Qualitative Interviews of Physicians Managing Patients With Methamphetamine‐Associated Pulmonary Arterial Hypertension: Understanding the Unmet Medical Needs From a Provider Lens

ABSTRACT

Limited guidance exists for the management of methamphetamine‐associated PAH (Meth‐APAH) and the experiences of physicians treating this population are not well documented. This study explored how physicians approach diagnosis and treatment and identified unmet needs in clinical care through structured interviews with 30 U.S. pulmonologists and cardiologists who manage patients with Meth‐APAH. Physicians relied heavily on patient self‐report to establish methamphetamine use; only 20% performed routine toxicology testing. Compared with patients with other forms of pulmonary arterial hypertension, those with methamphetamine‐associated disease were younger, more likely to present in the emergency department, and more often diagnosed at advanced functional class based on physician perspectives. Physicians reported caution with initiating triple therapy and often preferred oral or subcutaneous prostacyclin agents due to concerns about adherence and risks of intravenous therapy. Socioeconomic instability and stigma were identified as major contributors to delayed diagnosis, nonadherence, and poor outcomes. Unmet needs included earlier recognition by frontline providers and greater access to addiction support resources. This study highlights critical challenges in diagnosing and managing Meth‐APAH. Improving provider education, standardizing screening practices, and integrating addiction treatment into care pathways are essential to address unmet needs.

1. Introduction

Pulmonary arterial hypertension (PAH) is a rare and progressive condition characterized by increased pulmonary vascular resistance that remains a challenging disease with significant morbidity and reduced quality of life [1, 2]. Recent epidemiological studies estimate a prevalence of approximately 15–200 cases of PAH per million adults in the United States; PAH is viewed to be underreported due to misdiagnosis and late‐stage identification [1, 3].

Drug‐induced PAH has emerged as a critical form of concern, especially with the rise of methamphetamine use in the United States and worldwide. Methamphetamine‐associated pulmonary arterial hypertension (Meth‐APAH), a subset of drug‐induced PAH, has been increasingly recognized as a public health issue in the United States [4]. Methamphetamine, a potent central nervous system stimulant, is associated with adverse cardiovascular and pulmonary effects, including pulmonary and systemic hypertension, associated vascular dysfunction, and arrhythmia [5]. While Meth‐APAH has been well‐documented in the Western United States, where methamphetamine use is endemic, its prevalence is also increasing in the Midwest and South [3].

Despite the growing recognition of Meth‐APAH, the underlying pathogenesis remains poorly understood. Proposed mechanisms include direct pulmonary vascular injury, inflammation, and endothelial dysfunction, though a definitive consensus in the scientific community is lacking [2]. Use of methamphetamine can lead to systemic health complications, including cardiovascular disease, chronic obstructive pulmonary disease, and psychiatric disorders such as anxiety, depression, and psychosis. Many of these conditions closely resemble or exacerbate symptoms of PAH, such as dyspnea, fatigue, and chest pain, contributing to delayed diagnosis and treatment.

Meth‐APAH diagnosis and treatment are further complicated by the psychological and socioeconomic barriers associated with people with substance use disorders, including past and active methamphetamine users [4]. Coupled with the low awareness of Meth‐APAH, patients with undiagnosed Meth‐APAH face societal stigma, discrimination, socioeconomic instability, and increased rates of mental health disorders, all compounding the barrier to adequate medical care. Physicians who diagnose and manage patients with Meth‐APAH may also struggle with balancing PAH clinical care with reconciling the common clinical conundrum presented by those who continue to abuse meth PAH yet need aggressive treatment. Despite standardized guidelines directing the care of PAH at large, there is a paucity of literature to help providers navigate this special population.

This study aims to illuminate the real‐world perspectives of U.S. healthcare providers with experience managing patients with Meth‐APAH. Through qualitative interviews with 30 physicians who regularly care for patients with PAH, we explored key aspects of Meth‐APAH care, including (1) the prevalence and identification of Meth‐APAH among patients with PAH (2), the demographic characteristics of patients with Meth‐APAH (3), diagnostic strategies (4), management approaches, and (5) unmet needs in Meth‐APAH care. By examining the strategies these providers employ and the challenges they encounter, this study seeks to raise awareness and inform efforts to improve the nationwide recognition and management of Meth‐APAH.

