Remote monitored physiological response to therapeutic escalation and clinical worsening in patients with pulmonary arterial hypertension
Authors: Middleton Jennifer T , Binmahfooz Sarah , Zafar Hamza , Patel Junaid , Ashraf Cameron , Jake  , Neelam-Naganathan Dharshan , Battersby Christian , Pearson Charlotte , Roddis Chloe , Roman Stefan , Ablott Jenna , Reddy Ashwin , Watson Lisa , Dick Jennifer , Kyriacou Andreas , Morris Paul D , Varian Frances , Hamilton Neil , Armstrong Iain , Hurdman Judith , Hameed Abdul , Charalampopoulos Athanasios , Bigirumurame Theophile , Hiu Shaun K. W. , Wason James M. S. , Swift Andrew J , Thompson A A Roger , Condliffe Robin , Elliot Charlie , Kiely David G , Toshner Mark , Rothman Alexander M K 
Published: May 2023

Background

International guidelines recommend regular, hospital-based risk stratification to aid assessment and management of patients with pulmonary arterial hypertension. Technological advances enable daily, remote measurement of cardiopulmonary physiology and physical activity that have the potential to provide early evaluation of therapeutic efficacy and facilitate early intervention based on the physiological changes that precede clinical events. We sought to investigate the relationship between remote-monitored parameters and the COMPERA 2.0 4-strata risk score and evaluate physiological changes following therapeutic escalation and prior to clinical worsening events.

Methods

Eighty-seven patients with pulmonary arterial hypertension were implanted with insertable cardiac monitors including a nested set of twenty-eight patients also implanted with a pulmonary artery pressure monitor. Hospital measured and remote monitored physiological parameters were evaluated by 4-strata COMPERA 2.0 risk score. A time stratified bidirectional case-crossover study was undertaken to evaluate physiological changes at the time of therapy escalation and clinical worsening events in the nested group with insertable cardiac and pulmonary artery pressure monitors. A summary measure of remote physiological risk was calculated as the sum of the z-score of physical activity, heart rate reserve and total pulmonary resistance and applied to remote monitoring data.

Results

Insertable cardiac monitor-measured physical activity, heart rate variability and heart rate reserve were decreased and night heart rate increased in patients with increasing COMPERA 2.0 score (p<0.0001). Daily physical activity was related to incremental shuttle walk distance (p<0.0001) but not six-minute walk distance. Following therapeutic escalation mean pulmonary artery pressure and total pulmonary resistance were reduced and cardiac output, and physical activity increased at 7, 4, 22, and 42 days, respectively (p<0.05). Clinical worsening events were preceded by increased mean pulmonary artery pressure and total pulmonary resistance, reduced cardiac output and physical activity (p<0.05). Applying a remote physiological risk score to remote-monitored data demonstrated that following a clinically indicated increase in therapy, a reduction in physiological risk was identifiable at day three, and preceding a clinical worsening event, an increase in adverse physiology was observable at day - 16.

Conclusion

Approved devices accurately identify change in physiology in patients with pulmonary arterial hypertension following therapeutic intensification and before clinical worsening. A remote assessment of haemodynamic and cardiac monitoring may facilitate personalised, proactive medicine and innovative clinical study designs.

Condensed Abstract

Technological advances provide the capacity to remotely measure cardiopulmonary physiology. In 87 patients with insertable cardiac monitors and a nested group 28 patients with pulmonary arterial hypertension implanted with pulmonary artery pressure monitors, significant improvements in cardiopulmonary function and physical activity were observed following therapeutic escalation and preceding clinical worsening events. The study highlights the potential of remote monitoring for personalised management, early therapeutic evaluation, and innovative clinical trial designs in patients with pulmonary hypertension.

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#PHPEEPS Remote monitoring shows improved cardiopulmonary function just 7 days after therapy adjustments, and adverse changes 12 days before a worsening event. The future of personalised care?

Learning points

Pulmonary artery pressure monitor and insertable cardiac monitors offer safe and reliable data capture of physiological risk markers that change in response to therapy and preceding clinical worsening events.

Remote monitored measures of physiology differ between patients with low, int-low, int-high and high risk of one-year mortality stratified by COMPERA 2.0 4-strata risk model.

Remote risk evaluation may facilitate personalised medicine and proactive management for early evaluation of therapeutic efficacy and detection of clinical worsening.

Plain Language Summary

This study was undertaken in 87 patients diagnosed with pulmonary arterial hypertension (PAH). Treatments in PAH are based on a risk classification system with the aim of achieving a low-risk group. The usual in-hospital method uses the COMPERA 2.0 risk model which combines a field walk test, NT-proBNP (blood test) and World Health Organisation Functional Classification (WHO FC) which categorises level of breathlessness during everyday activity. The evidence for this is linked to risk of death, classified into four groups: low, intermediate-low, intermediate-high, and high risk. The aim of this study was to see whether newer medical technologies could grade risk in a remote setting.

The two technologies used in this study are safe and approved for use. The first is a pulmonary artery pressure monitor (CardioMEMS) that measures the pressure in the lungs. It is implanted during right heart catheterisation (RHC). Measurements can be taken at home and sent securely to a medical database for the healthcare team to view. Please see the plain graphical summary figure for more information on the CardioMEMS device. The second technology is an insertable cardiac monitor (ICM), which is implanted under the skin using local anaesthetic, and sends remote readings such as physical activity and heart rate. Both technologies were implanted into a subgroup of patients to investigate whether these technologies could help classify risk from home, and whether they could detect response to new treatments, or signs that a condition may be getting worse. 28 patients with both these devices took part in the study and a further 59 had an ICM only. A remote risk score was calculated using 3 things: physical activity, heart rate reserve (HRR: difference between maximum heart rate for age and resting heart rate) from the ICM and total pulmonary resistance (TPR: a measure of the pressure and flow through the lungs) from the CardioMEMS. The results showed that these measures could classify risk as well as the in-hospital COMPERA 2.0 model. The remote risk score detected response to treatment as early as 6 days and clinical worsening as early as 12 days before an event (e.g. hospitalisation) in the group observed.

Patient and Public Involvement and Engagement (PPIE)

The study was developed following the 2017 Pulmonary Hypertension Association UK (PHA UK) survey in which 39% of patients reported difficulties attending hospital for appointments.1A subsequent remote monitoring survey (2021) was positively received, with key themes highlighting benefits of ‘improving [disease] understanding’, ‘personalising treatment’, and ‘reducing interruptions or unnecessary visits’.2Patients from the study and volunteers from PHA UK provided feedback on the results of the research. Amendments were made to the lay summary and a graphical summary was introduced following this feedback. There was universal agreement that participation in the study was beneficial to patients and future research. Participants involved in the study agreed the devices offer enhanced accessibility to non-invasive risk stratification and improvements in home-based care with minimal personal effort. Furthermore, the minimally invasive devices offered empowerment, confidence, and reassurance, with “opportunity to play an active role in [their] health and personal wellbeing” and “greater confidence with day-to-day living”. No incentives were offered for the PPIE in this study.

Abstract Figure

Plain Graphical Summary:

CardioMEMS implantation covering frequently asked questions (FAQ). Created with BioRender.com