Abnormal Left Ventricular Relaxation Research Articles

Preclinical cardiac dysfunction in transfusion-dependent children and young adults detected with low-dose dobutamine stress echocardiography

Transfusion-dependent (TD) patients develop cardiac iron overload that will eventually lead to cardiac pump failure. Low-dose dobutamine stress echocardiography may complement resting echocardiography and identify preclinical myocardial dysfunction caused by early cardiac hemosiderosis. Twenty-six iron-overloaded TD patients had stress echocardiography with 5 μg/kg per minute of dobutamine. Indexed left ventricular (LV) mass, LV dimensions, meridional wall stress, and cardiac index were significantly increased. TD patients had similar LV shortening fraction by M-mode (40.5% ± 5.6% vs 39.4% ± 4.5%) but had a lower mean LV ejection fraction (53.3% ± 3.9% vs 46.8% ± 6.9%, P < .002) and a subnormal increase in cardiac index during dobutamine stress (35% ± 20% vs 11% ± 16%, P < .0001). Impairment in LV relaxation was demonstrated by a prolonged isovolumetric relaxation time (0.060 ± 0.005 vs 0.088 ± 0.019 seconds, P < .0001), increased peak mitral E wave, and abnormal E/A ratio. Asymptomatic TD patients demonstrate decreased systolic functional reserve and abnormal left ventricular relaxation that may be caused by cardiac hemosiderosis. Low-dose dobutamine stress echocardiography may be useful for detecting and following cardiac dysfunction in patients at risk for cardiac hemosiderosis. (J Am Soc Echocardiogr 1998;11:948-56.)

Effects of spontaneous respiration on transmitral Doppler flow patterns in normal subjects and patients with coronary artery disease

Background The potential effects of spontaneous respiration on Doppler mitral inflow patterns in patients with abnormal left ventricular diastolic function are poorly understood. Methods and Results The respiratory changes of Doppler transmitral flow velocity indexes were investigated in 20 healthy subjects and 20 patients with coronary artery disease. All patients had a mitral inflow pattern of abnormal left ventricular relaxation (reversal of early/late diastolic peak flow velocity ratio). The Doppler mitral inflow signals were measured at end-expiration and end-inspiration. In both groups, the early diastolic peak flow velocity and flow velocity integral, the ratio of early/late diastolic peak flow velocity, and the ratio of early/late diastolic flow velocity integral at end-inspiration were significantly lower than those at end-expiration. However, the late diastolic peak flow velocity and flow velocity integral were not significantly different between end-inspiration and end-expiration. During inspiration, the early diastolic peak flow velocity and the ratio of early/late diastolic peak flow velocity were reduced by an average of 23% and 22%, respectively, in normal subjects and were reduced by an average of 19% and 17%, respectively, in the patient group. Conclusions Left ventricular early diastolic filling can be substantially reduced by inspiration in normal subjects and in patients with abnormal left ventricular diastolic function. The potential effects of respiratory cycle should be taken into account when assessing left ventricular diastolic function by using Doppler echocardiography. (Am Heart J 1998;136:99-102.)

Load-sensitive diastolic relaxation in hypertrophied left ventricles.

We studied effects of enalaprilat and L-158,809, an angiotensin II type-1 receptor antagonist, on left ventricular (LV) diastolic relaxation in 11 normal control dogs and 16 LV hypertrophied (LVH) dogs with perinephritic hypertension. At baseline, LV systolic and end-diastolic pressures and end-systolic elastance were increased in the LVH group (all P < 0.01 vs. the control group). LV relaxation time constant was also prolonged (P < 0.01), suggesting impaired LV diastolic relaxation in this model of LVH. Before and after the administration of enalaprilat (0.25 mg/kg) and L-158,809 (0.30 mg/kg), LV relaxation was assessed over a wide range of LV loading conditions during vena caval occlusion. LV relaxation time constant was insensitive to load reduction in the control group, which was not affected by enalaprilat or L-158,809. In contrast, LV unloading caused a significant prolongation of the relaxation time constant in the LVH group. This load-sensitive LV relaxation abnormality was significantly improved by enalaprilat or L-158,809. These results support the concept that angiotensin II is involved in the pathogenesis of diastolic dysfunction in pressure-overloaded LVH and also suggest that angiotensin-converting enzyme inhibitors and angiotensin II type-1 receptor antagonists are potentially beneficial in the treatment of the hypertrophied heart.

