title: Impaired left ventricular global longitudinal strain in patients with heart failure with preserved ejection fraction: insights from the RELAX trial.
abstract: While abnormal left ventricular (LV) global longitudinal strain (GLS) has been described in patients with heart failure with preserved ejection fraction (HFpEF), its prevalence and clinical significance are poorly understood.
  
  
  
  Patients enrolled in the RELAX trial of sildenafil in HFpEF (LV ejection fraction ≥50%) in whom two-dimensional, speckle-tracking LV GLS was possible (n = 187) were analysed. The distribution of LV GLS and its associations with clinical characteristics, LV structure and function, biomarkers, exercise capacity and quality of life were assessed. Baseline median LV GLS was -14.6% (25th and 75th percentile, -17.0% and -11.9%, respectively) and abnormal (≥ - 16%) in 122/187 (65%) patients. Patients in the tertile with the best LV GLS had lower N-terminal pro-brain natriuretic peptide (NT-proBNP) [median 505 pg/mL (161, 1065) vs. 875 pg/mL (488, 1802), P = 0.008) and lower collagen III N-terminal propeptide (PIIINP) levels [median 6.7 µg/L (5.1, 8.1) vs. 8.1 µg/L (6.5, 10.5), P = 0.001] compared with the tertile with the worst LV GLS. There was also a modest linear relationship with LV GLS and log-transformed NT-proBNP and PIIINP (r = 0.29, P < 0.001 and r = 0.19, P = 0.009, respectively). We observed no linear association of LV GLS with Minnesota Living with Heart Failure scores, 6-min walk distance, peak oxygen consumption, or expiratory minute ventilation/carbon dioxide excretion slope.
  
  
  
  Impaired LV GLS is common among HFpEF patients, indicating the presence of covert systolic dysfunction despite normal LV ejection fraction. Impaired LV GLS was associated with biomarkers of wall stress and collagen synthesis and diastolic dysfunction but not with quality of life or exercise capacity, suggesting other processes may be more responsible for these aspects of the HFpEF syndrome.
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.|Department of Medicine, Duke University School of Medicine, 2400 Pratt Street, NP-8064, Durham, NC, 27705, USA.
authors.forename: Adam D
authors.initials: AD
authors.lastname: DeVore
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: McNulty
authors.affiliation: Department of Medicine, Duke University School of Medicine, 2400 Pratt Street, NP-8064, Durham, NC, 27705, USA.
authors.forename: Fawaz
authors.initials: F
authors.lastname: Alenezi
authors.affiliation: Department of Cardiology, The Heart Centre, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Ersboll
authors.affiliation: Department of Medicine, Division of Cardiology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Vader
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
authors.forename: Jae K
authors.initials: JK
authors.lastname: Oh
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Lin
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Lewis
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Semigran
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.|Department of Medicine, Duke University School of Medicine, 2400 Pratt Street, NP-8064, Durham, NC, 27705, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Anstrom
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.|Department of Medicine, Duke University School of Medicine, 2400 Pratt Street, NP-8064, Durham, NC, 27705, USA.
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Hernandez
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.|Department of Medicine, Duke University School of Medicine, 2400 Pratt Street, NP-8064, Durham, NC, 27705, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Velazquez
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D004452:Echocardiography; D017079:Exercise Tolerance / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D054143:Heart Failure, Systolic / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010101:Oxygen Consumption; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011788:Quality of Life; D012189:Retrospective Studies; D013318:Stroke Volume / Q000502:physiology*; D013997:Time Factors; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; C109794:pro-brain natriuretic peptide (1-76); C041876:procollagen Type III-N-terminal peptide; D020097:Natriuretic Peptide, Brain
keywords: Echocardiography; Heart failure; Strain