Serial intravascular ultrasound assessment of the efficacy of intracoronary gamma-radiation therapy for preventing recurrence in very long, diffuse, in-stent restenosis lesions.

BACKGROUND: The efficacy of coronary gamma-irradiation in preventing recurrent in-stent restenosis (ISR) is well established. However, brachytherapy may be less effective in very long, diffuse ISR lesions. METHODS AND RESULTS: We used serial intravascular ultrasound (IVUS) to study patients with long, diffuse ISR lesions (length, 36 to 80 mm) who were enrolled in (1) Long WRIST (Washington Radiation In-Stent Restenosis Trial), a double-blind, placebo-controlled trial of intracoronary gamma-irradiation (15 Gy at 2 mm from the source) and (2) high-dose (HD) Long WRIST, a registry that used a dose prescription of 18 Gy at 2 mm from the source. IVUS was performed using automated pullback (0.5 mm/s). Stent, lumen, and intimal hyperplasia were measured at 2-mm intervals. Complete postintervention and follow-up IVUS imaging was available in 30 irradiated and 34 placebo patients from Long WRIST and in 25 patients from HD Long WRIST. Stent length was longer in HD Long WRIST than in placebo or treated patients in Long WRIST (P=0.0064 and P=0.0125, respectively). Otherwise, baseline measurements were similar. At follow-up, the minimum lumen area was largest in the HD Long WRIST patients (4.0+/-1.4 mm(2)); areas were 2.9+/-1.0 mm(2) in irradiated patients in Long WRIST and 1.9+/-1.1 mm(2) in placebo patients in Long WRIST (P<0.005 for all comparisons). CONCLUSIONS: - Serial IVUS analysis shows that gamma-irradiation reduces recurrent in-stent neointimal hyperplasia in long, diffuse ISR lesions; however, it is even more effective when given at a higher dose.

Safety of intracoronary gamma-radiation on uninjured reference segments during the first 6 months after treatment of in-stent restenosis: a serial intravascular ultrasound study.

BACKGROUND: The effects of endovascular irradiation on uninjured reference segments during the treatment of in-stent restenosis are unknown. METHODS AND RESULTS: In the Washington Radiation for In-Stent restenosis Trial (WRIST), patients with in-stent restenosis were first treated with conventional catheter-based techniques and then randomized (blinded) to receive either gamma-irradiation ((192)Ir) or a placebo (dummy seeds). We identified all patients in whom the active (n=19) or dummy seeds (n=19) extended >10 mm proximal and distal to the in-stent restenosis lesion. Serial (postirradiation and follow-up) external elastic membrane (EEM), lumen, and plaque and media (EEM-lumen) areas were measured (using intravascular ultrasound) every 1 mm over 5-mm-long reference segments that were 6 to 10 mm proximal and distal to the in-stent restenosis lesion. During follow-up, a similar small increase occurred in the plaque and media area in the proximal and distal reference segments in both (192)Ir and placebo patients. However, in the (192)Ir patients, an increase in both proximal and distal EEM area occurred; as a result, no change in lumen area occurred. Conversely, in the placebo patients, the proximal reference EEM area decreased, and no change occurred in the distal reference EEM area; this contributed to a decrease in lumen area. CONCLUSIONS: There was no evidence of a deleterious effect of gamma-irradiation on angiographically normal uninjured reference segments in the first 6 months after the treatment of in-stent restenosis.

Mechanism of lumen enlargement during intracoronary stent implantation: an intravascular ultrasound study.

BACKGROUND: Intravascular ultrasound analysis has assessed mechanisms of lumen enlargement after nonstent interventions, but not after stenting. METHODS AND RESULTS: Preintervention and postintervention intravascular ultrasound was used to study 25 de novo native coronary lesions treated with single MultiLink stents without preatheroablation. External elastic membrane, lumen, and plaque and media (P&M) areas were measured every 1 mm to include the lesion and reference segments that were 5 mm proximal and distal to it. Lesion mean lumen area increased from 4.0+/-1.0 mm(2) before the intervention to 8.8+/-2.0 mm(2) after the intervention (P<0.0001) as a result of an increase in mean external elastic membrane area (14. 2+/-2.7 to 16.1+/-3.0 mm(2), P<0.0001) and a decrease in mean P&M area (10.2+/-2.2 to 7.2+/-1.8 mm(2), P<0.0001). The decrease in lesion P&M was accompanied by an increase in both proximal reference mean P&M (7.0+/-1.9 to 8.4+/-2.0 mm(2), P<0.0001) and distal reference mean P&M (5.8+/-2.1 to 7.2+/-2.1 mm(2), P<0.0001). Volumetric analysis showed an axial redistribution of plaque away from the center of the lesion toward the reference segments to increase the plaque burden in both the proximal and distal reference segments. Total (lesion plus reference) mean P&M decreased from 8. 6+/-2.1 to 7.5+/-1.8 mm(2) (P<0.0001). CONCLUSIONS: The mechanisms of lumen enlargement after stenting involved (1) significant axial redistribution of plaque from the lesion into the reference segments, (2) vessel expansion, and (3) either plaque embolization or compression.

