Clinical impact of second harmonic imaging and left heart contrast in echocardiographic stress testing.

Second harmonic imaging and left heart contrast agents are recent echocardiographic advancements that enhance the assessment of wall motion. Because little information exists concerning their clinical impact on echocardiographic stress testing in daily practice, this was determined for 9-month periods before (1997) and after (1998) their introduction. Harmonic imaging was used in all patients after its introduction. A second generation intravenous left heart contrast agent (Optison) was used at the discretion of the sonographer and physician team. Both exercise and dobutamine stress tests were included. At the time of study interpretation, diagnostic confidence was assigned as high, medium, or low. For all patients who underwent coronary angiography < or = 6 months after stress testing, the diagnostic accuracy was determined (true positive plus true negative/total studies). There were 574 studies before and 746 studies after implementation. Optison was used in 28% of the harmonic imaging studies. Study cancellations due to uninterpretable images fell from 6.4% to 1.2% (p <0.001) despite a more obese population completing testing (body mass index: 29 +/- 7 to 31 +/- 8 kg/m2, p = 0.02), whereas high diagnostic confidence increased from 55% to 64% (p <0.001). For the 7% of patients who underwent cardiac catheterization, the diagnostic accuracy remained unchanged (74 vs 73%) although a prior negative stress test was less common (40% to 20% p = 0.04). Thus, these new technologies had a favorable clinical impact.

Factors leading to progression of valvular aortic stenosis.

The rate of progression of aortic stenosis (AS) in adults is variable. To determine whether clinical or echocardiographic variables are associated with more rapid hemodynamic progression, we identified 91 AS patients (initial valve area < or = 2.0 cm2) with 2 technically adequate studies separated by > or = 6 months. From the first study, left ventricular dimensions and AS severity were measured by standard Doppler-echocardiographic methods. Each aortic valve was graded for severity of calcification and degree of restricted leaflet motion; the sum of these grades provided a severity index reflecting leaflet pathology. Clinical and electrocardiographic variables were abstracted from medical records. Mean age was 68 years (range 29 to 89) and 61 were women. Initial AS severity ranged from an aortic valve area of 0.6 to 2.0 cm2 (median 1.3 cm2). During a mean follow-up of 1.8 years the aortic valve area decreased 0.04 cm2/year. The patient group with more rapid progression (decrease in aortic valve area > or = 0.1 cm2/year) had a larger proportion of men (p <0.01) and patients with an elevated serum creatinine (p = 0.04), a higher left ventricular mass index (p = 0.01), and a higher severity index (p <0.001). Multivariable regression analysis identified the severity index (direct relation) and the initial aortic valve area (inverse relation) as the only independent variables associated with more rapid progression. In conclusion, the rate of AS progression, although highly variable, is more rapid when leaflet calcification is more marked.

Embolic risk based on aortic atherosclerotic morphologic features and aortic spontaneous echocardiographic contrast.

BACKGROUND: Different aortic atherosclerotic plaque morphologic features may have varying embolic potentials. Spontaneous echocardiographic contrast (SEC) in the aorta, as in the left atrium, has been associated with an increased risk of embolic events and often occurs with complex aortic atherosclerosis. Thus an evaluation of their isolated and combined association with embolic events was undertaken. METHODS: We retrospectively studied all patients who underwent biplane or multiplane transesophageal echocardiography meeting the following inclusion and exclusion criteria: age >/=55 years and no other cardiac pathologic condition known to be associated with embolic events other than aortic atherosclerosis or aortic SEC. The 105 patients meeting the criteria were divided into those with aortic atherosclerosis and/or aortic SEC (the study group) and those without these aortic pathologic conditions (the comparison group). Complex aortic atherosclerosis was defined as mobile, ulcerated, or protuberant (> 4 mm). SEC was defined as a pulsatile, swirling echo pattern within the aortic lumen. Embolic events included strokes, transient ischemic attacks, or peripheral emboli. RESULTS: The 61 study patients and 44 comparison patients did not significantly differ with respect to the reason for referral, age, or sex. Embolic events occurred in 35 patients. Those with ulcerated or mobile plaques had a greater prevalence of embolic events (odds ratio 4.50; 95% confidence interval, 1.30-15.5; P <.05). The highest embolic event rate was seen in patients with any complex atherosclerosis and concomitant SEC (odds ratio 9.00; 95% confidence interval, 2.06-39.3; P <.01). Patients with SEC alone or protuberant plaques alone did not have a higher event rate (odds ratio 1.71 and 0.60; 95% confidence interval, 0.57-5.17 and 0.15-2. 47, respectively). CONCLUSIONS: Embolic events were associated with the presence of ulcerated or mobile aortic plaques. In addition, the combination of aortic SEC and any complex atherosclerosis had the highest embolic association.

