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.     

Impairment of diastolic function by shortened filling period in severe left ventricular disease

A dilated left ventricle with reduced ejection fraction is usually attributed to impaired systolic function. To investigate the possibility that ventricular filling might also be disturbed, M mode echocardiograms, phonocardiograms, and Doppler cardiograms were recorded in 30 patients with ventricular disease of varying cause. All but four had functional mitral regurgitation. The size of the left ventricular cavity was increased in all and peak velocity of circumferential fibre shortening was reduced. Diastolic abnormalities included a short isovolumic relaxation time, and, on digitised M mode, a reduced rate of dimension increase and of posterior wall thinning. Although the timing of aortic valve closure was normal, mitral regurgitation persisted beyond it by 95 (35) ms and beyond mitral valve opening by 60 (40) ms. This reduced the effective filling time (the interval when the mitral valve was open and mitral regurgitation was absent) to less than 200 ms in seven patients. The effective filling time correlated closely with the RR interval, the regression equation indicating a reduction of 80 ms for each 100 ms fall in RR interval. It was also independently shortened by 2 ms a year with increasing age. The effective left ventricular filling time may thus be very short in patients with left ventricular cavity dilatation and functional mitral regurgitation. It is suggested that when diastolic function is also abnormal, this short filling time may physically limit ventricular inflow. Its close relation to heart rate might contribute to the therapeutic effect of beta blockade in such patients.     

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.     

Impairment of diastolic function by shortened filling period in severe left ventricular disease.

A dilated left ventricle with reduced ejection fraction is usually attributed to impaired systolic function. To investigate the possibility that ventricular filling might also be disturbed, M mode echocardiograms, phonocardiograms, and Doppler cardiograms were recorded in 30 patients with ventricular disease of varying cause. All but four had functional mitral regurgitation. The size of the left ventricular cavity was increased in all and peak velocity of circumferential fibre shortening was reduced. Diastolic abnormalities included a short isovolumic relaxation time, and, on digitised M mode, a reduced rate of dimension increase and of posterior wall thinning. Although the timing of aortic valve closure was normal, mitral regurgitation persisted beyond it by 95 (35) ms and beyond mitral valve opening by 60 (40) ms. This reduced the effective filling time (the interval when the mitral valve was open and mitral regurgitation was absent) to less than 200 ms in seven patients. The effective filling time correlated closely with the RR interval, the regression equation indicating a reduction of 80 ms for each 100 ms fall in RR interval. It was also independently shortened by 2 ms a year with increasing age. The effective left ventricular filling time may thus be very short in patients with left ventricular cavity dilatation and functional mitral regurgitation. It is suggested that when diastolic function is also abnormal, this short filling time may physically limit ventricular inflow. Its close relation to heart rate might contribute to the therapeutic effect of beta blockade in such patients.     

Left ventricular diastolic filling in patients with coronary artery disease and normal left ventricular function

Abnormal left ventricular diastolic filling (DF) has been noted in coronary disease (CD) patients with normal left ventricular function (NLVF). Inclusion of patients with regional wall disease, hypertension, and left ventricular hypertrophy may be responsible for abnormal DF. We evaluated left ventricular DF curves derived from gated blood pool scans in 21 normals (group 1), in 38 CD patients with NLVF specifically defined (group 2), and in 28 CD patients with ejection fractions greater than 50% and regional disease (group 3). The peak filling rate (PFR), mean filling rate (MFR), the percentage of stroke volume filled at one third of diastole (%SV-1/3 DT) and at the end of the rapid filling period (%SV-RFP) were determined. Groups 1 and 2 had similar DF parameters. Group 2 patients with 75% obstructive left anterior descending disease (LAD) had a reduced %SV-RFP and PFR (2.56 +/- 0.56 end-diastolic volumes/sec [EDV/S]) as compared to normals (3.11 +/- 0.65 EDV/S, p less than 0.01). Group 3 patients had a reduced PFR (2.14 +/- 0.53 EDV/S, p less than 0.001), MFR, %SV-1/3 DT, and %SV-RFP. DF in CD patients with NLVF was similar to normals in a select group of patients but was abnormal in patients with regional disease and greater than 75% LAD disease with NLVF.     

Coronary artery bypass grafting in patients with severe left ventricular dysfunction: predictive significance of left ventricular diastolic filling pattern.

