Left ventricular relaxation and filling pattern in different forms of left ventricular hypertrophy: An echocardiographic study

To study left ventricular relaxation and filling in different forms of left ventricular hypertrophy, echocardiograms of the left ventricle in 24 patients with hypertrophic obstructive cardiomyopathy and in 24 patients with chronic left ventricular pressure overload (due to aortic stenosis in 6 and to severe arterial hypertension in 18) were analyzed by computer and compared with those of 28 normal subjects. The relaxation time index (minimal left ventricular dimension to mitral valve opening) was 13 ± 15 ms in normal subjects. This index was prolonged in patients with cardiomyopathy (93 ± 37 ms) and overload (66 ± 31 ms). During the interval from minimal left ventricular dimension to mitral valve opening both groups with left ventricular hypertrophy showed a marked increase in left ventricular dimension of 4.0 ± 2.2 mm and 3.0 ±1.8 mm, respectively, which was significantly greater (p < 0.001) than in normal subjects (0.6 ± 0.5 mm). This was probably a result of an abnormal change in left ventricular shape during isovolumic relaxation.The rapid filling phase and the increase in dimension during this period were significantly reduced in hypertrophic obstructive cardiomyopathy and chronic pressure overload. In contrast to findings in the patients with cardiomyopathy, in those with pressure overload the reduced increase in left ventricular dimension during the rapid diastolic filling period was compensated for by a greater dimensional increase due to atrial contraction, resulting in a normal end-diastolic dimension. These data indicate that significant prolongation of isovolumic relaxation is seen in different forms of left ventricular hypertrophy and is often associated with an abnormal diastolic filling pattern.     

Diastolic relaxation and left ventricular blood filling in patients with hypertension

Disorders of left-ventricular diastolic relaxation and blood filling in patients with first- and second-stage essential hypertension are shown, by means of echo-, radio- and apexcardiography, to be due to the effects of arterial blood pressure, hemodynamic changes, heart rate and the magnitude of left-ventricular hypertrophy. Antihypertensive treatment, affecting major parameters of disease, brings about the recovery of the heart's diastolic function.     

Influence of alteration in preload on the pattern of left ventricular diastolic filling as assessed by Doppler echocardiography in humans

We examined the influence of alterations in preload on pulsed Doppler indexes of left ventricular diastolic function in 50 patients including 12 without cardiovascular disease, 29 with coronary artery disease, and nine with critical aortic stenosis. Micromanometer left ventricular pressure was recorded simultaneously with pulsed Doppler echocardiography of left ventricular inflow and M-mode echocardiography of left ventricular diameter. Chamber stiffness constants, kd and kv, were obtained from the diastolic pressure-diameter and pressure-volume relations, respectively. Relaxation was measured by the isovolumic relaxation time constants, TL and TD, derived from the exponential left ventricular pressure decay and maximum negative dP/dt. In 41 patients after nitroglycerin treatment, left ventricular end-diastolic pressure decreased from 18 +/- 5 to 13 +/- 4 mm Hg (p less than 0.001). The ratio of peak early to peak atrial filling velocities and time-velocity integral ratios decreased from 1.08 +/- 0.57 to 0.90 +/- 0.42 (p less than 0.001) and from 1.77 +/- 0.95 to 1.41 +/- 0.71 (p less than 0.001), respectively. The peak early filling velocity and time-velocity integral decreased from 56.1 +/- 15.7 to 49.9 +/- 14.5 cm/sec (p less than 0.001) and from 7.9 +/- 2.7 to 6.8 +/- 2.8 cm (p less than 0.001), respectively. Relaxation (TL, TD, and maximum negative dP/dt) and chamber stiffness (kd and kv) were not impaired after nitroglycerin administration. In 48 patients after ventriculography, left ventricular end-diastolic pressure increased from 18 +/- 6 to 22 +/- 8 mm Hg (p less than 0.001). The peak early and peak atrial filling velocities increased from 57.4 +/- 15.2 to 68.3 +/- 19.7 cm/sec (p less than 0.001) and from 61.0 +/- 22.7 to 69.4 +/- 23.2 cm/sec (p less than 0.01), respectively. As a result, the ratio of peak early to peak atrial filling velocity was unchanged. However, in the aortic stenosis group, the ratio of peak early to peak atrial filling velocity increased from 0.95 +/- 0.64 to 1.10 +/- 0.72 (p less than 0.02). Relaxation and chamber stiffness were unchanged. Thus, a reduction or increase in preload may induce a diastolic filling pattern that mimics or masks diastolic dysfunction, respectively. Preload conditions need to be accounted for when the status of diastolic function is extrapolated from the pulsed Doppler mitral inflow velocity profile.     

