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Background: Human tissue valves for aortic valve replacement have a limited durability that is influenced by interrelated determinants. Hierarchical linear modeling was used to analyze the relation between these determinants of durability and valve regurgitation measured by serial echocardiography., Methods and Results: In adult patients, 218 cryopreserved aortic allografts were implanted with the subcoronary (85) or the root replacement technique (133), and 81 patients had root replacement with a pulmonary autograft. Mean follow-up was 4.2 years (SD 2.7; range, 0 to 10.5). Patient age, operator experience with subcoronary implantation, and allograft diameter were independent predictors for reoperation. With repeated color Doppler echocardiography, the severity of aortic regurgitation was assessed by the jet length method and the jet diameter ratio. Multilevel hierarchical linear modeling was used to estimate initial aortic regurgitation (intercept), its change over time (slope), and the effect of 11 potential determinants of durability on aortic regurgitation. With the jet length method, the intercept was 0.94 grade and the slope was 0.11 grade per year. With the jet diameter ratio, the intercept was 0.34 and the annual increase was 0.01. Subcoronary implanted valves had more initial aortic regurgitation, but progression of aortic valve regurgitation did not differ from root replacement. At midterm follow-up, recipient age <40 years was the only independent predictor of aortic regurgitation., Conclusions: Subcoronary implantation has a learning curve, resulting in more initial aortic regurgitation and early reoperation compared with root replacement. In both techniques, progression of aortic regurgitation over time is small but accelerated in young adults.

Background: The purpose of this study was to assess the long-term value of dobutamine-atropine stress echocardiography (DSE) for prediction of late cardiac events in patients with proven or suspected coronary artery disease., Methods and Results: Clinical data and DSE results were analyzed in 1734 consecutive patients undergoing DSE between 1989 and 1997. Seventy-four patients who underwent revascularization within 3 months of DSE and 1 patient lost to follow-up were excluded; the remaining 1659 (median age, 62 years; range, 14 to 99 years) were followed up for 36 months (range, 6 to 96 months). Wall motion abnormalities at rest and the presence and extent of stress-induced wall motion abnormalities (ischemia) were scored for each patient. Cardiac events were related to clinical and ECG data and DSE results. Four hundred twenty-eight cardiac events occurred in 366, documented cardiac death in 108 (total death, 247), nonfatal infarction in 128, and late revascularization in 192 patients. In a multivariable Cox proportional-hazards model, the ratio of documented cardiac death or (re)infarction was increased in the presence of stress-induced ischemia (hazard ratio, 3.3; 95% CI, 2.4 to 4.4) and extensive rest wall motion abnormalities (hazard ratio, 1.9; 95% CI, 1.3 to 2.6). The number of ischemic segments was predictive for late cardiac events. A normal DSE carried a relatively good prognosis, with an annual event rate of cardiac death or infarction of 1.3% over a 5-year period., Conclusions: In a large group of patients, DSE has an added value for predicting late cardiac events during long-term follow-up, improving the separation between high- risk and very-low-risk patients.

Background: Automated systems for the quantitative analysis of three-dimensional (3D) sets of intravascular ultrasound (IVUS) images have been developed to reduce the time required to perform volumetric analyses; however, 3D image reconstruction by these nongated systems is frequently hampered by cyclic artifacts., Methods and Results: We used an ECG-gated 3D IVUS image acquisition workstation and a dedicated pullback device in atherosclerotic coronary segments of 30 patients to evaluate (1) the feasibility of this approach of image acquisition, (2) the reproducibility of an automated contour detection algorithm in measuring lumen, external elastic membrane, and plaque+media cross-sectional areas (CSAs) and volumes and the cross-sectional and volumetric plaque+media burden, and (3) the agreement between the automated area measurements and the results of manual tracing. The gated image acquisition took 3.9+/-1.5 minutes. The length of the segments analyzed was 9.6 to 40.0 mm, with 2.3+/-1.5 side branches per segment. The minimum lumen CSA measured 6.4+/-1.7 mm2, and the maximum and average CSA plaque+media burden measured 60.5+/-10.2% and 46.5+/-9.9%, respectively. The automated contour-detection required 34.3+/-7.3 minutes per segment. The differences between these measurements and manual tracing did not exceed 1.6% (SD<6.8%). Intraobserver and interobserver differences in area measurements (n=3421; r=.97 to.99) were <1.6% (SD<7.2%); intraobserver and interobserver differences in volumetric measurements (n=30; r=.99) were <0.4% (SD<3.2%)., Conclusions: ECG-gated acquisition of 3D IVUS image sets is feasible and permits the application of automated contour detection to provide reproducible measurements of the lumen and atherosclerotic plaque CSA and volume in a relatively short analysis time.