2. Methods

2.1. Participant Recruitment

Structured interviews were conducted with 30 U.S.‐based physicians. The interviews were conducted in April 2024. Characteristics of the included participants are summarized in the Results section. The target sample size was guided by principles of thematic saturation; interviews were conducted until thematic consistency was observed across participants within each U.S. census region, with no substantial new concepts emerging in later interviews based on ongoing reviews of interview transcripts.

Potential participants were identified through medical and pharmacy claims data from Komodo Health and Symphony Health Solutions, based on records of having managed PAH patients with a history of methamphetamine use. Participants were then invited to participate if they met the following inclusion criteria: (1) board‐certified in pulmonology or cardiology, (2) 3–30 years in clinical practice post‐residency, (3) primary treatment decision‐makers for three or more PAH patients in the past 12 months, and (4) primary treatment decision‐makers for one or more Meth‐APAH patient in the past 12 months. Participants with higher counts of patients with Meth‐APAH managed in the past 12 months were prioritized, while selection considered nationwide geographic representation in the sample.

As this study involved qualitative interviews with physicians regarding their clinical perspectives and management approaches, and no patient‐level data, identifiable or otherwise, were collected, this study did not meet the regulatory definition of human subjects research and did not require an IRB review. All participants provided informed written and verbal consent for their participation in this study, including the right to publish blinded, aggregated findings. Participants were compensated at fair market value for their participation. Confidentiality was strictly ensured throughout, with interview data anonymized at the time of transcription, stored on secure, access‐restricted systems, and findings are only reported in aggregate to ensure confidentiality, except for specific illustrative quotes which have been anonymized.

2.2. Data Collection

Interviews were conducted virtually and lasted approximately 60 min. A semi‐structured interview guide was developed in collaboration with the authors of this study, many of whom are experienced Meth‐APAH managing physicians (Supporting Information S1). The guide focused on five key themes of caring for Meth‐APAH: prevalence and patient demographics, diagnosis journey, treatment strategies, patient compliance and management experiences, and unmet needs.

To minimize potential biases, interviews were conducted by trained qualitative researchers from Putnam Associates with experience in healthcare research and physician interviews. Interviewers were not involved in patient care and did not have any prior relationships with participants. All interviews adhered to the interview guide with neutral, open‐ended questioning and did not provide clinical opinions or interpretations during interviews.

2.3. Data Analysis

A structured codebook was developed based on the interview guide. Audio recordings of the interviews were transcribed verbatim, and detailed notes were incorporated into the analysis. Thematic analysis was performed to identify common patterns and trends across participants' responses and was iteratively refined based on insights captured across the interviews. Coding reliability was ensured through the involvement of two coders, who independently reviewed and categorized the data. Findings were regularly reviewed with the authors throughout the study duration to ensure consistent interpretation of findings, minimize potential biases in interpretation, and assess data saturation.

For quantitative summaries derived from this qualitative study, responses were coded at the participant level, and the reported sample sizes reflect the number of physicians contributing to each response category. Where patient numbers are presented, these reflect aggregated physician‐reported estimates based on the number of patients managed by each respondent in the past 12 months, as recalled by participants during the interviews. Where quantitative comparisons are made, statistical testing was carried out to assess significance and is detailed in the figure legend.

3. Results

3.1. Characteristics of Meth‐APAH Treating Physicians in This Study

Thirty U.S.‐based physicians with experience managing patients with Meth‐APAH participated in this study. Participants represent all four census regions of the United States (Northeast, Midwest, South, and West) as well as the specialties common to PAH and Meth‐APAH care (i.e., pulmonology, cardiology) (Table 1). Most participants practiced in academic centers.

Table 1.

Characteristics of physicians interviewed in this study.

Meth‐APAH treating physicians (N = 30)
Specialty, % (N)
Cardiologist	37% (11)
Pulmonologist	63% (19)
Practice setting, % (N)
Academic	90% (27)
Community	10% (3)
Geographic distribution of physicians, % (N)
Midwest	13% (4)
Northeast	17% (5)
South	37% (11)
West	33% (10)
Number of patients with PAH managed in the past 12 months, % (N)
3–25	20% (6)
26–50	30% (9)
51–75	7% (2)
76–100	20% (6)
101+	23% (7)
Number of patients with Meth‐APAH managed in the past 12 months, % (N)
1–5	43% (13)
6–10	33% (10)
11–15	10% (3)
15+	13% (4)
Proportion of patients with Meth‐APAH among patients with PAH by region, %
All	13%
Midwest	10%
Northeast	6%
South	12%
West	25%

Note: All values are presented as number (percentage) for categorical variables and mean for continuous variables.

