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)

Comparative measures of systolic ejection during treadmill exercise by impedance cardiography and Doppler echocardiography.

Measurements of systolic ejection dynamics by impedance cardiography were compared with simultaneous Doppler echocardiography in normal subjects and coronary artery disease patients. Patients with chest pain admitted for elective coronary angiography were monitored by simultaneous impedance cardiography and Doppler echocardiography before, during, and after treadmill exercise. Ensemble-averaged ECG, impedance cardiogram (ICG), the first derivative of ICG (dZ/dt), and Doppler waveforms were analyzed to identify systolic ejection variables. The timing of aortic valve opening was well correlated (r = 0.78) the timing of peak ejection velocity was very well correlated (r = 0.86), and the timing of aortic valve closure was moderately correlated (r = 0.69 and r = 0.73) in these subjects. The thoracic electrical impedance acceleration and normalized impedance acceleration indices were moderately correlated with Doppler model acceleration (r = 0.74, r = 0.79). The impedance cardiogram waveforms are of complex origin and are related to both aortic blood velocity and aortic blood acceleration. Users of dZ/dt timing features for determining aortic valvular events might consider alternative impedance features to improve ejection time accuracy.

Cardiac adaptation to increased systemic blood pressure in borderline hypertensive men.

The present study examined cardiac characteristics of borderline hypertensive men with a positive parental history of hypertension. Hemodynamics in relation to left ventricular function and structure were evaluated in 15 borderline hypertensive men with a parental history of hypertension and in 20 normotensive control subjects with a negative parental history. Groups were matched in age, height, weight and percent body fat. Left ventricular mass and dimensions were measured by M-mode echocardiography, and left ventricular function was assessed by radionuclide ventriculography. Both groups had similar left ventricular mass, dimensions and wall thicknesses. In relation to control subjects, borderline hypertensive men had a significantly higher heart rate and blood pressure (BP) (p < 0.001), but a similar cardiac index. Borderline hypertensive men had a higher peripheral resistance index (p < 0.02), longer time to peak filling rate, and reduced cardiac efficiency, whereas they had higher contractility, minute and stroke work indexes than did control subjects (all p < 0.05); they also had higher diastolic BP (p < 0.03) during exercise, and sustained higher BP during recovery than did controls. Although this group of borderline hypertensive men did not have an altered cardiac anatomy, they had an increased vascular resistance, an altered diastolic function and a reduced cardiac efficiency while undergoing a greater work load. These cardiodynamic profiles are consistent with functional vascular changes and a parallel compensation by the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial septal lipomatous hypertrophy and ischemic heart disease: an unusual presentation.

Lipomatous hypertrophy of the interatrial septum consists of the abnormal accumulation of fatty tissue. We report a patient with unsuspected massive lipomatous hypertrophy of the interatrial septum scheduled to undergo coronary artery surgery. This patient had experienced atrial arrhythmias and obstructive symptoms preoperatively that were ascribed to her coronary artery disease (CAD). The perioperative anesthetic and surgical management of patients with lipomatous hypertrophy of the interatrial septum and CAD is discussed.

Relation of exercise Doppler left ventricular filling to thallium lung uptake.

The exercise-induced changes in left ventricular filling in patients with coronary artery disease are poorly understood. Therefore these changes were studied in relation to a noninvasive indicator of exercise pulmonary venous congestion, the lung-to-heart (L:H) ratio on symptom-limited thallium stress testing. Fifty-six patients undergoing diagnostic treadmill testing were studied; 50 of them had technically adequate Doppler recordings and became the subjects of this study. Doppler left ventricular filling was assessed with patients in the supine position both before and after exercise. Measurements included early (E) and late (A) filling velocities, their ratio, the diastolic time-velocity integral, and the diastolic filling time. The L:H ratio was considered abnormal if it was greater than the upper 95% confidence limit for a separate group of normal subjects. Twelve subjects had a documented prior myocardial infarction, 16 had stress-induced ischemia, and 20 had abnormal L:H ratios. A greater E and a longer diastolic filling time in the group with an abnormal L:H ratio were the only postexercise measurements that differed; however, E was the only filling parameter that both differed between groups after exercise (abnormal L:H group 87 +/- 25 cm/sec; normal 68 +/- 20 cm/sec; p < 0.01) and whose change from rest to after exercise was significantly different (p < 0.05). Since Doppler velocities are directly related to instantaneous gradients, the higher E in patients with evidence of exercise pulmonary congestion suggests a higher exercise early diastolic left atrial pressure.