Differences in Transmitral Flow Velocity Pattern during Increase in Preload in Patients with Abnormal Left Ventricular Relaxation

Changes in transmitral flow (TMF) and pulmonary venous flow (PVF) velocities during increases in preload were compared in patients with a higher peak atrial systolic velocity than peak early diastolic velocity (A/E > 1) for the TMF velocity to determine differences in hemodynamic response. Fifteen patients with dilated hearts, 22 with hypertrophied hearts and 15 control patients were studied. TMF and PVF velocities were recorded by transesophageal pulsed Doppler echocardiography before and during application of lower body positive pressure. The value for peak early diastolic velocity increased, while the isovolumic relaxation time decreased with increases in preload in all groups. The value for peak atrial systolic velocity decreased in the dilated-heart group, but increased in the hypertrophied-heart and control groups. The peak second systolic and early diastolic PVF velocities increased in the dilated- and hypertrophied-heart groups, but did not change in the control group. The peak atrial systolic PVF velocity and the difference in duration of the atrial systolic PVF and TMF velocities increased in the dilated- and hypertrophied-heart groups, and its changing rate was highest in the group with dilated hearts. These results suggest that both peak early diastolic and atrial systolic TMF velocities increase during increases in preload through the Frank-Starling mechanism in hypertrophied hearts. Furthermore, the left ventricular functional reserve was lower in the dilated-heart group. Thus, TMF and PVF velocities respond differently during increases in preload, depending on the underlying heart disease.

Clinical and echocardiographic correlates of mitral E-wave transmission inside the left ventricle: Potential insights into left ventricular diastolic function

The mitral inflow wave is initially directed to the left ventricular apex and then turns around facing the left ventricular outflow tract. The E and A waves are transmitted to the left ventricular outflow tract where they are registered as Er and Ar waves, respectively. We hypothesized that the E-wave transit time to the left ventricular outflow tract recorded as the E-Er interval may depend on left ventricular early diastolic performance such as relaxation. This hypothesis was tested in clinical settings known to have abnormal left ventricular relaxation. Mitral E and left ventricular outflow tract Er waves were recorded with pulsed wave Doppler technique in 63 subjects: 25 healthy subjects, 18 patients with secondary left ventricular hypertrophy, and 20 patients with hypertrophic cardiomyopathy. The E-Er interval was measured from the onset of E wave to the onset of Er wave timed to the R wave of the electrocardiogram. The E-Er interval ranged from 45 to 300 msec: 96 ± 28 msec in the controls, 127 ± 46 msec in patients with left ventricular hypertrophy ( p = 0.0091 versus controls), and 179 ± 57 msec in patients with hypertrophic cardiomyopathy ( p < 0.0001 versus controls). It correlated with left ventricular free wall thickness ( r = 0.42, p = 0.0006), thickness of the ventricular septum ( r = 0.43, p = 0.0004), left ventricular end-diastolic diameter ( r = –0.38, p = 0.0022), left ventricular end-systolic diameter ( r = –0.55, p < 0.0001), left ventricular isovolumic relaxation time ( r = 0.39, p = 0.0063), RR interval ( r = 0.28, p = 0.045), mitral E/A velocity ratio ( r = –0.33, p = 0.010), and E-wave deceleration time ( r = 0.38, p < 0.0044) but not with age. Multivariate analysis with all the previously mentioned variables and the group the patient belonged to as the dichotomous variable showed that the grouping variable was the sole independent determinant of the E-Er interval (multiple r = 0.74). The E-Er interval is an easily measurable Doppler parameter which is increased in left ventricular hypertrophy and hypertrophic cardiomyopathy. It is related to left ventricular wall thickness, left ventricular isovolumic relaxation time, mitral E/A velocity ratio, and E-wave deceleration time and may provide useful insight into left ventricular early diastolic performance—possibly the relaxation process. (J Am Soc Echocardiogr 1997;10:532-9.)

