title: Heart rate response to exercise in heart failure patients: The prognostic role of metabolic-chronotropic relation and heart rate recovery.
abstract: BACKGROUND
  The dynamics of the sinus node response to exercise is linked to functional capacity and outcome in heart failure (HF). The goal of the work was to analyze determinants and impacts of cardio-acceleration, described by the concept of metabolic-chronotropic relation (MCR) and of cardio-deceleration, described by heart rate recovery (HRR).
  
  
  METHODS
  A cohort of 25 healthy controls and 78 patients with advanced systolic HF and optimized medical and/or device therapy (97% receiving beta-blockers, 54% ICD) underwent maximal cardiopulmonary exercise test and were prospectively followed.
  
  
  RESULTS
  HF patients had impaired exercise performance compared with controls (pVO215±4 vs. 29±7ml.kg-1.min-1, p<0.0001) and lower both MCR slope (0.54±0.24 vs. 0.90±0.15, p<0.0001) and HRR (14.7±7.9 vs. 18.3±4.2min-1, p=0.03). In HF patients, MCR slope was inversely associated with beta-blocker dose (r=-0.24), NYHA class (r=-0.28) and HF duration (r=-0.25), whereas HRR with estimated glomerular filtration rate (eGFR, r=0.39), age (r=-0.28) and BMI (r=-0.31, all p<0.05). During a follow-up of 1269±933days, 64% patients experienced an adverse outcome (death, urgent transplantation, left ventricular assist device implantation). Those patients had higher NT-proBNP (p=0.02), worse left ventricular systolic function (LVEF, p=0.03) and lower MCR slope (p=0.02) but not HRR (p=0.19). MCR slope (but not HRR) was a significant outcome predictor (p=0.02 for Cox unadjusted model) even after adjustment for LVEF, serum natrium, systolic blood pressure, eGFR and NT-proBNP (p=0.04).
  
  
  CONCLUSIONS
  MCR slope is associated with different clinical variables than HRR. Compared to HRR, MCR slope provides significant prognostic information in HF patients.
authors.affiliation: Department of Cardiology, Institute for Clinical and Experimental Medicine-IKEM, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Hajdusek
authors.affiliation: Department of Cardiology, Institute for Clinical and Experimental Medicine-IKEM, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Kotrc
authors.affiliation: Department of Cardiology, Institute for Clinical and Experimental Medicine-IKEM, Prague, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Kautzner
authors.affiliation: Department of Cardiology, Institute for Clinical and Experimental Medicine-IKEM, Prague, Czech Republic.
authors.forename: Vojtech
authors.initials: V
authors.lastname: Melenovsky
authors.affiliation: Institute for History of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Benesova
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Petr
authors.initials: P
authors.lastname: Jarolim
authors.affiliation: Department of Cardiology, Institute for Clinical and Experimental Medicine-IKEM, Prague, Czech Republic. Electronic address: jan.benes@ikem.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Benes
mesh_terms: D015415:Biomarkers / Q000097:blood*; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test / Q000379:methods*; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011379:Prognosis; D011446:Prospective Studies; D020127:Recovery of Function; D012964:Sodium / Q000097:blood; D013599:Systole; D013997:Time Factors; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D012964:Sodium
keywords: Cardiopulmonary exercise testing; Heart failure; Heart rate recovery; Metabolic–chronotropic relation; Prognosis