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J Am Coll Cardiol, 2009; 54:36-46, doi:10.1016/j.jacc.2009.03.037
© 2009 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: HEART FAILURE

The Pathophysiology of Heart Failure With Normal Ejection Fraction

Exercise Echocardiography Reveals Complex Abnormalities of Both Systolic and Diastolic Ventricular Function Involving Torsion, Untwist, and Longitudinal Motion

Yu Ting Tan, MBBS*, Frauke Wenzelburger, MD*,{dagger}, Eveline Lee, MBChB{dagger}, Grant Heatlie, MBBS, PhD{dagger}, Francisco Leyva, MD*, Kiran Patel, MBBChir, PhD*, Michael Frenneaux, MD* and John E. Sanderson, MD*,*

* Department of Cardiovascular Medicine, University of Birmingham, Birmingham, United Kingdom
{dagger} University Hospital of North Staffordshire, Stoke-on-Trent, United Kingdom

Manuscript received November 18, 2008; revised manuscript received March 13, 2009, accepted March 17, 2009.

* Reprint requests and correspondence: Prof. John E. Sanderson, Department of Cardiovascular Medicine, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom (Email: j.e.sanderson{at}bham.ac.uk).

Objectives: The purpose of this study was to test the hypothesis that in heart failure with normal ejection fraction (HFNEF) exercise limitation is due to combined systolic and diastolic abnormalities, particularly involving ventricular twist and deformation (strain) leading to reduced ventricular suction, delayed untwisting, and impaired early diastolic filling.

Background: A substantial proportion of patients with heart failure have a normal left ventricular ejection fraction. Currently the pathophysiology is considered to be due to abnormal myocardial stiffness and relaxation.

Methods: Patients with a diagnosis of HFNEF and proven cardiac limitation by cardiopulmonary exercise testing were studied by standard, tissue Doppler, and speckle tracking echocardiography at rest and on submaximal exercise.

Results: Fifty-six patients (39 women; mean age 72 ± 7 years) with a clinical diagnosis of HFNEF and 27 age-matched healthy control subjects (19 women; mean age 70 ± 7 years) had rest and exercise images of sufficient quality for analysis. At rest, systolic longitudinal and radial strain, systolic mitral annular velocities, and apical rotation were lower in patients, and all failed to rise normally on exercise. Systolic longitudinal functional reserve was also significantly lower in patients (p < 0.001). In diastole, patients had reduced and delayed untwisting, reduced left ventricular suction at rest and on exercise, and higher end-diastolic pressures. Mitral annular systolic and diastolic velocities, systolic left ventricular rotation, and early diastolic untwist on exercise correlated with peak VO2max.

Conclusions: In HFNEF there are widespread abnormalities of both systolic and diastolic function that become more apparent on exercise. HFNEF is not an isolated disorder of diastole.

Key Words: diastolic • heart failure • rotation • strain • untwist

Abbreviations and Acronyms
  A' = peak late diastolic myocardial mitral annular velocity by pulse wave Doppler imaging
  Am = peak late diastolic myocardial mitral annular velocity by color tissue Doppler imaging
  DT = deceleration time
  E' = peak early diastolic myocardial mitral annular velocity by pulse wave Doppler imaging
  Em = peak early diastolic myocardial mitral annular velocity by color tissue Doppler imaging
  LV = left ventricle/ventricular
  NT-proBNP = N-terminal pro-brain natriuretic peptide
  S' = peak systolic myocardial mitral annular velocity by pulse wave Doppler imaging
  Sm = peak systolic myocardial mitral annular velocity by color tissue Doppler imaging
  VO2max = maximum oxygen consumption
  Vp = mitral flow propagation velocity


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