Disparity Between Diastolic Mitral Flow Characteristics and Left Ventricular Mass in Essential Hypertension

Because left ventricular (LV) hypertrophy and aging have been associated with abnormal LV relaxation, this study evaluated the impact of LV mass on the filling patterns derived by Doppler in a large population aged > or =50 years. Results suggest that in essential hypertension the intrinsic myocardial composition is more important than cardiac hypertrophy in determining LV diastolic properties. This apparent discrepancy between LV mass and diastolic filling patterns highlights the difficulty in establishing the diagnosis of diastolic dysfunction in elderly hypertensives.

Clinical Application of Pulsed Doppler Tissue Imaging for Assessing Abnormal Left Ventricular Relaxation

Conventional assessment of left ventricular (LV) relaxation by calculating the time constant of LV pressure decay during the isovolumic diastole requires an invasive approach. Conversely, noninvasive parameters obtained by measuring isovolumic relaxation time and transmitral flow velocity often give inaccurate information. Using LV pressure curve, pulsed Doppler echocardiography, and pulsed Doppler tissue imaging in 38 patients with heart disease and 12 control subjects, we calculated the time constant and recorded transmitral flow velocity and motion velocities at the endocardial portions of the ventricular septum and LV posterior wall. Compared with the controls, patients exhibited a prolonged time constant, a decreased peak early diastolic velocity of the LV posterior wall, and a prolonged time interval from the second heart sound to the peak of the early diastolic wave. The time constant correlated well with the isovolumic relaxation time and various parameters calculated from the transmitral flow velocity, except in patients with elevated LV end-diastolic pressure. In all subjects, the time constant correlated negatively with the peak early diastolic velocity of the posterior wall and positively with the time from the second heart sound to the peak of the early diastolic wave. Thus, early diastolic parameters derived from the motion velocity of the LV posterior wall by pulsed Doppler tissue imaging were closely related to the time constant. This technique may allow noninvasive evaluation of abnormal LV relaxation in patients with various heart diseases.We assessed left ventricular (LV) relaxation in 38 patients with heart disease using pulsed Doppler tissue imaging. The time constant correlated negatively with the peak early diastolic velocity and positively with the time from the second heart sound to the peak of the early diastolic wave in all patients. Doppler tissue imaging can noninvasively determine abnormal LV relaxation.

Retrograde atrial kick in acute aortic regurgitation. Study of mitral and pulmonary venous flow velocities by transthoracic and transesophageal echocardiography.

The purpose of this study was the comprehensive evaluation of the changes in pulmonary venous and mitral flow velocities of patients with acute and chronic severe aortic regurgitation. Transmitral flow velocities obtained with pulsed-wave Doppler echocardiography have been used to provide information on left ventricular (LV) filling and diastolic function. Pulmonary venous flow tracings are an important adjunct to LV inflow pattern in assessing LV diastolic function. Fourteen patients with severe aortic regurgitation (8 chronic and 6 acute) and in sinus rhythm were examined by transthoracic and transesophageal pulsed Doppler echocardiography. Mitral and pulmonary flow velocities were recorded and compared. All patients had ejection fractions > 40%. Early mitral flow peak velocity was higher in patients with acute regurgitation (p < 0.001). The mitral A wave was absent in five patients with acute regurgitation. In contrast, a prominent reverse atrial pulmonary systolic wave AR was demonstrated in these patients. Peak diastolic velocity of the pulmonary venous flow was greater in patients with acute aortic regurgitation (0.76 +/- 0.13) than in patients with chronic aortic regurgitation (0.40 +/- 0.09) (p < 0.001). Peak systolic velocity did not differ significantly between the two groups. The systolic fraction of pulmonary venous flow in patients with acute aortic regurgitation was lower (0.43 +/- 0.05) than that of patients with chronic regurgitation (0.63 +/- 0.1) (p < 0.01). All patients with acute aortic regurgitation had an S/D ratio < 1, while those with chronic regurgitation had an S/D > 1 (p < 0.001) and an E/A < 1. Patients with severe acute aortic regurgitation showed a retrograde atrial kick (absence of transmitral A wave with prominent pulmonary AR wave). These patients had an S/D ratio < 1 (restrictive Doppler pattern). Patients with chronic aortic regurgitation exhibited a Doppler pattern of abnormal LV relaxation (E/A < 1, S/D > 1).

Does dobutamine prevent the rise in left ventricular filling pressures observed during exercise after heart transplantation?

