Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

Peak rapid filling rate (PRFR) is often used clinically as an index of left ventricular relaxation, i.e., of early diastolic function. This study tests the hypothesis that early filling rate is a function of the atrioventricular pressure difference and hence is influenced by the left atrial pressure as well as by the rate of left ventricular relaxation. As indexes, we chose the left atrial pressure at the atrioventricular pressure crossover (PCO), and the time constant (T) of an assumed exponential decline in left ventricular pressure. We accurately determined the magnitude and timing of filling parameters in conscious dogs by direct measurement of phasic mitral flow (electromagnetically) and high-fidelity chamber pressures. To obtain a diverse hemodynamic data base, loading conditions were changed by infusions of volume and angiotensin LI. The latter was administered to produce a change in left ventricular pressure of less than 35% (A-1) or a change in peak left ventricular pressure of greater than 35% (A-2). PRFR increased with volume loading, was unchanged with A-1, and was decreased with A-2; T and PCO increased in all three groups (p < .005 for all changes). PRFR correlated strongly with the diastolic atrioventricular pressure difference at the time of PRFR (r = .899, p < .001) and weakly with both T (r = .369, p < .01) and PCO (r = .601, p < .001). The correlation improved significantly when T and PCO were both included in the multivariate regression (r = .797, p < .0001). PRFR is thus determined by both the left atrial pressure and the left ventricular relaxation rate and should be used with caution as an index of left ventricular diastolic function.Circulation 74, No. 1, 187-196, 1986. RELAXATION ABNORMALITIES are one of the earliest manifestations of cardiac dysfunction and frequently precede systolic dysfunction in many disease states.'' Early filling function has been evaluated in a variety of diseases, e.g., coronary artery disease, hypertrophic cardiomyopathy, hypertensive heart disease, aortic valve disease, and congestive cardiomyop-

Left ventricular (LV) diastolic pressure-volume (P-V) relations arise from a complex interplay of active decay of force (i.e., relaxation), passive elastic myocardial properties, and time-varying inflow across the mitral orifice. This study was designed to quantify the passive properties of the intact ventricle and the effects of elastic recoil by separating filling from relaxation with a method of LV volume clamping with a remote-controlled mitral valve. Eleven open-chest fentanyl-anesthetized dogs were instrumented with aortic and mitral flow probes, LV and left atrium micromanometers, and a remote-controlled mitral valve. We prevented complete (end-systolic volume clamping) or partial filling at different times in diastole. The ventricle thus relaxed completely at different volumes, and we generated P-V coordinates for the passive ventricle that included negative, as well as positive, values of pressure. We then estimated ventricular volumes from ventricular weight in eight dogs, using regression equations based on data in the literature, to determine the equilibrium volume (V0), that is, volume at zero transmural pressure, in the working ventricle. We abandoned the traditional exponential approach and characterized by the P-V relation with a logarithmic approach that included maximum LV volume (Vm), minimum volume (Vd), and stiffness parameters (Sp and Sn) for the positive (p) and negative (n) phases: Pp = -Sp In[(Vm - V)/(Vm - V0)] and Pn = Sn In[(V - Vd)/(V0 - Vd)]. With this formulation, the chamber compliance, dP/dV, is normalized by the LV operating volume, and Sp and Sn are size-independent chamber stiffness parameters with the units of stress. In eight ventricles with LV weight = 131 +/- 20 g, Vm = 116 +/- 18 ml, V0 = 37 +/- 6 ml, and Vd = 13 +/- 2 ml, stiffness Sp = 14.6 mm Hg and Sn = 5.1 mm Hg were determined from the slopes of the log-linearized equations. Also, the duration of LV relaxation is increased by the process of ventricular filling (161 +/- 31 msec, filling versus 108 +/- 36 msec, nonfilling, measured from dP/dtmin, p less than 0.0001). We conclude that volume clamping is a useful method of studying restoring forces and that the logarithmic approach is conceptually and quantitatively useful in characterizing the passive properties of the intact ventricle.

No abstract