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REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction (REVERSE)

Primary Purpose

Heart Failure

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Cardiac Resynchronization Therapy (CRT) Device or Implantable Cardioverter Defibrillator (ICD) with CRT
Sponsored by
Medtronic Cardiac Rhythm and Heart Failure
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure focused on measuring Heart Failure, Implantable Cardioverter Defibrillator, Cardiac Resynchronization Therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Subjects with previously symptomatic heart failure but no current symptoms (New York Heart Association (NYHA) Class I, Stage C) or subjects with mild heart failure that only sometimes interferes with daily activities (NYHA Class II) Subjects with a QRS of 120 ms or more (The QRS interval is a measurement of how the electrical signal involved in a heart beat travels/conducts through the ventricles. A wide QRS (120 ms or more) suggests that there is a conduction problem (or block) in the ventricles). Subjects with a left ventricular ejection fraction less than or equal to 40%. (The left ventricular ejection fraction (LVEF) is a measurement of how well the left ventricle pumps blood out to the rest of the body. The higher the LVEF the more blood the ventricle is pumping.) Subjects with a left ventricular end diastolic dimension (LVEDD) greater than or equal to 55. (The left ventricular end diastolic dimension (LVEDD) is a measurement of heart size taken during an echocardiogram that is one indication of the health of the left ventricle.) Exclusion Criteria: Subjects who are pacemaker dependent (heart would not beat without the help of an implanted device to pace it). Subjects with heart failure that severely limits daily activities (NYHA Class III) or subjects with severe heart failure with symptoms while resting (NYHA Class IV). Subjects hospitalized due to heart failure within past 3 months.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

CRT OFF

CRT ON

Arm Description

Cardiac Resynchronization Therapy (CRT) turned OFF in conjunction with optimal medical therapy

Cardiac Resynchronization Therapy (CRT) turned ON in conjunction with optimal medical therapy

Outcomes

Primary Outcome Measures

Percentage of Patients Worsened for Clinical Composite Response
Patients considered worsened if they died, were hospitalized with worsening heart failure (HF), crossed over to other arm, demonstrated worsening in New York Heart Association (NYHA) functional class, or reported moderately/markedly worse HF symptoms compared to before CRT implant.

Secondary Outcome Measures

Change in Left Ventricular End Systolic Volume, Indexed (LVESVi)
The change is LVESVi measured at 12 months minus LVESVi measured at baseline. The 12-month echocardiographic measurements were made with CRT programmed off, irespective of the treatment assignment. In CRT ON patients these measurements were recorded after a 10 minute washout period. Two core laboratories performed all echo measurements.

Full Information

First Posted
December 21, 2005
Last Updated
January 26, 2012
Sponsor
Medtronic Cardiac Rhythm and Heart Failure
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1. Study Identification

Unique Protocol Identification Number
NCT00271154
Brief Title
REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction (REVERSE)
Official Title
REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction (REVERSE)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2012
Overall Recruitment Status
Completed
Study Start Date
September 2004 (undefined)
Primary Completion Date
October 2007 (Actual)
Study Completion Date
November 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medtronic Cardiac Rhythm and Heart Failure

