Diastolic dysfunction beyond distensibility: adverse effects of ventricular dilatation.

Diastolic function has conventionally been assessed on the basis of the LV end-diastolic pressure-volume relation (Figure 1). A shift of this curve upward and to the left (curve A, Figure 1) has been considered to be the hallmark of diastolic dysfunction. In this situation, each LV end-diastolic volume is associated with a higher end-diastolic pressure, and therefore, the ventricle is less distensible. In contrast, in dilated cardiomyopathy, the LV end-diastolic pressure-volume relation is shifted substantially to the right (curve B, Figure 1). In this situation, each volume is associated with a lower pressure; thus, the ventricle is more distensible. This has been interpreted as indicating there is enhanced diastolic function. However, patients with dilated cardiomyopathy have abnormal LV filling dynamics, elevated left atrial pressure, and an inability to increase stroke volume without further elevation of left atrial pressure. The severity of heart failure and prognosis are related to the severity of the filling abnormalities regardless of ejection fraction.1 Why are measures of LV diastolic function so abnormal in a dilated ventricle with enhanced distensibility? Is this merely a manifestation of overfilling of the LV that has displaced the operating point to a portion of the pressure-volume relation at which the chamber stiffness ( P/ V) is high?2 Understanding the answer to this question and the contribution of Yotti et al,3 in this week’s issue of Circulation, requires additional consideration of the dynamics of LV filling. Although the LV end-diastolic pressure-volume relation describes the passive properties of the LV, LV diastolic filling is not a passive or slow process. In fact, the peak flow rate across the mitral valve is equal to or greater than the peak flow rate across the aortic valve. This rapid movement of blood flow into the LV in early diastole is due to a pressure gradient from the left atrium to the LV apex. During LV ejection, energy is stored as the myocytes are compressed and the elastic elements in the LV wall are compressed and twisted.4 Relaxation of myocardial contraction allows this energy to be released as the elastic elements recoil. This causes LV pressure to fall rapidly during isovolumetric relaxation. Furthermore, for the first 30 to 40 ms after mitral valve opening, the relaxation of LV wall tension is normally rapid enough to cause LV pressure to fall despite an increase in LV volume.5 This fall in LV pressure produces an early diastolic pressure gradient from the left atrium that extends to the LV apex.6 This accelerates blood out of the left atrium and produces rapid early diastolic flow that quickly propagates to the LV apex. Because the diastolic intraventricular pressure gradient pulls blood to the apex, it can be considered a measure of LV suction. It is reduced in experimental models of heart failure4,7 and ischemia8 and in patients with ischemia9 and hypertrophic cardiomyopathy.10 The rate of early LV filling is determined by the pressure gradient from the left atrium to the LV apex.5 Although peak filling occurs after the peak pressure gradient, the 2 are closely related. The lower the early diastolic LV pressures, the greater the gradient for filling, which allows the heart to function at low left atrial pressures. Furthermore, the ability to decrease LV early diastolic pressures in response to stress allows an increase in LV stroke volume without much increase in left atrial pressure.7 This ability to increase LV filling without an increase in left atrial pressure is reduced or absent in heart failure.7,11 After the filling of the LV begins, the pressure gradient from the left atrium to the LV apex decreases and then transiently reverses. The reversed mitral valve pressure gradient decelerates and then stops the rapid flow of blood into the LV early in diastole. The time for flow deceleration is determined predominately by LV chamber stiffness and provides a noninvasive measure of stiffness.12–14 During the midportion of diastole (diastasis), the pressure in the left atrium and LV equilibrates, and mitral flow nearly ceases. Late in diastole, atrial contraction produces a second left atrium–to-LV pressure gradient that again propels blood into the LV. After atrial systole, as the left atrium relaxes, its pressure decreases below LV pressure, which causes the mitral valve to begin closing. The onset of ventricular systole produces a rapid increase in LV pressure that seals the mitral valve and ends diastole. Under normal circumstances, more than two thirds of the stroke volume enters the LV during early diastole. The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association. From the Section of Cardiology, Wake Forest University School of Medicine, Winston-Salem, NC. Correspondence to William C. Little, MD, Cardiology Section, Wake Forest University School of Medicine, Medical Center Blvd, WinstonSalem, NC 27157-1045. E-mail [email protected] (Circulation 2005;112:2888-2890.) © 2005 American Heart Association, Inc.