Omar F AbouEzzeddine1, Phillip Haines2, Susanna Stevens3, Jose Nativi-Nicolau4, G Michael Felker5, Barry A Borlaug1, Horng H Chen1, Russell P Tracy6, Eugene Braunwald7, Margaret M Redfield8. 1. Department of Medicine, Mayo Clinic, Rochester, Minnesota. 2. Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 3. Department of Biostatistics and Bioinformatics, Duke Clinical Research Institute, Durham, North Carolina. 4. Department of Medicine, University of Utah Health Care, Salt Lake City, Utah. 5. Department of Medicine, Duke University Medical Center, Durham, North Carolina. 6. Department of Pathology and Biochemistry, University of Vermont, Burlington, Vermont. 7. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 8. Department of Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address: redfield.margaret@mayo.edu.
Abstract
OBJECTIVES: This study hypothesized that elevated galectin-3 (Gal-3) levels would identify patients with more advanced heart failure (HF) with preserved ejection fraction (HFpEF) as assessed by key pathophysiological domains. BACKGROUND: Gal-3 is implicated in the pathogenesis of cardiac fibrosis but is also increased with normal aging and renal dysfunction. Cardiac fibrosis may contribute to cardiac dysfunction, exercise intolerance, and congestion in HFpEF. METHODS:Two hundred eight patients from theRELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial of sildenafil in HFpEF had Gal-3 measured at enrollment. Pathophysiological domains assessed included biomarkers of neurohumoral activation, fibrosis, inflammation and myocardial necrosis, congestion severity and quality of life, cardiac structure and function, and exercise performance. Analysis adjusted for age, sex, and/or cystatin-C levels. Potential interaction between baseline Gal-3 and treatment (sildenafil) effect on the RELAX study primary endpoint (change in peak oxygen consumption) was tested. RESULTS:Gal-3 levels were associated with age and severity of renal dysfunction. Adjusting for age, sex, and/or cystatin-C, Gal-3 was not associated with biomarkers of neurohumoral activation, fibrosis, inflammation or myocardial necrosis, congestion or quality-of-life impairment, cardiac remodeling or dysfunction, or exercise intolerance. Gal-3 did not identify patients who responded to phosphodiesterase type 5 (PDE-5) inhibitors (interaction p = 0.53). CONCLUSIONS: In overt HFpEF, Gal-3 was related to severity of renal dysfunction and accounting for this, was not independently associated with severity of pathophysiological derangements or response PDE-5 inhibition. These findings underscore the need to adjust for renal function when interpreting Gal-3 levels, and call into question the value of Gal-3 to quantify disease severity in overt HFpEF.
RCT Entities:
OBJECTIVES: This study hypothesized that elevated galectin-3 (Gal-3) levels would identify patients with more advanced heart failure (HF) with preserved ejection fraction (HFpEF) as assessed by key pathophysiological domains. BACKGROUND:Gal-3 is implicated in the pathogenesis of cardiac fibrosis but is also increased with normal aging and renal dysfunction. Cardiac fibrosis may contribute to cardiac dysfunction, exercise intolerance, and congestion in HFpEF. METHODS: Two hundred eight patients from the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial of sildenafil in HFpEF had Gal-3 measured at enrollment. Pathophysiological domains assessed included biomarkers of neurohumoral activation, fibrosis, inflammation and myocardial necrosis, congestion severity and quality of life, cardiac structure and function, and exercise performance. Analysis adjusted for age, sex, and/or cystatin-C levels. Potential interaction between baseline Gal-3 and treatment (sildenafil) effect on the RELAX study primary endpoint (change in peak oxygen consumption) was tested. RESULTS:Gal-3 levels were associated with age and severity of renal dysfunction. Adjusting for age, sex, and/or cystatin-C, Gal-3 was not associated with biomarkers of neurohumoral activation, fibrosis, inflammation or myocardial necrosis, congestion or quality-of-life impairment, cardiac remodeling or dysfunction, or exercise intolerance. Gal-3 did not identify patients who responded to phosphodiesterase type 5 (PDE-5) inhibitors (interaction p = 0.53). CONCLUSIONS: In overt HFpEF, Gal-3 was related to severity of renal dysfunction and accounting for this, was not independently associated with severity of pathophysiological derangements or response PDE-5 inhibition. These findings underscore the need to adjust for renal function when interpreting Gal-3 levels, and call into question the value of Gal-3 to quantify disease severity in overt HFpEF.
