title: Trials of implantable monitoring devices in heart failure: which design is optimal?
abstract: Implantable monitoring devices have been developed to detect early evidence of heart failure (HF) decompensation, with the hypothesis that early detection might enable clinicians to commence therapy sooner than would otherwise be possible, and potentially to reduce the rate of hospitalization. In addition to the usual challenges inherent to device trials (such as the difficulty of double-blinding and potential for bias), studies of implantable monitoring devices present unique difficulties because they involve assessment of therapeutic end points for diagnostic devices. Problems include the lack of uniform approaches to treatment in study protocols for device alerts or out-of-range values, and the requirement of levels of evidence traditionally associated with therapeutic devices to establish effectiveness and safety. In this Review, the approaches used to deal with these issues are discussed, including the use of objective primary end points with blinded adjudication, identical duration of follow-up and number of encounters for patients in active monitoring and control groups, and treatment recommendations between groups that are consistent with international guidelines. Remote monitoring devices hold promise for reducing the rate of hospitalization among patients with HF. However, optimization of regulatory approaches and clinical trial design is needed to facilitate further evaluation of the effectiveness of combining health information technology and medical devices.
authors.affiliation: Division of Cardiovascular Medicine, The Ohio State University, 244 Davis Heart &Lung Research Institute, 473 West 12th Avenue, Columbus, OH 43210, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Abraham
authors.affiliation: Campbell University College of Pharmacy and Health Sciences, 143 Main Street, Buies Creek, NC 27506, USA.
authors.forename: Wendy G
authors.initials: WG
authors.lastname: Stough
authors.affiliation: Department of Medicine, Division of Cardiology, Montefiore Medical Centre, 111 East 210th Street, Bronx, NY, 10467, USA.
authors.forename: Ileana L
authors.initials: IL
authors.lastname: Piña
authors.affiliation: Department of Cardiology, Karolinska University Hospital and Karolinska Institute, 171 76 Solna, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Linde
authors.affiliation: The Howard Gilman Institute, State University of New York Downstate Medical Centre, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Borer
authors.affiliation: Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi, 19, Pavia 27100, Italy.
authors.forename: Gaetano M
authors.initials: GM
authors.lastname: De Ferrari
authors.affiliation: Zena and Michael A. Weiner Cardiovascular, Mount Sinai Medical Centre, 1 Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.affiliation: Boston Scientific Corporation, 4100 Hamline Avenue North, St. Paul, MN 55112-5798, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Stein
authors.affiliation: Medtronic, Route du Molliau 31, 1131 Tolochenaz, Switzerland.
authors.forename: Alphons
authors.initials: A
authors.lastname: Vincent
authors.affiliation: CardioMEMS, 387 Technology Circle Northwest #500, Atlanta, GA 30313, USA.
authors.forename: Jay S
authors.initials: JS
authors.lastname: Yadav
authors.affiliation: Centre for Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, University Medical Center Göttingen, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.affiliation: INSERM, Centre d'Investigation Clinique 9501 and Unité 961, 34 Cours Léopold, 54000 Nancy, France.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D004867:Equipment Design; D006333:Heart Failure / Q000175:diagnosis*; D006801:Humans; D008991:Monitoring, Physiologic / Q000295:instrumentation*
references.citation: J Am Coll Cardiol. 2013 Mar 26;61(12):1259-67
references.pmid: 23500328
references.citation: Europace. 2012 Feb;14(2):278-93
references.pmid: 22232544
references.citation: Circ Heart Fail. 2013 May;6(3):473-81
references.pmid: 23476054
references.citation: J Am Coll Cardiol. 2005 May 17;45(10):1654-64
references.pmid: 15893183
references.citation: Circulation. 2012 Jun 19;125(24):2965-7
references.pmid: 22626742
references.citation: Eur Heart J. 2012 Jan;33(2):176-82
references.pmid: 21900289
references.citation: Eur Heart J. 2011 Sep;32(18):2266-73
references.pmid: 21362703
references.citation: Congest Heart Fail. 2011 Mar-Apr;17(2):51-5
references.pmid: 21449992
references.citation: Eur J Heart Fail. 2009 Apr;11(4):420-7
references.pmid: 19252210
references.citation: J Am Coll Cardiol. 2013 Apr 16;61(15):1571-6
references.pmid: 23352783
references.citation: Circulation. 2011 Oct 18;124(16):1697-9
references.pmid: 21931082
references.citation: Lancet. 2011 Feb 19;377(9766):658-66
references.pmid: 21315441
references.citation: N Engl J Med. 2009 Apr 2;360(14):1418-28
references.pmid: 19339721
references.citation: Eur Heart J. 2012 Jul;33(14):1787-847
references.pmid: 22611136
references.citation: J Am Coll Cardiol. 2010 Apr 27;55(17):1803-10
references.pmid: 20413029
references.citation: Eur Heart J. 2013 Aug;34(31):2472-80
references.pmid: 23513212
references.citation: N Engl J Med. 2013 Mar 28;368(13):1175-7
references.pmid: 23465069
references.citation: Int J Cardiol. 2013 Oct 12;168(5):4723-8
references.pmid: 23962782
references.citation: Europace. 2013 Jun;15 Suppl 1:i40-i46
references.pmid: 23737229
references.citation: Eur Heart J. 2013 Sep;34(36):2792-4
references.pmid: 23892200
references.citation: Eur J Heart Fail. 2008 Nov;10(11):1143-8
references.pmid: 18805053
references.citation: J Am Coll Cardiol. 2008 Mar 18;51(11):1073-9
references.pmid: 18342224
references.citation: Eur Heart J. 2002 Jun;23(11):877-85
references.pmid: 12042009
references.citation: Eur J Heart Fail. 2011 Jul;13(7):796-804
references.pmid: 21555324
references.citation: Circulation. 2012 Jun 19;125(24):2985-92
references.pmid: 22626743
references.citation: Eur J Heart Fail. 2005 Oct;7(6):953-7
references.pmid: 16227134
references.citation: Circ Heart Fail. 2010 Jan;3(1):97-103
references.pmid: 19903931
references.citation: Congest Heart Fail. 2011 Sep-Oct;17(5):248-54
references.pmid: 21906250
references.citation: Circulation. 2014 Jan 21;129(3):e28-e292
references.pmid: 24352519
references.citation: Heart. 2012 Jul;98(13):967-73
references.pmid: 22572046
references.citation: Lancet. 2011 Aug 20;378(9792):731-9
references.pmid: 21856487
references.citation: Circulation. 2011 Oct 18;124(16):1719-26
references.pmid: 21931078
references.citation: Circulation. 2008 Sep 30;118(14):1433-41
references.pmid: 18794390
references.citation: Thromb Haemost. 2013 Mar;109(3):497-503
references.pmid: 23348922
references.citation: Curr Cardiol Rep. 2012 Oct;14(5):611-8
references.pmid: 22814631
references.citation: Am Heart J. 2010 Jul;160(1):42-8
references.pmid: 20598971
references.citation: Circulation. 2011 May 3;123(17):1873-80
references.pmid: 21444883
references.citation: Future Cardiol. 2012 May;8(3):425-37
references.pmid: 22642632
references.citation: J Am Coll Cardiol. 2009 Apr 14;53(15):e1-e90
references.pmid: 19358937