Abbreviations: Meth‐APAH, methamphetamine‐associated pulmonary arterial hypertension; PAH, pulmonary arterial hypertension.

The yearly median number of PAH patients treated per participant was 58, and the median number of patients with Meth‐APAH treated per participant was 10 (Table 1). Meth‐APAH represents an average or 13% of the participant providers' PAH patient population; the proportion of patients with Meth‐APAH among those with PAH was reported to be highest in participants practicing in the West (25%).

3.2. Real‐World Prevalence of Meth‐APAH in Practice

Participants were asked about their perspectives on what was estimated as 10% of patients with PAH having a history of meth use, with some states such as California being as high as 30%–40% based on a recent analysis of medical and pharmacy claims data [3]. Almost all participants (93%, N = 28/30 physicians) were unsurprised by these findings and agreed the numbers align with their general experience, including regional variations in the prevalence of Meth‐APAH. Participants expressed that the general low perceptions of Meth‐APAH prevalence may be due to patient hesitancy or embarrassment to report past or ongoing drug use, as well as inconsistent provider practices related to social history taking and drug screening during the initial evaluation.

Participants were also asked about their perspectives on the finding that 0.7% of the population with a history of methamphetamine use develop Meth‐APAH [6, 7]. Over half of the participants (53%, N = 16/30 physicians) believe this to be an underestimation of the true prevalence of Meth‐APAH among the population with a history of methamphetamine use. One participant from the South noted, “before I got into the PH space, it was surprising because you don't know how many people are really using meth[amphetamine]…. Once you get desensitized from the initial shock, meth‐APAH becomes kind of expected.” Participants noted several possible reasons for this underestimation, such as the practical inability to screen for PAH in all past or ongoing methamphetamine users and the frequent misattribution of PAH symptoms to substance abuse.

Among the participants, a notable difference in reported Meth‐APAH prevalence among PAH patients was observed between geography (Table 1) and physician tenure (Figure 1). Early‐tenure physicians (as defined as those with ≤ 10 years post‐residency) reported a higher proportion of Meth‐APAH patients of their entire PAH population (25%) compared to tenured and mid‐tenured physicians (as defined as > 20 years post‐residency and 10–20 years post‐residency, respectively), who estimated a prevalence of 10%–12%.

Figure 1.

Observed prevalence of Meth‐APAH among patients with PAH by physician tenure. Average prevalence of patients with Meth‐APAH among patients with PAH, calculated as the number of patients with Meth‐APAH managed in the past 12 months by the number of patients with PAH managed in the past 12 months, by physician tenure. Physicians were segmented into early‐tenure (< 10 years post‐residency), mid‐tenured (10–20 years of post‐residency), and tenured (≥ 20 years post‐residency). Statistical comparisons between segments were assessed using two = sided t tests; significant differences (p < 0.05) are denoted by “*.” Meth‐APAH, methamphetamine‐associated pulmonary arterial hypertension; ns, not significant.

3.3. Demographics of Patients With Meth‐APAH

3.3.1. Age, Gender, Race, and Ethnicity

Participants report an average age of 43 years across their patients with Meth‐APAH, and that patients with Meth‐APAH tend to be younger than their patients with PAH of other etiologies; this aligns with previous findings [3, 4, 8, 9] (Figure 2A). Participants also observed that patients who continue to use methamphetamines following PAH diagnosis tend to show faster disease progression than those who do not use.

Figure 2.

Physician‐reported characteristics of patients with Meth‐APAH. Demographic trends of patient population with Meth‐APAH as observed by participants. (A) Age distribution of all patients with Meth‐APAH managed by the participants; (B) gender distribution of all patients with Meth‐APAH managed by the participants; (C) relative prevalence of HIV infections in patients with Meth‐APAH compared to other PAH patients; (D) relative likelihood of patients with Meth‐APAH to be uninsured or on Medicaid compared to other PAH patients. HIV, human immunodeficiency virus; Meth‐APAH, methamphetamine‐associated pulmonary arterial hypertension; PAH, pulmonary arterial hypertension.

Participants report 58% of their patients with Meth‐APAH as male, which aligns. with previous analyses of Meth‐APAH cohorts, which showed a higher percentage of males compared to the female‐predominant overall PAH population [3, 4, 8, 9] (Figure 2B). Participants attribute the higher prevalence of male patients with Meth‐APAH to the higher percentage of men who use methamphetamine [10].

