Radionuclide left ventricular contractile indices and their relationship to heart size in dogs

To identify possible mechanisms to explain differences between the maximum time-varying elastance (Emax) and end-systolic pressure-volume (Ees) slope values calculated with radionuclide angiography and to establish whether they have a relationship to heart size, we studied 16 dogs that were instrumented with micromanometer left ventricular catheters and had red blood cells tagged with technetium-99m for radionuclide angiography. Hemodynamics and radionuclide angiograms were obtained under control conditions and during six additional steady-state loading conditions. Isochronal Emax averaged 7.14 +/- 2.54 mm Hg/ml, while Ees averaged 5.68 +/- 1.88 mm Hg/ml (p less than 0.01), but they were highly correlated (r = 0.95, p less than 0.001). This observation was related to the assumption of linearity when curvilinearity was present and to the important influence of timing on these relationships. The Emax and Ees slope values were compared to dog weight; left ventricular weight, which ranged from 85 to 142 gm (mean 113 +/- 18 gm); and left ventricular end-diastolic volume, which ranged from 15 to 56 ml (mean 29 +/- 10 ml) using multiple regression analyses. The Emax and Ees slope values demonstrated a comparable inverse linear relationship with only left ventricular end-diastolic volume (r = 0.76 and -0.69, p less than 0.001 and p less than 0.01). We conclude that the differences between Emax and Ees slope values calculated with radionuclide angiography are related to the assumption of linearity when curvilinearity is present and to the importance of the timing of systolic events and that both Emax and Ees are comparably related to left ventricular end-diastolic volume.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical usefulness of carotid arterial wave intensity in assessing left ventricular systolic and early diastolic performance

Wave intensity (WI) is a novel hemodynamic index, which is defined as (dP/dt)·(dU/dt) at any site of the circulation, where dP/dt and dU/dt are the derivatives of blood pressure and velocity with respect to time, respectively. However, the pathophysiological meanings of this index have not been fully elucidated in the clinical setting. Accordingly, we investigated this issue in 64 patients who underwent invasive evaluation of left ventricular (LV) function. WI was obtained at the right carotid artery using a color Doppler system for blood velocity measurement combined with an echo-tracking method for detecting vessel diameter changes. The vessel diameter changes were automatically converted to pressure waveforms by calibrating its peak and minimum values by systolic and diastolic brachial blood pressures. The WI of the patients showed two sharp positive peaks. The first peak was found at the very early phase of LV ejection, while the second peak was observed near end-ejection. The magnitude of the first peak of WI significantly correlated with the maximum rate of LV pressure rise (LV max. dP/dt) (r = 0.74, P 0.001). The amplitude of the second peak of WI significantly correlated with the time constant of LV relaxation (r = –0.77, P 0.001). The amplitude of the second peak was significantly greater in patients with the inertia force of late systolic aortic flow than in those without the inertia force (3080 ± 1741 vs 1890 ± 1291mmHgms^–3, P 0.01). These findings demonstrate that the magnitude of the first peak of WI reflects LV contractile performance, and the amplitude of the second peak of WI is determined by LV behavior during the period from late systole to isovolumic relaxation. WI is a noninvasively obtained, clinically useful parameter for the evaluation of LV systolic and early diastolic performance at the same time.     

Angiographic assessment of left ventricular volume, afterload and contractile state in normal children

Left ventricular (LV) volume, mass and end-systolic stress were determined angiographically in 20 normal children aged 3 months to 16 years. LV contractile state was assessed by the analysis of the relation between end-systolic stress and ejection phase index or end-systolic volume. The LV volume and mass closely correlated with the body surface area. The LV mass/end-diastolic volume ratio (0.94 +/- 0.13 g/ml), ejection fraction (0.67 +/- 0.03) and circumferential end-systolic stress (163 +/- 21 kdynes/cm2, 165 +/- 21 g/cm2) remained constant despite the extensive increase in LV volume with physical growth. In all subjects significant inverse correlations were observed between end-systolic stress and ejection fraction or mean normalized systolic ejection rate. The ratio of the circumferential end-systolic stress to end-systolic volume index ranged from 5.00 to 12.57 (7.49 +/- 1.88). The ratio inversely correlated with age (r = -0.74, p less than 0.001), indicating that this ratio for estimating LV contractility is associated with ventricular size. These results suggested that the LV mass increased adequately in response to the extensive increase in LV cavity volume to maintain the end-systolic stress during growth in childhood and that physiologic cardiac growth was associated with appropriate hypertrophy with no significant change in LV contractile state.     