The purpose of the study was to evaluate whether infusion of a beta-adrenergic agonist, prior to and during exercise, could compensate for reduced sympathetic stimulation and correct deficient acceleration of left ventricular relaxation, so preventing a rise in left ventricular filling pressures during exercise after cardiac transplantation. Abnormal left ventricular relaxation kinetics can contribute to exercise-induced diastolic dysfunction of the cardiac allograft. This was demonstrated in transplant recipients whose acceleration of left ventricular relaxation during exercise was almost negligible recently and whose elevation of left ventricular end-diastolic pressure was high. Decreased adrenergic tone due to denervation could be involved in deficient left ventricular lusitropic response to exercise, because acceleration of left ventricular relaxation during exercise depends on adequate sympathetic stimulation. Serial supine bicycle exercise was performed at an identical workload in eight transplant recipients while in the control state and during continuous infusion of dobutamine, titrated before exercise to achieve a heart rate matching the heart rate at peak exercise in the control state. During control exercise, heart rate rose from 87 +/- 8 to 104 +/- 12 beats.min-1 (P < 0.05), left ventricular end-diastolic pressure from 14 +/- 5 to 20 +/- 4 mmHg (P < 0.05), left ventricular dP/dtmax from 1374 +/- 172 to 1854 +/- 278 mmHg.s-1 (P < 0.05), and cardiac output from 5.8 +/- 0.9 to 8.5 +/- 1.1 l.min-1 P < 0.05). There was a small but significant decrease of the time constant of left ventricular pressure decay (T) from 42 +/- 6 to 38 +/- 6 ms (P < 0.05). During dobutamine infusion, exercise resulted in a further increase in heart rate from 108 +/- 11 to 122 +/- 17 mmHg (P < 0.05), in cardiac output from 7.4 +/- 0.9 to 10.3 +/- 2.5 l.min-1 (P < 0.05), and in left ventricular dP/dtmax from 2181 +/- 220 to 2620 +/- 214 mmHg.s-1 (P < 0.05). These values were higher than the measurements obtained at the end of the control exercise run (P < 0.05). T failed to change (29 +/- 4 vs 27 +/- 5 mmHg, P > 0.05) and left ventricular end-diastolic pressure increased from 5 +/- 3 to 11 +/- 5 mmHg (P < 0.05) but remained lower than at the end of the control exercise run (11 +/- 5 vs 20 +/- 4 mmHg, P < 0.05). Compensation for reduced sympathetic stimulation by administration of dobutamine improves exercise haemodynamics in cardiac transplant recipients, but cannot prevent the exercise-induced rise in left ventricular end-diastolic pressure and correct deficient acceleration of left ventricular relaxation. Abnormal exercise haemodynamics after heart transplantation are therefore only partly related to deficient sympathetic stimulation.

Exercise Training Improves Left Ventricular Diastolic Filling in Patients With Dilated Cardiomyopathy

