Article Text

Dynamic changes in left ventricular function on exercise in heart failure with preserved ejection fraction: the role of myocardial energy deficiency
  1. TT Phan1,
  2. K Abozguia1,
  3. G Nallur Shivu1,
  4. M Gnanadevan1,
  5. I Ahmed1,
  6. L Williams1,
  7. G Dwivedi1,
  8. K Patel1,
  9. P Steendijk2,
  10. H Ashrafian3,
  11. A Henning4,
  12. MP Frenneaux1
  1. 1University of Birmingham, Birmingham, UK
  2. 2Leiden University Medical Center, Leiden, The Netherlands,
  3. 3University of Oxford, Oxford, UK,
  4. 4Swiss Federal Institute of Technology Zurich (ETH), Zurich, Switzerland


Background Patients with heart failure with preserved ejection fraction (HFpEF) have dyspnoea on exertion and limited exercise capacity. In this study we evaluated the role of exercise-related changes in left ventricular relaxation and of vasculoventricular coupling (VVC) as the mechanism of this limitation and whether cardiac energetic impairment may underlie these abnormalities.

Methods We prospectively studied 37 patients with HFpEF. All had signs and/or symptoms of heart failure and a normal ejection fraction (>50%). Twenty age and gender-matched healthy volunteers were also studied. VVC and left ventricular filling characteristics were assessed at rest and on exercise by multiple uptake gated acquisition scan, and time to peak filling (nTTPF) was corrected for the RR interval (an indirect measure of the rate of left ventricular active relaxation) was derived. In vivo myocardial energetic state was assessed by 31P magnetic resonance spectroscopy at 3 Tesla. All subjects also underwent metabolic exercise testing, pulmonary function test and echocardiography.

Results nTTPF and the VVC ratio were similar in patients and controls. The cardiac phosphocreatine/adenosine triphosphate ratio was lower in patients than controls (1.57 ± 0.52 and 2.09 ± 0.62, respectively, p = 0.006). Peak maximum oxygen consumption (Vo2max) was lower in patients compared with controls (19 ± 4 ml/kg per minute and 36 ± 8 ml/kg per minute, respectively, p<0.001). During maximal exercise the increase in heart rate was lower in patients than controls (52 ± 16 and 81 ± 14 bpm, respectively, p<0.001) and the relative increases in stroke volume and cardiac output during submaximal exercise were lower in patients than controls (0.99 ± 0.34 vs 1.29 ± 0.48, p = 0.02; 1.36 ± 0.45 vs 2.25 ± 0.69, p<0.001). Whereas nTTPF fell during exercise in controls it paradoxically lengthened in patients (−0.03 ± 12 s and +0.07 ± 0.11 s, respectively, p = 0.005). The VVC ratio decreased on exercise in controls but was essentially unchanged in patients (−0.01 ± 0.15 and −0.25 ± 0.19, respectively, p<0.001). Heart rate, VVC ratio and nTTPF were independent predictors of peak Vo2max (mean ± SD) (see fig).

Abstract 114 Figure

Variables correlating with aerobic exercise capacity (maximum oxygen consumption; Vo2max). (A) Vo2max correlated negatively with exercise-induced changes in time to peak filling. (B) Vo2max correlated negatively with exercise-induced changes in the vasculoventricular coupling ratio. (C) Vo2max correlated directly with exercise-induced changes in heart rate. Black circles indicate patients with heart failure with preserved ejection fraction and open circles represents healthy controls. When patents on beta-blockers were excluded from analysis, the levels of significance were similar.

Conclusions Patients with HFpEF have abnormal cardiac energetic status that may underlie the marked dynamic slowing of left ventricular active relaxation and abnormal VVC on exercise. The latter two variables together with heart rate response on exercise are significant independent predictors of exercise capacity.

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