Left Ventricular Ejection Performance Research Articles

Effect of aortic valve stenosis (pressure overload) and regurgitation (volume overload) on left ventricular systolic and diastolic function

In secondary hypertrophy from chronic pressure or volume overload, or both, systolic as well as diastolic abnormalities of left ventricular (LV) function have been described, but their relation has not been defined. In 58 patients with aortic valve disease (28 with aortic valve stenosis, and 30 with aortic regurgitation) and in 11 control subjects, LV biplane cineangiography was performed simultaneously with LV high-fidelity pressure measurements. LV ejection performance was assessed by ejection fraction, and diastolic function by the time constant of LV pressure decay, the early and late peak filling rates, and the constants of chamber (pressure-volume relation) and myocardial stiffness (stress-strain relation). In the entire cohort (n = 69), ejection fraction was inversely related to the time constant of LV relaxation (r = −0.58, p < 0.001) and to the constant of myocardial stiffness (r = −0.62, p < 0.001). Despite preserved systolic contractile function (as evaluated from the ejection fraction-mean systolic stress relation), abnormalities in LV diastolic function were present in 9 of 18 patients with pressure overload and 20 of 22 with volume overload. None of the 58 patients with aortic valve disease had a reduced early peak filling rate, whereas a reduction in late peak filling rate was observed in 3 with aortic stenosis, but in none with aortic regurgitation. Thus, it appears that abnormalities of relaxation and passive diastolic myocardial stiffness precede alterations in myocardial contractility. Assessment of peak filling rates is not helpful to detect diastolic dysfunction in patients with aortic valve disease.

Left ventricular ejection performance in mitral stenosis, and effects of successful percutaneous transvenous mitral commissurotomy

Impaired left ventricular ejection performance was reported in pure mitral stenosis. The speculative mechanisms included insufficient preload, increased wall stress, high right ventricular pressure and unknown myocardial factors, but no definitive mechanism has been established. Fifteen patients with tight mitral stenosis who underwent successful percutaneous transvenous mitral commissurotomy were studied to ascertain whether ejection performance would improve with sufficient blood filling. The indexes of preload (end-diastolic volume) and ejection performance (stroke volume, ejection fraction, and mean systolic and mean normalized ejection rates) were calculated angiographically before and immediately after mitral commissurotomy. Improved blood filling (the result of successful mitral commissurotomy) produced an increase in end-diastolic volume (mean ± SD 99.0 ± 30.2 to 112.1 ± 30.1 ml/m 2; p < 0.05). All 4 indexes of ejection performance also improved. There was good correlation between end-diastolic and stroke volumes before intervention (stroke volume = 0.476 × end-diastolic volume + 16.77; r = 0.76), and the relation between them showed no change even after mitral commissurotomy. It is concluded that both left ventricular preload and ejection performance improved after successful percutaneous transvenous mitral commissurotomy. Insufficient preload could affect ejection performance in patients with tight mitral stenosis.

Left ventricular ejection performance, wall stress, and contractile state in aortic regurgitation before and after aortic valve replacement.

Left ventricular ejection performance, wall stress, and contractile state were evaluated in 35 patients with chronic aortic regurgitation. Cineangiography and pressure measurements were obtained before and a mean of 26 months after aortic valve replacement, and data were compared with those from 30 normal control subjects. The relation between quantitative changes in wall stress and changes in ejection fraction after surgery was determined. Preoperatively, end-systolic stress was elevated in patients with aortic regurgitation (218 +/- 45 vs. 160 +/- 23 kdynes/cm2 [mean +/- SD] for control subjects, p less than 0.01), and ejection fraction was depressed (0.46 +/- 0.11 vs. 0.65 +/- 0.05, p less than 0.01). End-systolic stress decreased postoperatively (151 +/- 41 kdynes/cm2, p less than 0.01) and ejection fraction increased (0.58 +/- 0.11, p less than 0.01). The magnitude of increase in ejection fraction correlated significantly and negatively (r = -0.65) with the quantitative change in end-systolic stress after surgery. Contractile function, as assessed by the ejection phase index-end-systolic stress relation, did not significantly change: 23 of 35 patients preoperatively and 18 of 35 patients postoperatively had values that clearly fell below the 95% confidence limit of the ejection fraction-end-systolic stress relation for controls. After surgery, individual ejection fraction-end-systolic stress relationships demonstrated a shift parallel to the regression curve for the control subjects. Moreover, persistent postoperative left ventricular hypertrophy was significantly associated with persistent contractile dysfunction. Thus, late improvement in left ventricular ejection performance after aortic valve replacement can be attributed to the reduction in end-systolic stress. Contractile function itself was not improved by surgery. Persistent postoperative hypertrophy may be a marker for myocardial contractile dysfunction.

