Remote monitored physiological response to therapeutic escalation and clinical worsening in patients with pulmonary arterial hypertension

Abstract

BackgroundInternational guidelines for the treatment of patients with pulmonary arterial hypertension (PAH) recommend the use of risk stratification to optimise therapy to achieve and maintain a low-risk profile. However, recommended methods require hospital-based investigations. We sought to develop a method for daily, remote risk evaluation.MethodsConsecutive patients (n=5820) with pulmonary hypertension (PH) were identified from the ASPIRE registry and stepwise Cox regression applied to identify parameters associated with survival. A physiological risk score was applied to all patients and survival assessed by the Kaplan-Meier method. Physical activity was measured in patients with PAH implanted with insertable cardiac monitors (ICM, n=80) to provide a remote measure of exercise capacity. In patients with PAH and implanted pulmonary artery pressure (PAP) monitor and ICM (n=28) we undertook a time-stratified bidirectional case–crossover study to determine the physiology of therapeutic escalation (TE) and clinical worsening and a remote physiological risk score applied to the data.ResultsAge, male sex, PH aetiology, WHO functional class (FC), incremental shuttle walk-distance (ISWD), heart rate reserve (HRR) and total pulmonary resistance (TPR) as independent predictors of survival. Mortality increased with each decile of baseline physiological risk (p<0.001). In patients with PAH, thresholds of physiological risk were used to classify patients into low-, intermediate-low-, intermediate-high-, and high-risk groups for one-year mortality, which were well matched to COMPERA-2.0 score-stratified groups (Cohen’s weighted Kappa 0.61). ICM-measured physical activity decreased with indicators of increased clinical risk (WHO-FC, NT-proBNP, ISWD, COMPERA-2.0, p<0.0001). Following TE, remote monitored mean PAP and TPR were reduced, and cardiac output (CO) and physical activity increased at days seven, four, 22 and 42 respectively (p<0.05). Clinical worsening events (CWE) were preceded by an increased remote monitored mean PAP and TPR and reduced CO and physical activity (p<0.05). Change in remote physiological risk score identifiable six days after TE and twelve days prior to a CWE (p<0.05).ConclusionRemote risk evaluation may facilitate personalised medicine and proactive management. The physiological risk score accurately stratifies patients with PH and may be applied to remote monitoring data for early evaluation of clinical efficacy and detection of clinical worsening.

Pulmonary Hypertension: Intensification and Personalization of Combination Rx (PHoenix): A phase IV randomized trial for the evaluation of dose‐response and clinical efficacy of riociguat and selexipag using implanted technologies

“…Eligible patients will be implanted with CardioMEMS and Confirm Rx ICM devices using standard techniques and remote monitoring data collected using regulatory‐approved online portals. 28 …”

“…Furthermore, studies of patients with PAH implanted with a PAP monitor and an insertable cardiac monitor (ICM) demonstrated that clinically indicated therapeutic changes altered physiological parameters associated with mortality, indicating that early, remote assessment of clinical efficacy may be achieved using these devices. 28 CardioMEMS™ HF System (Abbott) is a wireless, PAP monitor implanted at the time of right heart catheterization to provide remote measurement of cardiopulmonary hemodynamics. CardioMEMS is approved for routine clinical practice in the USA and Europe, and to date over 30,000 of these monitors have been implanted.…”

“…Furthermore, studies of patients with PAH implanted with a PAP monitor and an insertable cardiac monitor (ICM) demonstrated that clinically indicated therapeutic changes altered physiological parameters associated with mortality, indicating that early, remote assessment of clinical efficacy may be achieved using these devices. 28 …”