Joel S. Raichlen

Opacification and border delineation improvement in patients with suboptimal endocardial border definition in routine echocardiography : results of the phase III albunex multicenter trial

OBJECTIVESnThis study was designed to assess the safety and efficacy of intravenously administered sonicated human serum albumin for enhancing echocardiographic delineation of the left ventricular endocardium and improving assessment of wall motion in patients with incomplete depiction of noncontrast echocardiography.nnnBACKGROUNDnEchocardiographic regional wall motion analysis is impaired by incomplete endocardial definition in as many as 10% of patients. Sonicated human serum albumin is a stable contrast material that, unlike other agents, opacifies the left ventricle when administered intravenously.nnnMETHODSnOne hundred seventy-five patients were enrolled at eight centers on the basis of incomplete echocardiographic endocardial depiction. Sonicated 5% human serum albumin, a stable preparation of air-filled microspheres (size range 1 to 10 microns), was administered intravenously in divided doses: 0.08 ml/kg body weight in all patients, followed by 0.14 and 0.08 ml/kg or a single dose of 0.22 ml/kg, depending on the result of the initial dose. Investigators and independent reviewers blinded to the protocol scored the echocardiograms for degree of left ventricular opacification and improvement of endocardial border depiction.nnnRESULTSnOverall, 81% of patients had at least moderate left ventricular chamber opacification with at least one contrast dose, and endocardial definition was improved in 83%. In the subgroup with inadequate left ventricular opacification from the initial dose, a second, larger dose (0.22 ml/kg) improved endocardial depiction in 64%. No significant side effects occurred.nnnCONCLUSIONSnIn patients with incomplete echocardiographic endocardial definition, sonicated human serum albumin is a safe, effective contrast agent that, when administered intravenously, produces left ventricular chamber opacification, improves endocardial depiction and enhances regional wall motion analysis.

Pressure dependence of subharmonic signals from contrast microbubbles.

Noninvasive pressure estimation in heart cavities and in major vessels would provide clinicians with a valuable tool for assessing patients with heart and vascular diseases. Some microbubble-based ultrasound contrast agents are particularly well suited for pressure measurements because their substantial compressibility enables microbubbles to vary significantly in size in response to changes in pressure. Pressure changes should then affect reflectivity of microbubbles after intravenous injection of a contrast agent. This has been demonstrated with a galactose-based contrast agent using 2.0-MHz ultrasound tone bursts. Preliminary results indicate that, over the pressure range of 0-186 mmHg, the subharmonic amplitude of scattered signals decreases by as much as 10 dB under optimal acoustic settings and the first and second harmonic amplitudes decrease by less than 3 dB. An excellent correlation between the subharmonic amplitude and the hydrostatic pressure suggests that the subharmonic signal may be utilized for noninvasive detection of pressure changes.

Dynamic three-dimensional reconstruction of the left ventricle from two-dimensional echocardiograms

Using an open chest canine model, a method was developed for three-dimensional reconstruction of the contracting left ventricle from two-dimensional echocardiograms, which is applicable to intraoperative studies in humans. A mechanically held 5 MHz transducer was used to record parallel high resolution cross-sectional images with precise spatial registration. Myocardial borders were tracked manually and entered into a computer system. Regional filling and interpolation routines were applied to reconstruct the endocardial and epicardial surfaces of the ventricle. The myocardium can be displayed as a translucent, shaded three-dimensional solid surrounding the ventricular cavity. One or both surfaces can be rotated about any axis, sectioned through any plane and viewed in motion through systole and diastole. Studies before and after left anterior descending coronary artery occlusion showed the three-dimensional extent of abnormal left ventricular cavity and myocardial deformation. Quantitative examination of regions of interest permits the analysis of global and regional volumetric and myocardial thickness changes throughout the cardiac cycle. Thus, open chest three-dimensional echocardiography provides a powerful tool for the quantitative physiologic investigation of the left ventricle.

Phase III multicenter trial comparing the efficacy of 2% dodecafluoropentane emulsion (EchoGen) and sonicated 5% human albumin (Albunex) as ultrasound contrast agents in patients with suboptimal echocardiograms ☆