Patients with dilated cardiomyopathy (DCM) often have left ventricular (LV) diastolic dysfunction that can precede the development of systolic dysfunction. Recent reports showed that exercise training (ET) improves the exercise capacity of these patients. Although this improvement is primarily due to peripheral adaptations, the contribution of LV diastolic filling has not been well defined. The purpose of this study was to determine whether ET can induce changes in LV diastolic filling that can account for an increase in exercise capacity and whether these changes can influence prognosis. We prospectively studied 55 consecutive patients (mean age, 55 +/- 7 years) with DCM. Patients were randomized into a training group (36 patients) or a control untrained group (19 patients) and matched for clinical and functional characteristics. All patients underwent a pulsed Doppler echocardiographic study, a radionuclide angiographic study, and a cardiopulmonary exercise test before and after a 2-month ET program. On the basis of the Doppler LV diastolic filling pattern at the beginning of the study, patients were prospectively divided into three subgroups: A (restrictive pattern), B ("normal" pattern), and C (abnormal relaxation pattern). In the trained group, peak VO2 (+12%; P < .0001), peak workload (+8.5%; P < .005), and lactic acidosis threshold (+12%; P < .0001) were significantly increased after training without changes in LV ejection fraction. However, only subgroup C demonstrated significant improvement in peak VO2 (+15%; P < .005). No changes were observed in the untrained group. In the trained subgroups a significant increase in rapid filling fraction (RFF), peak filling rate (PFR), peak early filling velocity (E), and E/A ratio was noted. A significant decrease in atrial filling fraction (AFF), peak atrial filling velocity (A), deceleration time of early filling velocity (EDT), and isovolumic relaxation time (IVRT) was observed only in subgroup C. No changes were found in untrained subgroups. A good correlation was found between Doppler and radionuclide LV diastolic filling parameters before and after training (P < .0001). Multiple stepwise regression analysis demonstrated that pretraining E/A ratio (P < .0001) and peak heart rate (P < .0002) were positive predictors of pretraining peak VO2. Posttraining increase in exercise tolerance (P < .0001) and increase in E/A ratio (P < .0001) were the strongest predictors of an increase in peak VO2. The independent predictors of cardiac events were a greater RFF and a shorter IVRT and EDT. Stepwise logistic regression showed that Doppler LV diastolic filling patterns are independent predictors of overall cardiac events (P = .02), and restrictive pattern has a worse prognosis compared with B (P = .04) and C (P = .007). However, ET did not reach statistical significance (P = .54) as a predictor of cardiac events. These data demonstrate that ET induces significant improvement in exercise capacity only in patients with DCM and a pattern of abnormal LV relaxation. The improvement in peak VO2 is significantly correlated with an increase in peak early filling rate and peak filling rate as well as a decrease in atrial filling rate. Doppler echocardiography may be a valuable tool in the prognostic assessment of patients with DCM who will benefit from exercise training.

Beta-adrenergic receptors, adenylate cyclase activation, and myofibril enzyme activity in hypothyroid rats

A previous study in intact animals assessed cardiovascular alterations in surgically thyroidectomized rats. Hemodynamic challenge via isoproterenol infusion identified abnormal left ventricular relaxation. Challenge by aortic occlusion revealed a latent deficiency in left ventricular contractility which was not apparent during beta-agonist challenge. The present study utilized left ventricular cardiac tissue obtained from the identical control and thyroidectomized animals from which intact heart hemodynamic information had been obtained. Biochemical systems were selected for evaluation based on demonstrated hemodynamic alterations, i.e., beta-adrenergic receptor number/function and contractile protein enzyme properties. The number of beta-receptors on hypothyroid cardiac membranes was significantly decreased, but receptor agonist affinity was not influenced. Basal adenylate cyclase activity in cardiac membranes from control and thyroidectomized rats was nearly identical; however, isoproterenol activation was diminished in hypothyroid cardiac membrane, particularly at the higher levels of beta-agonist stimulation. Adenylate cyclase enzyme activation by forskolin was not influenced by thyroidectomy; however, activation by sodium fluoride was reduced approximately 30% when compared with preparations from control rats. Cardiac myofibrillar enzyme activity for adenosinetriphosphatase (ATPase) was significantly lower in thyroidectomized rats. Despite reduced ATPase activity, myofibrillar calcium sensitivity was unaltered. Myofibrillar creatine kinase enzyme activity was not influenced by thyroidectomy; therefore, compartmentalized ATP regeneration potential via creatine kinase was enhanced relative to substrate utilization via ATPase. Thus hemodynamically significant cardiac influences of hypothyroidism are mediated, at least in part, via 1) reduced beta-receptor number, 2) diminished catecholamine-induced activation of adenylate cyclase, and 3) reduced myofibrillar ATPase activity.

Endothelial control of vascular and myocardial function in heart failure.

The effect of vascular endothelium, endocardium, and coronary endothelium on vascular tone and myocardial contraction-relaxation sequence in heart failure is discussed. Vascular endothelium affects underlying vascular smooth muscle through paracrine secretion of relaxing and constricting factors. In heart failure, systemic vasoconstriction results not only from neuroendocrine activation, but also from disturbed local endothelial control of vascular tone because of impaired endothelial-dependent vasodilation and because of increased plasma concentration of endothelin. Experimental evidence obtained in isolated cardiac muscle strips established the influence of endocardial endothelium on the duration of myocardial contraction and on the onset of myocardial relaxation. By analogy to vascular endothelium, both diffusible agents that abbreviate (endothelial-derived relaxation factor-like substance) and those that prolong (endocardin) myocardial contraction have been shown to be released from the endocardium. Similar agents are released from the coronary endothelium and, because of the close proximity of capillaries and myocytes, could exert a major effect on myocardial performance. Endothelial dysfunction and concomitant lack of release of myocardial relaxant factors could explain left ventricular relaxation abnormalities observed in the cardiac allograft or in arterial hypertension. Since endothelial-derived relaxation factor or nitric oxide mediates the coronary reactive hyperemic response, a negative inotropic action of nitric oxide could contribute to left ventricular failure when left ventricular wall stress is elevated, as occurs after myocardial infarction in the noninfarcted zone and during left ventricular volume or pressure overload in the absence of adequate hypertrophy.