Aortic sinotubular junction calcium as a marker of severe aortic atherosclerosis.

Because the significance of calcification of the sinotubular junction is poorly understood, we retrospectively investigated its association with aortic atherosclerosis in 101 patients who underwent transesophageal echocardiography. Such calcification was found to be a marker of more severe aortic atherosclerosis and, specifically, aortic arch disease.

Atrial fibrillation: restoration and maintenance of sinus rhythm and indications for anticoagulation therapy.

PURPOSE: To review the efficacy and safety of electrical and pharmacologic conversion of atrial fibrillation, strategies for maintenance of sinus rhythm, and the importance of antithrombotic therapy. DATA SOURCES: English-language trials were identified from the MEDLINE database through 1995, bibliographic references, Current Contents, textbooks, and recent abstracts. STUDY SELECTION: Randomized trials (including abstracts) were selected. Cohort studies were used if randomized trials were not available. DATA EXTRACTION: Study design and data were extracted from clinical trials. Statistical analysis of combined data was not appropriate, given the marked variations in study designs and study populations. DATA SYNTHESIS: Cardioversion restores sinus rhythm in more than 80% of patients. In atrial fibrillation of recent onset, pharmacologic regiments have a success rate of 40% to 90%. Sinus rhythm at 1 year is maintained in 30% of patients without antiarrhythmic therapy but in 50% of patients with such therapy. The efficacy and safety of antiarrhythmic drugs relative to one another are not established because trials done to date have been small and cases vary. Successful cardioversion and maintenance of sinus rhythm are most predictable when the duration of atrial fibrillation is brief. Warfarin reduces the incidence of ischemic strokes and emboli in patients with nonvalvular atrial fibrillation from 4.5% to 1.4% per year. Aspirin (325 mg/d) appears to be equally effective in patients younger than 75 years of age who do not have hypertension or a history of thromboembolism or recent heart failure. Although warfarin is more effective than aspirin in preventing embolic strokes in patients older than 75 years of age, it may increase the incidence of hemorrhagic stroke and result in a similar rate of disabling stroke. CONCLUSION: Cardioversion remains the preferred method with which to re-establish sinus rhythm. Long-term antiarrhythmic therapy is warranted only if recurrences or initial clinical instability are seen; pro-arrhythmic concerns and potential side effects should guide drug selection. Antithrombotic therapy is indicated for all patients older than 60 years of age and in all patients younger than 60 years of age who have clinical evidence of a primary cardiac disorder.

Parental hypertension and cardiac alterations in normotensive children and adolescents.

The objective of this investigation was the examination of the relation of left ventricular mass (LVM) and function with cardiovascular response to exercise in normotensive adolescents at risk for hypertension. Carried out was a prospective, cross-sectional study of 47 subjects (age, 10 to 18 years), who underwent dynamic and isometric exercise, 24-hour Holter monitoring, and echocardiography. Twenty-nine had normotensive parents (group 2, "at risk"). Both groups were similar for age, race, sex, body mass index, blood pressures, and resting heart rates. Group 2 had a higher E/A ratio (2.3 +/- 0.5 vs 2.0 +/- 0.5; p = 0.039) and higher heart rates during stage IV of dynamic exercise (188 +/- 20 beats/min vs 176 +/- 18 beats/min; p = 0.046). The LVM, 24-hour heart rates, and exercise systolic blood pressures (SBP) were similar in both groups. Only in group 2, SBP at peak dynamic and isometric exercise correlated best with LVM (r = 0.74, p < 0.002; r = 0.82, p < 0.001). It is concluded that altered hemodynamic regulatory mechanisms may exist before the establishment of hypertension in normotensive subjects with parental hypertension.

Spontaneous echocardiographic contrast in the thoracic aorta: factors associated with its occurrence and its association with embolic events.

