Author + information
- Received July 27, 2018
- Revision received October 5, 2018
- Accepted October 12, 2018
- Published online January 28, 2019.
- Melissa A. Daubert, MDa,b,∗ (, )
- Kirkwood Adams, MDc,
- Eric Yow, MSb,
- Huiman X. Barnhart, PhDa,b,
- Pamela S. Douglas, MDa,b,
- Susan Rimmer, RDCSb,
- Casey Norris, MSb,
- Lawton Cooper, MD, MPHd,
- Eric Leifer, PhDd,
- Patrice Desvigne-Nickens, MDd,
- Kevin Anstrom, PhDa,b,
- Mona Fiuzat, PharmDa,
- Justin Ezekowitz, MBBCh, MSce,
- Daniel B. Mark, MD, MPHa,b,
- Christopher M. O’Connor, MDa,f,
- James Januzzi, MDg and
- G. Michael Felker, MDa,b
- aDuke University Medical Center, Durham, North Carolina
- bDuke Clinical Research Institute, Durham, North Carolina
- cUniversity of North Carolina, Chapel Hill, North Carolina
- dNational Heart, Lung, and Blood Institute, Bethesda, Maryland
- eUniversity of Alberta, Edmonton, Alberta, Canada
- fInova Heart and Vascular Institute, Falls Church, Virginia
- gMassachusetts General Hospital, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Melissa A. Daubert, Duke University and Duke Clinical Research Institute, 2400 Pratt St, Room 0311 Terrace Level, Durham, North Carolina 27705.
Objectives This study aims to assess the association between biomarker-guided therapy and left ventricular (LV) remodeling.
Background In patients with heart failure with reduced ejection fraction (HFrEF), it is unclear if lowering natriuretic peptides reflects structural and functional changes in the heart. This study aims to assess the association between biomarker-guided therapy and left ventricular (LV) remodeling.
Methods The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) Echo Substudy was a multicenter study that randomized 268 patients with HFrEF (EF ≤40%) to either pro-B-type natriuretic peptide (NT-proBNP)-guided treatment or usual care. Echocardiograms were performed at baseline and 12 months in 124 patients. Remodeling indices and clinical outcomes were compared between treatment arms and by achievement of the NT-proBNP goal of <1,000 pg/ml at 12 months.
Results At 12 months, the changes in EF and LV volumes were similar between the biomarker-guided and usual care arms with no difference in clinical outcomes; however, lowering NT-proBNP to <1,000 pg/ml, regardless of treatment strategy, was associated with a significantly greater increase in EF compared with those not reaching goal (9.9 ± 8.8% vs. 2.9 ± 7.9%; p < 0.001) and lower LV volumes. The extent of reverse remodeling correlated with the change in NT-proBNP: a decrease of 1,000 pg/ml was associated with an increase in EF of 6.7% and a reduction in systolic and diastolic volumes of 17.3 ml/m2 and 15.7 ml/m2, respectively. Adverse events were significantly lower among patients achieving the NT-proBNP goal (p < 0.001).
Conclusions Among patients with HFrEF, lowering NT-proBNP to <1,000 pg/ml by 12 months was associated with significant reverse remodeling and improved outcomes. A greater reduction in NT-proBNP was associated with more extensive reverse remodeling. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment [GUIDE-IT]; NCT01685840)
Duke Clinical Research Institute was the recipient of research grants from Roche Diagnostics. The GUIDE-IT Trial was funded by the National Heart, Lung, and Blood Institute. The GUIDE-IT Echo Substudy was funded by Roche Diagnostics. Dr. Daubert has received grant support from Roche Diagnostics. Dr. Douglas has received grant support from the National Institutes of Health. Drs. Cooper, Leifer, and Desvigne-Nickens are faculty of the National Heart, Lung, and Blood Institute; and were members of the Guiding Evidence Based Therapy Using Biomarker Intensified Treatment Steering Committee. Drs. Adams, Anstrom, Fiuzat, O’Connor, Mark, Januzzi, and Felker have received grant support from the National Institutes of Health and Roche Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Barry Greenberg, MD, served as Guest Editor for this paper.
- Received July 27, 2018.
- Revision received October 5, 2018.
- Accepted October 12, 2018.
- 2019 American College of Cardiology Foundation
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