Left ventricular intrinsic contractility in pure rheumatic mitral stenosis

The status of left ventricular (LV) intrinsic contractile function in isolated rheumatic mitral stenosis (MS) is an unsettled issue. Although the overall LV ejection performance is reduced in a number of patients with MS, 1–3 it is a product of interaction between intrinsic contractility, preload and afterload. Although intrinsic LV contractility in MS has been found to be normal in 2 studies, 3,4 other investigators, using methods still to be validated, found it to be decreased. 5,6 Recently, reliable load-independent indexes of intrinsic contractility have been validated and applied in clinical studies. These are end-systolic pressure or end-systolic meridian wall stress to end-systolic volume or dimension ratio 7 and fractional fiber shortening to end-systolic stress relations. 8 We assessed LV intrinsic myocardial contractile function as measured by the aforementioned methods in patients with isolated rheumatic MS.

Supernormal ejection performance is isolated to the ipsilateral congenitally pressure-overloaded ventricle

Congenital left ventricular pressure overload is associated with “excessive” hypertrophy that leads to subnormal afterload (wall stress), permitting enhanced ventricular ejection performance. Whether congenital right ventricular pressure overload is associated with a similar phenomenon is uncertain. It is also unknown whether supranormal ejection performance affects only the overloaded ventricle or is a general process affecting both ventricles. Conflicting data exist about whether the hypertrophic process associated with pressure overload is induced primarily by local loading conditions or by neuroendocrine influences. If the former postulate is true, the hypertrophic response should be confined to the overloaded ventricle; if the latter is true, one might predict that both ventricles would be affected by a less specific response to circulating catecholamines.To help resolve these issues, both right and left ventricular performance was examined in seven patients with isolated congenital pulmonary stenosis (average pulmonary pressure gradient 78 ± 13 mm Hg), six patients with isolated congenital aortic stenosis (average gradient 80 ± 10 mm Hg) and six normal subjects. Right ventricular ejection fraction was increased in patients with pulmonary stenosis (61 ± 2%) compared with the value in normal subjects (53 ± 2%, p < 0.01) and in patients with aortic stenosis (50 ± 3%, p = 0.007). Left ventricular ejection fraction was increased in patients with congenital aortic stenosis (84 ±4%) compared with the value in normal subjects (70 ± 4%, p < 0.01) and in patients with congenital pulmonary stenosis (65 ± 2%, p < 0.002).Thus, patients with congenital right ventricular pressure overload had enhanced right ventricular ejection performance with normal left ventricular ejection performance in contrast to those with congenital left ventricular pressure overload, who had enhanced left ventricular performance but normal right ventricular performance. These findings are consistent with the hypothesis that local loading is a key determinant of the congenital hypertrophic response.

Analysis of the early rise in aortic transvalvular gradient after aortic valvuloplasty

The relationship between dynamic changes in aortic valve gradient and left ventricular ejection performance in the early period after successful percutaneous aortic valvuloplasty has not been described in detail. Accordingly 20 adult patients with severe symptomatic calcific aortic stenosis underwent first-pass radionuclide angiography and Doppler echocardiography before, immediately after, and 2 to 4 days after the valvuloplasty procedure. A significant ( p < 0.001) reduction in peak-to-peak (72 ± 24 mm Hg to 36 ± 11 mmHg) and mean (60 ± 20 mm Hg to 34 ± 9 mm Hg) transaortic gradient and an increase in aortic valve area (0.5 ± 0.2 cm 2 to 0.8 ± 0.2 cm 2) were measured by high-fidelity micromanometer catheters immediately after aortic valvuloplasty. Results of Doppler echocardiography showed a significant ( p < 0.001) immediate decrease in peak instantaneous (81 ± 22 mm Hg to 53 ± 15 mm Hg) and mean (48 ± 14 mm Hg to 31 ± 9 mm Hg) aortic gradients. However, 2 to 4 days later a significant ( p < 0.001) return of peak (56 ± 15 mm Hg to 65 ± 20 mm Hg) and mean (31 ± 9 mm Hg to 39 ± 12 mm Hg) transvalvular gradient occurred. Aortic valve area as determined by the continuity equation also increased from 0.4 ± 0.2 cm 2 to 0.6 ± 0.2 cm 2 immediately after the procedure ( p < 0.001), then partially returned to baseline (0.5 ± 0.2 cm 2; p < 0.005) at 2 to 4 days. Results of serial first-pass radionuclide angiography performed at the same time as the Doppler evaluations showed a continued decrement in left ventricular end-diastolic volume (184 ± 42 ml to 158 ± 35 ml to 151 ± 35 ml) and a trend toward an increase in stroke volume. Additionally the mean ejection fraction continued to improve during this period (42 ± 18% to 49 ± 19% to 52 ± 19%). These data indicate that the early rise in aortic valve gradient seen after percutaneous aortic valvuloplasty is likely due to both remodeling of the aortic valve architecture and a small increase in stroke volume.

