Manual or semi-automated edge detection of the maximal far wall common carotid intima-media thickness: a direct comparison.

BACKGROUND: Automated edge detection is thought to be superior to manual edge detection in quantification of the far wall common carotid intima-media thickness (CIMT), yet published evidence making a direct comparison is not available. METHODS: Data were used from the METEOR study, a randomized placebo-controlled trial among 984 individuals showing that rosuvastatin attenuated the rate of change of 2 year change in CIMT among low-risk individuals with subclinical atherosclerosis. For this post hoc analysis, CIMT images of the far wall of the common carotid artery were evaluated using manual and semi-automated edge detection and reproducibility, relation to cardiovascular risk factors, rates of change over time and effects of lipid-lowering therapy were assessed. RESULTS: Reproducibility was high for both reading methods. Direction, magnitude and statistical significance of risk factor relations were similar across methods. Rate of change in CIMT in participants assigned to placebo was 0.0066 mm per year (SE: 0.0027) for manually and 0.0072 mm per year (SE: 0.0029) for semi-automatically read images. The effect of lipid-lowering therapy on CIMT changes was -0.0103 mm per year (SE: 0.0032) for manual reading and -0.0111 mm per year (SE: 0.0034) for semi-automated reading. CONCLUSION: Manual and semi-automated readings of the maximal far wall of the common CIMT images both result in high reproducibility, show similar risk factor relations, rates of change and treatment effects. Hence, choices between semi-automated and manual reading software for CIMT studies likely should be based on logistical and cost considerations rather than differences in expected data quality when the choice is made to use far wall common CIMT measurements.

C-reactive protein lowering with rosuvastatin in the METEOR study.

OBJECTIVES: In addition to its LDL-C-lowering effects, statin treatment reduces the level of C-reactive protein (CRP). Long-term data on this effect in low-risk populations are limited. Furthermore, whether the CRP reduction is a consequence of LDL-C lowering or occurs independently remains unclear. We studied these aspects in the Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin (METEOR) study, a randomized placebo-controlled trial amongst 984 low-risk subjects. METHODS: METEOR is a randomized placebo-controlled trial that evaluated the effect of 40 mg of rosuvastatin on 2-year change in carotid intima media thickness (CIMT) amongst 984 low-risk patients (10-year Framingham risk < 10%) with modest CIMT (CIMT > or = 1.2 and < 3.5 mm) and elevated LDL-C. CRP levels were measured at baseline and after 2 years of treatment. RESULTS: Median baseline CRP was 1.4 mg L(-1). Rosuvastatin lowered CRP significantly compared with placebo: -36% in the rosuvastatin group versus no change in the placebo group. There was no relation between change in CRP and change in LDL-C (Spearman correlation: 0.08; SE: 0.04). Stratified analyses showed that the CRP-lowering effect was present amongst all strata of baseline characteristics, including baseline lipids and CRP levels. However, the magnitude of CRP reduction was larger amongst women and participants older than 60 years. CONCLUSIONS: Rosuvastatin (40 mg) lowers CRP independently from its effects on LDL-C in low-risk subjects with normal baseline CRP levels and modest CIMT.

Intensive lipid lowering may reduce progression of carotid atherosclerosis within 12 months of treatment: the METEOR study.

