Using PAH-SYMPACT to assess quality of life in patients with pulmonary hypertension associated with chronic lung disease.

Chronic lung disease (CLD) is the second leading cause of pulmonary hypertension (PH) and is associated with significant morbidity and mortality. Although PH associated with CLD (PH-CLD) leads to impaired health-related quality of life (HRQOL), there are no validated tools to assess HRQOL in PH-CLD. The Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire (PAH-SYMPACT) is an HRQOL instrument aimed at assessing the symptoms and impact of PH on overall function and well-being. We performed a single-center prospective cohort study using PAH-SYMPACT scores to compare symptoms, exercise capacity and HRQOL in patients with PAH and PH-CLD. One hundred and twenty-five patients (99 patients with idiopathic/heritable PAH and 26 with PH-CLD) completed the PAH-SYMPACT questionnaire which consists of 22 questions that assess HRQOL across four domains: cardiopulmonary (CP) symptoms, cardiovascular (CV) symptoms, physical impact (PI), and cognitive/emotional (CE) impact. Higher scores indicate worse HRQOL. We compared patients with PAH and PH-CLD using a Wilcoxon rank sum or chi-squared test as appropriate. Multivariate linear regression analysis was used to assess the relationship between PH classification and SYMPACT scores. Compared to PAH, patients with PH-CLD were older, more likely to use oxygen and had worse functional class and exercise capacity. While there was no significant difference between the two groups in CP, CV, or CE domain scores, patients with PH-CLD had significantly worse PI scores by univariate (1.79 vs. 1.13, p < 0.001) and multivariate analysis (1.61 vs. 1.17, p = 0.02) and overall worse SYMPACT scores (1.19 vs. 0.91, p = 0.03). In conclusion, patients with PH-CLD have worse HRQOL as assessed by the PAH-SYMPACT questionnaire versus patients with PAH. Although PAH-SYMPACT has not been validated in PH-CLD, the results of this study can guide clinicians in understanding the symptoms and impact of PH-CLD relative to PAH.

Clinical Utility of Patient-Reported Outcome Instruments in the Management of Pulmonary Hypertension: A Systematic Review.

BACKGROUND: Despite the greater sensitivity and specificity of disease-specific patient-reported outcome measures (PROM) to detect clinical change, only recently have such instruments been developed for pulmonary hypertension (PH), specifically pulmonary arterial hypertension (PAH) and chronic thromboembolic disease (CTEPH). Although these valuable tools are now being incorporated into clinical studies of PH, they have not yet reached widespread integration into routine clinical care. OBJECTIVES: In this systematic review, the authors assess the psychometric properties of PROM developed for PH, compare PROM with other clinical outcomes in PH, and address the utility of PROM in clinical care. METHODS: The authors performed a systematic search of papers published between January 1, 2006, and October 1, 2022, using the MEDLINE database to identify PROM developed and validated for PH. The identified PROM were found to have been developed only in groups with PAH and CTEPH. The authors evaluated the identified instruments according to established psychometric criteria. An additional search was performed to identify randomized controlled trials (RCTs) utilizing these PROM for comparison with clinical outcomes. RESULTS: From 527 papers retrieved, a total of 35 PROM were identified. Of these, 5 disease-specific instruments were included in the final analysis. While both CAMPHOR (Cambridge Pulmonary Hypertension Outcome Review) and emPHasis-10 performed well in patients with PAH and CTEPH with regard to their psychometric properties, emPHasis-10 demonstrated superior feasibility for use in clinical practice due to its concise format. The Pulmonary Arterial Hypertension-Symptoms and Impacts Questionnaire performed well in the authors' analysis, though additional data is needed regarding interpretability and feasibility. CONCLUSIONS: EmPHasis-10 demonstrated strong psychometric properties and the greatest feasibility for clinical use. Further study assessing the integration of PROM into routine clinical care for PH is needed.