Left ventricular filling dynamics: influence of left ventricular relaxation and left atrial pressure

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 II. 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 less than .005 for all changes). PRFR correlated strongly with the diastolic atrioventricular pressure difference at the time of PRFR (r = .899, p less than .001) and weakly with both T (r = .369, p less than .01) and PCO (r = .601, p less than .001). The correlation improved significantly when T and PCO were both included in the multivariate regression (r = .797, p less than .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.     

Evaluation of left ventricular diastolic function from the pattern of left ventricular filling

The pattern of left ventricular (LV) filling can be determined by Doppler echocardiography. Normally most LV filling occurs early in diastole, with some additional filling occurring during atrial systole, late in diastole. In the absence of mitral stenosis, three patterns of LV filling indicate progressively greater diastolic dysfunction: (1) Reduced early diastolic filling with a compensatory increase in importance of atrial filling, termed a pattern of “impaired relaxation;” (2) “pseudo-normalization” with most filling early in diastole but with rapid deceleration of mitral flow; and (3) “restricted filling” with almost all filling of the LV occurring very early in diastole in association with very rapid deceleration of mitral flow. A large, prolonged atrial regurgitant flow in the pulmonary veins also indicates impaired diastolic performance. The time for early filling deceleration is predominantly determined by LV stiffness: the shorter the deceleration time, the stiffer the LV. Patients with short deceleration time have a poor prognosis.     

Alteration of left ventricular geometry during preload reduction and afterload increment

To ascertain whether or not left ventricular geometry changes during preload reduction and afterload increment, the shortening characteristics of small segments in the left ventricular free wall were examined using 4 pairs of ultrasonic crystals in 10 dogs. Three pairs of ultrasonic crystals were circumferentially implanted in the basal, the midventricular and the apical portion of the left ventricle. Another pair of crystals were longitudinally placed in the midventricle. In the control state, the shortening at the apex was largest of all segments. During preload reduction, the end-diastolic length decreased significantly in each segment. The percent shortening decreased significantly at the apical and the longitudinal segment, but it remained unchanged at the midventricular and the basal segment. During afterload increment, the end-diastolic length increased significantly, but the percent shortening remained unchanged in each segment. We concluded that left ventricular geometry was altered during preload reduction and that the apical part is more responsive to preload change than the other portion.     

Right ventricular pacing reduces the rate of left ventricular relaxation and filling

Right ventricular pacing alters left ventricular synchrony and loading conditions, each of which may independently influence left ventricular relaxation. Addition of a properly timed atrial contraction by using sequential atrioventricular (AV) pacing minimizes changes in left ventricular loading conditions, but ventricular asynchrony persists. To separate the effects of altered loading from those of asynchrony, the effects of right ventricular pacing and sequential AV pacing on the rate of isovolumic pressure decline (relaxation time constant), myocardial (segment) lengthening rate and chamber (minor axis dimension) filling rate were examined. In 12 open chest anesthetized dogs, left ventricular pressure (micromanometer) and either left ventricular free wall segment length transients (n = 6) or minor axis dimension transients (n = 6) were measured during right atrial, right ventricular and sequential AV pacing; length and dimension were measured using ultrasonic crystals. Compared with right atrial pacing, right ventricular pacing produced a decrease in systolic pressure, a reduction in fractional shortening, a prolongation of the relaxation time constant (23.5 +/- 0.7 to 29.8 +/- 0.8 ms, p less than 0.05), slower peak segment lengthening rate (6.2 +/- 0.6 to 4.6 +/- 0.8 s-1, p less than 0.05) and a slower rate of increase in chamber dimension (3.5 +/- 0.1 to 2.7 +/- 0.1 s-1, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of reduction of preload and afterload by nitroglycerin on left ventricular diastolic pressure-volume relations and relaxation in man.