A physiologic regurgitant cardiac valve phantom for magnetic resonance imaging or color Doppler ultrasound study.

Noninvasive imaging has proven successful in the evaluation of valvular heart disease; primarily with magnetic resonance imaging (MRI) and color Doppler ultrasound (CFM). However, the relationship between the morphology of regurgitant flow in MRI and CFM, as a function of hemodynamic parameters (chamber pressure difference, lesion size, compliance, etc.) is not understood. The goals for this work were: 1) to develop a computer-controlled regurgitant cardiac valve phantom, compatible with artifact-free CFM and MR imaging, 2) to create regurgitant lesions in the phantom which appear similar to those detected clinically, 3) to produce and measure physiologic pressure differences between chambers, compliances, and regurgitant fractions as seen in mild, moderate, and severe regurgitation. Mean chamber pressure differences ranged from 43-142 mmHg over the range of diseases simulated. Similarly, regurgitant flow rates ranged from approximately 0.54-18.6 L/min. Compliance values ranged from 0.83 to 21.95 cc/mmHg. No coherent or incoherent artifacts were observed in MRI or CFM images. Images show a high degree of similarity to regurgitant lesions detected with each modality, confirming that all design goals were met. The system should allow extensive comparative analysis of Doppler ultrasound and MRI flow jets under a wide range of controllable hemodynamic conditions in future experiments.

Detection of paradoxical cerebral echo contrast embolization by transcranial Doppler ultrasound.

Contrast echocardiography has been shown to be a sensitive method for detecting patent foramen ovale in embolic stroke, implying paradoxical embolization. However, not all two-dimensional echocardiographic studies are of diagnostic quality, and direct evidence for paradoxical cerebral embolization remains lacking. We addressed these problems by simultaneously using transcranial Doppler ultrasound and contrast echocardiography to compare relative sensitivity and concordance in the detection of right-to-left vascular shunting. Forty-six patients with stroke, transient neurologic defect, or question of atrial septal defect underwent study at rest and during Valsalva strain. Two-dimensional echocardiography detected shunting in 26% at rest and 15% during Valsalva strain, whereas transcranial Doppler study returned rates of 41% and 41%, respectively. Concordance was 82% and 75%, respectively. Discordant studies almost always had evidence of paradoxical contrast embolization by transcranial Doppler and intermediate findings by two-dimensional echocardiography. Transcranial Doppler is a sensitive, unambiguous technique for the detection of anatomic substrates and target organ involvement in patients suspected to have paradoxical cerebral embolization.

Doppler echocardiography in stress testing.

Doppler ultrasound may have a role in the stress testing laboratory for the identification of patients with coronary disease through the assessment of dynamic ventricular systolic function. Quantitative systolic ejection phase indexes of maximal acceleration, peak velocity, and volume of blood ejected from the left ventricle can be obtained in the exercising patient. Trials comparing stress Doppler ultrasound with ST-segment changes, gated blood pool radionuclide or echocardiographic studies of ejection fraction or wall motion abnormality, and thallium scintigraphic perfusion defects have returned comparable or better sensitivity and specificity referencing coronary angiography. Graded treadmill exercise, stationary bicycle exercise, and pharmacological stress (dipyridamole) have been used. The normal Doppler stress response is a near linear increase in peak ejection velocity with increasing cardiac work, as reflected in heart rate. Patients with coronary artery disease show blunted augmentation of Doppler ejection dynamics between rest and peak stress, and the degree of blunting appears to be proportional to the anatomic extent of coronary disease and the magnitude of ventricular perfusion and performance impairment. Stress Doppler ultrasound achieves diagnostic power for coronary disease with ultrasonic technology, inexpensive equipment, without ionizing radiation, and few personnel.