The feasibility and value of assessing patient-reported outcomes in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease that negatively impacts health-related quality of life (HRQOL). The PAH-symptoms and impact (PAH-SYMPACT) questionnaire is a validated disease-specific patient-reported outcome (PRO) instrument that assesses a patient's symptoms and the impact of PAH and its treatment on well-being. We performed a single-center prospective cohort study of patients with PAH to determine the feasibility of assessing PROs in clinical practice and to determine the association between PAH-SYMPACT domains and clinical characteristics and outcomes. One hundred and ten patients completed the 1-day version of the PAH-SYMPACT questionnaire which consists of 22 Likert-scale questions that assess HRQOL across four domains: cardiopulmonary (CP) symptoms, cardiovascular (CV) symptoms, physical impact (PI), and cognitive and emotional (CE) impact. Higher scores indicate worse HRQOL. Patients were predominantly female (n = 86, 78%) with a mean age of 57.8 ± 16.2 years. While several patient characteristics were associated with CP and PI domains, few were associated with CV and CE domains. PI and CE impact scores were associated with recent hospitalizations and mortality and CE impact score was independently associated with an increased risk of death after adjustment for disease severity (hazard ratio: 3.29, 95% confidence interval: 1.56-6.91, p = 0.002). In conclusion, the assessment of PROs in clinical practice using the PAH-SYMPACT questionnaire is both feasible and valuable. PAH-SYMPACT scores have independent prognostic value and are not adequately reflected by traditional measures of disease severity. These findings underscore the importance of assessing HRQOL in clinical practice.

BREEZE: Open-label clinical study to evaluate the safety and tolerability of treprostinil inhalation powder as Tyvaso DPI™ in patients with pulmonary arterial hypertension.

Inhaled treprostinil is an approved therapy for pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease in the United States. Studies have confirmed the robust benefits and safety of nebulized inhaled treprostinil, but it requires a time investment for nebulizer preparation, maintenance, and treatment. A small, portable treprostinil dry powder inhaler has been developed for the treatment of PAH. The primary objective of this study was to evaluate the safety and tolerability of treprostinil inhalation powder (TreT) in patients currently treated with treprostinil inhalation solution. Fifty-one patients on a stable dose of treprostinil inhalation solution enrolled and transitioned to TreT at a corresponding dose. Six-minute walk distance (6MWD), device preference and satisfaction (Preference Questionnaire for Inhaled Treprostinil Devices [PQ-ITD]), PAH Symptoms and Impact (PAH-SYMPACT®) questionnaire, and systemic exposure and pharmacokinetics for up to 5 h were assessed at baseline for treprostinil inhalation solution and at Week 3 for TreT. Adverse events (AEs) were consistent with studies of inhaled treprostinil in patients with PAH, and there were no study drug-related serious AEs. Statistically significant improvements occurred in 6MWD, PQ-ITD, and PAH-SYMPACT. Forty-nine patients completed the 3-week treatment phase and all elected to participate in an optional extension phase. These results demonstrate that, in patients with PAH, transition from treprostinil inhalation solution to TreT is safe, well-tolerated, and accompanied by statistically significant improvements in key clinical assessments and patient-reported outcomes with comparable systemic exposure between the two formulations at evaluated doses (trial registration: clinicaltrials.gov identifier: NCT03950739).

Symptoms, impacts, and suitability of the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT™) questionnaire in patients with sarcoidosis-associated pulmonary hypertension (SAPH): a qualitative interview study.

BACKGROUND: Sarcoidosis-associated pulmonary hypertension (SAPH) is a prevalent and serious complication of sarcoidosis. No SAPH-specific self-report instruments for assessing SAPH symptoms and their impact on patients are available to date. This study sought to determine whether the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT™) questionnaire is suitable for use in patients with SAPH. METHODS: Patients diagnosed with SAPH participated in qualitative one-on-one telephone interviews to better understand SAPH symptoms and their impacts on patients' lives and to determine the appropriateness of the PAH-SYMPACT™ for use in patients with SAPH. The interviews comprised concept elicitation, completion of the PAH-SYMPACT™, and cognitive debriefing. Interview transcripts were analyzed by content analysis. RESULTS: Eleven patients with SAPH were interviewed between August 2019 and June 2020. In the concept elicitation, all 11 participants endorsed shortness of breath and nine participants (82%) rated it as their "most bothersome or severe" symptom. Impacts endorsed by all 11 participants were difficulty walking uphill or up stairs and difficulty in performing daily activities. Cognitive debriefing indicated that the PAH-SYMPACT™ items were relevant and understandable to most participants and reflected their experiences of SAPH. Participants indicated that no key symptoms or impacts of SAPH were missing. They also reported that the PAH-SYMPACT™ instructions and response options were clear, and that it would be feasible to complete the 11 symptom items and one oxygen use item as part of their daily schedule. CONCLUSIONS: This study suggests the PAH-SYMPACT™ is suitable for assessing symptoms and their impact in patients with SAPH. However, larger longitudinal studies are needed to confirm that it is fit for use in this patient population and that it can be used to reliably detect temporal changes in patients' symptom status. Trial registration Not applicable.