AIMS: The aim of our study was to evaluate the influence of left ventricular (LV) diastolic filling impairment on postoperative results in patients (pts) with low LV ejection fraction (EF) (<35%) undergoing coronary artery bypass grafting (CABG). METHODS: The study covered 56 patients (mean age 58.9 +/- 17.1 years). Two dimensional Doppler echocardiographic investigations were performed pre- and 10-14 days post-CABG. Patients were divided into three groups according to the LV diastolic filling. RESULTS: Early postoperative mortality rate (including perioperative period and 2 weeks after surgery) was highest in the restriction group (33%) vs. pseudonormalization (12.5%) vs. impaired relaxation (13.6%). Postoperative cardiovascular complications rate was highest also in the restriction group, 55.5%, and did not differ between pseudonormalization (25%) and impaired relaxation group (27.2%). Logistic regression analysis showed that restrictive LV filling pattern, early diastolic filling deceleration time and LV end-diastolic diameter independently influence perioperative mortality. In the early postoperative period mean LV wall motion score (WMS) did not improve in 8/19 (42%), 6/14 (43%) and 8/12 (67%) patients, respectively, in the impaired relaxation, pseudonormalization and restriction group. CONCLUSIONS:In patients with severe LV dysfunction undergoing CABG, impaired relaxation and pseudonormal pattern of LV diastolic filling correlated with postoperative improvement in LV regional contraction, while restrictive pattern correlated with high early postoperative mortality, morbidity and minimal improvement in LV systolic function. Restrictive LV filling pattern, early diastolic filling deceleration time and LV end-diastolic diameter were found to be independent predictors of perioperative mortality.     

Relation of exercise capacity to left ventricular systolic function and diastolic filling in idiopathic or ischemic dilated cardiomyopathy

Although exercise intolerance is a cardinal symptom of patients with dilated cardiomyopathy (DC) and heart failure, the factors that limit exercise capacity in these patients remain a matter of debate. To assess the contribution of left ventricular (LV) diastolic filling to the variable exercise capacity of patients with DC, we studied 47 patients (60 +/- 12 years) with DC in stable mild-to-moderate heart failure with a mean LV ejection fraction of 28%. Exercise capacity was measured as total body peak oxygen consumption (VO2) during symptom-limited bicycle (10 W/min) and treadmill (modified Bruce protocol) exercise. LV systolic function and diastolic filling were assessed at rest before each exercise by M-mode, Doppler echocardiography, and radionuclide ventriculography. As expected, treadmill exercise always yielded higher peak VO2 than bicycle exercise (21 +/- 6 vs 18 +/- 5 ml/kg/min, range 12 to 35 and 7 to 30 ml/kg/min, respectively, p <0.001). Both of these VO2 measurements were highly reproducible (R = 0.98). With univariate analysis, close correlations were found between peak VO2 (with either exercise modalities) and Doppler indexes of LV diastolic filling, as well as with the radionuclide LV ejection fraction. Stepwise multiple regression analysis identified 3 nonexercise variables as independent correlates of peak VO2, of which the most powerful was the E/A ratio (multiple r2 = 0.38, p <0.0001), followed by peak A velocity (r2 = 0.54, p <0.0001) and mitral regurgitation grade (r2 = 0.58, p = 0.024). In conclusion, our data indicate that in patients with DC, peak VO2 is better correlated to diastolic filling rather than systolic LV function.     

Left ventricular diastolic filling abnormalities in left anterior descending disease

Reduced left ventricular diastolic filling (DF) has been noted in coronary disease (CD) patients with normal left ventricular systolic function (NLVF). However, previous studies have included patients with regional wall disease, hypertension, or left ventricular hypertrophy. In the absence of these factors, only a subgroup of patients who had greater than 75% luminal obstruction of the left anterior descending artery (LAD) demonstrated DF abnormalities. Using 60 frames/sec biplane contrast ventriculography, we evaluated the left ventricular filling curve and its derivative in 21 patients with normal coronary arteries and NLVF (group 1), 17 CD patients with NLVF and no LAD disease (group 2), and 18 patients with LAD disease and NLVF (group 3). The peak filling rate (PFR) as end diastolic volumes/sec (EDV/S) was reduced in group 3 patients (group 3: 3.00 +/- 0.51 EDV/S vs group 1: 3.59 +/- 0.84 EDV/S, p less than .05; and group 2: 3.61 +/- 0.91 EDV/S, p less than .05). There was marked overlap in the PFR's between the normal and LAD group. DF may be normal in CD patients with NLVF in the absence of LAD disease. LAD patients have abnormal DF, but these abnormalities lack predictive valve.     