Doppler echocardiographic evaluation of aortic regurgitation.

Aortic regurgitation is diverse in presentation, perhaps pursuing a long indolent course or presenting as a catastrophic acute illness. Aortic regurgitation of any degree may be difficult to detect clinically, but echocardiographic Doppler studies afford a sensitive means of detecting and quantifying the lesion noninvasively. Pulsed-wave, continuous-wave, and color-flow Doppler modalities are complementary in the evaluation of aortic regurgitation, and all should be utilized in individual patients when surgery is contemplated. M-mode echocardiography and two-dimensional echocardiography have endured as excellent noninvasive means for evaluating the adequacy of ventricular hypertrophy in response to the insufficiency lesion. Recent interest in wall stress analysis may allow an index of ventricular performance that lends quantitative support for decisions to intervene surgically. Newer surgical options such as aortic valve homografts and pulmonary autografts may make surgery more attractive for patients considered for aortic valve replacement.

Clinical evaluation of a diameter sensing Doppler cardiac output meter.

A concentric beam Doppler ultrasonic flowmeter has been developed. This instrument has capacity for independent assessment of volumetric flow, as it determines flow cross-section area, stroke length, and pulse rate from the Doppler signals alone. The method is practically independent of the angle of interrogation. We used this device and obtained noninvasive estimates of cardiac output in 54 patients undergoing invasive assessment of cardiac output by thermodilution, Fick, or indicator dye methods (x). Correlations against pooled cardiac output reference standards ranged from r = .86 (y = .86x + 1.03) in 26 studies of high confidence to r = .45 (y = .30x + 2.62) in 17 studies under difficult conditions. The overall correlation was r = .68 (y = .63x + 1.49, n = 87). Noninvasive results of experienced and inexperienced operators were similar (r = .87). The instrument returned accurate assessments of heart rate (r = .83), but underestimated stroke length (r = .72) and appeared to be limited in the assessment of aortic diameters less than 28 or greater than 31 mm (r = .23). We conclude that stand-alone Doppler assessment of cardiac output is appealing and feasible, but difficult or impossible in many ICU scenarios. Further evolution of the concentric beam Doppler approach is needed and anticipated.

Determination of aortic valve area by two-dimensional and Doppler echocardiography in patients with normal and stenotic bioprosthetic valves.

To assess the feasibility and accuracy of determining bioprosthetic aortic valve area from two-dimensional and Doppler echocardiographic measurements, three partially overlapping groups were selected from 55 patients with such bioprosthetic valves and adequate Doppler studies. These were Group 1, 37 patients with recent aortic valve replacement surgery and no clinical or echocardiographic evidence of valve dysfunction; Group 2, 12 patients with prosthetic valve stenosis documented by cardiac catheterization; and Group 3, 22 patients with both Doppler and catheterization studies in whom noninvasive and invasive determinations of aortic valve area could be directly compared. Left ventricular outflow tract diameter was measured from two-dimensional still frame images. Flow velocity proximal to the aortic valve, transvalvular velocity and acceleration time were determined from pulsed and continuous wave Doppler spectra. Aortic valve gradient was calculated with the modified Bernoulli equation and valve area by the continuity equation. In the 37 patients with a normally functioning valve, the calculated mean gradient ranged from 5 to 25 mm Hg (average 13.6 +/- 5.2) and valve area from 1.0 to 2.3 cm2 (mean 1.6 +/- 0.31). Linear regression analysis of prosthetic aortic valve area determined by Doppler imaging and cardiac catheterization demonstrated a high correlation (r = 0.93) between the two techniques. Comparison of the patients with and without prosthetic valve stenosis revealed statistically significant differences in mean gradient (42.8 +/- 12.3 versus 13.6 +/- 5.2 mm Hg; p = 0.0001), acceleration time (116 +/- 15 versus 80 +/- 13 ms; p = 0.0001) and valve area by the continuity equation (0.80 +/- 0.16 versus 1.6 +/- 0.31 cm2; p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term bepridil monotherapy for angina pectoris.