Electrocardiographic markers of impaired left ventricular ejection performance in aortic stenosis

To determine whether the ECG would be useful in the prediction of impaired left ventricular ejection performance in aortic valve stenosis, the authors evaluated 121 patients according to (1) the time relationship of the R peak in V 6 to the S peak in V 2 ; and (2) the negative P wave terminal force in V 1 (Morris index, n = 109). Left ventricular ejection fraction (LVEF) was significantly depressed in patients with the R peak in V 6 later than the S peak in V 2 (R peak delay in V 6 , n = 24), compared with those with the R peak in V 6 preceding the S peak in V 2 or with both peaks occurring simultaneously (n = 97) (LVEF 40.8 ± 11.8% vs 69.9 ± 13.3%, p = .000). LVEF < 55% was present in 87.5% of patients with the R peak delay in V 6 and in only 23.7% of those without this finding. The Morris Index was significantly greater in patients with LVEF < 55% (n = 39) than in those with LVEF ≥ 55% (n = 70) (Morris Index 0.063 ± 0.035 msec vs 0.030 ± 0.025 msec, p = .000). The R peak delay in V 6 is a highly specific (96.1%), but less sensitive (47.7%), indicator of depressed LVEF, its positive predictive value and predictive accuracy being 87.5% and 78.5%, respectively. Of the Morris indexes, only ≥ 0.06 msec (n = 28) indicates that depressed LVEF (< 55%) is nearly as reliable as the R peak delay in V 6 (sensitivity, 51.7%; specificity, 88.5%; positive predictive value, 75.6%; predictive accuracy, 73.5%). Thus, the criteria are useful indicators of reduced LVEF, which could reflect either abnormally high systolic wall stress or decreased myocardial contractility.

Electrocardiographic markers of impaired left ventricular ejection performance in aortic stenosis

To determine whether the ECG would be useful in the prediction of impaired left ventricular ejection performance in aortic valve stenosis, the authors evaluated 121 patients according to (1) the time relationship of the R peak in V 6 to the S peak in V 2; and (2) the negative P wave terminal force in V 1 (Morris index, n = 109). Left ventricular ejection fraction (LVEF) was significantly depressed in patients with the R peak in V 6 later than the S peak in V 2 (R peak delay in V 6, n = 24), compared with those with the R peak in V 6 preceding the S peak in V 2 or with both peaks occurring simultaneously (n = 97) (LVEF 40.8 ± 11.8% vs 69.9 ± 13.3%, p = .000). LVEF < 55% was present in 87.5% of patients with the R peak delay in V 6 and in only 23.7% of those without this finding. The Morris Index was significantly greater in patients with LVEF < 55% (n = 39) than in those with LVEF ≥ 55% (n = 70) (Morris Index 0.063 ± 0.035 msec vs 0.030 ± 0.025 msec, p = .000). The R peak delay in V 6 is a highly specific (96.1%), but less sensitive (47.7%), indicator of depressed LVEF, its positive predictive value and predictive accuracy being 87.5% and 78.5%, respectively. Of the Morris indexes, only ≥ 0.06 msec (n = 28) indicates that depressed LVEF (< 55%) is nearly as reliable as the R peak delay in V 6 (sensitivity, 51.7%; specificity, 88.5%; positive predictive value, 75.6%; predictive accuracy, 73.5%). Thus, the criteria are useful indicators of reduced LVEF, which could reflect either abnormally high systolic wall stress or decreased myocardial contractility.

