Role of Left Ventricular Stiffness in Heart Failure With Normal Ejection Fraction

Background—Increased left ventricular stiffness is a distinct finding in patients who have heart failure with normal ejection fraction (HFNEF). To elucidate how diastolic dysfunction contributes to heart failure symptomatology during exercise, we conducted a study using an invasive pressure-volume loop approach and measured cardiac function at rest and during atrial pacing and handgrip exercise. Methods and Results—Patients with HFNEF (n 70) and patients without heart failure symptoms (n 20) were enrolled. Pressure-volume loops were measured with a conductance catheter during basal conditions, handgrip exercise, and atrial pacing with 120 bpm to analyze diastolic and systolic left ventricular function. During transient preload reduction, the diastolic stiffness constant was measured directly. Diastolic function with increased stiffness was significantly impaired in patients with HFNEF during basal conditions. This was associated with increased end-diastolic pressures during handgrip exercise and with decreased stroke volume and a leftward shift of pressure-volume loops during atrial pacing. Conclusions—Increased left ventricular stiffness contributed to increased end-diastolic pressure during handgrip exercise and decreased stroke volume during atrial pacing in patients with HFNEF. These data suggest that left ventricular stiffness modulates cardiac function in HFNEF patients and suggests that diastolic dysfunction with increased stiffness is a target for treating HFNEF. (Circulation. 2008;117:2051-2060.)