Normal values for noninvasive estimation of left ventricular contractile state and afterload in children

The outcome and suitability for therapeutic interventions in children with congenital heart disease depend frequently on left ventricular function. Congenital heart disease is characterized by changes in loading conditions, making it difficult to assess ventricular contractility using conventional load-dependent indexes. Two-dimensional and M-mode echocardiography and arterial blood pressure were used to study left ventricular morphometrics and contractility in 44 normal children, aged 2 to 12 years. Left ventricular end-systolic and end-diastolic length, diameter, wall thickness, volume and mass all showed linear increases with body surface area (p less than 0.001 in all). Shortening and ejection fractions, velocity of circumferential fiber shortening, morphometric ratios and endocardial meridional and circumferential stress (mean 46 and 115 g/cm2, respectively) all remained constant. A load-independent measure of the normal resting left ventricular contractile state was determined by relating the rate-corrected velocity of circumferential fiber shortening to end-systolic endocardial meridional and circumferential stress; there was an inverse linear correlation (r = -0.641 and -0.557 respectively, p less than 0.001). These data provide a quantitative basis for assessment of myocardial hypertrophy, afterload and contractile state in childhood.     

Radionuclide determination of the relationship between left ventricular contractile state and ejection fraction

To determine whether the relationship between various measures of left ventricular (LV) contractile state and ejection fraction (EF) is linear in man, we studied 30 patients during right atrial pacing over a range of loading conditions. With the use of micromanometer LV pressures and radionuclide LV volumes, pressure-volume (P-V) loops were generated for each loading condition. Then isochronal, instantaneous P-V data points were obtained by linear regression analysis to attain the maximum slope (Emax) of these time-varying isochrones. Other measures of LV end systole were also used to calculate end-systolic P-V relations in a similar fashion, and indirect P-V relations were obtained from the linear regression analysis of brachial artery peak pressure vs minimum LV volume data points. When the slopes of these LV contractile measures were compared to the radionuclide LV EFs, the linear correlation coefficients ranged from 0.53 to 0.67. After natural log transformation of the LV contractile state and EF data, the correlation coefficients for the polynomial curve fits ranged from 0.80 to 0.88. When the correlation coefficients for the polynomial curve fits of the natural log transformed data were compared to those for the linear regression analyses of the raw data, significant improvements were evident (p less than 0.05). Thus the relationship between various measures of LV contractile state and EF obtained with radionuclide angiography is best approximated by a complex, curvilinear relationship that is due, in part, to the wide range of LV contractile states within the relatively narrow normal range of LV ejection fractions.     

Myocardial mechanics in hyperthyroidism: importance of left ventricular loading conditions, heart rate and contractile state

Hyperthyroidism has been reported to affect all of the major determinants of left ventricular performance in a manner that would augment ventricular shortening characteristics. The hypothesis tested in this study is that reduced afterload in conjunction with increased preload and heart rate, rather than augmented contractility, accounts for much of the increase in left ventricular performance noted previously in these patients. To investigate this hypothesis, 11 hyperthyroid patients were evaluated serially over 4 +/- 2 months. With therapy, serum total thyroxin (T4) decreased significantly (p less than 0.001). Ventricular hemodynamics were assessed by two-dimensional targeted M-mode echocardiograms and calibrated carotid pulse tracings. Ventricular preload was estimated by end-diastolic dimension, whereas afterload was measured as end-systolic wall stress. Overall left ventricular performance was quantitated by the extent and velocity of shortening, whereas myocardial work was assessed by ventricular systolic stress-length relations. With therapy, overall left ventricular performance declined (p less than 0.01). This change was associated with no change in end-diastolic dimension or end-systolic wall stress, and a 24% fall in heart rate (p less than 0.01). This latter finding has been shown previously to have no significant effect on left ventricular contractile state over the range of heart rates encountered in this study. In all cases, the end-systolic stress/rate-corrected shortening velocity relation fell with attainment of normal thyroid status, characteristic of a decline in contractility. There was a strong positive correlation between left ventricular contractility and serum thyroid hormone level (r = 0.83). In addition, ventricular minute work declined with therapy (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of contractile state and myosin isozymes of rat right and left ventricular myocardium

