title: Contributions of Nondiastolic Factors to Exercise Intolerance in Heart Failure With Preserved Ejection Fraction.
abstract: BACKGROUND
  Heart failure with preserved ejection fraction (HFpEF) has a complex etiology. Factors responsible for development of impaired exercise tolerance and disease progression are incompletely defined.
  
  
  OBJECTIVE
  The authors sought to define the contributions of contractile reserve, ventriculo-arterial coupling (VAC) reserve, and chronotropic response to the progression of HFpEF.
  
  
  METHODS
  We performed echocardiography at rest and immediately post-cardiopulmonary exercise test in 207 patients (63 ± 8 years of age) with stage C heart failure (HF) (exertional dyspnea, New York Heart Association functional class II to III, exercise capacity <80% of normal, left ventricular ejection fraction >50%, and diastolic dysfunction) and 60 patients with stage B HF (normal exercise tolerance with left ventricular hypertrophy, and/or reduced global longitudinal strain, with diastolic dysfunction).
  
  
  RESULTS
  Symptomatic patients were grouped as stage C1 (ratio of peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity [E/e'] <13 both at rest and exercise; n = 63), C2 (E/e' >13 only at exercise; n = 118), and C3 (E/e' >13 both at rest and exercise; n = 26) HF. Exercise capacity and cardiovascular functional reserve were less impaired in stage C1 than in stages C2 and C3. Chronotropic response was more disturbed in stage C3 than C1 and C2. Changes from rest to exercise in E/e' (-0.6 ± 1.7 vs. 3.7 ± 2.8; p < 0.0001), global longitudinal strain (2.9 ± 2.0 vs. 1.6 ± 2.8; p < 0.002), VAC (-0.21 ± 0.17 vs. -0.09 ± 0.15; p < 0.0001), and in VO2-HR gradient (0.30 ± 0.07 vs. 0.26 ± 0.11; p < 0.01) were significantly different in stages B and C.
  
  
  CONCLUSIONS
  Normal E/e' response to exertion in symptomatic HFpEF is associated with less profound impairment of exercise capacity and is accompanied by derangements of contractile state and VAC. The transition from asymptomatic to overt HFpEF is linked to diastolic, systolic, and chronotropic deficits and an increasing degree of hemodynamic disturbances in stage C HF.
authors: Cardiology Department, Wroclaw Medical University, Wroclaw, Poland; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
authors: Wojciech
authors: W
authors: Kosmala
authors: Cardiology Department, Wroclaw Medical University, Wroclaw, Poland.
authors: Aleksandra
authors: A
authors: Rojek
authors: Cardiology Department, Wroclaw Medical University, Wroclaw, Poland.
authors: Monika
authors: M
authors: Przewlocka-Kosmala
authors: Cardiology Department, Wroclaw Medical University, Wroclaw, Poland.
authors: Andrzej
authors: A
authors: Mysiak
authors: Cardiology Department, Wroclaw Medical University, Wroclaw, Poland.
authors: Bozena
authors: B
authors: Karolko
authors: Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia. Electronic address: tom.marwick@utas.edu.au.
authors: Thomas H
authors: TH
authors: Marwick
mesh_terms: D003430:Cross-Sectional Studies; D003971:Diastole; D004452:Echocardiography; D005080:Exercise Test; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption; D011446:Prospective Studies; D013318:Stroke Volume / Q000502:physiology*; D016277:Ventricular Function, Left / Q000502:physiology*
keywords: chronotropic reserve; diastolic dysfunction; exercise capacity