Filling patterns in left ventricular hypertrophy: A combined acoustic quantification and Doppler study

Objectives. The purpose of this study was to evaluate the potential of acoustic quantification compared with Doppler echocardiography for assessment of left ventricular diastolic dysfunction.Background. Diastolic dysfunction usually accompanies left ventricular hypertrophy. Although Doppler echocardiography is widely used, it has known limitations in the diagnosis of diastolic abnormalities. The ventricular area-change waveform obtained with acoustic quantification technology may provide an alternative to assess diastolic dysfunction.Methods. Potential acoustic quantification variables (peak rate of area change and mean slope of area change rate during rapid filling, amount of relative area change during rapid filling and atrial contraction) were obtained and compared with widely used Doppler indexes of ventricular filling (isovolumetric relaxation time, pressure half-time, peak early diastolic velocity/peak late diastolic velocity ratio, rapid filling, atrial contribution to filling) ia 16 healthy volunteers and 30 patients with left ventricular hypertrophy.Results. Criteria for abnormal relaxation were present in 68% of patients by acoustic quantification and in 64% of patients by Doppler echocardiography. However, abnormal relaxation was identified in 89% of patients by one or both methods. Acoustic quantification indicated abnormal relaxation in the presence of completely normalized Doppler patterns and in patients with mitral regurgitation or abnormal rhythm with unreliable Doppler patterns.Conclusions. Acoustic quantification potentially presents a new way to assess diastolic dysfunction. This technique may be regarded as complementary to Doppler echocardiography. The combined use of the methods may improve the diagnosis of left ventricular relaxation abnormalities.

Altération de la fonction ventriculaire gauche diastolique au cours du syndrome primitif des anticorps antiphospholipides

Previous studies have shown that left ventricular (LV) diastolic function is frequently impaired in patients with systemic lupus erythematosus. We prospectively studied echo-Doppler indices of LV diastolic function in 18 patients with primary antiphospholipid syndrome (PAPS), who where compared to a group of 18 healthy controls. Heretofore undescribed LV relaxation abnormalities were found in the PAPS group: this finding suggests the existence of a causal link.

Determinants of left ventricular filling dynamics: alteration in the Doppler-derived transmitral filling profile with progressive impairment of cardiac function in a dog preparation.

To clarify the factors determining transmitral filling, left ventricular and atrial pressures (LVP and LAP) and Doppler-derived diastolic indices were analysed in six anaesthetized dogs at various right atrial pacing rates during dextran infusion. The relationship of the late to early diastolic peak velocity ratio (A/E ratio) to end-diastolic LVP (LVEDP) showed a quadratic curve concave to the LVEDP axis in five animals (r2 = 0.320-0.588). An elevation in LVEDP up to 25 mmHg accompanied an increase in A/E ratio (ascending limb), and further LVEDP elevation caused its inverse decline (descending limb). Multiple regression analysis indicated that A/E ratio correlated positively with maximal LVP, a-wave LAP and heart rate, and negatively with v-wave LAP in both limbs. The time constant of isovolumic LVP decline, which was prolonged as LVEDP was elevated, was a positive correlate of A/E ratio in the ascending limb, but lost its influence on A/E ratio in the descending limb. An elevation in v-wave LAP must have masked the expected effect of left ventricular relaxation abnormality on A/E ratio in this limb. Thus, the transmitral filling profile did not alter unidirectionally, but returned to that seen before volume loading, with a simultaneous progressive impairment of cardiac function.

Changes in left ventricular function and wall thickness in heart transplant recipients and their relation to acute rejection: an assessment by digitised M mode echocardiography.