Alterations in left ventricular geometry, wall stress, and ejection performance after correction of congenital aortic stenosis.

Children with congenital aortic stenosis have "excessive" left ventricular hypertrophy with reduced resting systolic wall stress that allows for supernormal ejection performance. If aortic stenosis is uncorrected, this pattern persists until adulthood. The effect of removing the aortic pressure gradient on left ventricular hypertrophy and wall stress in children with congenital aortic stenosis is unknown. To test the hypothesis that removal of the stimulus for hypertrophy by aortic valve replacement or repair would normalize left ventricular mass and wall stress, we measured left ventricular ejection performance, wall stress, and contractile function in seven patients at cardiac catheterization before and 36 +/- 7 months after surgical correction of congenital aortic stenosis. After aortic valve replacement or repair, the aortic valve gradient fell from 87 +/- 12 to 7 +/- 4 mm Hg, and peak left ventricular pressure fell from 187 +/- 14 to 128 +/- 8 mm Hg. Left ventricular ejection fraction decreased postoperatively from 86 +/- 4% to 74 +/- 4% (p less than 0.001), whereas velocity of circumferential fiber shortening decreased from 2.15 +/- 0.15 to 1.6 +/- 0.11 (p less than 0.002). Left ventricular mass remained unchanged preoperatively (121 +/- 14 g/m2) and postoperatively (121 +/- 16 g/m2), but wall thickness (h) decreased in relation to ventricular radius (r) (h/r = 0.55 +/- 0.05 preoperatively, 0.36 +/- 0.02 postoperatively; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Relation between serum nifedipine concentration and hemodynamic effects in nonobstructive hypertrophie cardiomyopathy

The relation between nifedipine concentration and hemodynamic effects after sublingual administration of 10 or 20 mg was examined in 13 patients with nonobstructive hypertrophie cardiomyopathy (HC). Serum nifedipine concentrations were determined by gas chromatography and were not related to dose. Peripheral vascular resistance decreased as a function of nifedipine concentration (r = −0.63, p < 0.001); this was associated with a concentration-related increase in heart rate (r = 0.56, p < 0.001) and in cardiac index (r = 0.50, p < 0.001). However, evidence for a pure vasodilator effect of nifedipine was inconsistent, in that the change in stroke volume index with nifedipine was not significant. Although stroke volume index increased at nifedipine concentrations between 60 and 120 ng/ml (38 ± 6 to 42 ± 4 ml/m 2, p < 0.01), it decreased at concentrations >120 ng/ml (40 ± 3 to 38 ± 4 ml/m 2, p < 0.01). Moreover, pulmonary artery wedge pressure increased at nifedipine concentrations >120 ng/ml (11 ± 2 to 16 ± 4 mm Hg, p < 0.001), suggesting either depressed left ventricular (LV) systolic function or reduced LV filling. To investigate these possible mechanisms, LV systolic and diastolic function was studied during catheterization with a nonimaging scintillation probe in 6 of the 13 patients. In these subjects, heart rate was held constant by atrial pacing. Nifedipine, at concentrations ≤120 ng/ml did not alter end-diastolic volume, but increased LV stroke volume and ejection fraction; concentrations >120 ng/ml were associated with increased end-diastolic and end-systolic volumes, reduced ejection fraction and end-systolic pressure-volume ratio. No beneficial effects on LV diastolic function were observed at these higher concentrations, as the time constant of isovolumic relaxation increased (32 ± 13 to 60 ± 11 ms, p < 0.01). These results indicate that the hemodynamic effects of nifedipine are related closely to nifedipine concentration in patients with nonobstructive HC. Peripheral vasodilating effects are evident over a wide range of nifedipine levels. At low and medium concentrations, these effects result in augmentation of LV ejection performance; however, negative inotropic effects predominate at high concentrations.

Contractile function, myosin ATPase activity and isozymes in the hypertrophied pig left ventricle after a chronic progressive pressure overload.