Background: Debate exists regarding the relationship between angiographic and intracoronary ultrasound (ICUS) measurements of minimal luminal cross-sectional area after coronary intervention. We investigated this and the factors that may influence it by using ICUS and quantitative angiography., Methods and Results: Patients who underwent successful balloon angioplasty (n=100) or directional atherectomy (n=50) were examined by using ICUS and quantitative angiography (edge-detection [ED] and videodensitometry [VID]) before and after intervention. Luminal damage postintervention was qualitatively graded into three categories based on angiographic results (smooth lumen, haziness, or dissection). Correlation of minimal luminal cross-sectional area measurements by ICUS and ED was .59 before and .47 after balloon angioplasty. Correlation between ICUS and VID was .50 before and .63 after balloon angioplasty. Postintervention, the difference between ICUS and VID was less than the difference between ICUS and ED (P<.01). Additionally, the correlation was .74 between ICUS and ED measurements and .78 between ICUS and VID measurements in the smooth lumen group, .46 and .63, respectively, in the presence of haziness, and .26 and .46, respectively, in lesions with dissection. Similar results were obtained after directional atherectomy: the agreement between ICUS and quantitative angiography deteriorated according to the degree of vessel damage, but less so with VID than ED., Conclusions: Complex morphological changes induced by intervention may contribute to discordance between the two quantitative imaging techniques. In the absence of ICUS, VID may be a complementary technique to ED in lesions with complex morphology after balloon angioplasty and directional atherectomy.

Background: Pharmacological stress echocardiography and myocardial perfusion scintigraphy are used frequently for risk stratification in patients with suspected myocardial ischemia. However, their relative prognostic strength has never been explored., Methods and Results: Two hundred twenty consecutive patients with chest pain (mean age, 60 +/- 12 years; 124 men, 115 with previous myocardial infarction) were studied with dobutamine-atropine stress echocardiography (ECHO) and simultaneous 99mTc sestamibi single photon emission computed tomography imaging (MIBI). Ischemia was defined as deterioration in left ventricular wall motion and reversible perfusion defects, respectively. ECHO was positive for ischemia in 76 and MIBI in 91 patients (agreement, 77%; kappa = .51). During follow-up of 31 +/- 15 months, 24 patients had hard cardiac events (nonfatal myocardial infarction or cardiac death). By univariate analysis, age, history of congestive heart failure, and any abnormality or ischemia on ECHO or MIBI were associated with cardiac events. Multivariate analysis revealed that age, abnormal ECHO (odds ratio [OR], 18.9; 95% CI, 2.5 to 146.0) or MIBI (OR, 12.8; 95% CI, 1.7 to 98.3), and ischemia on ECHO (OR, 4.0; 95% CI, 1.6 to 9.9) or MIBI (OR, 3.0; 95% CI, 1.2 to 7.4) had independent predictive values. When ECHO was used as a first option, the addition of MIBI to all nonischemic ECHO studies decreased the OR from 4.0 (95% CI, 1.6 to 9.9) to 3.8 (95% CI, 1.4 to 10.2). Addition of MIBI confined to nonischemic ECHO studies in which target heart rate was not attained (nondiagnostic studies) increased the OR to a maximal 5.7 (95% CI, 2.2 to 15.0). In contrast, the addition of ECHO to nondiagnostic MIBI studies was not useful., Conclusions: Dobutamine-atropine ECHO and MIBI provide comparable prognostic information. The addition of MIBI to ECHO may be useful in patients with nondiagnostic ECHO studies.

Background: Demonstration and quantification of site-specific intracoronary administration of compounds has been confined thus far to the experimental animal laboratory. The aim of this study was to describe a scintigraphic method to demonstrate site-specific intracoronary drug delivery in humans. The methods allow on-line visualization and off-line quantification of site-specifically infused gamma-emitting compounds., Methods and Results: In 12 patients after balloon angioplasty, 99mTc-labeled heparin was administered at the site of dilatation by use of a coil balloon. Both the infusion period and the washout period after the end of infusion were monitored with a gamma-camera. A curve of counts per pixel as a function of time was derived that showed an accumulation phase during infusion followed by washout phase after the end of infusion. Both phases were fitted by regression analysis and showed a linear accumulation pattern and a biexponential washout pattern. After correction for background counts, 99mTc decay, and body attenuation, peak heparin amount and regional bioavailability were calculated. Peak amount was defined as the initial point of the slow washout component of the biexponential curve (elimination component), and regional bioavailability was defined as the area under the curve of accumulation and washout phase. Half-life and retention time, define as seven half-lives, were obtained by use of the elimination component after correction for 99mTc decay. Mean peak delivered amount was 45 +/- 44 IU (236 +/- 228 micrograms), corresponding to an efficiency of delivery ranging from 1% to 8% of the totally infused dose. Total regionally bioavailable heparin reached 244 +/- 194 IU.h (1.28 +/- 1.01 mg.h). Retention time varied from 12 to 90 hours (mean, 50:33 +/- 22:50 hours:minutes)., Conclusions: Site-specific intracoronary heparin delivery after angioplasty by means of the coil balloon was demonstrated in humans, and regional pharmacokinetics was quantified by use of a radioisotopic technique.

