Telemedicine in heart failure: Pre-specified and exploratory subgroup analyses from the TIM-HF trial

Abstract

Background

Meta-analyses have suggested that remote telemedical management (RTM) positively affects clinical outcomes in chronic HF patients. The results of two recent randomised RTM trials do not corroborate these results. We aim to report prospectively defined and exploratory subgroup analyses for the TIM-HF trial and to identify a patient profile that could potentially benefit from RTM for further investigation in randomised clinical trials.

Methods

In TIM-HF, 710 stable chronic HF patients, in NYHA class II or III with a history of HF decompensation within 2 years previously or a LVEF ≤ 25% were randomly assigned (1:1) to RTM or usual care. The primary outcome was total death and secondary outcomes included days lost due to death or HF hospitalisation and a composite of cardiovascular death and HF hospitalisation. Twelve subgroups were prospectively defined and patient profiling was investigated for the subgroup with a prior history of HF decompensation, an LVEF ≥ 25% and a PHQ-9 score < 10.

Results

The subgroup treatment effects were significant for total mortality for the PHQ-9 subgroup only (p for interaction < 0.027). For the outcome ‘number of days lost due to hospitalisation for HF or death’, the subgroup treatment effects were significant (p for interaction < 0.05) for patients with a prior HF decompensation or an ICD implant or a PHQ score of < 10 and for the patient-profiling subgroup.

Conclusions

Telemedicine management may not be appropriate for all HF patients. Future research needs to investigate which HF population may benefit from this intervention.

Introduction

The number of patients with chronic heart failure (HF) continues to increase worldwide, and this syndrome exerts a substantial burden on society and on healthcare systems in terms of morbidity, mortality and high consumption of resources primarily caused by repeated and in some instances, lengthy hospital stays [1], [2]. Chronic HF is a multifaceted condition and the evolution of its medical management over the past two decades, from the 90's in particular, reflects the understanding of the underlying patho-physiology of this diagnosis and the results of randomised clinical trials have shown that selective poly-therapy for patients with mild-to-moderate heart failure reduces its progression and mortality risk [3].

In recent years, the focus for the management of chronic HF has shifted as developments in modern telecommunication technologies have created new options to deliver telemedical care as an adjunct to the medical management of HF patients [4]. It has been suggested that well structured out-patient care may prevent the need for hospitalisation, facilitate early intervention thus preventing ‘crisis’ management, prevent complications or the progression to a more severe disease status [5]. Recent meta-analyses [6], [7], [8] have shown that telemedical monitoring in chronic HF can reduce total mortality during a follow-up of 6 to 12 months in addition to reducing the number and duration of hospitalisations for worsening HF. Since the publication of these meta-analyses, two recently reported prospectively conducted randomised multi-centre clinical trials do not corroborate these findings [9], [10].

These contrasting results pose a challenge to the medical profession as the answers to the following issues need to be re-addressed: Does remote telemedical management (RTM) have a role in the management of HF patients? If yes, which HF population is most likely to benefit from this intervention, which type of telemedical support is warranted and which clinically meaningful outcome can be positively affected by this intervention? In this report, we address two of these challenges, namely how the potential HF population which could benefit from RTM could be identified and which outcome could be the most meaningful to use for this intervention from a clinical perspective. To this end, we present the results of the prospectively defined subgroup analyses and two additional post hoc analyses from the Telemedical Interventional Monitoring in Heart Failure (TIM-HF trial) [10], [11].