BACKGROUND: In several statin trials, vascular event rates for treatment groups begin to separate 1 year after commencement of treatment. For atherosclerosis progression, the temporal sequence of the effect has not been defined. We used data from the Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin (METEOR) trial to determine the earliest time point at which significant differences in atherosclerosis progression rates could be detected after initiation of statin therapy. METHODS: The METEOR trial was a double-blind, randomized placebo-controlled trial that studied the effect of LDL-C lowering with 40 mg rosuvastatin on the rate of change of carotid intima media thickness (CIMT) measured by B-mode ultrasound amongst 984 low risk subjects. Ultrasound assessments were made at baseline and every 6 months up to 2 years. RESULTS: Rosuvastatin treatment was associated with a 49% reduction in LDL-C-C, a 34% reduction in total cholesterol, an 8.0% increase in HDL-C and a 16% reduction in triglycerides (all P < 0.0001 compared with placebo). The difference in rate of mean maximum CIMT progression between the rosuvastatin and placebo groups (based on near and far wall measurements from both left and right common carotid and internal carotid segments and carotid bifurcation) was not statistically significant after 6 months (0.0023 mm year(-1) and 0.0106 mm year(-1), respectively P = 0.34). After 12 months, CIMT progression rates were significantly different between the groups: 0.0032 mm year(-1) and 0.0133 mm year(-1) in the rosuvastatin-treated and placebo-treated groups, respectively (P = 0.049). This divergence grew with further follow-up: -0.0009 mm year(-1) and 0.0131 mm year(-1) after 18 months (P < 0.001) and -0.0014 mm year(-1) and 0.0131 mm year(-1) after 24 months of treatment (P < 0.001). Results were stronger for the mean common CIMT progression (based on near and far wall measurements from both left and right common carotid segments). CONCLUSION: Aggressive LDL-C lowering seems to exert its beneficial effect on atherosclerosis progression during the first 12 months of treatment. This parallels the timing of event reduction seen in clinical trials and suggests that the efficacy of lipid lowering treatment on CIMT progression can be evaluated in trials with a duration of 1 year, given sufficient sample size, high precision of measurements and a treatment effect comparable to that seen in METEOR.

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.

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.

OBJECTIVES: This 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. BACKGROUND: The 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. METHODS: This 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. RESULTS: Full 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). CONCLUSIONS: This 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.

Computer-assisted myocardial thickening analysis of gated MIBI SPECT images.

RATIONALE AND OBJECTIVES: The purpose of this study is to use the relationship between the partial volume effect, count density, matrix size, and reconstruction filter in gated single photon emission computer tomography (SPECT) to recover myocardial thickness, and to validate measurements generated using a computer-assisted automatic contour method with a phantom model and with thickness changes measured by echocardiography. METHODS: Regional myocardial contour was defined automatically using shape constraints, gray level thresholding, and a gradient method applied to gated technetium-99m (99mTc)-methoxy-isobutyl-isonitile (MIBI) SPECT images. A heart phantom with wall thickness ranging from 0.8 cm to 1.3 cm was constructed. SPECT images were acquired and reconstructed using different matrix sizes, count densities, and filters. Wall thickness determinations derived from the reconstructions made with each combination of matrix size, type of filter, and cutoff frequency were correlated with the measured thicknesses. The best combination was applied to the gated MIBI SPECT images of 55 patients who also had echocardiography and coronary arteriography. Count density measurements were made across each regional myocardial segment to evaluate wall thickness at end-diastole and end-systole. Systolic wall thickening measurements made with this automated computer-assisted contour technique were compared with echocardiographic measurements made from segments with normal perfusion and from regions containing infarcted tissue. RESULTS: Different reconstruction filters and cutoff frequencies affected the accuracy of measurements of myocardial wall thickness determined from gated myocardial SPECT images. A matrix size of 64 x 64, with a minimum of 10 counts/pixel/frame, and use of a Hanning filter with 0.5 cyc/cm cutoff frequency gave the best combination for myocardial thickness determination and spatial resolution. Application of these factors to the phantom yielded results that correlated very well with the thickness measurements (r = 0.986, P < 0.001). Application of the technique to the clinical SPECT studies yielded measurements of myocardial wall thickening that were not significantly different from that determined by echocardiography. CONCLUSION: Computer-assisted contour analysis of gated SPECT images enables accurate determination of regional wall thickening using the count density changes within each myocardial segment.

Usefulness of combined color Doppler/contrast in providing complete delineation of left ventricular cavity.

Contrast-enhanced 2-dimensional echocardiography without color Doppler did not result in complete filling of the left ventricular cavity in 21 patients studied. However, contrast-enhanced color Doppler was very effective and provided complete opacification of the left ventricular cavity in 20 of these 21 patients.

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.

False-positive reversible perfusion defect during dobutamine-thallium imaging in left bundle branch block.