Experimental right ventricular pressure-overload hypertrophy in small mammals is associated with early muscle dysfunction, even before the onset of overt pump failure. Experimental results are quite heterogeneous regarding muscle function of the pressure hypertrophied left ventricle. Muscle dysfunction of the right or left ventricle, when found, may be causally related to alterations of myosin ATPase activity and isozyme type. However, the effect of a gradual pressure overload, analogous to that which occurs in human aortic stenosis, on myocardial contractile function and myosin ATPase activity has not been studied in a large animal whose normal myosin isozyme pattern resembles that of man. We therefore studied pump performance, myocardial contractile function, and myosin ATPase activity and isozyme pattern in pigs with severe, gradually applied left ventricular pressure overload. Thirteen weeks after supravalvular aortic banding, 10 pigs grew more than 7-fold in body weight and were found to have an aortic stenosis area of 0.5 +/- 0.1 cm2 with a gradient of 93 +/- 12 mm Hg. Compared with nine control animals, the banded animals had a 67% increase in left ventricular mass relative to body weight without overt pump failure as measured by cardiac index and pulmonary artery wedge pressure. Left ventricular ejection performance, measured as shortening fraction, was maintained except in three animals with extreme hypertrophy, in which depressed ejection performance may have been due to an afterload mismatch, myocardial dysfunction, or both. Myocardial contractile function, determined from the end-systolic stress-diameter relationship, was normal except in two pigs in which ejection performance was depressed and left ventricular mass was more than doubled. Only the slow V3 isozyme of myosin ATPase was found in both normal and hypertrophied pig myocardium, and the ATPase activity was normal in pigs with all degrees of hypertrophy. Thus, in a large animal model of severe, gradual left ventricular pressure overload, in which myosin isozyme pattern remains apparently unaltered, moderate hypertrophy can be associated with normal myosin ATPase activity and contractile function that is normal by current methods of evaluation.

Asymmetric septal hypertrophy in patients with aortic stenosis: An adaptive mechanism or a coexistence of hypertrophic cardiomyopathy

Myocardial histologic features and left ventricular dynamics were assessed in 24 patients with severe aortic stenosis, 12 with (group 1) and 12 without (group 2) associated asymmetric septal hypertrophy. In 10 patients from group 1, echocardiography showed a septal/pos-terior wall ratio of 1.5; in the other 2, asymmetric septal hypertrophy was diagnosed by direct inspection at the time of surgery. Septal myectomy in all 12 patients in group 1 was completed at the time of aortic valve replacement. Septal histologic features were assessed from surgical specimens in 10 patients in group 1. Transseptal endomyocardial biopsy specimens of the anterolateral wall taken during preoperative cardiac catheterization were evaluated by light microscopy in 10 patients from group 1 and all patients of group 2. Left ventricular end-diastolic and peak systolic pressure, peak pressure gradient, calculated valve area and angiographic muscle mass did not differ significantly in groups 1 and 2; ejection fraction (68 versus 58%; probability [p] < 0.01) was larger and end-diastolic volume (109 versus 144 ml/m 2 ; difference not significant [NS]) was smaller in group 1 than in group 2. Muscle fiber diameter of the anterolateral wall was similar in groups 1 and 2 (26.5 versus 29.1 μ; NS), but muscle fiber diameter of the septum in group 1 was significantly smaller (24.4 μ; p < 0.01) than that of the anterolateral wall in group 2. No morphologic abnormalities typical for hypertrophic cardiomyopathy (fiber disarray) were seen in samples from the patients in either group. By 18 months postoperatively, septal wall thickness had decreased significantly from 2.0 to 1.5 cm (p < 0.01) and posterior wall thickness from 1.4 to 1.2 cm (p < 0.05) in group 1. In group 2, septal wall thickness decreased from 1.5 to 1.3 cm (NS) and posterior wall thickness from 1.4 to 1.2 cm (NS) 8 months postoperatively. Asymmetric septal hypertrophy in patients with aortic stenosis is an adaptive mechanism to the long-standing pressure overload, and hence there is no evidence of coexistence of idiopathic hypertrophic cardiomyopathy and aortic valve disease. Although the degree of valve obstruction was similar in both groups, left ventricular ejection performance was significantly lower in the group without asymmetric hypertrophy, probably because these patients had a more advanced stage of myocardial disease. After successful valve replacement, there is a significant regression of septal hypertrophy in patients with aortic stenosis and asymmetric septal hypertrophy.

Left ventricular ejection performance and systolic muscle function in patients with mitral stenosis.

Left ventricular ejection performance and systolic muscle function in patients with mitral stenosis.

Determinants of ventricular function in pressure-overload hypertrophy in man.

Determinants of ventricular function in pressure-overload hypertrophy in man.