Background: Automated stenosis analysis is a common feature of commercially available quantitative coronary angiography (QCA) systems, allowing automatic detection of the boundaries of the stenosis, interpolation of the expected dimensions of the coronary vessel at the point of obstruction, and angiographically derived estimation of atheromatous plaque size. However, the ultimate meaning of this type of analysis in terms of the degree of underlying atherosclerotic disease remains unclear. We investigated the relationship between stenosis analysis performed with QCA and the underlying degree of atherosclerotic disease judged by intracoronary ultrasound (ICUS) imaging., Methods and Results: In 40 coronary stenoses, automated identification of the sites of maximal luminal obstruction and the start of the stenosis was performed with QCA by use of curvature analysis of the obtained diameter function. Plaque size at these locations also was estimated with ICUS, with an additional ICUS measurement immediately proximal to the start of the stenosis. Crescentlike distribution of plaque, indicating an atheroma-free arc of the arterial wall, was recorded. At the site of the obstruction, total vessel area measured with ICUS was 16.65 +/- 4.04 mm2, whereas an equivalent measurement obtained from QCA-interpolated reference dimensions was 7.48 +/- 3.30 mm2 (P = .0001). Plaque area derived from QCA data was significantly less than that calculated from ICUS (6.32 +/- 3.21 and 13.29 +/- 4.22 mm2, respectively; mean difference, 6.92 +/- 4.43 mm2; P = .0001). At the start of the stenosis identified by automated analysis, ICUS plaque area was 9.38 +/- 3.17 mm2, and total vessel area was 18.77 +/- 5.19 mm2 (50 +/- 11% total vessel area stenosis). The arterial wall presented a disease-free segment in 28 proximal locations (70%) but in only 5 sites (12%) corresponding to the start of the stenosis and none at the obstruction (P = .0001). At the site of obstruction, all vessels showed a complete absence of a disease-free segment, and the atheroma presented a cufflike or all-around distribution with a variable degree of eccentricity., Conclusions: At the site of maximal obstruction, QCA underestimated plaque size as measured with ICUS. Atherosclerotic disease was consistently present at the start of the stenosis and was used as a reference site by automated stenosis analysis. At the start of the stenosis, ICUS demonstrated a mean 50 +/- 11% total vessel area stenosis, with a characteristic loss of disease-free arcs of arterial wall present in proximal locations. Thus, the site identified by automated stenosis analysis as the start of the stenosis does not represent a disease-free site but rather the place where compensatory vessel enlargement fails to preserve luminal dimensions, a phenomenon that seems related to the observed loss of a remnant arc of normal arterial wall.

Background: Three-dimensional echocardiography is a promising technique for calculation of left ventricular ejection fraction, because it allows its measurement without geometric assumptions. However, few data exist that study its reproducibility and accuracy in patients., Methods and Results: Twenty-five patients underwent radionuclide angiography and three-dimensional echocardiography that used the rotational technique (2 degrees interval and ECG and respiratory gating). Left ventricular volume and ejection fraction were calculated by use of Simpson's rule at a slice thickness of 3 mm. Analyses were performed to define the largest slice thickness required for accurate calculation of left ventricular volume and ejection fraction. Three-dimensional echocardiography showed excellent correlation with radionuclide angiography for calculation of left ventricular ejection fraction (mean +/- SD, 38.9 +/- 19.8 and 38.5 +/- 18.0, respectively; r = .99); their mean difference was not significant (0.03 +/- 0.17; P = .3), and they had a close limit of agreement (-0.385, 0.315). Intraobserver variability for radionuclide angiography and three-dimensional echocardiography was 4.2% and 2.6%, respectively, whereas interobserver variability was 6.2% and 5.3%, respectively. There was no significant difference between left ventricular volume and ejection fraction calculated at a slice thickness of 3 mm and that calculated at different slice thicknesses up to 24 mm. However, the standard deviation of the mean difference showed a stepwise increase, particularly at thicknesses > 15 mm. At a slice thickness of 15 mm, the probability of three-dimensional echocardiography to detect > or = 6% difference in ejection fraction was 80%., Conclusions: Three-dimensional echocardiography has excellent correlation with radionuclide angiography for calculation of left ventricular ejection fraction in patients and has an observer variability similar to that of radionuclide angiography. We recommend the use of a 15-mm-thick slice for accurate and rapid measurement of left ventricular volume and ejection fraction.