In the presence of pre-existing left bundle branch block (LBBB) exercise stress thallium scans have been associated with false-positive septal and apical perfusion abnormalities. Recent reports have documented a lower incidence of false-positive septal perfusion defects when pharmacologic agents such as dipyridamole or adenosine are utilized in patients with LBBB. Dobutamine, a synthetic catecholamine, is being used with increasing frequency in combination with perfusion agents for the diagnosis of coronary artery disease in patients unable to achieve an adequate exercise workload. Because the positive inotropic and chronotropic actions of doubtamine are similar to the physiologic effects of treadmill exercise, it is conceivable that false-positive perfusion abnormalities will be observed in patients with pre-existing LBBB undergoing dobutamine perfusion imaging. We describe a patient with underlying LBBB who underwent dobutamine thallium imaging which revealed septal and periapical defects. Subsequent coronary angiography showed these abnormalities to be false-positive. It is concluded that septal and periapical perfusion abnormalities during dobutamine thallium imaging may be false-positive and should be interpreted cautiously.

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.

Opacification and border delineation improvement in patients with suboptimal endocardial border definition in routine echocardiography: results of the Phase III Albunex Multicenter Trial.

OBJECTIVES: This 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. BACKGROUND: Echocardiographic 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. METHODS: One 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. RESULTS: Overall, 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. CONCLUSIONS: In 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.

The radiology of cardiac valve prostheses.

The radiographic findings associated with the complications of valve implantation are presented. Complementary roles of echocardiography and cine fluoroscopy in the recognition of complications associated with this procedure are emphasized. Identification of prosthetic valves and the knowledge of the modes of action of the various types of valves are stressed.

Rest and exercise radionuclide ventriculography in the ambulatory monitoring of patients with valvular heart disease.

Radionuclide angiography serves as a valuable adjunct in the noninvasive evaluation and monitoring of patients with valvular heart disease. Although estimations of regurgitant fractions and the differences between left and right ventricular stroke volumes can be made, the limitations of the techniques do not enable adequate quantitation of the severity of valvular insufficiency to warrant routine use in ambulatory management. The importance of radionuclide ventriculography, however, lies in its ability to examine global ventricular function both at rest and with exercise, thus enabling assessment of the functional reserve of the left and right ventricles. Such data are of considerable value in determining the need for invasive evaluation and the timing of valve replacement in patients with valvular heart disease.

Tricuspid valve prolapse.

Tricuspid valve prolapse is an infrequent echocardiographic finding that is most commonly associated with mitral valve prolapse. When compared with patients exhibiting isolated prolapse of the mitral valve, patients with tricuspid valve prolapse are somewhat older individuals with a slightly higher frequency of neurologic symptoms, fatigue, weakness, supraventricular arrhythmias (especially atrial fibrillation) and skeletal deformities. Tricuspid valve prolapse may serve as a marker of more-diffuse connective tissue abnormalities, and its identification also should prompt an echocardiographic search for evidence of prolapse and regurgitation of the other heart valves.

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.

Importance of risk factors in the angiographic progression of coronary artery disease.

Although specific risk factors correlate with the development of clinical coronary events, little is known about their importance in patients with established coronary artery disease (CAD). A numerical scoring system was used to assess serial coronary angiograms in subjects who had detailed risk factor determinations. Strong linear correlations were demonstrated between the extent of progression of CAD and diastolic blood pressure (BP) (p = 0.002), systolic BP (p = 0.094), the number of cigarette pack-years smoked among current smokers (p = 0.022), fasting blood glucose level (p = 0.017) and low levels of physical activity at leisure (p = 0.097). This analysis of sequential coronary angiograms identifies BP, cigarette smoking, diabetes mellitus and physical activity as important risk factors in the progression of CAD. These variables merit attention in the management of patients with symptomatic CAD and in secondary coronary prevention trials investigating risk factor modification.

Assessment of the site of ventricular activation by Fourier analysis of gated blood-pool studies.

We studied the use of first-harmonic Fourier analysis of gated blood-pool images to assess the site of ventricular activation in a group of 12 patients undergoing electrophysiologic pacing studies. We acquired gated blood-pool studies during pacing at up to four sites at each of two different rates. A total of 50 studies were made. At a pacing rate of 100 beats/min, when the pacing electrode was at the right-ventricular apex, 9/13 times the Fourier activation site agreed; at the right-ventricular outflow tract, 7/8; at the anterolateral left-ventricular wall, 4/4. When the Fourier activation site was at the right-ventricular apex, 9/9 times the pacing electrode was there; at the right-ventricular outflow tract, 7/10; in the left ventricle, 4/4. Fourier analysis of gated blood-pool studies can help identify the site of ventricular activation but is not sufficiently accurate to fully replace endocardial mapping.