Assessment of changes in left ventricular diastolic function and wall thickness after heart transplantation to verify whether these changes predicted acute rejection assessed by endomyocardial biopsy. Follow up according to a predefined protocol of consecutive patients from the first week after transplantation. Heart transplantation unit of the Thoraxcentre, University Hospital Rotterdam Dijkzigt, The Netherlands. All 32 patients undergoing orthotopic heart transplantation from 1 January 1989 to 31 March 1990 were examined. Two were excluded from the analysis. Patients were treated with cyclosporin and low dose steroids. Data obtained by digitised M mode echocardiography were compared with the results of endomyocardial biopsy (Billingham classification). Mean values for left ventricular wall thickness, internal dimension, and their standardised rates of change and fractional shortening were determined from 4-6 consecutive expiratory beats. Mean values and individual trends during follow up were also investigated for each ultrasound variable. The results of these average values were compared with values in a group of 10 healthy volunteers. Median follow-up was 177 days (range 10-399). Two hundred and sixty three consecutive M mode studies were examined in relation to concurrent biopsy results. No significant differences were observed between the ultrasound variables at the time of moderate acute rejection (Billingham class 2, n = 37) and other biopsy classes (n = 226). Nor did changes in individual patients predict (moderate) acute rejection episodes. Twenty six of the 30 patients had an abnormal (slow) left ventricular relaxation pattern throughout follow up. Digitised left ventricular M mode echocardiography did not predict the presence of acute rejection. In most patients there was a persistent slow left ventricular relaxation pattern.

Left ventricular systolic and diastolic time intervals in familial amyloid polyneuropathy.

To determine left ventricular (LV) systolic and diastolic properties in patients with familial amyloid polyneuropathy (FAP), we analyzed simultaneous recordings of the electrocardiogram, phonocardiogram, carotid arterial pulse, and apex cardiogram in 14 patients and 21 normal subjects. LV systolic and diastolic time intervals were measured. Correlations between the intervals and neurologic disabilities, duration of illness, and age were examined. We found that in patients with FAP, 1) LV relaxation was impaired, especially in early diastole, whereas systolic function was generally preserved, 2) abnormal LV relaxation could be seen before the development of both clinically identifiable heart disease and the abnormalities in systolic function, 3) indexes of LV systolic function and relaxation decreased in parallel with the progress of the disease, duration of illness, and age, and 4) electromechanical delay was markedly increased.

Diastolic filling in acute left ventricular dysfunction: Role of the pericardium

Patients with congestive heart failure and elevated left ventricular filling pressures demonstrate an abnormal pattern of diastolic filling that is characterized by a redistribution of diastolic filling to early diastole with reduced reliance on late diastolic filling. The diastolic filling pattern superficially resembles that which is seen with constrictive pericarditis. To examine potential mechanisms for these clinical findings, a model of ischemic left ventricular dysfunction was produced in seven dogs by repeated coronary microsphere embolization, producing a dilated left ventricle with reduced systolic function.Measurements of left ventricular systolic and end-diastolic pressures, rate of rise of left ventricular pressure (dP/dt) and echocardiographic end-diastolic and end-systolic areas were obtained at baseline, during intermediate embolization (moderate left ventricular systolic dysfunction, dilation and mild increases in left ventricular end-diastolic pressure), postembolization (further embolization resulting in severe left ventricular systolic dysfunction, dilation and marked increases in left ventricular end-diastolic pressure), after thoracotomy and after pericardiectomy. The filling fraction at 1/3 and 1/2 of diastole and the time constant of left ventricular pressure decline were also determined.Repetitive coronary microembolization caused progressive left ventricular dilation and decreasing systolic function, which did not change after opening the chest or pericardium. The filling fraction at 1/3 and 1/2 of diastole declined with intermediate embolization (12.0 ± 5.6% and 23.1 ± 10.8%, respectively) as compared with baseline values (29.0 ± 11.9%, 42.9 ± 15.6%, p < 0.05). After embolization, there was an increase in the 1/3 and the 1/2 filling fraction (47.5 ± 8.9%, 72.0 ± 6.0%, respectively, p < 0.01) as compared with baseline values. This increase was associated with a marked increase in left ventricular end-diastolic pressure (baseline, 8 ± 3 mm Hg; postembolization, 25 ± 6 mm Hg; p < 0.001) and in the time constant of left ventricular pressure decline. Opening the chest produced no changes, but opening the pericardium decreased the 1/3 and the 1/2 filling fraction (19.1 ± 9.2%, 35.9 ± 11.8%, respectively, p < 0.001) as compared with postembolizalion values. Opening the chest or pericardium produced no changes in left ventricular areas, area ejection fraction, time constant of pressure decline or end-diastolic pressures.Redistribution of diastolic filling to early in diastole occurs in the acutely dilated left ventricle with elevated filling pressures despite marked abnormalities of left ventricular relaxation and is mediated by pericardial restraint.

