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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

Thanh T. Phan, MB, ChB (Hons)^_*,_*, Khalid Abozguia, MBBCh^_*, Ganesh Nallur Shivu, MBBS^_*, Gnanadevan Mahadevan, MBBS^_*, Ibrar Ahmed, MB, ChB^_*, Lynne Williams, MB, ChB^_*, Girish Dwivedi, MBBS^_*, Kiran Patel, PhD^_*, Paul Steendijk, PhD, Houman Ashrafian, MA, Anke Henning, PhD and Michael Frenneaux, MD^_*

^_* Department of Cardiovascular Medicine, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, United Kingdom
Leiden University Medical Center, Leiden, the Netherlands
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

Manuscript received December 26, 2008; revised manuscript received April 20, 2009, accepted May 5, 2009.

^_* Address reprint requests and correspondence: Dr. Thanh T. Phan, Department of Cardiovascular Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom (Email: ttpquang{at}hotmail.com).

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

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