Pathophysiology and Natural History Valvuiar Heart Disease

The new concept of systolic myocardial stiffness was applied to the study of ejection mechanics in aortic valve disease. Frame-by-frame analysis of stress (a) and volume (V) was performed for two differently loaded beats in 26 patients who underwent simultaneous cineangiography and micromanometry: nine normal subjects, eight with isolated aortic regurgitation (AR), and nine with aortic stenosis (AS). Maximum myocardial stiffness (maxEaJ) was defined as the slope of the endsystolic (es) stress-strain relationship. End-systole was defined as the frame where stiffness was maximal, and strain was defined as E = loge (Dm/Dom), where Dm is left ventricular midwall diameter and Do. is the theoretical Dm at zero stress. Expressed in terms of cavity volume, E = y log, (V/V0), where y is the geometric factor relating Dm to V during systole. V. was obtained by extrapolating to Ces 0 the function, ces = maxEay, y*loge (Ves/Vo), which was fit to the end-systolic data. VO always had a value greater than zero. MaxEav was preserved in the AR group (1575 ± 565) and increased in the AS group (1877 ± 544; p = .02) compared with normal (1320 ± 268), suggesting maintenance of contractile force per unit of myocardium in these two lesions. However, theoretical "unloaded" shortening fraction (SFO) was depressed in the AS group (0.30 ± 0.06; p = .01) compared with normal (0.37 ± 0.04), preserved in the AR group (0.34 + 0.07; p = .24), and inversely related to maxEav (r .66, p .01), suggesting a disparity between shortening potential and force potential. Systolic csV profiles had a characteristic pattern in the presence of AS when ejection fraction was normal, with stiffness approaching maximum earlier in ejection than in normal subjects or in the AR group. This difference in early systolic myocardial stiffness might be caused by ventricular resistance arising from different velocity profiles or from different aortic outflow resistance. Circulation 75, No. 5, 964-972, 1987. THE INOTROPIC STATE of hypertrophied human left ventricles has been assessed by various methods with differing results. Although the nature of the hypertrophy and the inciting stimulus may be important,1 methodologic differences may account for some of the disparities, since most of the methods previously used are limited by their load dependence. The inotropic state of normal canine left ventricles has been assessed by the systolic elastance model.' According to this model, active stiffening of the ventricular chamber during systole reflects, in part, the time course of myofilament activation3 and can be expressed as E (t) = P (t)/[V (t)-V.], where E (t), P (t), From the Veterans Administration and University of Kentucky Medical Centers, Lexington. Supported in part by a grant from the American Heart Association, Kentucky Affiliate. Address for correspondence: Thomas Wisenbaugh, M.D. MN 670 Cardiovascular Division, University of Kentucky Medical Center, 800 Rose St., Lexington, KY 40536. Received May 16, 1986; revision accepted Feb. 12, 1987. Presented in part at the 59th Scientific Session of the American Heart Association, Dallas, November 1986. and V (t) are the instantaneous values of chamber elastance, pressure, and volume, respectively. V. is the theoretical volume at zero total pressure (active plus passive) and can be derived from linear regression of P (tm.. ) against V (t.0) for differently loaded beats, where tmax is the time of maximal elastance near end ejection.2 Although the instantaneous pressure-volume relationship may be influenced by the extent and velocity of ejection4 and by the aortic input impedence,5 the Emax of the ventricle at end-systole is determined largely by inotropic state and not by circumstances earlier in the beat such as end-diastolic volume or the dynamics of the afterload.5'6 Although Emax is sensitive to short-term changes in inotropic state and relatively insensitive to short-term changes in load, its sensitivity to size7 confounds any comparison of function between normal and hypertrophied ventricles. It has therefore been suggested that stress-strain analysis is preferable to pressure-volume analysis for comparing stiffness between ventricles of different size, since stress effectively normalizes for CIRCULATION 964 by gest on M ay 1, 2017 http://ciajournals.org/ D ow nladed from PATHOPHYSIOLOGY AND NATURAL HISTORY-VALVULAR HEART DISEASE the influence of wall thickness on pressure, and strain normalizes for differences in volume.8 The primary goal of this study was to examine myocardial function in aortic valve disease using the new concept of systolic myocardial stiffness8 as derived from stress-strain analysis. A secondary objective was to examine the influence of aortic valve disease on the dynamics of systolic myocardial stiffness by analyzing stress-strain data frame by frame throughout systole.