Care Center PAH Causes Differ from National Registry, Study Reveals

Connective tissue disorders, toxins were leading causes at most care centers

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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The identified cause of pulmonary arterial hypertension (PAH) in patients seen at a specialized care center differed substantially from national registry data, a study revealed.

Most care center patients were diagnosed with PAH associated with connective tissue disorders and exposure to toxins, whereas idiopathic PAH (IPAH), of unknown cause, was most prevalent in the national database.

“Differences in our population may reflect the regional variation of the referral site, but it is noteworthy for its contrast with historically reported [clinical characteristics],” the researchers wrote.

Toxin-associated PAH occurred at a much higher rate in care center patients compared to national registry data, with most of these cases secondary to the use of methamphetamine, a stimulant drug known for its psychoactive effects.

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“The lack of nationally accepted standardized drug screening protocols and the established prevalence of methamphetamines in the western US may contribute to these differences, but further investigation is warranted,” the researchers noted.

The study,” Characteristics of Patients With Pulmonary Arterial Hypertension in a Pulmonary Hypertension Association-Accredited Comprehensive Care Center: A Contrast in Features When Compared With US National Registry Data,” was published in Cureus.

In PAH, the small blood vessels, called the pulmonary arteries, that transport blood through the lungs, narrow —  restricting blood flow and causing high blood pressure, or hypertension.

Narrowing of the pulmonary arteries can be associated with other conditions, or associated PAH (APAH). Risk factors for APAH include connective tissue disorders, liver disease, congenital heart disease, viral infections, certain medicines, and exposure to various toxins.

In the absence of a detectable cause, many cases are labeled as idiopathic PAH. However, recent evidence suggests that a third of those with PAH are misdiagnosed due to a lack of a thorough work-up, where all necessary data for diagnosing and treating patients is collected.

University of Utah researchers noted “the common failure to perform a good work-up, including inadequately assessing PAH risk factors, could contribute to the large number of patients who are defined as idiopathic PAH (IPAH).”

Comparing characteristics of PAH

The research team compared the clinical characteristics of PAH adults seen by the University of Utah Pulmonary Hypertension Comprehensive Care Center, where PAH-risk factors were systematically collected and recorded, to those of PAH patients in the United States Pulmonary Hypertension Scientific Registry (USPHSR).

Between August 2020 and November 2021, 242 adult patients were evaluated at the care center and enrolled in the University of Utah Pulmonary Hypertension Registry (UUPHR). Overall, 71.9% were female and the average age was 58, with 11.6% over 75.

Enrolled patients were classified into PAH subtypes based on an interview for comprehensive health history, medication and toxin exposures, and a review of medical records. Supportive diagnostic tests included right heart catheterization (insertion of a catheter to measure blood pressure), electrocardiogram (ECG), lung function tests, the distance walked in six minutes, chest images, sleep studies, toxicology screening, and blood tests.

Among the UUPHR patients, 71.1% were classified as APAH, and 26.4% were deemed IPAH. These findings significantly contrasted with the USPHSR national registry data wherein 51% of PAH patients were classified as APAH, and 44% were labeled IPAH. In the remaining UUPHR cases, 1.7% were familial PAH (caused by genetic defects) and 0.8% were caused by pulmonary veno-occlusive disease (arterial blockages).

We believe that toxin-associated PAH is under-represented in national registry data.

Of the APAH subtypes, connective tissue disorders were associated with 39% of cases, representing 28% of all PAH patients in UUPHR, while 33% were toxin-associated PAH, representing 28% of cases. Only 4.8% were classified as toxin-APAH in the USPHSR database.

“We believe that toxin-associated PAH is under-represented in national registry data,” the team wrote.

Toxin-APAH occurred in 89.5% of cases, secondary to the use of methamphetamines, representing 21.5% of all care center patients. This contrasts with the reported 4.5% in the USPHSR database.

PAH caused by connective tissue disorders was the largest subtype for those over 75 (14.9%) and female patients accounted for most of connective disease cases at 91%.

The total UUPHR population had an average mean pulmonary artery pressure (mPAP) of 41.46 mmHg, above the diagnostic criteria of 20 mmHg or higher, diagnostic data showed. The highest mPAP was seen in those with toxin-associated APAH (47.42 mmHg), whereas the lowest mPAP occurred in patients with porto-pulmonary hypertension (36.89 mmHg), a complication of liver disease.

Regarding NYHA functional class, 59.5% were class 2 patients with symptoms while performing regular activities with some limitation to activities, while 26.0% were class 3 patients with symptoms during regular activity and a marked limitation of activity. In comparison, USPHR reported the most common as class 3 (45.2%).

Prescribing therapies

Nearly 98% of UUPHR patients were prescribed at least one PAH-specific therapy. Of those, 34% were on monotherapy, 33% received dual therapy, and 26% were on triple combination therapy. Although treatments for UUPHR patients were consistent with the nationally reported use, more UUPHR cases received triple PAH therapy than USPHSR reports (26% vs. 15%).

Discrepancies in NYHA class and therapy use “may reflect the benefit of earlier initiation of combination therapy,” the researchers noted.

“In the UUPHR, APAH accounts for most patients with PAH, with a significant portion of the population classified as toxin-associated PAH,” they concluded. “An increased publication of regional registry data is required to accurately reflect regional variations in the burden of subclasses of PAH.”

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