To clarify the mechanisms of afterload reduction on left ventricular diastolic function, the influence of nitroglycerin upon ventricular diastolic pressure-volume relations was studied in 22 patients during catheterization. After nitroglycerin, average ventricular systolic pressure declined by 25 mm Hg (18%) and end-diastolic pressure by 7 mm Hg (28%) (P less than 0.005). End-systolic and diastolic ventricular volumes decreased by 37% and 23% respectively (P less than 0.005). Although peak negative dP/dt fell by 22% (P less than 0.0005), "T", an index of the time course of isovolumic diastolic ventricular relaxation, was insignificantly changed. Diastolic pressure-volume curves were significantly displaced downward and leftward without significant change in slope, suggesting that a family of pressure-volume curves for each ventricle with similar slope but positions depend upon immediate loading conditions. Absence of change in slope or of "T" suggests that this displacement may be mediated indirectly, perhaps by relaxation of extracardiac constraints to ventricular distensibility. Accordingly, improvement in ventricular function by vasodilators may be partly due to downward displacement of the pressure-volume relation, with associated reduction of wall tension and myocardial oxygen consumption.     

Echocardiographic assessment of left ventricular relaxation and cardiac filling pressures

Echocardiography is the cornerstone for the assessment of left ventricular diastolic function in routine clinical practice. The technique can provide a comprehensive evaluation of left ventricular structure and function in patients with normal and depressed ejection fraction. Aside from two-dimensional imaging, Doppler measurements include mitral inflow, pulmonary venous flow, flow propagation velocity, and tissue Doppler imaging. Using recently published algorithms, left ventricular relaxation and filling pressures can be estimated, and the grade of diastolic dysfunction can be classified.     

Influence of preload on left ventricular relaxation in isolated ejecting hearts during myocardial depression

BACKGROUND:

The controversially discussed intrinsic effect of end-diastolic pressure (EDP) on ventricular relaxation (lusitropy) is a prerequisite for interpretation of lusitropic changes induced by physiological and pharmacological interventions because the latter usually alter the ventricular loading conditions.

OBJECTIVES:

Characterization of the lusitropic effect of preload changes at low and high absolute EDP and after spontaneous cardiodepression.

METHODS:

Repeated preload tests (increasing cardiac inflow at constant mean aortic pressure) were performed in isolated ejecting rat and guinea pig hearts. Preload was quantified by left ventricular EDP, lusitropy was quantified using peak negative left ventricular pressure change velocity (−dP/dt), and relaxation time constant τ was calculated from monoexponential and four-parametric logistic pressure fall models. Regression coefficients of relaxation indexes, −dP/dt and τ versus EDP, were calculated and compared at different degrees of cardiac depression.

RESULTS:

Increasing EDP in the ejecting hearts less than 2 h after isolation caused τ to decrease and −dP/dt to increase initially at low EDP levels. Both parameters remained constant or even reversed at higher EDP levels. In the spontaneously depressed hearts, over 3 h after isolation, basic τ values were higher and −dP/dt values were lower, but EDP changes no longer had significant lusitropic effects. The same behaviour was observed in pentobarbital depressed hearts.

CONCLUSIONS:

A positive lusitropic effect (falling τ, rising −dP/dt) was observed when preload was increased in the range of lower EDP values in undepressed hearts early after isolation. However, preload changes did not influence lusitropy in isolated hearts either early after isolation at high EDP levels or in the spontaneously depressed condition at any EDP level.     

