Author + information
- Received February 11, 2016
- Revision received July 25, 2016
- Accepted August 10, 2016
- Published online November 1, 2016.
- Parul U. Gandhi, MDa,b,
- Hanna K. Gaggin, MD, MPHc,
- Margaret M. Redfield, MDd,
- Horng H. Chen, MDd,
- Susanna R. Stevens, MSe,
- Kevin J. Anstrom, PhDe,
- Marc J. Semigran, MDc,
- Peter Liu, MDf and
- James L. Januzzi Jr., MDc,∗ ()
- aVA CT Healthcare System, West Haven, Connecticut
- bYale University School of Medicine New Haven, Connecticut
- cMassachusetts General Hospital, Boston, Massachusetts
- dMayo Clinic Rochester, Minnesota
- eDuke Clinical Research Institute, Durham, North Carolina
- fUniversity of Ottawa Heart Institute, Ottawa, Ontario, Canada
- ↵∗Reprint requests and correspondence to:
Dr. James L. Januzzi Jr., Department of Cardiology/Internal Medicine, Massachusetts General Hospital, 32 Fruit Street, Yawkey 5984, Boston, Massachusetts 02114.
Objectives This study sought to investigate relationships between insulin-like growth factor–binding protein-7 (IGFBP7) and parameters of diastolic function or functional capacity in patients with heart failure and preserved ejection fraction (HFpEF) who were randomized to receive sildenafil or placebo.
Background IGFBP7 was previously found to be associated with diastolic function in heart failure with reduced ejection fraction, but it is unclear whether these associations are present in HFpEF.
Methods At baseline and 24 weeks, IGFBP7, imaging studies, and peak oxygen consumption (Vo2max) were obtained and compared in 160 patients with HFpEF who were randomized to receive sildenafil or placebo.
Results Patients with supramedian baseline IGFBP7 concentrations were older, had signs of systemic congestion and worse renal function, and had higher concentrations of prognostic heart failure biomarkers including amino-terminal pro-B-type natriuretic peptide (p < 0.05). Higher baseline IGFBP7 was modestly correlated with worse diastolic function: higher E velocity (Spearman correlation [ρ] = 0.40), E/E′ (ρ = 0.40), left atrial volume index (ρ = 0.39), and estimated right ventricular systolic pressure (ρ = 0.41; all p < 0.001) and weakly correlated with transmitral E/A (ρ = 0.26; p = 0.006). Notably, change in IGFBP7 was significantly correlated with change in E, E/A, E/E′, and right ventricular systolic pressure. Elevated baseline IGFBP7 was associated with lower baseline Vo2max (13.2 vs. 11.1 ml/min/kg; p < 0.001), and change in IGFBP7 was weakly inversely correlated with change in Vo2max (ρ = −0.19; p = 0.01). Subjects receiving sildenafil had a decrease in IGFBP7 over 24 weeks, in contrast to placebo-treated patients (median change in IGFBP7 −1.5 vs. +13.6 ng/ml; p < 0.001).
Conclusions In patients with HFpEF, IGFBP7 may be a novel biomarker of diastolic function and exercise capacity.
- diastolic function
- heart failure with preserved ejection fraction
- insulin-like growth factor–binding protein 7
Dr. Gandhi is supported by the Dennis and Marilyn Barry Fellowship in Cardiology. Dr. Gaggin is supported in part by the Clark Fund for Cardiac Research Innovation; has received grant support from Roche and Portola; has received consulting income from Roche Diagnostics, American Regent, Boston Heart Diagnostics, Critical Diagnostics, and Amgen; and has received research payments for clinical endpoint committees for EchoSense. Dr. Januzzi has received grants and consulting fees from Roche; grants from Singulex and Prevencio; consulting fees from Critical Diagnostics, Sphingotec, and Philips; was a member of the Data and Safety Monitoring Board of Amgen; received consulting and Clinical Events Committee fees from Novartis, Boeringer Ingelheim, and Janseen; and is supported in part by the Hutter Family Professorship in Medicine in the Field of Cardiology. Dr. Liu has received peer-reviewed research grants from Genome Canada, with which Roche Diagnostics is a partner. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
John R. Teerlink, MD, served as Guest Editor for this paper.
- Received February 11, 2016.
- Revision received July 25, 2016.
- Accepted August 10, 2016.
- American College of Cardiology Foundation