Participants note their patients with Meth‐APAH are predominantly non‐Hispanic White, consistent with national methamphetamine use trends [10].

3.3.2. Socioeconomic Considerations

Participants reported their patients with Meth‐APAH have lower levels of education and higher rates of unemployment compared to their overall PAH population. Additionally, most participants reported that their patients with Meth‐APAH were more likely to be uninsured or on Medicaid than other PAH patients (Figure 2D).

These trends are consistent with previous reports on the insurance status of populations with methamphetamine use and of patients with Meth‐APAH to patients with PAH of other etiologies [9, 10]. Participants also recalled patient anecdotes of losing employment‐tied insurance due to their methamphetamine addiction. Participants observed that patients who are uninsured often delay seeking care or treatment till their symptoms are severe, with one participant in the West describing “…about 60% of [my] meth‐PAH patients are uninsured. Some don't have stable housing, and the lack of insurance is a big driver in not seeking medical care. We have grants that help them get meds (sic), but [lack of insurance] is a big deterrent for a lot of people.”

3.3.3. Comorbidities

Participants noted a higher proportion of their patients with Meth‐APAH have comorbidities compared to their patients with PAH of other etiologies. Infections, particularly HIV and hepatitis, were more frequently observed in their patients with Meth‐APAH, especially when compared to their patients with PAH of other etiologies (Figure 2C). Beyond infections, participants reported that patients with Meth‐APAH frequently had other substance use, chronic respiratory diseases such as chronic obstructive pulmonary disease, cardiovascular conditions such as cardiomyopathy, and mental health disorders. Some participants (17%, N = 5/30 physicians), however, noted that their patients with Meth‐APAH tended to be healthy apart from their PAH diagnosis; they link this observation to the younger average age of patients with Meth‐APAH, which may reduce the likelihood of developing age‐associated comorbidities.

3.4. Diagnosis of Meth‐APAH

Participants defined Meth‐APAH as PAH occurring in patients with a history of “extensive” past or ongoing methamphetamine use and no other identifiable etiology for PAH, though there was a lack of consensus around what should be defined as “extensive” use. Participants reported variability in their methods for identifying ongoing methamphetamine use among their PAH patients (Figure 3A). The most common approach, used by nearly half of the participants (43%; N = 13/30 physicians), was reliance on patient self‐reporting. Although these participants acknowledge self‐reports may not always be reliable, they were cognizant of focusing on building trust with patients to encourage self‐disclosure.

Figure 3.

Identification of methamphetamine use in patients suspected with PAH. Meth‐APAH treating physicians' behavior to diagnose patients with Meth‐APAH. (A) Distribution of Meth‐APAH treating physicians who rely on patient self‐reporting, use toxicology panels on some patients and use toxicology panels on all patients to determine drug use; (B) distribution of early‐tenure (< 10 years of post‐residency, N = 9), mid‐tenured (10–20 years of post‐residency, N = 12), and tenured (> 30 years of post‐residency, N = 9) physicians who regularly perform toxicology panels compared to those that do not; (C) distribution of patients with Meth‐APAH who present first in an outpatient setting versus at the ER of N = 26 physicians; patient counts of N = 4 physicians were not included as they were unable to provide the distribution of their patients who first presented at the ER versus outpatient setting; (D) distribution of Meth‐APAH treating physicians who face challenges while performing RHCs in active meth users. Significant differences (p < 0.05) are denoted with a “*”; a chi‐square test was used to assess the association between routine testing and physician tenure in (B). ER, emergency room; Meth‐APAH, methamphetamine‐associated pulmonary arterial hypertension; ns, not significant; PAH, pulmonary arterial hypertension; RHC, right heart catheterization.

Some participants (37%, N = 11/30 physicians) selectively perform toxicology screening based on clinical judgment and specific indicators of possible ongoing drug use, such as behavioral or physical signs at diagnosis or poor adherence to treatments. For example, one participant from the Midwest who selectively screens noted, “if they are an 85‐year‐old grandmother, I don't usually test them. If they're younger and I've got suspicions or they had drug abuse issues, I may test them.” Only 20% of participants (N = 6/30 physicians) routinely perform toxicology screening as part of their diagnostic work‐up for all patients suspected of PAH. Routine testing was more commonly practiced among early‐tenure physicians (as defined as those ≤ 10 years post‐residency), with 44% of this group performing routine drug tests compared to just 8% and 11% of more tenured physicians (as defined as 10–20 and > 20 years post‐residency, respectively) (Figure 3B).