Effect of verapamil on left ventricular isovolumic relaxation time and regional left ventricular filling in hypertrophic cardiomyopathy

The effect of verapamil on global and regional left ventricular relaxation as well as on regional left ventricular filling was measured in 11 patients with hypertrophic obstructive or nonobstructive cardiomyopathy in a combined phonocardiographic and echocardiographic study. Five to 10 minutes after intravenous injection of verapamil (0.15 mg/kg body weight) prolonged isovolumic left ventricular relaxation time, measured from the aortic component of the second heart sound to the mitral valve opening in the echocardiogram, significantly decreased from 93 ± 10 to 67 ± 15 ms (p <0.001). This reduction during that time period was associated with a smaller increase in regional left ventricular dimension (3.8 +- 1.9 to 2.4 ±1.4 mm, p < 0.005). Left ventricular filling improved significantly with regard to the peak rate of posterior wall thinning, which increased from 64 +- 30 to 89 ± 38 mm/s, p < 0.001, the Increase in left ventricular dimension during the left ventricular filling period from 14.4 ± 2.4 to 16.4± 2.4 mm; p < 0.01) and the duration of the relative filling period from 47.2± 4.6 to 49.0 ± 5.3 percent; p <0.01). Left ventricular end-systolic dimension, fractional shortening of the left ventricular minor axis, cycle length and systolic blood pressure showed no significant change.

These data show that an abnormal prolongation of the left ventricular relaxation time in patients with hypertrophic cardiomyopathy can be significantly shortened by intraveneus application of verapamil and that this treatment is associated with an improvement of left ventricular filling.     

Right ventricular pacing and left ventricular filling pattern. An echo-Doppler study

The influence of right ventricular pacing on left ventricular filling has not been completely clarified. The aim of the study was to analyze the possible alteration in and effects on left ventricular filling resulting from right ventricular pacing. The study population consisted of two groups; group A was comprised of 12 patients with a spontaneous left bundle branch block, and group B had 12 patients without left bundle branch block. All the patients underwent an interrogation of the mitral valve inflow by Doppler echocardiography, in order to measure isovolumic relaxation time, early and late peak velocity (E and A wave), E/A ratio and deceleration time. The study was performed at spontaneous rhythm and after, inhibition of the pacemaker. In group A, there were no changes in the Doppler parameters when passing from a spontaneous to an 80/min electrically induced rhythm. Analysis of group B revealed a statistically significant lengthening of IVR and Dec t with electrical stimulation. No statistically significant differences were found when we compared the Doppler parameters of the two populations at the same pacing frequency. Right ventricular pacing causes interventricular asynchrony and abnormalities in diastolic filling times, which resulted in a lengthening of either IVR and Dec t, simulating a pattern of abnormal relaxation.     

Triphasic diastolic pattern and delayed timing of myocardial relaxation identify dynamic changes of left ventricular filling pressure

The case reported concerns a woman with hypertensive emergency, showing triphasic diastolic pattern with mid-diastolic velocity both at transmitral inflow and at pulsed tissue Doppler-derived septal/lateral mitral annulus. In addition, the time from EKG R wave peak to annular early diastolic velocity (Em) onset was longer than the time occurring between R peak and transmitral E velocity. E/Em ratio was 14.6 and left atrium enlarged. After blood pressure fall and clinical stabilization, the triphasic diastolic patterns were again observed. However, the timing of early diastolic velocity was the same at mitral inflow and annular tissue Doppler. E/Em ratio and left atrial volume were reduced. The present report highlights the additional value of pulsed tissue Doppler to detect alteration of diastolic properties and dynamic changes of left ventricular filling pressure.     

