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OBJECTIVES: We sought to evaluate the role of exercise-related changes in left ventricular (LV) relaxation and of LV contractile function and vasculoventricular coupling (VVC) in the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and to assess myocardial energetic status in these patients. BACKGROUND: To date, no studies have investigated exercise-related changes in LV relaxation and VVC as well as in vivo myocardial energetic status in patients with HFpEF. METHODS: We studied 37 patients with HFpEF and 20 control subjects. The VVC and time to peak LV filling (nTTPF, a measure of LV active relaxation) were assessed while patients were at rest and during exercise by the use of radionuclide ventriculography. Cardiac energetic status (creatine phosphate/adenosine triphosphate ratio) was assessed by the use of (31)P magnetic resonance spectroscopy at 3-T. RESULTS: When patients were at rest, nTTPF and VVC were similar in patients with HFpEF and control subjects. The cardiac creatine phosphate/adenosine triphosphate ratio was reduced in patients with HFpEF versus control subjects (1.57 +/- 0.52 vs. 2.14 +/- 0.63; p = 0.003), indicating reduced energy reserves. Peak maximal oxygen uptake and the increase in heart rate during maximal exercise were lower in patients with HFpEF versus control subjects (19 +/- 4 ml/kg/min vs. 36 +/- 8 ml/kg/min, p < 0.001, and 52 +/- 16 beats/min vs. 81 +/- 14 beats/min, p < 0.001). The relative changes in stroke volume and cardiac output during submaximal exercise were lower in patients with HFpEF versus control subjects (ratio exercise/rest: 0.99 +/- 0.34 vs. 1.25 +/- 0.47, p = 0.04, and 1.36 +/- 0.45 vs. 2.13 +/- 0.72, p < 0.001). The nTTPF decreased during exercise in control subjects but increased in patients with HFpEF (-0.03 +/- 12 s vs. +0.07 +/- 0.11 s; p = 0.005). The VVC decreased on exercise in control subjects but was unchanged in patients with HFpEF (-0.01 +/- 0.15 vs. -0.25 +/- 0.19; p < 0.001). CONCLUSIONS: Patients with HFpEF have reduced cardiac energetic reserve that may underlie marked dynamic slowing of LV active relaxation and abnormal VVC during exercise.

Original publication




Journal article


J Am Coll Cardiol

Publication Date





402 - 409


Aged, Case-Control Studies, Energy Metabolism, Exercise, Female, Heart Failure, Humans, Male, Middle Aged, Myocardial Contraction, Stroke Volume, Ventricular Dysfunction, Left