Ischemia-induced impairment of left ventricular relaxation: Relation to reduced diastolic filling rates of the left ventricle

An investigation was performed in order to better define the cause of reduced diastolic filling rates of the left ventricle (LV) observed in the setting of acute myocardial ischemia. Seven closed chest, anesthetized pigs were instrumented by placing a micromanometer-tip catheter in the LV and a balloon tip catheter in the midportion of the left anterior descending coronary (LAD) artery. The animal's red blood cells were labeled with technetium-99m and LV time-activity curves obtained by means of a computer-controlled, nonimaging cardiac probe (collimated, 3.5 cm DIA, sodium iodide crystal). Nuclear data obtained simultaneously with LV pressure data were used to evaluate diastolic pressure-count rate (i.e., volume) relations of the LV under control conditions and at 5 and 10 minutes after balloon occlusion of the animal's LAD. Diastolic filling rates, the time constant (“T”) of ventricular relaxation, the chamber passive stiffness constant (“K”), and maximum negative left ventricular $\text{DP}\text{DT}$ were computed for each experimental condition. Maximum negative $\text{DP}\text{DT}$ decreased compared with control (1690 + 699 mm Hg/sec; mean ± 1 SD) at both 5 minutes (1040 ± 493, p < 0.01) and 10 minutes (1360 ± 588, p < 0.05) after occlusion. Likewise “T” was prolonged versus control (45.3 ± 6.4) at both 5 minutes (56.8 ± 12.8, p < 0.01) and 10 minutes (54.0 ± 8.7, p < 0.05) after occlusion. In contrast both “K” and calculated left ventricular pressure at zero counts (i.e., volume) remained constant throughout the study. Left ventricular end-diastolic pressure also did not change significantly during the study. The mean, maximal, and mid to late LV diastolic filling rates all were prolonged significantly (p < 0.05) versus control at 5 minutes and 10 minutes after occlusion. The rate of early diastolic filling of the LV did not change significantly during the study, although it tended to decline along with the other rates. Thus, ischemia-induced changes in diastolic filling rates may be seen in the absence of changes in left ventricular chamber stiffness, and ischemia-induced impairment of left ventricular relaxation alone is sufficient to reduce the rate of diastolic filling of the LV.     

Effect of inotropic and vasodilator therapy on left ventricular diastolic filling in dogs with severe left ventricular dysfunction

Inotropic and vasodilator therapy for congestive heart failure improve left ventricular systolic performance by different mechanisms. However, the nature and extent to which diastolic filling is altered have not been well described. Acute severe left ventricular dysfunction was induced in 21 dogs by severe left ventricular global ischemia produced by left main coronary artery microsphere embolization until left ventricular end-diastolic pressure was greater than or equal to 18 mm Hg. Dobutamine was infused in seven dogs until the peak positive first derivative of left ventricular pressure (dP/dt) increased by greater than or equal to 33%. Nitroprusside was infused in seven dogs until left ventricular end-diastolic pressure was less than 15 mm Hg. Seven dogs were observed for 1 h after the induction of acute severe left ventricular dysfunction and served as the control group. In all groups of dogs, severe left ventricular dysfunction resulted in left ventricular dilation, reduction in area ejection fraction, elevation of left ventricular end-diastolic pressure and an early redistribution of diastolic filling (increased 1/3 and 1/2 filling fractions) despite a markedly abnormal time constant of relaxation. No changes were noted in any variable after 1 h of observation in the seven control dogs. Nitroprusside reduced left ventricular size and filling pressure, increased cardiac output, improved relaxation and redistributed diastolic filling to later in diastole as characterized by a reduced 1/3 filling fraction (19.4 +/- 7.4% versus 51.4 +/- 10%, p less than 0.001). The pressure-area curve was shifted downward and leftward.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation between left ventricular diastolic function and exercise tolerance in patients with left ventricular dysfunction

Previous studies show no correlation between resting systolic left ventricular performance assessed as the ejection fraction and exercise tolerance. This study examined the relation between left ventricular diastolic performance and exercise tolerance in 63 patients with left ventricular dysfunction (ejection fraction less than 50%) due to known or suspected coronary artery disease. The 51 men and 12 women, aged 54 +/- 8 years (mean +/- standard deviation), underwent symptom-limited upright exercise testing on a bicycle ergometer. The exercise end-points were angina (n:5), dyspnea (n:16), and fatigue (n:42). The patients were divided into three groups: group 1 (n:28) with normal exercise tolerance (9.5 +/- 2.4 minutes), group 2 (n:18) with mild exercise intolerance (5.8 +/- 0.5 minutes), and group 3 (n:17) had severe exercise intolerance (3.7 +/- 0.9 minutes). The three groups did not differ in age, ejection fraction, end-diastolic volume, exercise end-point, exercise heart rate, and left ventricular peak filling rate at rest. The exercise peak filling rate was, however, significantly higher in group 1 (p = 0.03). Stepwise multivariate discriminant analysis of important variables identified the exercise peak filling rate as the only predictor of exercise tolerance (F = 6.0). Thus, variation in exercise peak filling rate may in part explain the variability of exercise tolerance in patients with left ventricular dysfunction; patients with preserved exercise capacity have higher exercise peak filling rate than those with exercise intolerance.     