Significance of left atrial pressure and left ventricular relaxation as determinants of left ventricular early diastolic filling flow in man

We analyzed the relationships among parameters of left ventricular (LV) early diastolic filling flow (EDF) obtained with pulsed Doppler echocardiography, mean pulmonary wedge pressure (PCWP) and the time constant of LV pressure fall calculated by either Weiss' (Tw) or Thompson's (Tb) method. PCWP correlated with the peak velocity (R) (r = 0.537, p less than 0.05), acceleration (Ac) (r = 0.545, p less than 0.05) and deceleration (Dc) (r = 0.606, p less than 0.01) of LVEDF. In contrast, Tb correlated only with the time to the peak of LVEDF (TPF) (r = 0.487, p less than 0.05), and Tw did not correlate with the Doppler-derived indices significantly. After correcting for the effect of PCWP, significant partial correlations between R and Tw (r = -0.535, p less than 0.05), and between Ac and both Tw (r = -0.606, p less than 0.01) and Tb (r = -0.569, p less than 0.05) were found. Dc did not correlate with Tw or Tb. These results suggest that the level of left atrial pressure may mask the relationship between parameters of LVEDF and LV relaxation, and that the relations among these variables vary with individual indices of LVEDF.     

Abnormal left ventricular filling with increasing age reflects abnormal myocardial characteristics independent of ischemia or hypertrophy

Abnormal left ventricular (LV) filling may occur with increasing age despite apparently normal LV size and function, and is usually attributed to LV hypertrophy and coronary artery disease. The purpose of this study was to determine whether myocardial abnormalities could be identified in 67 such patients (36 men, mean age 57 +/- 9 years) whose LV hypertrophy and coronary artery disease were excluded by dobutamine echocardiography. All patients underwent gray scale and color tissue Doppler imaging from 3 apical views, which were stored and analyzed off line. Disturbances in structure and function were assessed by averaging the cyclic variation of integrated backscatter, strain rate, and peak systolic strain from each myocardial segment. Calibrated integrated backscatter (corrected for pericardial backscatter intensity) was measured in the septum and posterior wall from the parasternal long-axis view. Abnormal LV filling was present in 36 subjects (54%). Subjects with and without abnormal LV filling had similar LV mass, but differed in age (p <0.01), cyclic variation (p = 0.001), strain rate (p <0.01), and peak systolic strain (p <0.001). Multivariate logistic regression analysis demonstrated that age (p = 0.016) and cyclic variation (p = 0.042) were the most important determinants of abnormal LV filling in these apparently normal subjects.     

Reduction of left ventricular preload by lower body negative pressure alters Doppler transmitral filling patterns

The objective of this study was to evaluate the effect of alterations in preload induced by lower body negative pressure on Doppler transmitral filling patterns. Echocardiograms and Doppler recordings were performed in 18 normal young men (aged 23 to 32 years) during various levels of lower body negative pressure (0, -20 and -50 mm Hg). Lower body negative pressure induced a reduction in diastolic velocity integral (from 12.17 +/- 0.79 to 8.42 +/- 0.71 cm, p = 0.0067) and consequently left ventricular diastolic diameter (from 5.11 +/- 0.09 to 4.45 +/- 0.1 cm, p less than 0.0001). There was a significant reflex increase in heart rate from 59.9 +/- 1.9 to 77.1 +/- 2.4 beats/min (p less than 0.0001), but blood pressure was unchanged. This reduction in preload altered Doppler transmittral filling patterns as follows: 1) peak early velocity (E) decreased from 59.2 +/- 3.8 to 39.1 +/- 1.7 cm/s (p less than 0.0001); 2) atrial filing velocity (A) was unchanged (35.58 +/- 1.5 to 33.52 +/- 1.4 cm/s, p = 0.517); 3) E/A ratio decreased from 1.7 +/- 0.13 to 1.19 +/- 0.08 (p = 0.0087); 4) mean acceleration (from 482 +/- 37 to 390 +/- 27 cm/s2, p = 0.03) and mean deceleration (from 327 +/- 31 to 169 +/- 21 cm/s2, p less than 0.001) of the early filling wave were significantly reduced; and 5) peak acceleration (from 907 +/- 42 to 829 +/- 29 cm/s2) and peak deceleration (from 771 +/- 94 to 547 +/- 76 cm/s2) also decreased, but not significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation of filling pattern to diastolic function in severe left ventricular disease

