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August 17, 2026Journal of the American College of Cardiology340 citations

Heart Failure With Preserved Ejection Fraction Is Characterized by Dynamic Impairment of Active Relaxation and Contraction of the Left Ventricle on Exercise and Associated With Myocardial Energy Deficiency

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KAKhalid AbozguiaGSGanesh Nallur ShivuGMGnanadevan Mahadevan

Key Result

Patients with HFpEF exhibited a reduced cardiac creatine phosphate/adenosine triphosphate ratio compared to controls (1.57 vs 2.14; p=0.003) and dynamic slowing of LV active relaxation during exercise.

Key Points

  • To determine how exercise alters left ventricular relaxation, contractile function, and vasculoventricular coupling in patients with HFpEF, and to evaluate resting myocardial energetic status.
  • Assessed 37 patients with HFpEF and 20 control subjects at rest and during exercise.
  • Measured vasculoventricular coupling (VVC) and normalized time to peak left ventricular filling (nTTPF) using radionuclide ventriculography.
  • Evaluated myocardial energetic status via creatine phosphate to adenosine triphosphate (PCr/ATP) ratio using 31P magnetic resonance spectroscopy at 3-T.
  • Resting cardiac PCr/ATP ratio was significantly lower in HFpEF patients compared to controls (1.57 ± 0.52 vs. 2.14 ± 0.63, p = 0.003), demonstrating depleted energy reserves.
  • During exercise, nTTPF prolonged in HFpEF but shortened in controls (+0.07 ± 0.11 s vs. -0.03 ± 0.12 s, p = 0.005), and VVC failed to decline in HFpEF compared to controls (-0.01 ± 0.15 vs. -0.25 ± 0.19, p < 0.001).
  • HFpEF patients exhibited reduced peak oxygen uptake (19 ± 4 vs. 36 ± 8 ml/kg/min, p < 0.001) and attenuated exercise-to-rest cardiac output increase (1.36 ± 0.45 vs. 2.13 ± 0.72, p < 0.001).

Study Design

Type

Case-Control (n=57)

Structured PICO

Do patients with HFpEF exhibit impaired myocardial energetics and abnormal exercise-related changes in LV relaxation and vasculoventricular coupling compared to controls?

P
Population
37 patients with HFpEF and 20 control subjects assessed for left ventricular relaxation, vasculoventricular coupling, and myocardial energetic status at rest and during exercise.
E
Exposure
Exercise testing with radionuclide ventriculography and 31P magnetic resonance spectroscopy
C
Comparator
Control subjects
O
Outcome
Exercise-related changes in left ventricular (LV) relaxation (time to peak LV filling [nTTPF]), vasculoventricular coupling (VVC), and myocardial energetic status (creatine phosphate/adenosine triphosphate ratio)surrogate

Patients with HFpEF exhibit reduced cardiac energetic reserve, which may explain the dynamic impairment of LV active relaxation and abnormal vasculoventricular coupling observed during exercise.

Main Result

Absolute Event Rate: 1.57% vs 2.14%

p-value: p=0.003

Abstract

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.

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Cite This Study

Abozguia et al. (2009) conducted a case-control in Heart failure with preserved ejection fraction (HFpEF) (n=57). Heart failure with preserved ejection fraction (HFpEF) vs. Control subjects was evaluated on Cardiac energetic status (creatine phosphate/adenosine triphosphate ratio) (p=0.003). Patients with HFpEF exhibited a reduced cardiac creatine phosphate/adenosine triphosphate ratio compared to controls (1.57 vs 2.14; p=0.003) and dynamic slowing of LV active relaxation during exercise.

synapsesocial.com/papers/6a829fed4ebdac16ce2268cdhttps://doi.org/10.1016/j.jacc.2009.05.012
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