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Heart failure is a progressive disease that decreases the pumping action of the heart. This may cause a backup of fluid in the heart and may result in heart beat changes. When there are changes in the heart beat sometimes an implantable heart device is used to control the rate and rhythm of the heart beat. The purpose of the REVERSE clinical trial is to determine whether pacing in both the left and right ventricles using Cardiac Resynchronization Therapy (CRT) can help slow the progression of heart failure in people who have mild or previous symptoms and poor heart pumping function. This kind of therapy has previously been shown to reduce symptoms and improve exercise capacity in people with more advanced forms of heart failure.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
Heart Failure, Implantable Cardioverter Defibrillator, Cardiac Resynchronization Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
684 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CRT OFF
Arm Type
Placebo Comparator
Arm Description
Cardiac Resynchronization Therapy (CRT) turned OFF in conjunction with optimal medical therapy
Arm Title
CRT ON
Arm Type
Active Comparator
Arm Description
Cardiac Resynchronization Therapy (CRT) turned ON in conjunction with optimal medical therapy
Intervention Type
Device
Intervention Name(s)
Cardiac Resynchronization Therapy (CRT) Device or Implantable Cardioverter Defibrillator (ICD) with CRT
Intervention Description
All randomized patients will be implanted with a market-released Medtronic CRT or CRT/ICD device.
Primary Outcome Measure Information:
Title
Percentage of Patients Worsened for Clinical Composite Response
Description
Patients considered worsened if they died, were hospitalized with worsening heart failure (HF), crossed over to other arm, demonstrated worsening in New York Heart Association (NYHA) functional class, or reported moderately/markedly worse HF symptoms compared to before CRT implant.
Time Frame
12 Months
Secondary Outcome Measure Information:
Title
Change in Left Ventricular End Systolic Volume, Indexed (LVESVi)
Description
The change is LVESVi measured at 12 months minus LVESVi measured at baseline. The 12-month echocardiographic measurements were made with CRT programmed off, irespective of the treatment assignment. In CRT ON patients these measurements were recorded after a 10 minute washout period. Two core laboratories performed all echo measurements.
Time Frame
Baseline to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects with previously symptomatic heart failure but no current symptoms (New York Heart Association (NYHA) Class I, Stage C) or subjects with mild heart failure that only sometimes interferes with daily activities (NYHA Class II) Subjects with a QRS of 120 ms or more (The QRS interval is a measurement of how the electrical signal involved in a heart beat travels/conducts through the ventricles. A wide QRS (120 ms or more) suggests that there is a conduction problem (or block) in the ventricles). Subjects with a left ventricular ejection fraction less than or equal to 40%. (The left ventricular ejection fraction (LVEF) is a measurement of how well the left ventricle pumps blood out to the rest of the body. The higher the LVEF the more blood the ventricle is pumping.) Subjects with a left ventricular end diastolic dimension (LVEDD) greater than or equal to 55. (The left ventricular end diastolic dimension (LVEDD) is a measurement of heart size taken during an echocardiogram that is one indication of the health of the left ventricle.) Exclusion Criteria: Subjects who are pacemaker dependent (heart would not beat without the help of an implanted device to pace it). Subjects with heart failure that severely limits daily activities (NYHA Class III) or subjects with severe heart failure with symptoms while resting (NYHA Class IV). Subjects hospitalized due to heart failure within past 3 months.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cecilia Linde, MD, PhD
Organizational Affiliation
Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
Official's Role
Principal Investigator
Facility Information:
City
Huntsville
State/Province
Alabama
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United States
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Anchorage
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Alaska
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United States
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Redwood City
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California
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San Diego
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California
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Atlantis
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Jacksonville
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Springfield
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Illinois
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Indianapolis
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Indiana
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Des Moines
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Boston
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Massachusetts
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Burlington
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Massachusetts
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Ann Arbor
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Michigan
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Saginaw
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Coon Rapids
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Minnesota
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Tupelo
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Mississippi
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Lincoln
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Nebraska
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United States
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East Syracuse
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New York
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Manhasset
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New York
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Winston-Salem
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North Carolina
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Cincinnati