Background: Postmortem-derived findings support the common beliefs that lipid-rich coronary plaques with a thin, fibrous cap are prone to rupture and that rupture and superimposed thrombosis are the primary mechanisms causing acute coronary syndromes. In vivo imaging with intracoronary techniques may disclose differences in the characterization of atherosclerotic plaques in patients with stable or unstable angina and thus may provide clues to which plaques may rupture and whether rupture and thrombosis are active., Methods and Results: We assessed the characteristics of the ischemia-related lesions with coronary angiography and intracoronary angioscopy and determined their compositions with intracoronary ultrasound in 44 patients with unstable and 23 patients with stable angina. The angiographic images were classified as noncomplex (smooth borders) or complex (irregular borders, multiple lesions, thrombus). Angioscopic images were classified as either stable (smooth surface) or thrombotic (red thrombus). The ultrasound characteristics of the lesion were classified as poorly echo-reflective, highly echo-reflective with shadowing, or highly echo-reflective without shadowing. There was a poor correlation between clinical status and angiographic findings. An angiographic complex lesion (n = 33) was concordant with unstable angina in 55% (24 of 44); a noncomplex lesion (n = 34) was concordant with stable angina in 61% (14 of 23). There was a good correlation between clinical status and angioscopic findings. An angioscopic thrombotic lesion (n = 34) was concordant with unstable angina in 68% (30 of 44); a stable lesion (n = 33) was concordant with stable angina in 83% (19 of 23). The ultrasound-obtained composition of the plaque was similar in patients with unstable and stable angina., Conclusions: Angiography discriminates poorly between lesions in stable and unstable angina. Angioscopy demonstrated that plaque rupture and thrombosis were present in 17% of stable angina and 68% of unstable angina patients. Currently available ultrasound technology does not discriminate stable from unstable plaques.

Background: Although both 201Tl scintigraphy and low-dose dobutamine echocardiography (LDDE) have been proposed as effective methods of assessing myocardial viability, their relative efficacies are unknown. The aim of the present study was to compare the two imaging techniques in the prediction of improvement of regional left ventricular (LV) function after surgical revascularization., Methods and Results: Thirty-eight patients with severe chronic LV dysfunction (ejection fraction < or = 40%, one or more akinetic [Ak] or severely hypokinetic [SH] segments on resting echocardiogram) who underwent uncomplicated coronary artery bypass graft surgery were studied with simultaneous dobutamine stress echocardiography and poststress reinjection 201Tl single-photon emission computed tomography (SPECT) before surgery. The Ak or SH segments were considered viable by LDDE when wall thickening improved during the infusion of 10 micrograms.kg-1 min 1 dobutamine. Scintigraphic definition of viability was the presence of normal 201Tl uptake, totally reversible defect, partially reversible defect, or moderately severe fixed defect. The postoperative improvement of dyssynergic segments was determined with a rest echocardiogram 3 months after surgery. Of 608 LV segments, 169 were classified as Ak and 51 as SH on resting preoperative echocardiography. Of these, 170 were successfully revascularized. Wall motion during LDDE improved in 33 severely dyssynergic segments and was more frequent in SH than in Ak segments (19 of 44 versus 14 of 126, P < .0001). Viability was detected by 201Tl SPECT criteria in 103 SH or Ak segments. Thirty-two of the 33 segments from LDDE responders were judged viable on 201Tl SPECT, whereas 201Tl viability was also detected in 71 of 137 segments from LDDE nonresponders. The sensitivity and the specificity for the prediction of postoperative improvement of segmental wall motion were 74% (95% confidence interval [CI], 67% to 81%) and 95% (95% CI, 92% to 98%) by LDDE and 89% (95% CI, 84% to 94%) and 48% (95% 40% to 56%) by 201Tl SPECT, respectively. Positive predictive value of LDDE was higher than that of 201Tl SPECT (85%, [95% CI, 80% to 90%] versus 33% [95% CI, 26% to 40%]). Thirty-six patients had angina before and only 1 had angina 3 months after revascularization. High-dose dobutamine echocardiography demonstrated significant reduction in stress-induced ischemia (new or worsening of preexisting wall motion abnormalities) after surgery (from 163 to 23 LV segments)., Conclusions: In patients with severe chronic LV dysfunction, LDDE is a good predictor of the improvement of dyssynergic segments after revascularization. Because 201Tl SPECT overestimates the probability of postoperative improvement of dyssynergic segments, LDDE should be the preferred imaging technique for preoperative assessment of these patients.