Relation between extent of left ventricular hypertrophy and diastolic filling abnormalities in hypertrophic cardiomyopathy

In hypertrophic cardiomyopathy, the relation between left ventricular diastolic impairment and magnitude of left ventricular hypertrophy has not been clearly defined. In the present study, Doppler echocardiographic indexes of left ventricular diastolic filling were compared in 78 patients with hypertrophic cardiomyopathy and in 72 normal control subjects of similar age, and the relation between abnormalities of diastolic filling and magnitude of left ventricular hypertrophy was assessed. In patients with hypertrophic cardiomyopathy, isovolumic relaxation was prolonged (94 +/- 25 ms); peak early diastolic flow velocity (53 +/- 18 cm/s), deceleration of flow velocity in early diastole (341 +/- 142 cm/s2) and the ratio between early and late peaks of flow velocity (1.6 +/- 0.9) were reduced; and peak late diastolic flow velocity was increased (38 +/- 15 cm/s) compared with values in control subjects (76 +/- 12 ms, 65 +/- 12 cm/s, 512 +/- 131 cm/s2, 2.3 +/- 0.8 and 30 +/- 7 cm/s, respectively; p less than 0.001). Individual patient analysis showed that diastolic filling was abnormal in 52 (67%) of the 78 patients with hypertrophic cardiomyopathy. However, within the patient group, none of the Doppler diastolic indexes showed a significant correlation with maximal left ventricular wall thickness or the wall thickness index (correlation coefficients ranged from -0.15 to 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)     

Intraventricular filling flows in assessment of left ventricular diastolic function in the elderly

AIM: To assess effect of old age on Doppler parameters of intraventricular filling flows. MATERIAL: Echocardiography with determination of velocity and time of early diastolic flow propagation, degree of its deceleration, maximal regional intraventricular flow velocity, and late diastolic interval A-Ar was carried out in healthy elderly (age 68.0+/-7.5 years, n=20) and middle aged (mean age 45.9+/-5.9 years, n=20) persons. RESULTS: Elderly compared with middle aged persons had decreased velocity (42.1+/-1.6 and 57.6+/-0.9 cm/sec, respectively, p=0.0001) and prolonged time (29.3+/-4.3 and 18.4+/-2.2 ms, respectively, p=0.02) of intraventricular early diastolic flow propagation, lower Eiv (0.64+/-0.04 and 0.92+/-0.04 ms, respectively, p=0.0001) and E(iv)/E (0.85+/-0.04 and 1.14+/-0.07, respectively, p=0.006), similar A-Ar (55.2+/-3.5 and 0.54+/-0.04 ms, respectively, p=0.78). CONCLUSION: Advanced age is associated with worsened active relaxation of the myocardium which is not accompanied by substantial changes of late diastolic left ventricular stiffness.     

Left ventricular diastolic filling in patients with left ventricular dysfunction

The pattern of abnormal left ventricular diastolic filling and its specificity in coronary disease patients with severe left ventricular dysfunction has received little attention. We evaluated the left ventricular diastolic filling curve derived from gated blood pool scans in 21 normals, 61 coronary disease patients with ejection fractions less than or equal to 30%, and 51 congestive cardiomyopathy patients with ejection fraction less than or equal to 30%. The peak filling rate (PFR), peak ejection rate (PER), PFR/PER and the % stroke volume filled at 1/3 of diastole (%SV-1/3 DT) and at the end of the rapid filling period (%SV-RFP) were determined for each group. The PFR and PER were reduced in both coronary disease and congestive cardiomyopathy groups. The PFR/PER was increased in the coronary disease group (1.19 +/- 0.28) and congestive cardiomyopathy group (1.21 +/- 0.32) as compared to normals (0.93 +/- 0.20, P less than 0.001). A greater %SV-1/3 DT and %SV-RFP were noted in both coronary disease and congestive cardiomyopathy groups. Coronary disease and congestive cardiomyopathy patients with a mean pulmonary capillary pressure (PCP) greater than or equal to 18 mm Hg had a greater PFR/PER, %SV-1/3 DT, and %SV-RFP than patients with a PCP less than 18 mm Hg. An abnormal and nonspecific pattern of left ventricular diastolic filling is present in both coronary disease and congestive cardiomyopathy patients and is characterized by an increased PFR/PER, a greater %SV-1/3 DT, and a greater %SV-RFP. This pattern may be related to elevated PCPs.     

