title: Implant-based multiparameter telemonitoring of patients with heart failure (IN-TIME): a randomised controlled trial.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Biotronik SE & Co. KG.
authors.affiliation: Herzzentrum Leipzig, Leipzig, Germany. Electronic address: gerhard.hindricks@medizin.uni-leipzig.de.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hindricks
authors.affiliation: Department of Internal Medicine I-Cardiology, Faculty of Medicine and Dentistry, Olomouc, Czech Republic.
authors.forename: Milos
authors.initials: M
authors.lastname: Taborsky
authors.affiliation: Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Glikson
authors.affiliation: Praxis Dr Heinrich, Nordhausen, Germany.
authors.forename: Ullus
authors.initials: U
authors.lastname: Heinrich
authors.affiliation: Herz-und Gefäßklinikum GmbH Bad Neustadt, Bad Neustadt, Germany.
authors.forename: Burghard
authors.initials: B
authors.lastname: Schumacher
authors.affiliation: Barzilai Medical Center, Ashkelon, Israel.
authors.forename: Amos
authors.initials: A
authors.lastname: Katz
authors.affiliation: Klinikum Coburg GmbH, Coburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Brachmann
authors.affiliation: Isar Herzzentrum, Munich, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Lewalter
authors.affiliation: St Vincenz Krankenhaus GmbH, Paderborn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Goette
authors.affiliation: Klinik Augustinum, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Block
authors.affiliation: Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Kautzner
authors.affiliation: Klinikum Schwabing, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sack
authors.affiliation: Herzzentrum Leipzig, Leipzig, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Husser
authors.affiliation: Herzzentrum Leipzig, Leipzig, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Piorkowski
authors.affiliation: Heart Centre and Clinical Institute, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Søgaard
mesh_terms: D000368:Aged; D001315:Australia; D017147:Defibrillators, Implantable; D005060:Europe; D005260:Female; D006333:Heart Failure / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D007557:Israel; D008297:Male; D018670:Monitoring, Ambulatory / Q000295:instrumentation*; D017216:Telemedicine / Q000379:methods*; D016896:Treatment Outcome