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STATE-OF-THE-ART PAPER

Heart Failure With Normal Left Ventricular Ejection Fraction

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    = time constant of the isovolemic left ventricular pressure decline

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