We compared myocardial mechanics and myosin isozymes of right and left ventricular papillary muscles from adult (6 to 8 month old) male rats. Analysis of force velocity relations indicate that right ventricular papillary muscles contract more rapidly than left at light loads (2.68 +/- 0.13 vs 2.18 +/- 0.07 muscle lengths/s measured 75 ms following stimulation, at 0.5 g/mm2; P less than 0.01). Right ventricular papillary muscles had significantly more of the alpha heavy chain containing V1 myosin isozyme and less of the V3 containing beta heavy chain myosin isozyme than left ventricular preparations (P less than 0.05). Papillary muscle and ventricular free wall myosin isozyme distribution were not significantly different within their respective chambers. The presence of a relatively larger proportion of the alpha heavy chain containing myosin isozyme (V1) in right ventricle papillary muscles relative to left correlated with the more rapid velocities of shortening seen in right ventricular papillary muscles (r = 0.60; P less than 0.01).     

'Programmed' left ventricular angiography: a new method for assessing left ventricular compliance

In the present study a new method for evaluating left ventricular chamber compliance is reported. We induced a programmed postextrasystolic beat during routine left ventricular angiography through a temporary pacing catheter, placed at the sinoatrial junction (S1-S1 = 600 ms; S1-S2 = 400 ms; S2-S3 = 800 ms). Thirty-two patients with documented critical coronary artery disease and 5 normal subjects represent the study group. The method allows to have two couples of end-diastolic pressure and end-diastolic volume and we calculated the modulus of chamber stiffness with the formula: K = (1n EDP 3 - 1n EDP 1)/(EDVI 3 - EDVI 1), where EDP 1-3 and EDVI 1-3 are end-diastolic pressure and end-diastolic volume index in basal beat and in the postextrasystolic pause, respectively. Left ventricular chamber compliance (dV/dP) and specific compliance (dV/VdP) were also calculated. In order to assess the clinical value of the method, we divided the patients with coronary artery disease into three groups: 12 patients had angina and no previous myocardial infarction; 15 had a previous myocardial infarction and responded to postextrasystolic potentiation with an increase in left ventricular ejection fraction greater than or equal to 0.08 and 5 patients had myocardial infarction and did not respond to postextrasystolic potentiation. Diastolic indices showed significant differences between subgroups; patients with more severe disease and with systolic dysfunction had the highest values of the modulus of chamber stiffness and the lowest values of chamber compliance. Moreover, these indices were not correlated with basal end-diastolic volumes, but they were directly and significantly correlated with the actual increase in left ventricular filling.     

Responsiveness of the maximum time-varying elastance to alterations in left ventricular contractile state in man