Participants shared that even after identifying methamphetamine use in PAH patients, they may not code for it in claims due to common barriers associated with coding, such as time constraints, uncertainty about appropriate billing codes, and the perception that such documentation does not impact diagnostic or treatment decisions. One participant shared, “I don't necessarily code for current or former meth use as a diagnosis code. I don't code what is not billable…. If someone were to come to do claims database research, well, you wouldn't pick my Meth‐PAH patients up because they're not coded that way.”

3.5. Meth‐APAH Patient Presentation

Participants observed that patients with Meth‐APAH were more likely to first present at the ER setting compared to their patients with PAH of other etiologies, with 31% of their current patients having presented at the ER amongst participants who could recall (Figure 3C).

All participants follow the same diagnostic workup for patients suspected of having Meth‐APAH as for their patients suspected with idiopathic PAH. Most (87%, N = 26/30 physicians) did not note challenges with right heart catheterization (RHC) in patients with Meth‐APAH though some (13%, N = 4/30 physicians) have experienced difficulties in interpreting its results in patients with ongoing meth use (Figure 3D). One participant prefers to withhold RHC in patients with active methamphetamine use until the patient has ceased use for a few weeks.

Patients with Meth‐APAH were also observed to present at a worse functional class compared to patients with PAH of other etiologies based on participants' experience and recall (Figure 4A), with 27% of their current patients with Meth‐APAH having presented at functional class IV. There was no clear consensus on why Meth‐APAH patients tended to present at a worse functional class. Some participants conjectured that this observation is likely due to delays in diagnosis due to factors such as shame—as one participant shared, “Meth‐APAH patients, they're ashamed of their condition because they think they self‐inflicted it”—as well as lack of access to care, as one participant from the Midwest observed “…. lack of access to healthcare and potentially a misdiagnosis in meth users.” Others however, viewed the worse functional class of Meth‐APAH patients at presentation as attributable to the faster progression of Meth‐APAH. One participant from the Northeast noted “meth (sic) is extremely variable, and the progression of Meth‐APAH is very different than PAH patients since meth is driving vascular remodeling in an adverse fashion.”

Figure 4.

Functional class and risk of hospitalization for patients with Meth‐APAH. Conditions of patients with Meth‐APAH at presentation. (A) Distribution of all patients with PAH (N = 2708) and with Meth‐APAH (N = 333) managed by the participants in the past 12 months according to their WHO functional class at diagnosis, based on participant recall; (B) perspectives on the risk of hospitalization of patients with Meth‐APAH in comparison to the patients with PAH. Significant differences (p < 0.05) are denoted with a “*”; a chi‐square was used to assess the differences in the distribution of each functional class between patients with PAH and patients with Meth‐APAH in (A). Meth‐APAH, methamphetamine‐associated pulmonary arterial hypertension; ns, not significant; PAH, pulmonary arterial hypertension.

Though patients with Meth‐APAH exhibit similar overall symptoms to other PAH patients, participants reported a higher frequency of more severe PAH symptoms—among their patients with Meth‐APAH. Symptoms such as dyspnea and exercise intolerance were observed at similar rates between patients with Meth‐APAH and PAH of other etiologies. Furthermore, participants advised that Meth‐APAH patients have higher rates of hospitalization compared to their patients with PAH of other etiologies (Figure 4B).

3.6. Approach to Meth‐APAH Management

Participants generally determine the initial treatment of their patients with Meth‐APAH based on the patient's functional class at presentation. Majority of participants (87%, N = 26/30 physicians) commonly initiate treatment with dual therapy of a phosphodiesterase‐5 inhibitor (PDE‐5i) and an endothelin receptor antagonist (ERA), regardless of methamphetamine use history (Figure 5A). A smaller proportion of participants (10%, N = 3/30 physicians) initiate with a monotherapy of a PDE‐5i in their patients with Meth‐APAH to observe patient behavior, adherence and build physician‐patient trust before adding any additional agents with one participant from the West sharing “We try to start Meth‐PAH patients on 1 oral medication, and if they show some compliance with follow up, we can optimize that treatment and add more.”

Figure 5.