Spontaneous echocardiographic contrast is associated with embolic events when it occurs in the left atrium. Because little is known about spontaneous echocardiographic contrast in the aorta, we investigated this association retrospectively in 343 patients without aortic dissection or aneurysm who had undergone transesophageal echocardiography. Two independent readers concurred on the presence of spontaneous echocardiographic contrast in the aorta in 93% of the study patients, with the remainder agreed on by consensus. Spontaneous echocardiographic contrast was found in 65 patients (19%) and was associated with older age (p < 0.0001), male sex (p < 0.0001), slightly larger aortas (p < 0.0001), and complex aortic atherosclerosis (p = 0.0001). Thirty-four (28.6%) of 119 patients with clinical embolic events had spontaneous echocardiographic contrast in the aorta in contrast to 31 (13.8%) of 224 patients referred for other reasons (p = 0.0001). This finding remained significant when spontaneous echocardiographic contrast in the aorta was the only abnormality allowed (n = 207, p = 0.0065) or when other echocardiographic variables known to be related to embolic events were included in a multivariate analysis. Thus, spontaneous echocardiographic contrast in the aorta can often be detected by transesophageal echocardiography and is associated with a higher prevalence of embolic events.

The relationship of autonomic function to age-related changes in left ventricular filling in normal subjects.

Heart rate and age are independent variables associated with the pattern of normal left ventricular filling. Since heart rate variability also varies with age, the relationship between these and left ventricular filling in normal subjects was assessed. In 31 subjects (age range 21 to 71 years), power spectral analysis of heart rate variability was determined from 24 h Holter tapes, and left ventricular filling was assessed by Doppler echocardiography. Relationships between heart rate variability and left ventricular filling were assessed by univariate and multivariate regression analyses. Total, low frequency and high frequency power each significantly correlated with the peak filling velocity with atrial systole (A) (r = -0.70, P < 0.0001; r = -0.69, P < 0.0001; r = -0.54, P < 0.01, respectively), but did not correlate with measures of early diastolic left ventricular filling. Although age and A were related (r = 0.46, P < 0.010), age was no longer a significant variable when measures of heart rate variability were included in the multivariate regression model for A. Thus, the variability in measures of early diastolic filling in normal subjects appears to be independent of measures of heart rate variability, whereas, A is significantly associated with these measures.

Prognostic value of dobutamine stress echocardiography in patients referred because of suspected coronary artery disease.

To determine whether dobutamine stress echocardiography (DSE) provides prognostic information beyond that available from routine clinical data, we reviewed the outcome of 210 consecutive patients referred for DSE to evaluate chest pain, perioperative risk, and myocardial viability. Dobutamine was infused in increments of 10 micrograms/kg/min in 5-minute stages to a maximum of 40 micrograms/kg/min. The dobutamine stress echocardiogram was considered abnormal only if dobutamine induced a new wall motion abnormality as determined by review of the digitized echocardiographic images in a quad screen format and on videotape. Thirty percent of tests were abnormal. An abnormal test was more common (p < or = 0.02) in men and patients with angina pectoris, in patients taking nitrate therapy, or those with prior myocardial infarction or abnormal left ventricular wall motion at rest. Twenty-two deaths, 17 of which were cardiac, occurred over a median follow-up of 240 days (range 30 to 760). Sixteen cardiac deaths occurred in the 63 patients with versus 1 cardiac death among the 147 without a new wall motion abnormality (p < or = 0.0001). Other variables associated with cardiac death (p < or = 0.05) were age > 65 years, nitrate therapy, ventricular ectopy during DSE, suspected angina pectoris, and hospitalization at the time of DSE. When cardiac death, myocardial infarction, and revascularization procedures were all considered as adverse outcomes, a new wall motion abnormality continued to be the most powerful predictor of an adverse cardiac event.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient myocardial ischemia in infants prenatally exposed to cocaine.

This prospective study examined whether neonates of pregnant women who used cocaine during pregnancy are at a risk for the development of transient myocardial ischemia and altered autonomic function, as in adults. We studied 21 of 35 infants with a history of prenatal exposure to cocaine. The ST segment changes and heart rate variability were evaluated from three-channel Holter monitors within 48 hours of birth. The data were compared with those on 20 control infants with similar birth weight, gestational age, and postnatal age. Six infants (29%) who were exposed to cocaine in utero had transient ST segment elevation, versus only one infant (5%) from the control group (odds ratio = 7.6; 95% confidence interval, 1.14, 50.64). Heart rates, results of total power and low-frequency power spectral analyses for heart rate variability, and arrhythmias were not significantly different in the two groups. However, a lower ratio of low-to high-frequency power reflected increased vagal activity in cocaine-exposed infants. We conclude that cocaine use in pregnant mothers is associated with transient ST segment abnormalities in their infants. These abnormalities are consistent with transient myocardial ischemia.

Alterations in cardiac diastolic function in patients with ankylosing spondylitis.