This investigation was designed to establish the relative responsiveness of maximum time-varying elastance (Emax) slope values to alterations in left ventricular contractile state in comparison with isovolumic and ejection phase indices in man. Accordingly, nine patients had a bipolar right atrial pacing catheter and micromanometer left ventricular catheter placed and red blood cells tagged with technetium-99m for radionuclide angiography. Hemodynamic measurements and radionuclide angiograms were acquired simultaneously over a range of loading conditions produced by methoxamine or nitroprusside infusions during both the basal and enhanced contractile states. Enhanced left ventricular contractility was produced by a steady-state dobutamine infusion of 2 to 10 mu/kg/min. The mean (+)dP/dtmax increased from 1510 +/- 460 mm Hg/sec during the basal state to 2537 +/- 546 mm Hg/sec (p less than 0.001) during the dobutamine infusion. The mean Emax slope value also increased from 4.34 +/- 1.40 mm Hg/ml during the basal state to 6.41 +/- 1.90 mm Hg/ml (p less than 0.001) during the dobutamine infusion. The average percent change in the Emax slope value (51 +/- 26%) was less than those for the isovolumic indices (57% to 112%), while it was more than those for the ejection phase indices (11% to 53%). When the variability in the percent changes for each of these contractile indices was incorporated into the analysis, the Emax slope values demonstrated a greater responsiveness to changes in left ventricular contractility than did the isovolumic and ejection phase indices. In conclusion, the Emax slope value calculated by this method is a contractile index, which is less affected by measurement variability and the influences of loading conditions than are the isovolumic and ejection phase indices, and therefore may improve our ability to both detect and quantitate changes in left ventricular contractility in man.     

Evaluation of relationship between myocardial contractile state and left ventricular function in patients with aortic regurgitation

We studied the relationship between myocardial contractile state and left ventricular functional response to exercise in 14 asymptomatic patients with isolated moderate-to-severe aortic regurgitation and six control subjects. The slope of the systolic blood pressure-left ventricular end-systolic volume (pressure-volume) relationship determined by radionuclide ventriculography during angiotensin infusion was used as an indirect measure of myocardial contractility and was compared with left ventricular ejection fraction at rest and during both isometric handgrip and dynamic bicycle exercise. The slope of the pressure-volume relationship was significantly lower in patients with aortic regurgitation than in the control subjects (1.75 +/- 0.57 vs 2.78 +/- 0.42, p less than 0.01). The slope correlated exponentially with resting ejection fraction and was linearly related to changes in left ventricular ejection fraction during both handgrip and bicycle exercise. In patients with aortic regurgitation, resting ejection fraction may overestimate myocardial function. The slope of the pressure-volume relationship measured during afterload stress and left ventricular ejection fraction response to exercise intervention more reliably reflect the degree of left ventricular dysfunction.     

End-systolic pressure-volume relations of isolated ejecting rabbit left ventricles after quick diastolic volume changes

The aim of the study was to investigate the influence of quick diastolic volume changes on systolic performance of ejecting left ventricles. To measure left ventricular systolic performance the maximum ratio of ventricular pressure (P) and volume (V) was calculated on beat-to-beat basis when the diastolic loading conditions were varied in different ways. These end-systolic P-V (P-VES) points were obtained from both isovolumic and ejecting contractions. A deviation from the P-VES relation is thought to result from factors changing the inotropic condition of the heart. When steady state isovolumic and ejecting P-VES data were collected linear P-VES relations were found. The relations coincided when stroke volumes were not too large. When the diastolic volume was quickly changed (ie 10 to 20 ms) late in diastole, the P-VES points of the resulting contractions showed a significant deviation from the steady state relation (p less than 0.001). This deviation was dependent on the magnitude of the volume step. After quick volume infusions the heart ejected to end-systolic volume (ESV) values that were smaller than expected from the steady state P-VES relation and the end-systolic pressure (ESP) was larger. After quick volume withdrawals ESV values were larger and ESP was smaller than expected. The magnitude of the effect was not dependent on the preset basic diastolic volume if the volume changes were considered as fractions end-diastolic volumes (EDV). It is concluded that when diastolic volumes are varied just before stimulation, a significant deviation of the P-VES point from the steady state P-VES relation is found in the following contraction. This phenomenon suggests an alteration in the inotropic state of the heart.     