The long-term efficacy of bepridil as once-a-day monotherapy was studied in 19 men with stable angina pectoris. After 2 weeks of single-blind placebo therapy and a 12-week parallel placebo-controlled, dose-response study, each patient received open-label bepridil. After a dose-titration period of 3 months, patients received bepridil (100 to 400 mg once a day, mean 290 mg) for 24 months. The response to treatment was assessed by patient diaries and serial treadmill exercise testing 24 hours after dose administration, every 3 months. Only 2 patients were released from the study due to therapeutic failure. Compared with placebo, 3 months of bepridil therapy resulted in a significant reduction in the weekly frequency of angina from 10.3 +/- 9.1 to 1.8 +/- 3.5 (p less than 0.002) and nitroglycerin consumption from 5.0 +/- 5.4 to 1.4 +/- 2.3 (p less than 0.01). In addition, there was a simultaneous significant increase in the walking time to angina from 5.2 +/- 2.3 to 7.9 +/- 2.6 minutes (p less than 0.001) and total exercise time from 7.1 +/- 2.2 to 8.8 +/- 1.9 minutes (p less than 0.001). These favorable effects were sustained throughout the 24 months of the study. Although resting QTc interval was prolonged by 36 to 42 ms (p less than 0.001) during bepridil therapy, ventricular dysrhythmias were not observed immediately before or during exercise testing and were not manifested by symptoms. Neurologic and gastrointestinal side effects of mild to moderate severity were observed, but none required discontinuation of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive evaluation of aortic stenosis severity utilizing Doppler ultrasound and electrical bioimpedance.

Aortic valve area was calculated noninvasively in 30 patients with aortic stenosis undergoing cardiac catheterization. Continuous wave Doppler ultrasound was employed to estimate the mean transvalvular pressure gradient. The mean left ventricular outflow tract flow velocity and cross-sectional area were determined from pulsed Doppler and two-dimensional ultrasound recordings. Electrical transthoracic bioimpedance cardiography performed simultaneously with the ultrasonic study and repeated at the time of catheterization measured heart rate, systolic ejection period and cardiac output. These noninvasive data permitted calculation of aortic valve area using the Gorlin equation (range 0.21 to 1.75 cm2) and the continuity equation (range 0.25 to 1.9 cm2). Subsequent cardiac catheterization showed valve area to range from 0.21 to 1.75 cm2. The mean Doppler pressure gradient estimate was highly predictive of the gradient measured at catheterization (r = +0.92, SEE = 10). Bioimpedance cardiac output measurements agreed with the average of Fick and indicator dye estimates (r = +0.90, SEE = 0.52). Valve area estimates utilizing continuous wave Doppler ultrasound and electrical bioimpedance were superior (r = +0.91, SEE = 0.12) to estimates obtained utilizing the continuity equation (r = +0.76, SEE = 0.29) and were more reliable in the detection of patients with severe aortic stenosis (9 of 11 versus 6 of 11). These data show that 1) electrical bioimpedance methods accurately estimate cardiac output in the presence of aortic stenosis; 2) the hybridized bioimpedance-Doppler ultrasound method yields accurate estimates of aortic stenosis area; and 3) the speed, accuracy and cost-effectiveness of aortic stenosis evaluation may be improved by this hybridized approach.

Usefulness of twice-daily isosorbide-5-mononitrate in preventing development of tolerance in angina pectoris.

