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

Abstract

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. 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. 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. 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 VO(2)max. 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.