Authors: G Michael Felker; Mona Fiuzat; Linda K Shaw; Robert Clare; David J Whellan; Luca Bettari; Shailesh C Shirolkar; Mark Donahue; Dalane W Kitzman; Faiez Zannad; Ileana L Piña; Christopher M O'Connor Journal: Circ Heart Fail Date: 2011-10-20 Impact factor: 8.790
Authors: Ravi V Shah; Annabel A Chen-Tournoux; Michael H Picard; Roland R J van Kimmenade; James L Januzzi Journal: Eur J Heart Fail Date: 2010-06-05 Impact factor: 15.534
Authors: W H Wilson Tang; Kevin Shrestha; Zhili Shao; Allen G Borowski; Richard W Troughton; James D Thomas; Allan L Klein Journal: Am J Cardiol Date: 2011-05-19 Impact factor: 2.778
Authors: Dirk J A Lok; Peter Van Der Meer; Pieta W Bruggink-André de la Porte; Erik Lipsic; Jan Van Wijngaarden; Hans L Hillege; Dirk J van Veldhuisen Journal: Clin Res Cardiol Date: 2010-02-04 Impact factor: 5.460
Authors: John G F Cleland; John J V McMurray; John Kjekshus; Jan H Cornel; Peter Dunselman; Cândida Fonseca; Ake Hjalmarson; Jerzy Korewicki; Magnus Lindberg; Naresh Ranjith; Dirk J van Veldhuisen; Finn Waagstein; Hans Wedel; John Wikstrand Journal: J Am Coll Cardiol Date: 2009-11-10 Impact factor: 24.094
Authors: Hendrik Milting; Peter Ellinghaus; Michael Seewald; Hamdin Cakar; Birte Bohms; Astrid Kassner; Reiner Körfer; Martina Klein; Thomas Krahn; Lothar Kruska; Aly El Banayosy; Frank Kramer Journal: J Heart Lung Transplant Date: 2008-06 Impact factor: 10.247
Authors: Rudolf A de Boer; Dirk J A Lok; Tiny Jaarsma; Peter van der Meer; Adriaan A Voors; Hans L Hillege; Dirk J van Veldhuisen Journal: Ann Med Date: 2010-12-28 Impact factor: 4.709
Authors: Benjamin W Van Tassell; Leo F Buckley; Salvatore Carbone; Cory R Trankle; Justin M Canada; Dave L Dixon; Nayef Abouzaki; Claudia Oddi-Erdle; Giuseppe Biondi-Zoccai; Ross Arena; Antonio Abbate Journal: Clin Cardiol Date: 2017-05-05 Impact factor: 2.882
Authors: Michael R Zile; Pardeep S Jhund; Catalin F Baicu; Brian L Claggett; Burkert Pieske; Adriaan A Voors; Margaret F Prescott; Victor Shi; Martin Lefkowitz; John J V McMurray; Scott D Solomon Journal: Circ Heart Fail Date: 2016-01 Impact factor: 8.790
Authors: Ravi B Patel; Rupal Mehta; Margaret M Redfield; Barry A Borlaug; Adrian F Hernandez; Sanjiv J Shah; Ruth F Dubin Journal: J Card Fail Date: 2020-01-11 Impact factor: 5.712
Authors: Baris Afsar; Patrick Rossignol; Loek van Heerebeek; Walter J Paulus; Kevin Damman; Stephane Heymans; Vanessa van Empel; Alan Sag; Alan Maisel; Mehmet Kanbay Journal: Heart Fail Rev Date: 2017-11 Impact factor: 4.214
Authors: Marat Fudim; Jacob P Kelly; Aaron D Jones; Omar F AbouEzzeddine; Andrew P Ambrosy; Stephen J Greene; Yogesh N V Reddy; Kevin J Anstrom; Brooke Alhanti; Gregory D Lewis; Adrian F Hernandez; G Michael Felker Journal: Am Heart J Date: 2019-11-16 Impact factor: 4.749
Authors: Joerg C Schefold; Gerasimos Filippatos; Gerd Hasenfuss; Stefan D Anker; Stephan von Haehling Journal: Nat Rev Nephrol Date: 2016-08-30 Impact factor: 28.314
Authors: Michael S Sabbah; Ahmed U Fayyaz; Simon de Denus; G Michael Felker; Barry A Borlaug; Surendra Dasari; Rickey E Carter; Margaret M Redfield Journal: Circ Heart Fail Date: 2020-07-29 Impact factor: 8.790