Comparative efficacy of gamma-irradiation for treatment of in-stent restenosis in saphenous vein graft versus native coronary artery in-stent restenosis: An intravascular ultrasound study.

BACKGROUND: We used serial volumetric (post-irradiation and follow-up) intravascular ultrasound (IVUS) to compare the effectiveness of gamma-irradiation ((192)Ir) in saphenous vein graft (SVG) versus native coronary artery in-stent restenosis (ISR). METHODS AND RESULTS: The study population consisted of 47 patients with native coronary artery ISR from WRIST (Washington Radiation for In-Stent Restenosis Trial) and 31 patients with SVG ISR (12 from the WRIST and 19 from SVGWRIST). After irradiation and at 6-month follow-up, stent, lumen, and intimal hyperplasia (IH, stent minus lumen) areas were measured every 1 mm. ISR length was similar in the 2 groups (29+/-12 versus 29+/-14 mm, P=0.9). Post-intervention measurements of stent (280+/-154 versus 324+/-270 mm(3), P=0.4), lumen (184+/-91 versus 214+/-172 mm(3), P=0.3), and IH (96+/-77 versus 109+/-119 mm(3), P=0.5) volumes were similar in the 2 groups. The post-intervention minimum lumen cross sectional areas tended to be smaller in native artery ISR lesions (4.7+/-1.7 versus 5.4+/-1.6 mm(2), P=0.11). During follow-up, there was a slight increase in IH volume (9+/-38 mm(3)) in native artery ISR lesions and a slight decrease in IH volume in SVG ISR lesions (-9+/-32 mm(3), P=0.0463). There was also a slight decrease in minimum lumen area in the native artery ISR lesions versus a slight increase in minimum lumen area in the SVG ISR lesions (-0.8+/-1.7 versus 0.2+/-1.1, P=0.0087). As a result, the follow-up minimum lumen area in native artery lesions was smaller than in SVG ISR lesions (4.1+/-2.1 mm(2) versus 5.6+/-2.2 mm(2), P=0.0067). CONCLUSION: gamma-Irradiation with (192)Ir brachytherapy appears to be as effective in SVGs as it is in native artery ISR lesions.

Effect of intracoronary gamma-radiation therapy on in-stent restenosis: An intravascular ultrasound analysis from the gamma-1 study.

BACKGROUND: The aim of this study was to use serial volumetric intravascular ultrasound to evaluate the effect of gamma-radiation on recurrent in-stent restenosis. METHODS AND RESULTS: After successful reintervention, patients were randomized to receive either (192)Ir or placebo. Intravascular ultrasound studies with motorized pullback (0.5 mm/s) were performed immediately after irradiation and at 8-month follow-up in 70 patients. Paired volumetric analysis of the stented segment and of 5-mm proximal and distal reference segments was performed; this included measurements of the external elastic membrane, lumen, plaque and media (external elastic membrane minus lumen), stent, and intimal hyperplasia (stent minus lumen). Baseline proximal reference, stent, and distal reference measurements were similar in both groups. The changes in proximal and distal reference measurements of the external elastic membrane, plaque and media, and lumen areas were similar in both groups. However, the decrease in stented segment lumen volume was less in the (192)Ir patients than the placebo patients (-25+/-34 mm(3) versus -48+/-42 mm(3); P:=0.0225), and the increase in the volume of intimal hyperplasia in the stented segment was less in the (192)Ir patients than in the placebo patients (28+/-37 mm(3) versus 50+/-40 mm(3); P:=0.0352). When averaged over the length of the stented segment (32+/-13 mm versus 33+/-14 mm; P:=0.9), the increase in mean area of intimal hyperplasia was 0.8+/-1.0 mm(2) in the (192)Ir group and 1.6+/-1.2 mm(2) in the control group (P:=0.0065). Late stent-vessel wall malapposition was noted in one placebo patient and no (192)Ir patients. CONCLUSIONS: gamma-Radiation therapy can effectively prevent recurrent in-stent restenosis by inhibiting neointimal formation within the stent. At the stent edge, there were no significant differences between (192)Ir and placebo patients.