Treatment strategies and observations of patients with Meth‐APAH. Therapy type, treatment preferences, and adherence as observed by participants. (A) Initial treatment for patients with Meth‐APAH (N = 30 Meth‐APAH treating physicians); (B) distribution of Meth‐APAH treating physicians between those who would consider prescribing a parenteral PPA for patients with Meth‐APAH versus those who would not; (C) rates of treatment prescription and initiation of patients with Meth‐APAH—not all participants were able to provide an estimate; and (D) compliance rates of patients with PAH compared to those with Meth‐APAH based on participant recall—not all participants were able to provide an estimate. In (D), differences between groups were assessed using a two‐sided t test; significant differences (p < 0.05) are denoted by a “*.” Meth‐APAH, methamphetamine‐associated pulmonary arterial hypertension; PAH, pulmonary arterial hypertension; PPA, prostacyclin pathway agent.

While triple therapy remains standard of care for high‐risk PAH, physicians reported greater caution when escalating patients with Meth‐APAH to triple therapy. Two‐thirds of the participants (67%, N = 20/30 physicians) considered patients' behavioral cues in addition to the clinical needs when adding a prostacyclin pathway agent (PPA), such as evidence of treatment adherence, ongoing methamphetamine abstinence, or reliable attendance of follow‐up visits. Participants noted that these additional considerations are due to the resource‐intensive nature of PPAs that require strict adherence, particularly with intravenous administration. As such, one participant from the West shared “we are reluctant to start parenteral therapy because of how resource intensive it is and how much committed the patients needs to be.” Some participants (27%, N = 8/30 physicians) would never prescribe a parenteral PPA to their patients with Meth‐APAH, holding a strong preference for oral PPAs (Figure 5B). Among participants who do prescribe parenteral PPAs to their patients with Meth‐APAH, oral PPAs were preferred, followed by subcutaneous or inhaled PPAs due to concerns about hygiene, risks of catheter‐related infections, and potential misuse in patients with a history of intravenous drug use.

Participants unanimously agreed that ongoing methamphetamine use is not a barrier to initiating treatment, but emphasized the importance of counseling patients with Meth‐APAH about addiction support during the workup. Most participants (63%, N = 19/30 physicians) are dissatisfied with the limited institutional resources available to help patients quit methamphetamine use, citing this as a significant unmet need in the management of Meth‐APAH. Participants report that patients who reduce or cease methamphetamine use show improved treatment outcomes. One participant from the South stated, “Generally, if they [Meh‐APAH patients] quit using meth, take treatment, and come to their follow‐ups, they do pretty well. A few of them have actually improved their symptoms quite a lot.”

Lower treatment initiation following diagnostic confirmation and adherence to treatment was observed among patients with Meth‐APAH by the participating physicians. While all patients diagnosed with Meth‐APAH were prescribed a treatment plan following diagnosis, participants observed that on average 81% of their patients with Meth‐APAH actually initiate treatment (Figure 5C). Participants also report an average treatment adherence rate of 56% among their patients with Meth‐APAH, which is markedly lower than the average adherence rate of 90% observed in their patients with PAH of other etiologies (Figure 5D).

3.7. Unmet Needs in Meth‐APAH Patient Care

Participants identified several critical unmet needs in the care and management of patients with Meth‐APAH (Figure 6). A key challenge was the lack of adequate resources to help patients overcome methamphetamine addiction. Methamphetamine use was described as one of the most difficult substance addictions to address, and many participants desired expanded resources, including social workers, detoxification and rehabilitation programs, and community‐based support systems. Without these resources, participants are concerned that patients with Meth‐APAH with ongoing methamphetamine use face insurmountable barriers to breaking the cycle of addiction and improving their overall health outcomes.

Figure 6.

Unmet needs in the care of patients with Meth‐APAH. Barriers and challenges in Meth‐APAH diagnosis and treatment management as felt by Meth‐APAH treating participants of this study. Participants were allowed to state multiple unmet needs. CT, clinical trials; HCP, healthcare professionals; Meth‐APAH, methamphetamine‐associated pulmonary arterial hypertension; PAH, pulmonary arterial hypertension.

Participants also noted the lack of a clear definition of Meth‐APAH and limited research into Meth‐APAH pathophysiology and treatment as a fundamental barrier in improving patient outcomes, as more research is needed to come up with a consensus on how best to manage patients with Meth‐APAH. The frequent exclusion of patients with Meth‐APAH in clinical trials was noted as a barrier to identifying treatments tailored to these patients [11, 12].