OBJECTIVESnThis study was performed to compare the safety and efficacy of intravenous 2% dodecafluoropentane (DDFP) emulsion (EchoGen) with that of active control (sonicated human albumin [Albunex]) for left ventricular (LV) cavity opacification in adult patients with a suboptimal echocardiogram.nnnBACKGROUNDnThe development of new fluorocarbon-based echocardiographic contrast agents such as DDFP has allowed opacification of the left ventricle after peripheral venous injection. We hypothesized that DDFP was clinically superior to the Food and Drug Administration-approved active control.nnnMETHODSnThis was a Phase III, multicenter, single-blind, active controlled trial. Sequential intravenous injections of active control and DDFP were given 30 min apart to 254 patients with a suboptimal echocardiogram, defined as one in which the endocardial borders were not visible in at least two segments in either the apical two- or four-chamber views. Studies were interpreted in blinded manner by two readers and the investigators.nnnRESULTSnFull or intermediate LV cavity opacification was more frequently observed after DDFP than after active control (78% vs. 31% for reader A; 69% vs. 34% for reader B; 83% vs. 55% for the investigators, p < 0.0001). LV cavity opacification scores were higher with DDFP (2.0 to 2.5 vs. 1.1 to 1.5, p < 0.0001). Endocardial border delineation was improved by DDFP in 88% of patients versus 45% with active control (p < 0.001). Similar improvement was seen for duration of contrast effect, salvage of suboptimal echocardiograms, diagnostic confidence and potential to affect patient management. There was no difference between agents in the number of patients with adverse events attributed to the test agent (9% for DDFP vs. 6% for active control, p = 0.92).nnnCONCLUSIONSnThis Phase III multicenter trial demonstrates that DDFP is superior to sonicated human albumin for LV cavity opacification, endocardial border definition, duration of effect, salvage of suboptimal echocardiograms, diagnostic confidence and potential to influence patient management. The two agents had similar safety profiles.

Effect of contrast enhancement on measurement of carotid artery intimal medial thickness

Previous studies have used standard B-mode ultrasound to quantify the aggregate mean intimal medial thickness (IMT) of the near and far wall of the common carotid artery (CCA). Many investigators have had difficulty in accurately evaluating the near wall IMT secondary to difficulty in discerning the vessel lumen and intima. The purpose of this study is to determine the effect of contrast enhanced ultrasound on IMT measurement when compared with non-enhanced images. Twenty-six patients who had standard carotid ultrasounds completed over a 6-month period were evaluated, with 24 imaged by the same sonographer. Five to six measurements of the near and far walls were obtained over a 1 cm distance, beginning and ending 0.5 cm and 1.5 cm proximal to the carotid bifurcation. The measurements were made with and without the contrast agent OptisonTM (perflutren protein type-A microspheres), which was given as an IV bolus (0.5-0.7 cc). Of those imaged by the same sonographer, 40 carotid arteries were examined and a total of 867 measurements were obtained. A total of 10% of the carotid ultrasounds were restudied approximately 1 month after the initial interpretation to assess observer accuracy. The near wall CCA mean (SD) IMT was 0.075 (0.019)cm for left with contrast versus 0.067 (0.023)cm for left without contrast and 0.089 (0.024)cm for right with versus 0.071 (0.022)cm for right without, p 0.0001 both sides. For the far wall of the CCA, the mean (SD) IMT comparison was 0.075 (0.021)cm for left with versus 0.070 (0.016)cm for left without, p = 0.005, and 0.070 (0.023)cm for right with versus 0.070 (0.016) cm for right without, p = 0.68. In conclusion, contrast-enhanced IMT measurement showed a highly statistically significant difference in near carotid wall thickness determinations versus non-contrast values. The thicker measurement is in agreement with previously reported data showing that non-contrast images underestimated near wall common carotid IMT in histologic samples.

ST-segment depression during adenosine infusion as a predictor of myocardial ischemia

The incidence and hemodynamic changes associated with ST-segment depression during adenosine stress testing are poorly defined. To examine this, 550 consecutive patients who underwent adenosine perfusion testing were evaluated for the development of ST-segment depression. At least 1 mm of horizontal or downsloping depression developed in 82 patients (15.9%) and was observed with similar frequency in patients with normal scans and those with only fixed defects. ST depression developed in 58 of 242 patients with reversible defects (sensitivity = 24%) and in only 24 of 275 patients without reversible defects (specificity = 91%). Its presence was highly predictive of reversible perfusion defects (predictive accuracy = 71%). Similar findings were observed in patients with and without ECG evidence of left ventricular hypertrophy. Patients with ST depression had perfusion defects in more vessel distributions, had more severe defects, and had a greater increase in heart rate during adenosine infusion. Thus ST-segment depression occurs infrequently during adenosine infusion but is specific for and predictive of myocardial ischemia, as evidenced by reversible perfusion scan defects. Patients with ST depression have more severe disease and develop faster heart rates during infusion, which could result in decreased coronary perfusion during diastole allowing for the development of myocardial ischemia.

Adenosine radionuclide perfusion imaging in the preoperative evaluation of patients undergoing peripheral vascular surgery.