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Columbus
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Marion
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Ohio
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Doylestown
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Pennsylvania
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Hershey
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West Reading
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Charleston
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South Carolina
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Germantown
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Tennessee
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Kingsport
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Tennessee
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Austin
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Texas
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Houston
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Texas
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Salt Lake City
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Utah
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Norfolk
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Virginia
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Richmond
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Virginia
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Madison
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Wisconsin
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United States
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St. Polten
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Austria
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Weiner Neustadt
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Austria
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Leuven
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Belgium
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Kingston
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Ontario
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Canada
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Brno
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Czech Republic
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Olomouc
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Czech Republic
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Aalborg
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Denmark
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Aarhus
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Denmark
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Copenhagen
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Denmark
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Odense
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Denmark
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Lyon
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France
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Marseille
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France
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Montpellier
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France
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Nantes
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France
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Rennes
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France
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Bochum
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Germany
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Hamburg
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Germany
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Hannover
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Germany
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Budapest
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Hungary
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Szeged
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Hungary
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Dublin
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Ireland
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Busto Arsizio
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Italy
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Florence
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Italy
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Milano
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Italy
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Rome
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Italy
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Kristiansand
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Norway
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Madrid
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Spain
City
Valencia
Country
Spain
City
Linkoping
Country
Sweden
City
Stockholm
Country
Sweden
City
Blackpool
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
19038680
Citation
Linde C, Abraham WT, Gold MR, St John Sutton M, Ghio S, Daubert C; REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) Study Group. Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol. 2008 Dec 2;52(23):1834-1843. doi: 10.1016/j.jacc.2008.08.027. Epub 2008 Nov 7.
Results Reference
result
PubMed Identifier
18401214
Citation
Linde C, Gold M, Abraham WT, Daubert JC; REVERSE Study Group. Baseline characteristics of patients randomized in The Resynchronization Reverses Remodeling In Systolic Left Ventricular Dysfunction (REVERSE) study. Congest Heart Fail. 2008 Mar-Apr;14(2):66-74. doi: 10.1111/j.1751-7133.2008.07613.x.
Results Reference
result
PubMed Identifier
33640347
Citation
Gold MR, Rickard J, Daubert JC, Zimmerman P, Linde C. Redefining the Classifications of Response to Cardiac Resynchronization Therapy: Results From the REVERSE Study. JACC Clin Electrophysiol. 2021 Jul;7(7):871-880. doi: 10.1016/j.jacep.2020.11.010. Epub 2021 Feb 24.
Results Reference
derived
PubMed Identifier
29759777
Citation
Senfield J, Daubert C, Abraham WT, Ghio S, St John Sutton M, Cerkvenik J, Linde C, Gold MR. The Impact of the PR Interval in Patients Receiving Cardiac Resynchronization Therapy: Results From the REVERSE Study. JACC Clin Electrophysiol. 2017 Aug;3(8):818-826. doi: 10.1016/j.jacep.2017.01.017. Epub 2017 Apr 26.
Results Reference
derived