Ankylosing spondylitis is associated with a decreased survival that appears attributable to cardiovascular causes. To determine whether alterations in systolic or diastolic cardiac function precede overt cardiac disease, 20 ankylosing spondylitis patients without clinical evidence of cardiovascular disease and 25 healthy age and gender matched controls were studied by cross-sectional and Doppler echocardiography. Systolic function was assessed by wall motion analysis and ejection velocities. Diastolic function was measured by the peak velocity of early ventricular inflow, peak velocity in late diastole during atrial systole, the ratio of these velocities and the diastolic filling time. Atrial, ventricular and aortic dimensions were similar in patients and controls. Ejection indexes and systolic wall motion were normal in both groups. Diastolic function differed in patients as evidenced by a shorter diastolic filling period [405 +/- 68 ms vs 548 +/- 136 ms, p = 0.0001], a reduced velocity of early mitral inflow [0.55 +/- 0.09 m/s vs 0.63 +/- 0.11 m/s (p = 0.005)], and lower ratios of early/late inflow velocities [1.21 +/- 0.33 vs 1.60 +/- 0.35 (p = 0.0005) for mitral and 1.36 +/- 0.34 vs 1.71 +/- 0.42 (p = 0.016) for tricuspid]. These changes are consistent with impaired ventricular relaxation in some patients with ankylosing spondylitis.

Predicting left heart failure after a myocardial infarction: a preliminary study of the value of echocardiographic measures of left ventricular filling and wall motion.

Heart failure occurs from both systolic and diastolic dysfunction. To determine whether simple Doppler echocardiographic measures of left ventricular filling could improve upon the ability of systolic function to predict heart failure after infarction, patients with acute myocardial infarction were studied within the first 36 hours by Doppler and two-dimensional echocardiography. Forty-eight patients who did not have heart failure before the Doppler echocardiographic study and who did not have myocardial revascularization, moderate or severe mitral regurgitation, or other complications during recovery were monitored for 6 months or to the onset of heart failure (n = 10). The univariate predictors of heart failure were age (p less than 0.05), anterior infarction (p less than 0.05), early diastolic peak filling velocity (p = 0.05), filling velocity with atrial systole (p less than 0.05), the ratio of these velocities (p less than 0.001), the percentage of filling with atrial systole (p less than 0.001), and the wall motion score index (p less than 0.001). However, the only independent predictors of heart failure by use of multivariant stepwise logistic regression analysis were the wall motion score index (p less than 0.05) and either the ratio of early and late peak filling velocities (p less than 0.001) or the percentage of filling with atrial systole (p less than 0.001). The combined use of a measure of systolic function and measures of the relative contribution of atrial systole to ventricular filling were useful predictors in identifying patients likely to develop subsequent heart failure after myocardial infarction.

Left ventricular filling shortly after an uncomplicated myocardial infarction as a predictor of subsequent exercise capacity.

Resting measurements of left ventricular systolic function do not reliably predict exercise capacity in patients with cardiac disease. Therefore left ventricular filling shortly after a myocardial infarction was prospectively studied to determine whether it could predict subsequent exercise time. Consecutive patients with an acute infarction underwent Doppler and two-dimensional echocardiography within 36 hours of infarction. The study group was composed of the 26 men who did not have reperfusion, who had an uncomplicated myocardial infarction, and who had undergone symptom-limited stress testing during recovery (modified Bruce protocol, 44 +/- 23 days after myocardial infarction). Systolic function was measured by ejection fraction and a wall motion score. Ventricular filling was assessed by the peak transmitral Doppler velocity in early diastole (E), with atrial systole (A), their ratio (A/E), and the percentage of filling from atrial systole. The only parameter of systolic or diastolic function that correlated with exercise time was E (r = 0.65, p less than 0.001). This relationship was particularly strong for the 16 subjects taking beta blockers at the time of stress testing (r = 0.88, p less than 0.001). Stepwise multivariate regression analysis showed that only E and beta blocker therapy at the time of stress testing contributed to the model predicting recovery exercise time (R2 = 0.55). In summary, E, measured soon after an uncomplicated myocardial infarction, is one factor that predicts exercise capacity during recovery.

Exercise performance in patients with hypertension. Relation to electrocardiographic criteria for left ventricular hypertrophy.