The low awareness of Meth‐APAH among frontline healthcare providers, such as primary care physicians, hospitalists, and emergency department staff, was identified as a major gap to improving early diagnosis by the participants. As Meth‐APAH is often not recognized until patients present with advanced symptoms, participants see the value in increasing awareness among those most likely to interact with patients with Meth‐APAH when they first present. Another significant concern was the underdiagnosis of PAH among methamphetamine users. Physicians attributed this to a combination of limited engagement with the healthcare system by methamphetamine users, poor access to care, and inconsistent screening for methamphetamine use in patients presenting with PAH‐like symptoms.

Lastly, participants also flagged insufficient patient education, insurance hurdles, and pill burden as unmet needs in improving Meth‐APAH care. In particular, participants believe increasing education among past or active methamphetamine users could be potentially helpful in improving patient self‐identification. The high pill burden for some PAH treatments was observed as a pain point by some participants, as it can lead to a decrease in treatment adherence over time.

4. Discussion

Meth‐APAH represents a growing public health concern, yet its pathogenesis, diagnosis, and management remain poorly understood. This study provides insights into physician‐reported experiences treating patients with Meth‐APAH, shedding light on key challenges in diagnosis, treatment, and care delivery. Several critical unmet needs were identified, including gaps in addiction support, underdiagnosis, and low awareness among frontline healthcare providers. These findings emphasize the need for systemic changes in Meth‐APAH care to improve outcomes in this vulnerable patient population.

This study revealed a discrepancy in the approaches used to identify past or ongoing methamphetamine use during the PAH workup, in addition to lack of clear standardized definition for what constitutes as “extensive” methamphetamine use. Only a fifth of the participating physicians routinely screen all PAH patients for ongoing drug use, and nearly a third selectively screen, while nearly half rely only on patient self‐reporting. Among physicians who selectively perform toxicology screens, they were more likely to screen younger patients or those with overt signs of drug use but were less likely to test older patients or those without visible risk factors. While this selective approach may be more practical in busy clinical settings, it risks underdiagnosing patients whose methamphetamine use is less physically apparent or actively concealed, promoting a profile bias to equitable care. Given that ongoing methamphetamine use is associated with an increased risk of hospitalization and worse outcomes in general [5, 13, 14], routine screening of all patients at diagnosis, continued screening of patients who test positive, and accurate documentation of methamphetamine use can be beneficial to informing future diagnoses, enhancing epidemiological understanding, and ultimately improving patient outcomes [15].

The greater likelihood of early‐tenure physicians to perform routine toxicology screenings when compared to their more tenured counterparts may suggest a generational shift towards routine testing. Regardless, non‐uniform approaches highlight the need for a consensus‐driven statement or recommendation for drug testing to be included as standard of care in the evaluation and management of all patients suspected of PAH to standardize practices.

Participating physicians emphasized the urgency of addressing their observation that patients with Meth‐APAH are more frequently diagnosed in emergency room settings and at a higher functional class, often with advanced symptoms and acute episodes [9, 16], compared to patients with PAH of other etiologies. These signs of missed and delayed diagnoses are likely driven by limited awareness, socioeconomic barriers to healthcare, and perceived stigma associated with methamphetamine use, leading to diagnosis only after significant disease progression.

While the initial treatment of patients with Meth‐APAH often approximates that of patients with PAH of other etiologies, there are differences suggested herein. Initiation of PDE‐5i monotherapy is more common in the meth‐APAH population compared to dual or triple combination therapy in other PAH patients. Though not specifically queried, the most likely explanation for this is ease of drug acquisition, early onset of action with improved functionality, and low‐risk tolerance profile. Additionally, participants approach escalation to triple therapy more cautiously for their patients with Meth‐APAH. Several participants reported that patient compliance and behavior heavily influenced their decision‐making, with many requiring adherence to initial therapy before the addition of prostacyclin pathway agents. Oral prostacyclin was the preferred route of administration, followed by subcutaneous formulations, with IV therapy reserved for select patients due to concerns about hygiene, catheter‐related infections, and potential misuse in patients with a history of intravenous drug use. It is notable that three‐quarters of the physicians are comfortable with prescribing parenteral prostacyclin agents to patients with Meth‐APAH, with a preference towards subcutaneous delivery.

