SUMMARY The contractile capacity of the human ventricle when chronically pressure-overloaded by aortic stenosis remains a subject of major debate. The compensatory mechanisms used to maintain normal resting cardiac output and ejection fraction, and the relation of compensatory mechanisms to symptoms, have not been fully documented. In this report we examined ventricular performance and the relationship of compensatory mechanisms to symptoms in 11 patients with severe aortic stenosis and congestive heart failure symptoms (AS-CHF group), in 10 patients with significant aortic stenosis but no heart failure symptoms (AS-C group), and in 12 normal subjects. Alterations in afterload, preload and wall thickness in aortic stenosis may adversely affect the validity of indexes of contractile function, so we attempted to account for or avoid the effect of such alterations. The natural variations in ventricular volume were used to estimate group ventricular function relationships relating peak systolic wall stress to end-diastolic volume index (Frank-Starling), and to estimate group relationships of end-systolic pressure or stress to end-systolic volume (Sagawa). The slope of the linear regression lines that estimated the Frank-Starling index and the Sagawa index showed statistically significant depression (p < 0.01) of left ventricular contractile function in the AS-CHF patients, while ventricular contractile function was relatively normal in the AS-C patients. End-diastolic volume index and pressure were significantly increased (p < 0.01) only in the AS-CHF group. Peak systolic left ventricular wall stress, ejection fraction, resting cardiac index, and the ratio of ventricular mass to volume were not statistically different from normal in either group.ISOLATED cardiac muscle and intact animal hearts have shown decreased contractile function in the severely and acutely pressure-overloaded hypertrophied and failing heart.-.' When the pressure overload is less intense and less acute and when heart failure does not develop, ventricular performance is variable.6' 7 In experimental animals, it appears that depression of myocardial function is directly related to the severity of the overload, the presence of congestive failure and, possibly, the duration of the overload. 3,6,7 Despite these experimental studies, ventricular contractile function in patients with chronic pressure overload caused by aortic stenosis is still debated.8 17 From the limited patient studies available, it seems reasonable to postulate that ventricular contractile function is depressed when severe pressure overload has caused congestive failure, but normal when the overload is less severe and failure has not occurred.s9 11,16, 17 In this study, we tested this hypothesis by determining hemodynamic values and quantitative ventricular function measurements in three groups of patients. Patients with severe aortic stenosis and congestive heart failure symptoms were compared with

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SUMMARYPatients with prolapsing mitral leaflet syndrome (PML) frequently have chest pain of undetermined etiology. Twenty-three patients with PML underwent cardiac hemodynamic, angiographic, and metabolic studies. The latter were performed during control spontaneous heart rate and tachycardia by right atrial pacing. Myocardial supply-demand ratio (DPTI:SPTI) was estimated from the planimetric integration of the diastolic area (diastolic pressure time index = DPTI) and systolic area (systolic pressure Myocardial metabolic studies were performed during control state and right atrial pacing tachycardia.

SUMMARY Chronic pressure overload leads to hypertrophy, depressed mechanical function, and reduced myosin ATPase activity. However, it is not known whether the lowered myosin ATPase activity results from the hypertrophic process per se or whether the elevated afterload is required for the depressed myosin ATPase activity. Further, a causal relationship between lowered myosin ATPase and weakened mechanical function in pressure overload has not been established. Chronic volume overload on the myocardium, leading to hypertrophy equivalent to that in pressure overload, allows the effects of pressure overload to be separated from the effects of hypertrophy and provides insight into the association between myosin ATPase and mechanical function. We produced large atrial septal defects (ASD) with a transvenous biopsy catheter in six adult cats. This resulted in 63% right ventricular hypertrophy, normal CHRONIC pressure overload on the myocardium leads to cardiac hypertrophy and severly impaired mechanical function (Spann et al., 1967;Spann et aL, 1972;Carey et al., 1978aCarey et al., , 1978b. It also has been shown that depressed myosin ATPase activity accompanies the contractile deficit characteristic of severe afterload hypertrophy (Aras and Haas, 1962;Shiverick et al., 1976;Swynghedauw et al., 1973;Wikman-Coffelt et al., 1975b). Recently we demonstrated that myosin ATPase activity returns to normal in parallel with contractile function upon relief of the hemodynamic stress and reversal of hypertrophy (Carey et al., 1978a(Carey et al., , 1978b. Since mechanical function and myosin ATPase activities decline and recover together, one could hypothesize that decreased myosin ATPase activity and the decreased contractile function in hypertrophy and congestive heart failure are causally related. Conversely, normal contractile function is associated with volume overload-induced hypertrophy of a magnitude equal to that observed in pressure overload (Cooper et al., 1973). Thus pressure overload rather than cardiac hypertrophy per se is required for weakened mechanical function. However, it is not known whether elevated afterload is required for a decline in myosin ATPase activity or whether hypertrophy alone is sufficient to cause a defect in myosin ATPase. Investigation of volume overload (VO) hypertrophy equal in magnitude to that observed in pressure overload allows the biochemical phenomenon associated with hypertrophy to be separated from the combined effects of hypertrophy and mechanical impairment. The purpose of this study, therefore, was to examine myosin ATPase activity in VO hypertrophy. If hypertrophy per se did not result in lowered myosin ATPase activity (and since hypertrophy alone does not cause reduced mechanical function), then additional support would be given to the hypothesis that the decline in myosin ATPase and mechanical function are causally related in pressure overload and heart failure.