The influence of the electrocardiographic diagnosis of left ventricular hypertrophy on exercise performance was assessed in 101 hypertensive patients and 37 control subjects referred to an exercise testing laboratory. Maximal exercise capacity was measured by the duration of a symptom-limited, treadmill test using the modified Bruce protocol. The Romhilt-Estes point score system, as modified by Murphy, was used to define left ventricular hypertrophy by electrocardiographic criteria. After adjusting for age differences between hypertensive and control subjects, the hypertensive group without left ventricular hypertrophy had a shorter exercise duration than the control group (13.0 +/- 3.0 vs. 15.3 +/- 2.5 min, respectively; p less than 0.01). The 16 hypertensive patients with electrocardiographic evidence of hypertrophy had a shorter exercise duration than those without (10.9 +/- 2.0 vs. 13.0 +/- 3.0 min, respectively; p less than 0.01). Multivariate regression analysis indicated that age, gender, systolic blood pressure, and electrocardiographic point score were all significant independent variables in predicting exercise duration (R2 = 0.48, p less than 0.0001). Exercise duration was unrelated to QRS amplitude. The authors conclude that electrocardiographic evidence of left ventricular hypertrophy, as manifested by P wave and T wave abnormalities, is associated with an impaired exercise capacity in a hypertensive population without prior myocardial infarction.

Time course of systolic loading is an important determinant of ventricular relaxation.

We studied the dependency of left ventricular relaxation on the timing of an abrupt increase in systolic load. In 10 canine isolated heart-lung preparations, a load step of 15 mmHg was imposed at specific intervals throughout systole, and the time of loading was defined as the interval from the R wave to the completion of the load step (R-load interval). Preload was held constant. The right atrium was paced at a cycle length of 450 ms. The decay of left ventricular pressure during isovolumic relaxation was described by a single exponential time constant (Texp). Load effects on isovolumic relaxation were expressed as a percent change in Texp as compared with Texp of the beat preceding the load intervention. Loads imposed early in systole consistently prolonged Texp [mean delta Texp = +17.01 +/- 1.64% (SE) for R-load intervals less than or equal to 120 ms]. Load changes late in systole consistently abbreviated Texp [mean delta Texp = -9.49 +/- 0.86% (SE) for R-load intervals greater than or equal to 130 ms]. The transition from augmentation to diminution of Texp always occurred when the R-load interval was 120-130 ms. The mean time interval of electromechanical systole for the test beats was not significantly different (P greater than or equal to 0.05) from that of the control beats [R-load intervals less than or equal to 120: test = 247.0 +/- 27.8 (SD) ms; control = 246.6 +/- 26.8 (SD) ms] [R-load intervals greater than or equal to 130: test = 243.3 +/- 29.1 (SD) ms; control = 243.8 +/- 28.4 (SD) ms].(ABSTRACT TRUNCATED AT 250 WORDS)

Relative tachycardia in ambulant children with borderline hypertension.

Borderline hypertensives who demonstrate tachycardia have a tendency toward the development of essential hypertension. However, the documentation of tachycardia in previous studies has been generally based on brief periods of observation. In the present study, we measured heart rates through a 24-hour period in 16 ambulatory mildly hypertensive subjects (ages 5 to 23 years). When compared with normal matched controls, significantly (p less than 0.05) higher heart rates were observed during the waking periods (99 +/- 9 vs 90 +/- 11) and sleep periods (72 +/- 12 vs 62 +/- 7). Similar observations were also made for 24 hours (90 +/- 8 vs 79 +/- 8). In addition, hypertensives also demonstrated thickened (during diastole) left ventricular posterior wall (0.96 +/- 0.17 vs 0.85 +/- 0.13 cm; p less than 0.05) and interventricular septum (0.98 +/- 0.17 vs 0.84 +/- 0.19 cm; p less than 0.05). It is suggested that tachycardia may be an early manifestation of borderline hypertension in children.

Left ventricular filling in endurance-trained subjects.

Whether exercise-induced increases in left ventricular mass can alter left ventricular diastolic function was evaluated by measuring transmitral flow velocities at rest by Doppler echocardiography in 15 amateur endurance-trained runners and 15 age- and sex-matched sedentary control subjects. Ventricular mass index, end-diastolic volume index and stroke volume index were derived from measurements of M-mode echocardiograms recorded under two-dimensional guidance. All three variables were increased in the runners (p less than 0.01). These findings, plus the lower heart rate at rest (p less than 0.001), were consistent with endurance training. Although the runners had an almost twofold greater myocardial mass index, their peak early diastolic filling velocity and time to peak filling velocity did not differ from those of the sedentary subjects. In runners, the peak filling velocity with atrial systole tended to be lower (p = 0.12), the ratio of peak filling velocity with atrial systole to that of early diastole was less (p less than 0.05) and the percent of stroke volume contributed by atrial systole was less (p less than 0.001). These differences in atrial filling may be related to the lower heart rates at rest in runners. In summary, significant increases in left ventricular mass, when associated with endurance training, do not alter the early diastolic filling of the left ventricle.