Effects of verapamil and nifedipine on rate of left ventricular relaxation in coronary arterial disease patients

We have evaluated the effects of nifedipine and verapamil on rate of left ventricular relaxation in 26 patients having coronary arterial disease with normal ejection fraction and normal left ventricular contractility. None of the patients had myocardial infarction. All patients showed normal contractile indices and abnormally high values of T constant, neg. dP dt and left ventricular protodiastolic pressure, suggesting an impairment of left ventricular relaxation. Nifedipine, injected intravenously (15 μg/kg) in 14 patients induced a significant reduction of afterload parameters and an increase of contractility. Nifedipine also improved left ventricular relaxation, as it induced a reduction of the T constant from 42 ± 2 msec to 33 ± 2 msec ( P < 0.01). It induced a tendency to a reduction of negative dP dt and protodiastolic pressure without reaching statistical significance. Verapamil, injected intravenously in the remaining 12 patients (0.1 mg/kg as a bolus followed by chronic infusion of 0.005 mg/kg/min for 3 min) induced a reduction of the T constant from 43 ± 10 to 37 ± 6 msec ( P < 0.01). It reduced the negativity of dP dt from 2302 ± 273 to 2021 ± 252 mm Hg/sec ( P < 0.05) and of left ventricular protodiastolic pressure from 3.2 ± 1.4 to 1.5 ± 1.1 mm Hg ( P < 0.01). Verapamil, like nifedipine, reduced the afterload parameters although to a lesser extent. It did not substantially affect the left ventricular contractility. These data suggest that abnormalities of left ventricular relaxation may precede changes in systolic function and that nifedipine and verapamil favourably modify the indices of left ventricular diastolic function in patients with coronary arterial disease.

Effects of verapamil on contraction and relaxation of cultured chick embryo ventricular cells during calcium overload

The calcium channel blocking agents verapamil and nifedipine have been reported to lessen abnormalities of left ventricular relaxation in patients with severe left ventricular hypertrophy or coronary artery disease. Whether these effects in human beings are related in part to a direct effect on myocardial calcium metabolism is difficult to determine because of complicating drug influences on ventricular loading via systemic arterial vasodilation, on myocardial blood supply via coronary artery vasodilation and on reflex changes in sympathetic tone. For this reason, the effects of verapamil were investigated in a cellular model of impaired relaxation using spontaneously contracting tissue cultured monolayers of chick embryo ventricular cells exposed to high external calcium ([Ca]o). Under control conditions ([Ca]o, 0.9 mM), verapamil (2 X 10(-8)M) induced a 57 +/- 8% decrease in amplitude of cell contraction monitored with a phase contrast microscope video motion detector system. Elevation of [Ca]o from 0.9 to 8.0 mM resulted in a decrease in amplitude and velocity of contraction and a decrease in velocity of relaxation associated with an upward shift in diastolic cell wall position, suggesting a failure of normal myofilament dissociation. These abnormalities were completely reversible on reperfusion with [Ca]o, 0.9 mM. On re-exposure of the cells to [Ca]o, 8.0 mM, in the presence of verapamil, there was an increase in amplitude of contraction (0.56 +/- 0.11 to 1.03 +/- 0.09 micron, p less than 0.01) and velocity of relaxation (4.97 +/- 0.89 to 9.94 +/- 0.87 micron/s, p less than 0.01) compared with exposure to [Ca]o, 8.0 mM, alone, and an attenuation of the upward shift in diastolic cell wall position.(ABSTRACT TRUNCATED AT 250 WORDS)