Development of tolerance to nitrates during long-term therapy is a major concern. It has been suggested that isosorbide-5-mononitrate (IS-5MN), an active metabolite of isosorbide dinitrate, administered twice daily 12 hours apart does not lead to development of tolerance. The duration of effects of IS-5MN at a dose of 20 and 40 mg and of placebo was studied in patients with angina pectoris who responded to nitrates after the first dose (n = 12) and after 1 week of twice-daily therapy (n = 9). The study was double-blind, randomized and crossover in design. Compared with placebo values, after the first dose of 20 and 40 mg IS-5MN, exercise duration was higher at 2 hours (p less than 0.001) and 6 hours (p less than 0.02). After 1 week of twice-daily therapy at these doses, exercise duration increased at 2 hours (p less than 0.05) but not at 6 or 10 hours after the dose. After the first dose of 20 and 40 mg IS-5MN, standing systolic blood pressure decreased at 2 hours (p less than 0.02). Blood pressure did not change significantly after chronic therapy. Tolerance to antianginal effects during twice-daily therapy with 20 and 40 mg of IS-5MN developed despite higher plasma IS-5MN concentrations at 2 and 6 hours during twice-daily therapy than after the first dose. The tolerance during twice-daily therapy with IS-5MN was characterized by a reduced peak effect at 2 hours and shortened duration of action compared with first-dose effects.

Isosorbide-5-mononitrate in angina pectoris: plasma concentrations and duration of effects after acute therapy.

In a double-blind, randomized, crossover study, the duration of effects of single oral doses of 20 and 40 mg isosorbide-5-mononitrate (IS-5MN) and matching placebo were studied in 12 male patients with angina pectoris. Plasma IS-5MN concentrations (mean +/- SD) 2 and 6 hours after administration were 300 +/- 60 and 144 +/- 43 ng/ml after 20 mg IS-5MN and 551 +/- 191 and 376 +/- 129 ng/ml after 40 mg IS-5MN. Exercise time to the onset of angina 2 and 6 hours after administration increased after 20 mg IS-5MN (5.88 +/- 1.85; P less than 0.001 and 5.08 +/- 1.97 minutes; P less than 0.002) and 40 mg IS-5MN (6.17 +/- 1.88; P less than 0.001 and 5.78 +/- 1.72 minutes; P less than 0.001) in comparison to placebo (4.57 +/- 1.22 and 4.15 +/- 1.22 minutes). Similarly, total exercise duration increased at 2 (P less than 0.001) and 6 hours (P less than 0.002) after both doses of IS-5MN. Compared with placebo, ECG ST segment depression during exercise was less (P less than 0.05) 2 hours after both doses of IS-5MN. Thus single oral doses of 20 and 40 mg IS-5MN exert antianginal and anti-ischemic effects for at least up to 6 hours.

Duration of effects and tolerance of slow-release isosorbide-5-mononitrate for angina pectoris.

Isosorbide-5-mononitrate (IS-5MN) is an active metabolite of isosorbide dinitrate, but unlike its parent compound, is nearly 100% bioavailable after oral administration. Once-a-day therapy with a slow-release formulation of IS-5MN is used widely in Europe for 24-hour prophylaxis of angina pectoris. In a randomized, crossover, double-blind, placebo-controlled study, the duration of effects of 50 and 100 mg of slow-release IS-5MN were evaluated after the first dose and after once-a-day therapy for 1 week in 9 patients with stable angina pectoris. Compared with placebo values, standing blood pressure decreased (p less than 0.001) and exercise time to the onset of angina and total exercise duration increased (p less than 0.008 and p less than 0.003) at 4 hours, but not at 20 or 24 hours after first dose of 50 and 100 mg of slow-release IS-5MN. After once-a-day therapy for 1 week, no improvement in exercise duration or reduction in ST-segment depression was seen after 50 or 100 mg of slow-release IS-5MN at 4, 20 or 24 hours despite high plasma IS-5MN concentrations. Thus, despite therapeutic plasma concentrations, 50 and 100 mg of slow-release IS-5MN did not exert antianginal or anti-ischemic effects at 20 and 24 hours after the first dose and at 4, 20 and 24 hours after sustained once-a-day therapy for 1 week.

Doppler echocardiographic profiles in obstructive right and left atrial myxomas.