Quality of life in ambulatory pulmonary arterial hypertension in connective tissue diseases and its relationship with risk stratification.

The Pulmonary Arterial Hypertension Symptoms and Impact Questionnaire (PAH-SYMPACT) is a PAH-specific patient-reported outcome scale assessing patients' quality of life from four aspects: cardiopulmonary symptoms, cardiovascular symptoms, physical impacts and cognitive/emotional impacts. This study aimed to validate the Chinese version of PAH-SYMPACT and explore its relationship with risk stratification in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH). In addition, 75 patients with CTD-PAH confirmed by right heart catheterization were invited to complete questionnaires including PAH-SYMPACT, the 36-item Medical Outcomes Study Short Form Survey (SF-36) and EuroQol five dimensions questionnaire (EQ-5D). The demographic, clinical, laboratory and treatment data were collected. The endpoint was treatment goal achievement status in 6-12 months after completing the questionnaires, defined as an integrated outcome. Participants' mean age was 36.4 ± 11.9 years and the mean pulmonary arterial pressure was 38.9 ± 13.67 mmHg. The reliability of the PAH-SYMPACT domains ranged from 0.83 to 0.88. Results of factor analysis basically conformed the original PAH-SYMPACT. The treatment goal achievement (TGA) status in 6-12 months was significantly associated with physical impacts scores (odds ratio: 0.180, 95% confidence interval: 0.036-0.908, P=0.038). The Chinese version of PAH-SYMPACT is a reliable measurement to evaluate quality of life in CTD-PAH patients and is also a potential predictor of patient's condition change in routine clinical practice.

Symptoms, impacts, and suitability of the Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT™) questionnaire in patients with chronic thromboembolic pulmonary hypertension (CTEPH): a qualitative interview study.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare form of pulmonary hypertension caused by blood clots and scar tissue in the blood vessels of the lungs. Health-related quality of life is often significantly impaired in patients with CTEPH. However, a better understanding of how CTEPH symptoms affect patients' lives is needed to optimally assess the impact of the disease and treatment. OBJECTIVES: This qualitative study aimed to better understand the symptoms of CTEPH and how they affect patients' lives, as well as to determine the appropriateness of the Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT™) questionnaire for use in this patient population. METHODS: Adults diagnosed with CTEPH, recruited from two clinical sites in the US, participated in one-to-one qualitative telephone interviews. They described their experience of CTEPH symptoms and the impact these symptoms have on their lives. They also provided feedback on the comprehensibility and relevance of the PAH-SYMPACT™'s instructions, items, and response options. RESULTS: Participants (N = 12) had a mean age of 62.5 years. Two thirds were female and most (83%) had undergone pulmonary endarterectomy and/or balloon pulmonary angioplasty. The most frequently endorsed symptoms were shortness of breath (endorsed by all 12 participants), fatigue (11 participants), and lightheadedness (10 participants). All participants identified shortness of breath as an "extremely important" symptom, and seven participants rated fatigue as "extremely important." The most frequent impacts of CTEPH were on ability to walk quickly (endorsed by all 12 participants), ability to walk up inclines or stairs (11 participants), and ability to carry things (11 participants). The PAH-SYMPACT™ items were relevant to most participants and reflected their experience of CTEPH. All participants indicated that no important CTEPH symptoms were missing from the PAH-SYMPACT™. Overall, the instructions, items, and response options of the PAH-SYMPACT™ were clear and easy to understand. CONCLUSIONS: The symptoms and impacts experienced by patients with CTEPH align with items included in the PAH-SYMPACT™. The PAH-SYMPACT™ appears to be fit for purpose for assessing disease status in patients with CTEPH.