Digital Tracking of Physical Activity, Heart Rate, and Inhalation Behavior in Patients With Pulmonary Arterial Hypertension Treated With Inhaled Iloprost: Observational Study (VENTASTEP)

Abstract

Background: Pulmonary arterial hypertension restricts the ability of patients to perform routine physical activities. As part of pulmonary arterial hypertension treatment, inhaled iloprost can be administered via a nebulizer that tracks inhalation behavior. Pulmonary arterial hypertension treatment is guided by intermittent clinical measurements, such as 6-minute walk distance, assessed during regular physician visits. Continuous digital monitoring of physical activity may facilitate more complete assessment of the impact of pulmonary arterial hypertension on daily life. Physical activity tracking with a wearable has not yet been assessed with simultaneous tracking of pulmonary arterial hypertension medication intake.

Objective: We aimed to digitally track the physical parameters of patients with pulmonary arterial hypertension who were starting treatment with iloprost using a Breelib nebulizer. The primary objective was to investigate correlations between changes in digital physical activity measures and changes in traditional clinical measures and health-related quality of life over 3 months. Secondary objectives were to evaluate inhalation behavior, adverse events, and changes in heart rate and sleep quality.

Methods: We conducted a prospective, multicenter observational study of adults with pulmonary arterial hypertension in World Health Organization functional class III who were adding inhaled iloprost to existing pulmonary arterial hypertension therapy. Daily distance walked, step count, number of standing-up events, heart rate, and 6-minute walk distance were digitally captured using smartwatch (Apple Watch Series 2) and smartphone (iPhone 6S) apps during a 3-month observation period (which began when iloprost treatment began). Before and at the end of the observation period (within 2 weeks), we also evaluated 6-minute walk distance, Borg dyspnea, functional class, B-type natriuretic peptide (or N-terminal pro-B-type natriuretic peptide) levels, health-related quality of life (EQ-5D questionnaire), and sleep quality (Pittsburgh Sleep Quality Index).

Results: Of 31 patients, 18 were included in the full analysis (observation period: median 91.5 days, IQR 88.0 to 92.0). Changes from baseline in traditional and digital 6-minute walk distance were moderately correlated (r=0.57). Physical activity (daily distance walked: median 0.4 km, IQR -0.2 to 1.9; daily step count: median 591, IQR -509 to 2413) and clinical measures (traditional 6-minute walk distance: median 26 m, IQR 0 to 40) changed concordantly from baseline to the end of the observation period. Health-related quality of life showed little change. Total sleep score and resting heart rate slightly decreased. Distance walked and step count showed short-term increases after each iloprost inhalation. No new safety signals were identified (safety analysis set: n=30).

Conclusions: Our results suggest that despite challenges, parallel monitoring of physical activity, heart rate, and iloprost inhalation is feasible in patients with pulmonary arterial hypertension and may complement traditional measures in guiding treatment; however, the sample size of this study limits generalizability.

Trial registration: ClinicalTrials.gov NCT03293407; https://ichgcp.net/clinical-trials-registry/NCT03293407.

International registered report identifier (irrid): RR2-10.2196/12144.

Keywords: 6-minute walk distance; 6MWD; Breelib; PAH; Ventavis; behavior; cardiology; daily physical activity; digital monitoring; health-related quality of life; heart; iloprost; inhalation behavior; mobile phone; monitoring; physical activity; pulmonary arterial hypertension; sleep; sleeping behavior.

Conflict of interest statement

Conflicts of Interest: BS, MK, VI, and CM are employees of Bayer Vital GmbH, which is the local representative of the marketing authorization holder (Bayer AG) for inhaled iloprost in Europe. DD has received support from Bayer Vital, Actelion, Novartis, and Boehringer. DD also received payments for lectures/consulting honorarium/travel support from Actelion, AstraZeneca, Bayer Healthcare, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Med. Clinic III, UKSH Campus Lübeck and received compensation for participation in clinical trials from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Merck, Novartis, Pfizer, Bayer HealthCare, BMS, MSD, and Novartis Roche. EG has received fees for lectures or consultations from Actelion, Bayer, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Pfizer, and United Therapeutics. FK is an employee of Bayer AG. HK has received support from Bayer Vital, Actelion, Novartis, Boehringer, Janssen, Merck Sharp & Dohme, GlaxoSmithKline, and United Therapeutics. MR has received support from United Therapeutics and Bayer Pharma AG, speaker fees from Actelion, Bayer Pharma AG, Mundipharma, Roche, and OMT, and consultancy fees from Bayer 202. MS has received support from Bayer Vital GmbH, GlaxoSmithKline, Johnson & Johnson, Merck Sharp & Dohme, and Pfizer. RE has received honoraria or fees for consultancy from Janssen Pharmaceutical Companies of Johnson & Johnson, Bayer Vital, and OMT and as a corporate board member for Actelion Pharmaceuticals Ltd, OMT, and Novartis. RE has received grants from Janssen Pharmaceutical Companies of Johnson & Johnson, Boehringer Ingelheim, OMT, Berlin Chemie, and Novartis.

©Barbara Stollfuss, Manuel Richter, Daniel Drömann, Hans Klose, Martin Schwaiblmair, Ekkehard Gruenig, Ralf Ewert, Martin C Kirchner, Frank Kleinjung, Valeska Irrgang, Christian Mueller. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 08.10.2021.

Figures

Figure 1

Patient disposition. CTEPH: chronic thromboembolic pulmonary hypertension; PAH: pulmonary arterial hypertension.

Figure 2

Median heart rate Data collected by smartwatch during 6-minute walk distance test before (baseline) and under (last visit) inhaled iloprost therapy. Error bars show IQR.

Figure 3

Heart rate recovery data collected by smartwatch at the end of the 6-minute walk distance (6MWD) test before (baseline) and under (last visit) inhaled iloprost therapy. Error bars show IQR.

Figure 4

(A) Distance walked and (B) number of steps (measured at 15-minute intervals for 3 hours after the end of each iloprost inhalation session) over the whole observation period.