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Potential for Precision Medicine Approach in PAH Explored in New Study

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This new study of pulmonary arterial hypertension (PAH) among women examined the in-common symptoms of different disease phenotypes to see where they overlap and ultimately to define the “symptome” according to symptom cluster and characteristics.

The ability to predict worsening symptoms and disease outcomes in the pulmonary arterial hypertension (PAH) space could potentially benefit from the 3 symptom cluster phenotypes identified in a new study published in Pulmonary Circulation.

Investigators identified mild (n = 28; 47%), moderate (n = 20; 33%), and severe (n = 12; 20%) symptom cluster phenotypes among a study population of women whose mean (SD) age was 50.6 (17.8) years and who reported ethnicities of non-Hispanic White (51%), non-Hispanic Black (32%), White (Hispanic) (10%), and Asian (7%). According to World Health Organization (WHO) Group 1 criteria, the most common PAH etiologies among the 60 women studied were idiopathic disease (38%), connective tissue disease (35%), and congenital heart disease (12%). Forty-five percent had WHO functional class II disease and 47% had WHO functional class III disease.

The cross-sectional study population was administered the Pulmonary Arterial Hypertension Symptom Scale (PAHSS), Pittsburgh Sleep Quality Index (PSQI), Multidimensional Dyspnea Profile (MDP), Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function, PROMIS Sleep-Related Impairment, and the EmPHasis 10. They also underwent several tests: transthoracic echocardiography, phlebotomy, 6-minute walk distance, and actigraphy.

“Women with PAH experience multiple symptoms, including dyspnea, fatigue, and sleep disturbance, that impair their health-related quality of life (HRQOL),” the study authors wrote. “The objectives of this study were to define the ‘symptome’ by symptom cluster phenotypes and compare characteristics such as biomarkers, cardiac structure and function (echocardiography), functional capacity (6-minute walk distance) and HRQOL between the groups.”

They used the variables of dyspnea, fatigue, and sleep disturbance to define each of the symptom clusters.

Overall, significant correlations were seen among dyspnea and fatigue (ρ = .638; P < .001), dyspnea and sleep disturbance (ρ = .531; P < .001), and sleep disturbance and fatigue (ρ = .655; P < .001).

A cluster analysis revealed that the mild, moderate, and severe symptom groups had similar ages, race/ethnicities reported, and occurrence of PAH type. Ages were 49.4 (21.2), 52.7 (15.8), and 50.0 (11.9) years, respectively; 50%, 55%, and 50% were White; and the 2 most common types of PAH etiology were idiopathic disease (39%, 35%, and 42%) and connective tissue disease (32%, 45%, and 25%).

The groups differed significantly, however, in the following disease characteristics: WHO functional class (P < .001), norepinephrine levels (P = .029), right atrial pressure (P = .001), physical function (P < .001), sleep onset latency (P = .040), and HRQOL (P < .001). And among the echocardiographic variables evaluated, only right atrial pressure was associated with severity of symptom cluster.

Worsened HRQOL and self-reported physical function levels were more common in the moderate and severe phenotypes, elevated depression and levels were more common in the severe phenotype, NT-proBNP levels were significantly higher in the moderate and severe phenotypes, and sleep onset latency was most prolonged in in the severe phenotype.

“Given the importance of symptoms to sufferers of PAH, our findings could provide a useful framework for diagnostic, prognostic, clinical trials and treatment paradigms for the future, even if our data require confirmation in larger cohorts,” the authors concluded. “Patients could be screened to identify their symptom cluster phenotype membership to best match symptom management interventions, taking a ‘precision medicine’ approach to symptom management.”

Because their study findings could be limited by their study population of all women, they emphasized that future studies should focus on men, because although PAH is rarer among these patients, the outcomes are typically worse. Their results also should be validated in larger, and longitudinal, studies with more diverse populations.

Reference

Matura LA, Fargo JD, Boyle K, et al. Symptom phenotypes in pulmonary arterial hypertension: the PAH “symptome”. Pulm Circ. Published online September 6, 2022. doi:10.1002/pul2.12135

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