PubMed Identifier
29314424
Citation
Linde C, Cleland JGF, Gold MR, Claude Daubert J, Tang ASL, Young JB, Sherfesee L, Abraham WT. The interaction of sex, height, and QRS duration on the effects of cardiac resynchronization therapy on morbidity and mortality: an individual-patient data meta-analysis. Eur J Heart Fail. 2018 Apr;20(4):780-791. doi: 10.1002/ejhf.1133. Epub 2018 Jan 4.
Results Reference
derived
PubMed Identifier
28254126
Citation
Gold MR, Padhiar A, Mealing S, Sidhu MK, Tsintzos SI, Abraham WT. Economic Value and Cost-Effectiveness of Cardiac Resynchronization Therapy Among Patients With Mild Heart Failure: Projections From the REVERSE Long-Term Follow-Up. JACC Heart Fail. 2017 Mar;5(3):204-212. doi: 10.1016/j.jchf.2016.10.014. Epub 2017 Jan 11.
Results Reference
derived
PubMed Identifier
28254122
Citation
St John Sutton M, Linde C, Gold MR, Abraham WT, Ghio S, Cerkvenik J, Daubert JC; REVERSE Study Group. Left Ventricular Architecture, Long-Term Reverse Remodeling, and Clinical Outcome in Mild Heart Failure With Cardiac Resynchronization: Results From the REVERSE Trial. JACC Heart Fail. 2017 Mar;5(3):169-178. doi: 10.1016/j.jchf.2016.11.012.
Results Reference
derived
PubMed Identifier
26363005
Citation
St John Sutton M, Cerkvenik J, Borlaug BA, Daubert C, Gold MR, Ghio S, Chirinos JA, Linde C, Ky B. Effects of Cardiac Resynchronization Therapy on Cardiac Remodeling and Contractile Function: Results From Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE). J Am Heart Assoc. 2015 Sep 11;4(9):e002054. doi: 10.1161/JAHA.115.002054.
Results Reference
derived
PubMed Identifier
24125796
Citation
Gold MR, Daubert JC, Abraham WT, Hassager C, Dinerman JL, Hudnall JH, Cerkvenik J, Linde C. Implantable defibrillators improve survival in patients with mildly symptomatic heart failure receiving cardiac resynchronization therapy: analysis of the long-term follow-up of remodeling in systolic left ventricular dysfunction (REVERSE). Circ Arrhythm Electrophysiol. 2013 Dec;6(6):1163-8. doi: 10.1161/CIRCEP.113.000570. Epub 2013 Oct 14.
Results Reference
derived
PubMed Identifier
24014828
Citation
Linde C, Daubert C, Abraham WT, St John Sutton M, Ghio S, Hassager C, Herre JM, Bergemann TL, Gold MR; REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) Study Group. Impact of ejection fraction on the clinical response to cardiac resynchronization therapy in mild heart failure. Circ Heart Fail. 2013 Nov;6(6):1180-9. doi: 10.1161/CIRCHEARTFAILURE.113.000326. Epub 2013 Sep 6.
Results Reference
derived
PubMed Identifier
23900696
Citation
Cleland JG, Abraham WT, Linde C, Gold MR, Young JB, Claude Daubert J, Sherfesee L, Wells GA, Tang AS. An individual patient meta-analysis of five randomized trials assessing the effects of cardiac resynchronization therapy on morbidity and mortality in patients with symptomatic heart failure. Eur Heart J. 2013 Dec;34(46):3547-56. doi: 10.1093/eurheartj/eht290. Epub 2013 Jul 29.
Results Reference
derived
PubMed Identifier
23641006
Citation
Linde C, Gold MR, Abraham WT, St John Sutton M, Ghio S, Cerkvenik J, Daubert C; REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction Study Group. Long-term impact of cardiac resynchronization therapy in mild heart failure: 5-year results from the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) study. Eur Heart J. 2013 Sep;34(33):2592-9. doi: 10.1093/eurheartj/eht160. Epub 2013 May 2.
Results Reference
derived
PubMed Identifier
22781424
Citation
Gold MR, Thebault C, Linde C, Abraham WT, Gerritse B, Ghio S, St John Sutton M, Daubert JC. Effect of QRS duration and morphology on cardiac resynchronization therapy outcomes in mild heart failure: results from the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) study. Circulation. 2012 Aug 14;126(7):822-9. doi: 10.1161/CIRCULATIONAHA.112.097709. Epub 2012 Jul 10.
Results Reference
derived
PubMed Identifier
22285578
Citation
Thebault C, Donal E, Meunier C, Gervais R, Gerritse B, Gold MR, Abraham WT, Linde C, Daubert JC; REVERSE study group. Sites of left and right ventricular lead implantation and response to cardiac resynchronization therapy observations from the REVERSE trial. Eur Heart J. 2012 Nov;33(21):2662-71. doi: 10.1093/eurheartj/ehr505. Epub 2012 Jan 26.
Results Reference
derived
PubMed Identifier
21185401
Citation
Gold MR, Linde C, Abraham WT, Gardiwal A, Daubert JC. The impact of cardiac resynchronization therapy on the incidence of ventricular arrhythmias in mild heart failure. Heart Rhythm. 2011 May;8(5):679-84. doi: 10.1016/j.hrthm.2010.12.031. Epub 2010 Dec 23.
Results Reference
derived
PubMed Identifier
21087711
Citation
Linde C, Abraham WT, Gold MR, Daubert C; REVERSE Study Group. Cardiac resynchronization therapy in asymptomatic or mildly symptomatic heart failure patients in relation to etiology: results from the REVERSE (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction) study. J Am Coll Cardiol. 2010 Nov 23;56(22):1826-31. doi: 10.1016/j.jacc.2010.05.055.
Results Reference
derived
PubMed Identifier
20823398
Citation
Linde C, Daubert C. Cardiac resynchronization therapy in patients with New York Heart Association class I and II heart failure: an approach to 2010. Circulation. 2010 Sep 7;122(10):1037-43. doi: 10.1161/CIRCULATIONAHA.109.923094. No abstract available.
Results Reference
derived
PubMed Identifier
19858419
Citation
St John Sutton M, Ghio S, Plappert T, Tavazzi L, Scelsi L, Daubert C, Abraham WT, Gold MR, Hassager C, Herre JM, Linde C; REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) Study Group. Cardiac resynchronization induces major structural and functional reverse remodeling in patients with New York Heart Association class I/II heart failure. Circulation. 2009 Nov 10;120(19):1858-65. doi: 10.1161/CIRCULATIONAHA.108.818724. Epub 2009 Oct 26.
Results Reference
derived
PubMed Identifier
19800193
Citation
Daubert C, Gold MR, Abraham WT, Ghio S, Hassager C, Goode G, Szili-Torok T, Linde C; REVERSE Study Group. Prevention of disease progression by cardiac resynchronization therapy in patients with asymptomatic or mildly symptomatic left ventricular dysfunction: insights from the European cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial. J Am Coll Cardiol. 2009 Nov 10;54(20):1837-46. doi: 10.1016/j.jacc.2009.08.011. Epub 2009 Oct 1.
Results Reference
derived

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REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction (REVERSE)

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