Elsevier

The Lancet

Volume 384, Issue 9943, 16–22 August 2014, Pages 583-590
The Lancet

Articles
Implant-based multiparameter telemonitoring of patients with heart failure (IN-TIME): a randomised controlled trial

https://doi.org/10.1016/S0140-6736(14)61176-4Get rights and content

Summary

Background

An increasing number of patients with heart failure receive implantable cardioverter-defibrillators (ICDs) or cardiac resynchronisation defibrillators (CRT-Ds) with telemonitoring function. Early detection of worsening heart failure, or upstream factors predisposing to worsening heart failure, by implant-based telemonitoring might enable pre-emptive intervention and improve outcomes, but the evidence is weak. We investigated this possibility in IN-TIME, a clinical trial.

Methods

We did this randomised, controlled trial at 36 tertiary clinical centres and hospitals in Australia, Europe, and Israel. We enrolled patients with chronic heart failure, NYHA class II–III symptoms, ejection fraction of no more than 35%, optimal drug treatment, no permanent atrial fibrillation, and a recent dual-chamber ICD or CRT-D implantation. After a 1 month run-in phase, patients were randomly assigned (1:1) to either automatic, daily, implant-based, multiparameter telemonitoring in addition to standard care or standard care without telemonitoring. Investigators were not masked to treatment allocation. Patients were masked to allocation unless they were contacted because of telemonitoring findings. Follow-up was 1 year. The primary outcome measure was a composite clinical score combining all-cause death, overnight hospital admission for heart failure, change in NYHA class, and change in patient global self-assessment, for the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT00538356.

Findings

We enrolled 716 patients, of whom 664 were randomly assigned (333 to telemonitoring, 331 to control). Mean age was 65·5 years and mean ejection fraction was 26%. 285 (43%) of patients had NYHA functional class II and 378 (57%) had NYHA class III. Most patients received CRT-Ds (390; 58·7%). At 1 year, 63 (18·9%) of 333 patients in the telemonitoring group versus 90 (27·2%) of 331 in the control group (p=0·013) had worsened composite score (odds ratio 0·63, 95% CI 0·43–0·90). Ten versus 27 patients died during follow-up.

Interpretation

Automatic, daily, implant-based, multiparameter telemonitoring can significantly improve clinical outcomes for patients with heart failure. Such telemonitoring is feasible and should be used in clinical practice.

Funding

Biotronik SE & Co. KG.

Introduction

In selected patients with heart failure and left ventricular systolic dysfunction, treatment with implantable cardioverter-defibrillators (ICDs) or cardiac resynchronisation therapy defibrillators (CRT-Ds) reduces all-cause mortality and hospital admissions for heart failure and other major cardiovascular events.1, 2 These devices afford the chance to automatically monitor physiological and technical data.3, 4, 5, 6, 7 Early detection of worsening heart failure, or of upstream factors predisposing to worsening heart failure, by a telemonitoring implant could enable pre-emptive medical intervention and improve outcomes beyond those achieved with stand-alone implantable devices, but the evidence is weak.3, 4, 5, 6, 7, 8, 9, 10, 11 The predisposing factors and precursors for poor clinical outcome or heart failure exacerbation include ventricular tachyarrhythmia, defibrillation shocks, onset of atrial fibrillation, low heart rate variability, low percentage of biventricular pacing, change in patient activity, abnormal sensing and other technical issues, lung fluid accumulation, and some haemodynamic variables.3, 4, 5, 6, 7, 8, 9, 10, 11

We did the INfluence of home moniToring on mortality and morbidity in heart failure patients with IMpaired lEft ventricular function (IN-TIME) trial to evaluate the incremental benefit of automatic multiparameter telemonitoring for patients with heart failure treated with an ICD or a CRT-D.

Section snippets

Study design and participants

We did this randomised controlled trial at 36 tertiary clinical centres, in Australia (one site), Europe (33 sites), and Israel (two sites; appendix). Details of the trial design have been published previously. 10 Consenting patients who were at least 18 years old were enrolled if they had chronic heart failure lasting for at least 3 months, New York Heart Association (NYHA) functional class II or III, a left ventricular ejection fraction of no more than 35%, and an indication for dual-chamber

Results

From July 24, 2007, to Dec 17, 2010, 716 patients were enrolled, of whom 664 were randomly assigned (figure 1 ): 333 to the telemonitoring group, 331 to the control group. Characteristics at enrolment were reasonably well balanced between the two groups (table 1 ). Mean age at enrolment was 65·5 years (SD 9·4), and 536 (81%) patients were men. Mean left ventricular ejection fraction was 26% (SD 7%). 582 (88%) of 664 patients completed follow-up, 37 died (6%), and 45 (7%) terminated the study

Discussion

In patients with heart failure treated with ICDs and CRT-Ds, automatic, daily, implant-based telemonitoring of rhythmic and technical parameters had a significantly beneficial effect on the composite clinical score and all-cause mortality. The favourable effect of telemonitoring seemed to arise from careful attention to various kinds of remote data without a single, typical scenario. In our opinion, three mechanisms contributed in parallel to the improved clinical outcome, but their relative

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