Ongoing methamphetamine use is not considered a barrier to treatment initiation among experienced providers of this cohort, but participants recognize it presents unique challenges to long‐term treatment adherence and outcomes. However, participants were concerned that only one in five of their patients with Meth‐APAH never initiated therapy despite their PAH diagnosis and recommended treatment plan; participants shared that anecdotally, unstable socioeconomic conditions (including lack of insurance) and relapse in drug use have contributed to never‐initiation of pharmacologic treatment. Participants also noted that overall compliance with treatment is lower in patients with Meth‐APAH, though they do observe high compliance in patients with worse functional class who relied on their PAH treatments to sustain a tolerable quality of life. Although participants did not otherwise observe a relationship between pill burden and compliance, some participants expressed concerns about patients being inconsistent with ERAs due to the lack of immediately perceivable benefits.

Participants expressed frustration with the lack of institutional resources available to support addiction cessation, citing this as a critical unmet need. They emphasized the importance of robust social support systems, including counseling and rehabilitation services, to allow healthcare providers to focus more effectively on the clinical management of Meth‐APAH. Overcoming the barriers to multidisciplinary care that integrates addiction treatment is needed for comprehensive and sustainable Meth‐APAH management.

These findings have significant implications for the diagnosis and management of patients with Meth‐APAH in clinical practice. Routine toxicology screening or standardized inquiries about drug use should be considered for all PAH patients to minimize diagnostic variability and address potential biases. Enhancing provider education about Meth‐APAH—particularly its growing prevalence, uniform toxicology screening, and strategies for nonjudgmental approaches to compassionate care is important to improving earlier diagnosis and treatment initiation. Additionally, increasing awareness of Meth‐APAH among primary care and emergency room physicians can support recognition and timely referral of patients with Meth‐APAH. Integration of addiction support systems into PAH care pathways is equally critical to adequate care of this population. Future efforts should focus on establishing standardized diagnostic criteria for Meth‐APAH and developing best practices for coordinating care that addresses the intersectional clinical, socioeconomic, and psychological challenges faced by these patients, ultimately enhancing treatment adherence and outcomes.

Meth‐APAH is a growing public health concern that has become a prevalent and growing subtype of PAH in many US‐based PH centers [8]. Significant challenges in understanding pathogenesis, diagnosis, and management demand additional attention. This study highlights key physician‐reported strategies and barriers to care, which include underdiagnosis, limited addiction support, and low awareness among frontline providers. Addressing these gaps through systemic changes, such as improved provider education, enhanced screening practices, and integrated addiction resources, is critical to advancing Meth‐APAH diagnosis and management and ultimately improving patient outcomes for this vulnerable population.

5. Limitations

Though this study provides valuable qualitative insights from physicians with experience managing patients with Meth‐APAH, these findings should be interpreted in light of certain limitations. The sample size and reliance on self‐reported data may limit generalizability and introduce recall bias, such as for those with quantitative aspects, such as PAH and meth‐APAH patient counts, meth‐APAH prevalence, treatment adherence, and relative hospitalization rates, and these numbers should be taken to be directional and illustrative in nature, as they do not represent patient‐level data extracted from medical records. Additionally, many physicians had higher Meth‐APAH and PAH patient volumes than the average clinician, which may not fully reflect the broader landscape of Meth‐APAH care. The physicians are also primarily based in academic institutions, as opposed to community practice, which may skew both the patient population and available resources to manage them.

Author Contributions

All authors conceived the study design. H.G.L., M.S., D.L., A.A., and N.G. coordinated data collection and analysis. J.F.K., M.S., D.L., H.G.L., A.A., and N.G. led the initial drafting of the manuscript. All authors contributed to interpretation of findings and critical revision of the manuscript for important intellectual content. All authors reviewed and approved the final version of the manuscript and agree to be accountable for all aspects of the work. D.L. accepts full responsibility for the integrity of the work as a whole, from inception to published article, and serves as guarantor.

Ethics Statement

The authors have nothing to report.

Conflicts of Interest

J.C.R. serves as a site PI for clinical trials sponsored by Gossamer Bio, Merck, and Johnson & Johnson and is a consultant for Johnson & Johnson; J.F.K., N.H.K., S.B., and L.M.G. are consultants for Johnson and Johnson. M.S., D.L., A.A., N.G., and M.C. are employees of Johnson and Johnson. H.G.L. has no conflicts to disclose. Sponsor‐affiliated authors did not conduct interviews, control or have access to raw data, or influence the reporting of findings. All interpretations were discussed and agreed upon by the full author group.

Supporting information

Supplemental File

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.