Potential for a precision medicine approach to PAH explored in new study

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

Researchers identified mild (n=28; 47%), moderate (n=20; 33%) and severe (n=12; 20%) symptom cluster phenotypes in a study population of women whose mean (SD) age was 50.6 Years was (17.8) years old and reported races 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%). 45% 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 EmPHasis 10. They also underwent multiple tests: transthoracic echocardiography, phlebotomy, 6-minute walk distance, and actigraphy.

“Women with PAH experience multiple symptoms, including dyspnea, fatigue and sleep disturbances, that impact their health-related quality of life (HRQOL),” the study authors write. “The aim of this study was to define the ‘symptom’ based on symptom-cluster phenotypes and to 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 dyspnea, fatigue and sleep disturbances to define each cluster of symptoms.

Overall, there were significant correlations between dyspnea and fatigue (ρ = 0.638; P < .001), dyspnea and sleep disturbances (ρ = .531; P < 0.001) and sleep disturbances and fatigue (ρ = 0.655; P < 0.001).

Cluster analysis revealed that the mild, moderate, and severe symptom groups were similar in age, race/ethnicity, and occurrence of PAH type. Age was 49.4 (21.2), 52.7 (15.8), and 50.0 (11.9) years; 50%, 55% and 50% were White; and the 2 most common types of PAH etiology were idiopathic disorders (39%, 35%, and 42%) and connective tissue disorders (32%, 45%, and 25%).

However, the groups differed significantly in the following disease characteristics: WHO functional class (P < 0.001), norepinephrine levels (P = 0.029), right atrial pressure (P = .001), physical function (P <0.001), sleep onset latency (p=0.040), and HRQOL (P < 0.001). And among the echocardiographic variables evaluated, only right atrial pressure was associated with symptom cluster severity.

Deterioration in HRQOL and self-reported physical functioning scores were more common in the moderate and severe phenotypes, elevated depression and scores were more common in the severe phenotypes, NT-proBNP levels were significantly higher in the moderate and severe phenotypes, and sleep onset latency was significantly higher longest in the severe phenotype.

“Given the importance of symptoms for PAH patients, our results could provide a useful framework for future diagnostic, prognostic, clinical studies and treatment paradigms, even if our data need to be confirmed 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 results may be limited by their study population of women only, they emphasized that future studies should focus on men because although PAH occurs less frequently in these patients, the results are typically worse. Their results should also be validated in larger and longitudinal studies with more diverse populations.

Relation

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