The ST segment/heart rate slope as a predictor of coronary artery disease: comparison with quantitative thallium imaging and conventional ST segment criteria.

The ST segment shift relative to exercise-induced increments in heart rate, the ST/heart rate slope (ST/HR slope), has been proposed as a more accurate ECG criterion for diagnosing significant coronary artery disease (CAD). Its clinical utility, with the use of a standard treadmill protocol, was compared with quantitative stress thallium (TI) and standard treadmill criteria in 64 unselected patients who underwent coronary angiography. The overall diagnostic accuracy of the ST/HR slope was an improvement over TI and conventional ST criteria (81%, 67%, and 69%). For patients failing to reach 85% of their age-predicted maximal heart rate, its diagnostic accuracy was comparable with TI (77% and 74%). Its sensitivity in patients without prior myocardial infarctions was equivalent to that of thallium (91% and 95%). The ST/HR slope was directly related to the angiographic severity (Gensini score) of CAD in patients without a prior infarction (r = 0.61, p less than 0.001). The ST/HR slope was an improved ECG criterion for diagnosing CAD and compared favorably with TI imaging.

Effects of loading conditions and inotropic state on rapid filling phase of left ventricle.

Afterload, activation sequence, inotropism, and extent of shortening affect the time constant (T) of left ventricular (LV) isovolumic pressure decay, yet it is unknown if they modify peak lengthening velocity of the LV minor axis [(dD/dt)/D]. Accordingly, we studied their effects on (dD/dt)/D, measured by sonomicrometry, in nine anesthetized open-chest dogs during atrial pacing at 2 Hz. Afterload was increased 20-40 mmHg by 1) constricting the ascending aorta and 2) occluding the descending aorta for four beats. Activation was altered by right ventricular pacing. These interventions, plus constriction of venae cavae, were studied during four inotropic states. Aortic stenosis increased (dD/dt)/D (P less than 0.05), whereas occlusion of the descending aorta, vena caval constriction, and right ventricular pacing decreased (dD/dt)/D (P less than 0.05). Left atrial pressure was constant except during vena caval constriction. Alterations in inotropic state modified (dD/dt)/D (P less than 0.001). Extent of shortening and (dD/dt)/D were directly related (r = 0.80, P less than 0.001). Changes in (dD/dt)/D and T were inversely related (r = 0.70, P less than 0.001), and alterations in the interval from -dP/dtpeak to the end of rapid filling were directly related to changes in T (r = 0.75, P less than 0.001). We conclude that (dD/dt)/D can be modified by systolic and diastolic load perturbations, activation sequence, and inotropic interventions. These effects relate to changes in extent of shortening, time course of inactivation, or both.

The relation of heart rate and shortening fraction to echocardiographic indexes of left ventricular relaxation in normal subjects.

To determine the relation of heart rate and systolic function to echocardiographically derived indexes of left ventricular relaxation, M-mode echocardiograms of the left ventricle and mitral valve with a simultaneous phonocardiogram were recorded at rest from 28 normal men. The effects of altering the inotropic state and ventricular loading conditions were examined during isometric handgrip exercise and the Valsalva maneuver in a subset of 15 men. The left ventricular endocardial echocardiograms were digitized to provide a display of left ventricular internal dimension and its first derivative (dD/dt). The time course of relaxation, defined as the interval from left ventricular minimal systolic dimension to the point when the rate of change of dimension (dD/dt) decreased to 50% of peak, was directly related to the RR interval (r = 0.64, p less than 0.0001) in the entire group, and this relation remained throughout the interventions. The slopes of the regression lines of relaxation time (RT) and electromechanical systole (QS2) on the RR interval were similar. Diastolic time decreased proportionately more than relaxation time as the RR interval decreased, so that the proportion of diastole occupied by the relaxation time varied with cycle length. Peak diastolic dD/dt, normalized for variations in end-diastolic dimensions [( dD/dt]/D), was directly related to left ventricular shortening fraction (r = 0.71 p less than 0.0001) and this relation remained during isometric grip. There was no correlation between the heart rate at rest and (dD/dt)/D over the range of 44 to 99 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)