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J Am Coll Cardiol, 2009; 53:905-918, doi:10.1016/j.jacc.2008.12.007
© 2009 by the American College of Cardiology Foundation
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STATE-OF-THE-ART PAPER

Heart Failure With Normal Left Ventricular Ejection Fraction

Micha T. Maeder, MD and David M. Kaye, MD, PhD*

Heart Failure Research Group, Baker IDI Heart and Diabetes Institute, and Heart Center, Alfred Hospital, Melbourne, Australia

Manuscript received July 29, 2008; revised manuscript received December 2, 2008, accepted December 8, 2008.

* Reprint requests and correspondence: Prof. David M. Kaye, Cardiology and Therapeutics Division, Baker IDI Heart and Diabetes Institute, P.O. Box 6492, St Kilda Road, Central Melbourne 8008 VIC, Australia (Email: David.kaye{at}bakeridi.edu.au).

It is estimated that approximately 50% of the heart failure population has a normal left ventricular ejection fraction, a complex broadly referred to as heart failure with normal left ventricular ejection fraction (HFNEF). While these patients have been considered in epidemiologic studies and clinical trials to represent a single pool of patients, limited more detailed studies indicate that HFNEF patients are a very heterogeneous group, with a number of key pathophysiologic mechanisms. This review summarizes and critically analyzes available data on the pathophysiology of HFNEF, placing it into context with a recently developed diagnostic algorithm. We evaluate the utility of commonly applied echocardiographic measures and biomarkers and integrate mechanistic observations into potential future therapeutic directions.

Key Words: heart failure • normal ejection fraction • diastolic function • pathophysiology • diagnosis

Abbreviations and Acronyms
  ATP = adenosine triphosphate
  β = left ventricular passive stiffness constant
  BNP = B-type natriuretic peptide
  E' = early diastolic peak mitral annulus velocity assessed by pulse-waved tissue Doppler
  E/E' = transmitral peak velocity during early relaxation to early diastolic peak mitral annulus velocity
  HF = heart failure
  HFNEF = heart failure with normal left ventricular ejection fraction
  LV = left ventricle/ventricular
  LVEDP = left ventricular end-diastolic pressure
  LVEF = left ventricular ejection fraction
  NT-proBNP = N-terminal pro-B-type natriuretic peptide
  NYHA = New York Heart Association
  {tau} = time constant of the isovolemic left ventricular pressure decline


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