M mode and Doppler echocardiograms, apex cardiograms, and phonocardiograms were recorded in 50 patients with severe ventricular disease of varying aetiology to examine how left ventricular filling is disturbed by cavity dilatation. The size of the left ventricular cavity was increased in all with a mean (SD) transverse diameter of 7.2 (0.8) cm at end diastole and 6.3 (0.8) cm at end systole. All were in sinus rhythm and 35 had functional mitral regurgitation. In nine patients, in whom filling period was less than 170 ms, transmitral flow showed only a single peak, representing summation. In the remainder there was a strikingly bimodal distribution of filling pattern. In 12 the ventricle filled dominantly with atrial systole (A fillers). Isovolumic relaxation was long (75 (35) ms) and wall motion incoordinate; mitral regurgitation was present in only one. In most (29) the left ventricle filled predominantly during early diastole (E fillers). Mitral regurgitation, which was present in 26, was much more common than in the A fillers, while the isovolumic relaxation time (10 (24) ms) was much shorter and the normal phase relations between flow velocity and wall motion were lost. In 24 E fillers no atrial flow was detected. In four there was no evidence of any mechanical activity, suggesting "atrial failure". In 20, either the apex cardiogram or the mitral echogram showed an A wave, implying that atrial contraction had occurred but had failed to cause transmitral flow, showing that ventricular filling was fundamentally disturbed in late diastole. A series of discrete abnormalities of filling, beyond those shown by Doppler alone, could thus be detected in this apparently homogeneous patient group by a combination of non-invasive methods. The presence and nature of these abnormalities may shed light on underlying physiological disturbances.     

Interaction of left ventricular relaxation and filling during early diastole in human subjects

Seventeen patients with coronary artery disease were studied with cineangiography and simultaneous tip manometry at resting heart rate and submaximal tachycardia induced by atrial pacing. During early diastole, defined as the interval from the opening of the mitral valve to the point of minimal left ventricular pressure, 20 percent of total ventricular filling took place at resting heart rate, but 62 percent occurred during tachycardia. Minimal pressure was significantly correlated with the time constant of pressure decay during the isovolumic phase (r = 0.75 at resting heart rate and r = 0.81 during tachycardia). The measured minimal pressure could be predicted by extrapolating the exponential decay of ventricular isovolumic pressure to the time of occurrence of the minimal pressure, which occurred on average 2.7 time constants from the peak negative rate of change of pressure. At resting heart rate the time constant of relaxation was inversely correlated with ventricular inflow volume (r = ?0.64) and inflow rate (r = ?0.72). It is concluded that left ventricular relaxation has a relevant role in early diastolic pressure-volume relations and increases during tachycardia.     

Changes in left ventricular filling pattern during dobutamine stress Doppler echocardiography.

AIMS: To study the left ventricular filling pattern during stress Doppler echocardiography and its utility in the detection of myocardial ischaemia. METHODS AND RESULTS:Fifty-seven consecutive patients underwent dobutamine stress echocardiography. The left ventricular filling pattern (E-wave velocity; A-wave velocity; E/A ratio; E-wave deceleration time) was analysed at baseline and at maximum heart rate reached. The percentage increase in these parameters from baseline to peak heart rate was also determined. Myocardial ischaemia (regional contractility worsening) was induced in 19 cases (ischaemic group) but not in 38 cases (non-ischaemic group). There were no differences between both groups at baseline. E-wave deceleration time decreased in the non-ischaemic group (197+/-63 vs. 167+/-65 ms, P=0.01) and increased in the ischaemic group (203+/-42 vs. 315+/-135 ms, P<0.0001). A percentage increase in E-wave deceleration time of >30% showed a positive predictive value of 93% and a negative predictive value of 86% for detecting ischaemia, and in the multivariate analysis it was the only Doppler parameter (P<0.0001) that predicted the induction of ischaemia. CONCLUSION: We conclude that myocardial ischaemia provokes an increase in E-wave deceleration time. Analysis of left ventricular filling could help in the identification of those cases which are positive for ischaemia.