, you have to ask if they live around people who are actively using.

So, that's where you're having a social worker to take a social history, where that patient lives, what connections they have to the community. These things are also important because part of what drives the success of an intervention here is knowing where the patient lives and where they work when they're not in clinic. They're responding to a more complex environment filled with pressures that can change on a day-by-day basis. These can be triggers that can lead to a patient to have a recurrence in their use or even be exposed. I think also it's important to really involve these patients early on with addiction services, especially those patients that are actively using.

I think ultimately the most important thing that I think is not being done right now, especially in areas where there may not be large pockets of pulmonary hypertension patients or we're really not asking our patients straight up. I do feel that the screening of patients is critical. I don't know if at this point in time we are ready to say that we should absolutely screen everybody everywhere. I can see this being a controversial intervention, but I do feel that if you're in a geographic area where based on our map right now you're seeing that the number of meth patients is rising in your community, I think you can certainly be more aggressive and justify having standard screening as part of your battery workup.

This patient population is very heterogeneous. Yes, you get the traditional patient who's unemployed, who's homeless, who hangs out with the wrong crowd, they have a criminal record, kind of like what you will pigeonhole a typical meth patients. Interestingly enough, over the years we've seen an evolution where that phenotype is no longer the dominant phenotype of meth PH patients. What we're seeing now is a transition to an older patient population. These are patients that are using methamphetamine as a way to cope with work, to cope with fatigue, to cope with depression, to cope with ADHD. This is where having that patient be evaluated and treated by a psychiatrist, not just an addition specialist but even perhaps also a psychiatrist to look for an undiagnosed psychiatric disorder becomes important.

I will say right now that the typical meth PH patient that we are seeing is somebody who is using meth as part of their work-life routine in order to maintain a at work, and to cope with the pressures of life in a way that will allow them to maintain a socioeconomic status. At the same time, it hints at underlying psychiatric illnesses that are not being appropriately treated. So, that adds another layer of complexity to the management whereby it's important to help that patient not just with their pulmonary hypertension or their addiction, but also with finding proper treatment for their psychiatric disorders.

The most important thing that I think is not being done which has absolutely no extra cost, is to ask the patient in a non-judgmental, non-threatening way about the use of methamphetamine. It's not just asking. It is asking in a way that the patient doesn't feel like they're being grilled, that they're being judged or they're being placed in an uncomfortable position. For me, what I'm asking patients, same as their sexual history, these are very sensitive questions. Yes, you're a doctor and yes you are in a private room, but patients can become very defensive. Again, I think that's very fair, because you are getting into a part of their life that they're not necessarily happy sharing with anyone, especially somebody that they're meeting for the very first time. They already know that there's already a society bias that goes against whatever these behaviors that they have.

So, of course, they're going to be protective, they're going to be suspicious. I think it's really important for the physician to ask this question in a way where the patient feels like they're not being judged. This is part of what needs to happen in order to push forward with the right diagnosis. So, the way I normally do this is I ask the patient about drug use. I like to go down a list so I don't just jump in and say, “Have you used meth?” I start off with like, "Listen, there's a set of drugs that have been associated with pulmonary hypertension, and I'm going to ask that you give me an honest response whether it's being active or you did it years ago. I just want you to be aware that I'm not passing judgment, nor will I share this with any authorities. This stays between us. It's going to be part of the record, but I only ask because this is part of a workup that we use on every patient."

With that, I go through each drugs like have you used fenfluramine? Then, have you use cocaine and have you use meth? I'm looking at the body language of patients during that meeting. Once you get to illicit drugs, by now I've done this for more than 20 years, so there is already a body language that I can read or a way that the patients take that question. Again, it's important to reassure them like, "Listen, I'm not here to judge. I'm here to help and all I need is to know, because let me tell you, this is why." Once you put it on the table, you present the patient with the data like, this is what we know about the drugs. Our group has looked at that, so that's why I am asking. So let me ask you again.

Surprisingly, I think the more the patient is reassured and sharing with the patient the data that supports the question and why it's important, allows the patient to be open. I think this is also crucial because moving forward, if I'm talking with a patient who's an active meth user, I do break down with them what that will imply in terms of their management. So, the patients will receive the care they deserve. However, we're very clear in terms of what we cannot offer like intravenous therapies. We can definitely offer subcutaneous therapies, we can offer sotatercept. So, we are very aggressive. We are also very open to the patients that we really need them to be honest about whether or not they're using. They may have stopped using but they may end up using again.

We're very clear that we understand that addiction is a very difficult disease to tackle. If a patient, once again, falls and starts using again, we just want to know and we want to take that into account and again, help the patient. I think where the biggest challenge come is when patients stop coming to appointments or they stop taking medications, they miss their shipments or they're not responding, because at that point in time it puts us in a very difficult position as we're responsible for these patients.

We're responsible for providing them with these prescriptions and not taking some of these medications can pose a real risk where the patients can worsen acutely. And, suddenly, they may end up in cardiogenic shock in some cases, especially if they are actively using. These are the most challenging cases because you know that these are the people that as a physician, you are responsible to treat them. But when the patient is not complying, then you have to really draw a hard line and set some expectations in order to be able to help that patient. This is teamwork.

One of our colleagues, Dr. Clapham talked about how the management of pulmonary hypertension associated with meth has to be multidisciplinary. I will argue that a big part of that approach has to be the patient itself. They need to know that they're part of the operation and their willingness to comply is essential for the success of that intervention.

My name is Vinicio de Jesus Perez, and I'm aware that my patients are rare.

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