To define the clinical and adenosine test variables that predicted perioperative cardiac events, 122 patients who received adenosine radionuclide perfusion imaging before peripheral vascular surgery were reviewed. Events included pulmonary edema, an ischemic end point of acute myocardial infarction (AMI) or cardiac death. Five patients underwent coronary revascularization before the surgical procedure. Of the 117 remaining patients, 19 had pulmonary edema, 10 had an AMI, and 2 died after peripheral vascular surgery. Most of the patients (78%) were in an intermediate-risk group as indicated by the presence of > or = 1 clinical risk factor as defined by the Eagle criteria. The only predictor of perioperative pulmonary edema was a history of congestive heart failure (33% vs 4%; p = 0.002). No clinical variables predicted AMI or death. The adenosine variables that were univariate predictors of AMI and death were the number of reversible perfusion defects (1.75 +/- 1.84 vs 0.75 +/- 0.90; p = 0.001) and the number of coronary artery distributions with a radionuclide perfusion defect (1.33 +/- 0.64 vs 0.85 +/- 0.67; p = 0.022). The number of reversible perfusion defects was the only multivariate predictor of ischemic events (p = 0.017). The presence of > 1 reversible defect was associated with an increased frequency of ischemic events (68% vs 28%; p = 0.045). The sensitivity and specificity of > 1 reversible defect was 58% and 73%, respectively, with a positive and negative predictive value of 19% and 94%.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic significance of ST-segment depression during adenosine perfusion imaging

To determine the significance of ST-segment depression during adenosine perfusion imaging for predicting future cardiac events, 188 patients with interpretable electrocardiograms were assessed 1 to 3 years (mean 21.5 +/- 6.6 months) after adenosine testing. At least 1 mm of ST-segment depression was observed in 32 (17%) patients, with > or = 2 mm of ST-segment depression in 10 (5.3%). Thirty-seven cardiac events occurred during the study period: 2 cardiac deaths, 5 nonfatal myocardial infarctions, 6 admissions for unstable angina, and 24 revascularizations. Univariate predictors of events were a history of congestive heart failure, previous non-Q-wave myocardial infarction, previous coronary angioplasty, use of antianginal medication, ST-segment depression during adenosine infusion (particularly > or = 2 mm), any reversible perfusion defect, transient left ventricular cavity dilation, and the severity of perfusion defects. Multivariate analysis identified > or = 2 mm ST-segment depression as the most significant predictor of cardiac events (relative risk [RR] = 6.5; p = 0.0001). Other independent predictors of events were left ventricular dilation (RR = 3.8; p = 0.002), previous coronary angioplasty (RR = 3.3; p = 0.001), a history of non-Q-wave myocardial infarction (RR = 2.3; p = 0.01), and the presence of any reversible defect (RR = 2.0; p = 0.05). We conclude that ST-segment depression occurs uncommonly during adenosine infusion, but the presence of > or = 2 mm of ST-segment depression is an independent predictor of future cardiac events and provides information in addition to that obtained from clinical variables and the results of adenosine perfusion imaging.

Quantitative assessment of right and left ventricular growth in the human fetal heart: a pathoanatomic study.

We quantitated the growth patterns of the normal fetal heart and the right and left ventricles from postmortem hearts obtained from 55 spontaneously aborted human fetuses from the completion of cardiogenesis to term. Fetal gestational age was assessed by menstrual history of the mother, crown-rump length, head circumference, and body weight and ranged from 8 to 40 weeks. Each heart was perfused and fixed at constant pressure and dissected to obtain right and left ventricular free wall, left ventricular, and total heart weights. Right and left ventricular free wall thicknesses were measured and the respective surface areas were calculated. The changes in each of these parameters with gestational age were examined by regression analysis. Total heart and right and left ventricular wall weights increased linearly with body weight, but exponentially with head circumference, crown-rump length, and menstrual history. Right and left ventricular free wall weights were similar throughout gestation and the percent that each contributed to total heart weight were constant at 29 +/- 2% and 30 +/- 2%, respectively. Right and left ventricular wall thicknesses did not differ significantly, increasing linearly with menstrual age, crown-rump length, head circumference, and body weight from 8 to 40 weeks. The surface areas of the right and left ventricular free walls that we used as an index of changing ventricular architecture were indistinguishable throughout the period of gestation studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive LV Pressure Estimation Using Subharmonic Emissions From Microbubbles

To develop a new noninvasive approach to quantify left ventricular (LV) pressures using subharmonic emissions from microbubbles, an ultrasound scanner was used in pulse inversion grayscale mode; unprocessed radiofrequency data were obtained with pulsed wave Doppler from the aorta and/or LV during Sonazoid infusion. Subharmonic data (in dB) were extracted and processed. Calibration factor (mm Hg/dB) from the aortic pressure was used to estimate LV pressures. Errors ranged from 0.19 to 2.50 mm Hg when estimating pressures using the aortic calibration factor, and were higher (0.64 to 8.98 mm Hg) using a mean aortic calibration factor. Subharmonic emissions from ultrasound contrast agents have the potential to noninvasively monitor LV pressures.