Previous reports have suggested that atrioventricular (AV) flow disturbances accompanying atrial myxomas mimic mitral stenosis. Two patients complaining of orthostatic syncope and positional intolerance had a large right and left atrial myxoma, respectively. Doppler flow records showed abrupt early diastolic flow cessation and normal velocity half-times, unlike AV valve stenosis. Large, obstructing atrial myxomas may behave as ball valves.

Clinically silent atrial septal defects with evidence for cerebral embolization.

The cause of stroke in young patients frequently cannot be established. Eleven consecutive patients, age 50 and younger, had clinical evidence of cerebral embolization. Results of physical, radiographic, electrocardiographic, and two-dimensional echocardiographic examinations were normal in all patients. During normal respiration, eight of the patients had right-to-left shunts at the atrial level shown by microcavitation contrast two-dimensional echocardiography. Six of the eight patients with positive contrast studies had cardiac catheterization. Five of six patients had an atrial septal defect, normal right and left heart pressures, and small right-to-left shunts during a Valsalva strain. Four patients had surgical closure of the defect, which ranged in size from 5 to 10 mm. The remaining patients received anticoagulants. Interatrial communications appear to be common in young patients with stroke, suggesting paradoxical embolization as a possible mechanism. Contrast two-dimensional echocardiography should be done in such patients because it is the only noninvasive technique that reliably finds these defects.

Transdermal nitroglycerin patches in angina pectoris. Dose titration, duration of effect, and rapid tolerance.

The duration of effect of transdermal nitroglycerin patches was studied in 14 patients with angina pectoris. By titrating the dose to achieve specific circulatory effects, we chose a patch size that produced a consistent fall in systolic blood pressure of 10 mm Hg or greater for each patient (10 cm2 in 7 patients, 20 cm2 in 5, and 40 cm2 in 2; releasing 5, 10, and 20 mg of nitroglycerin per 24 hours, respectively). The effects of these individualized patches were compared with those of placebo patches. Compared with placebo, nitroglycerin patches increased exercise duration to the onset of angina (257 +/- 72 compared with 383 +/- 130 seconds, p less than 0.0001) and total exercise time (338 +/- 89 compared with 456 +/- 119 seconds, p less than 0.0001) and decreased ST segment depression (1.0 +/- 0.5 compared with 0.6 +/- 0.4 mm, p less than 0.05) at 4 hours but not at 24 and 48 hours. We conclude that nitroglycerin patches do not show objective evidence of antianginal or antiischemic effects for 24 hours. Tolerance to the circulatory and antianginal effects probably develops within 24 hours of patch application.

Quantification of aortic regurgitation utilizing continuous wave Doppler ultrasound.

Aortic regurgitation and mitral stenosis are hemodynamically similar, insofar as both result in passive ventricular filling across a narrow orifice driven by a declining pressure gradient. Because mitral stenosis is successfully characterized by Doppler ultrasound determination of the velocity half-time, or time constant, aortic regurgitation might be quantified in an analogous fashion. Eighty-six patients with diverse causes of aortic regurgitation underwent continuous wave Doppler examination before cardiac catheterization or urgent aortic valve replacement. The Doppler velocity half-time was defined as the time required for the diastolic aortic regurgitation velocity profile to decay by 29%, whereas catheterization pressure half-time was calculated as the time required for transvalvular pressure to decay by 50%. Doppler velocity and catheterization pressure half-times were linearly related (r = 0.91). Doppler velocity half-times were inversely related to regurgitant fraction (r = -0.88). Angiographic severity (1+ = mild to 4+ = severe) was also inversely related to pressure and velocity half-time; a Doppler half-time threshold of 400 ms separated mild (1+, 2+) from significant (3+, 4+) aortic regurgitation with high specificity (0.92) and predictive value (0.90). The Doppler velocity half-time was independent of pulse pressure, mean arterial pressure, ejection fraction and left ventricular end-diastolic pressure. Estimation of transvalvular aortic pressure half-time utilizing continuous wave Doppler ultrasound is a reliable and accurate method for the noninvasive evaluation of the severity of aortic regurgitation.