Abnormal left ventricular diastolic filling in eccentric left ventricular hypertrophy of obesity.

Left ventricular (LV) diastolic filling pattern of obese subjects with eccentric LV hypertrophy was studied. Findings were compared with those of normal control subjects and hypertensive patients with concentric LV hypertrophy. M-mode, 2-dimensional and Doppler echocardiograms were recorded in 11 obese (body mass index greater than 30 kg/m2) normotensive patients with eccentric LV hypertrophy, 10 normal control subjects, and 18 nonobese, hypertensive patients with concentric LV hypertrophy whose antihypertensive medications were discontinued 2 weeks before study. LV hypertrophy was defined as LV mass/height greater than 143 g/m. Hypertrophy in the obese patients was eccentric: Their LV internal dimension (61 +/- 3 mm) was greater than that of hypertensive patients (55 +/- 5 mm, p less than 0.001) and normal control subjects (55 +/- 2 mm, p less than 0.01); their septal (10.7 +/- 0.7 mm) and posterior (10.9 +/- 0.6 mm) wall thicknesses were smaller than those of the hypertensive patients (12.2 +/- 1.7 mm, p less than 0.05 and 11.7 +/- 1.2 mm, respectively, difference not significant). Pulsed-wave Doppler echocardiographic filling indexes were used to evaluate LV diastolic filling. Obese patients had a higher peak velocity of atrial filling (69 +/- 14 vs 54 +/- 15 cm/s, p less than 0.05), lower early/atrial filling velocity ratio (1.0 +/- 0.26 vs 1.32 +/- 0.21, p less than 0.05), prolonged deceleration half-time (108 +/- 9 vs 86 +/- 15 ms, p less than 0.01) and lower peak filling rate corrected to stroke volume (4.08 +/- 0.68 vs 4.96 +/- 0.88 stroke volume/s, p less than 0.05) than normal control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Echocardiographic assessment of left ventricular diastolic function and filling pressure in atrial fibrillation

Diastolic dysfunction has been linked to 2 epidemics: atrial fibrillation (AF) and heart failure. The presence and severity of diastolic dysfunction are associated with an increased risk for first AF and first heart failure in patients with sinus rhythm. Furthermore, the risk for heart failure is markedly increased once AF develops. The evaluation of diastolic function once AF has developed remains a clinical challenge. The conventional use of Doppler echocardiography for the assessment and grading of diastolic dysfunction relies heavily on evaluating the relation of ventricular and atrial flow characteristics. The mechanical impairment of the left atrium and the variable cycle lengths in AF render the evaluation of diastolic function difficult. A few Doppler echocardiographic methods have been proved clinically useful for the estimation of diastolic left ventricular filling pressures in AF, but these appear to be underutilized. Several innovative methods are emerging that promise to provide greater precision in diastolic function assessment, but their clinical utility in AF remains to be established. In conclusion, this review provides an up-to-date discussion of the evaluation of diastolic function assessment in AF and how it may be important in the clinical management of patients with AF.     

Influence of left ventricular diastolic filling on symptoms and survival in patients with decreased left ventricular systolic function

The relation between left ventricular (LV) filling variables measured by gated blood pool radionuclide ventriculography and clinical symptoms and survival was examined in 93 patients who had decreased LV systolic function. The diastolic data were not significantly associated with clinical symptoms. Time to peak filling rate, peak filling rate and ejection fraction were associated independently with survival free of cardiac death (chi-square = 7.74, 5.91 and 3.92, respectively, by stepwise Cox regression analysis). A short time to peak filling rate or increased peak filling rate was associated with decreased survival, whereas the opposite indicated a good prognosis. One-year Kaplan-Meier survival was 73 and 98% when time to peak filling rate was below or above the median value of 167 ms, respectively, 82 and 90% when peak filling rate was above or below the median value of 1.67 end-diastolic volumes per second, respectively, and 76 and 95% when LV ejection fraction was below or above the median value of 0.35, respectively. Thus, filling variables (time to peak filling rate and peak filling rate) measured by radionuclide ventriculography may be valuable in predicting survival in patients with decreased LV systolic function.