End-systolic pressure-volume relationships obtained by conductance catheter and transient inferior vena caval occlusion: their clinical usefulness]

Whether beneficial hemodynamic effects of cardiovascular drugs are due to changes in the inotropic or loading conditions has been difficult to determine in clinical settings. In this study, the end-systolic pressure-volume relationship, known as a load-independent measurement of cardiac contractility, was obtained by a volumetric conductance catheter and transient inferior vena caval occlusion. We applied this technique to determine the major mode of hemodynamic action of a new inotropic vasodilator, OPC-8490, in comparison to that of dobutamine. In 7 patients with anterior myocardial infarction, an 8F conductance catheter with pressure micromanometer was inserted into the left ventricle. Absolute volume calibration was accomplished by injection of hypertonic saline into the pulmonary artery. Left ventricular pressures and volumes were simultaneously and continuously measured during transient inferior vena caval occlusion using a balloon catheter. Left ventricular end-systolic pressure-volume relationships were determined during the initial 8-sec of balloon occlusion, before baroreceptor-mediated cardiac stimulation was initiated. OPC-8490 decreased both the left ventricular systolic pressure and end-systolic volume without changing the heart rate. Dobutamine increased the systolic pressure and heart rate but decreased the end-systolic volume. The reduction in the end-systolic volume with dobutamine, was caused by an increase in the slope of the end-systolic pressure-volume relationship, while with OPC-8490, it resulted from a decrease in the end-systolic pressure without an appreciable change in the slope of the end-systolic pressure-volume relationship.(ABSTRACT TRUNCATED AT 250 WORDS)     

End-systolic left ventricular pressure-dimension shift during acute relief of volume overload in the conscious dog

To test whether left ventricular (LV) end-systolic dimensions are determined only by end-systolic pressure for a given inotropic state, 7 conscious dogs were studied during abrupt closure of a fistula created between the left subclavian artery and the left atrial appendage. The dogs were instrumented with an LV pressure micromanometer and ultrasonic crystals measuring LV major- and minor-axis diameters and ventricular wall thickness. During beta-blockade treatment and for the same end-systolic pressure, closure of the fistula produced a 40% decrease in cardiac output; end-diastolic diameter decreased by 1.5 mm and end-systolic diameter decreased by 0.9 mm. Calculated end-systolic volume was similarly decreased by 1.3 ml for a decrease of 2.9 ml of end-diastolic volume. Thus, large end-diastolic dimensional variations associated with peripheral resistance decrease significantly modify the end-systolic pressure-diameter (and volume) relations in the conscious animal. It is suggested that indexes obtained from these relations should not be used in patients when systolic pressure variations are associated with large stroke volume variations.     

Effects of revascularisation and contractile reserve on left ventricular remodelling in patients with impaired left ventricular function

OBJECTIVE: We sought to define the influence of revascularisation and contractile reserve on left ventricular (LV) remodelling in patients with LV dysfunction after myocardial infarction. Revascularisation of viable myocardium is associated with improved regional function, but the effect on remodelling is undefined. METHODS: We studied 70 patients with coronary artery disease and LV dysfunction, 31 of whom underwent revascularisation. A standard dobutamine stress echocardiogram (DbE) was carried out. All patients underwent standard medical treatment; the decision to revascularise was made clinically, independent of this study. LV volumes and ejection fraction were measured by 3D echocardiography at baseline and after an average of 40 weeks. RESULTS: There was no significant difference in baseline ejection fraction or volumes between patients who underwent revascularisation and the remainder. Compared to medically treated patients, revascularised patients had significant improvements in ejection fraction and end-systolic volume in follow-up. The impact of baseline variables on remodelling was assessed by dividing patients into tertiles of LV ejection fraction and volumes. Revascularised patients in the lowest tertile of ejection fraction at baseline (<38%) had a significant improvement in end-systolic volume and ejection fraction, larger than obtained in medically treated patients with low ejection fraction. Revascularised patients with an ejection fraction >38% did not show significant improvement in volumes compared to baseline. Revascularised patients in the largest tertiles of end-systolic (>88 ml) or end-diastolic volume (>149 ml) at baseline had a significant improvement in end-systolic volume. CONCLUSION: Remodeling appears to occur independent of the presence of regional contractile reserve but does correlate with the volume response to low-dose dobutamine.