Quarterly Focus Issue: Heart Failure
Heart Failure With Preserved Ejection Fraction
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

https://doi.org/10.1016/j.jacc.2009.05.012Get rights and content
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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 31P 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.

Key Words

heart failure
diastole
radionuclide ventriculography
spectroscopy
exercise

Abbreviations and Acronyms

ATP
adenosine triphosphate
HFpEF
heart failure with preserved ejection fraction
HR
heart rate
LV
left ventricular
LVEF
left ventricular ejection fraction
MRS
magnetic resonance spectroscopy
nTTPF
time to peak left ventricular filling
PCr
creatine phosphate
PKA
protein kinase A
SVI
stroke volume index
TDI
tissue Doppler imaging
TnI
troponin I
VO2max
maximal oxygen uptake
VVC
vasculoventricular coupling

Cited by (0)

Prof. Frenneaux is an advisory consultant to Medtronic, Biotronik, and St. Jude. He has received honoraria for attending consultancy meetings and has applied for a method of use patent for the use of Perhexiline in heart failure.