Effects of prolonging peak dobutamine dose during stress echocardiography.

OBJECTIVES: This study sought to test whether the physiologic advantage of a prolonged dobutamine stage during stress echocardiography can be effectively combined with a clinically practical infusion protocol. BACKGROUND: Dobutamine has a half-life of 2 min and requires up to 10 min to achieve steady state. Despite these known pharmacodynamics, dobutamine stress echocardiography is routinely performed by advancing doses at 3-min intervals. Canine studies have shown that dobutamine stress echocardiography end points will occur at a lower dose if each stage is prolonged, but these findings have yet to be used in the clinical setting. METHODS: The standard 3-min dobutamine dose stage during stress echocardiography was modified by extending the peak dose (40 micrograms/kg body weight per min) for an additional 2 min. Consecutive patients underwent this modified protocol to test whether the requirement for atropine could be reduced. According to this modified protocol, if a dobutamine stress echocardiographic end point (85% of maximal predicted heart rate, new wall motion abnormalities, hypotension, arrhythmia or intolerable symptoms) was not reached at 3 min of the peak dose, this dose was prolonged for an additional 2 min. If a doubtamine stress echocardiographic end point was still not attained, atropine (up to 1.0 mg intravenously) was administered. RESULTS: The study included 84 patients, 22 of whom (26.2%) achieved a dobutamine stress echocardiographic end point using the standard 3-min stage. Of the 62 patients who did not reach an end point in the initial 3 min of peak dobutamine dose, the additional 2 min of dobutamine increased heart rate (from 99.6 +/- 23.8 to 107.2 +/- 23.2 beats/min, p < 0.01) and allowed 20 patients (32.3%, p < 0.01) to attain an end point. Of the remaining 42 patients, 23 never achieved a stress echocardiographic end point, despite 1.0 mg of atropine. One patient developed supraventricular tachycardia during the additional 2 min of dobutamine, and one developed nonsustained ventricular tachycardia after receiving atropine. CONCLUSIONS: These data demonstrate that a significant number of patients (32%) who do not reach a dobutamine stress echocardiographic end point with the standard protocol can safely attain an end point solely by extending the duration of the peak dose. Adoption of this strategy may reduce the need for supplemental atropine and its potential adverse effects.

Prevalence of valvular-regurgitation associated with dexfenfluramine three to five months after discontinuation of treatment.

OBJECTIVES: The goal of this study was to determine the prevalence of valvular regurgitation and abnormal valve morphology in patients three to five months after discontinuation of dexfenfluramine (Dexfen) therapy. BACKGROUND: We previously reported the results of a randomized, double-blind, placebo-controlled trial of valvular structure and function in 1,073 patients treated either with Dexfen, with an investigational sustained-release dexfenfluramine (Dexfen SR), or with a placebo, with echocardiograms performed approximately one month from the last dose. Using FDA criteria (aortic regurgitation [AR] > or =mild and/or mitral regurgitation [MR] > or =moderate) we found no statistical difference among the groups, but when all degrees of valvular regurgitation were considered and when the two Dexfen groups were combined, there was a higher prevalence of any degree of AR, any degree of MR, and restricted posterior mitral leaflet mobility. However, it was unknown whether these differences in prevalence persisted. METHODS: The double blind was maintained, and all patients were invited to return for a follow-up echocardiogram. Echocardiograms were acquired using a standardized protocol and assessed blindly to determine the degree of valvular regurgitation and valve leaflet thickness and mobility. We had an 80% power to detect a statistically significant change in paired proportions using the McNemar test (alpha = 0.05). RESULTS: Echocardiograms were obtained on 941 patients with a median of 137 days after drug discontinuation. Aortic regurgitation (of any degree) was present in 13.8% of Dexfen (p = 0.41 compared to placebo), 10.7% of Dexfen SR (p = 0.64 compared to placebo), and 11.9% of placebo patients. The minor differences between patients treated with active drug versus placebo, which were found in the previous study, were no longer significant even when the groups were combined (p = 0.83 compared to placebo). Mitral regurgitation (of any degree) was present in 71.5% (p = 0.15 compared to placebo), 69.8% (p = 0.30 compared to placebo), and 70.5%, respectively. This was also not significantly different from placebo when both Dexfen groups were combined (p = 0.16). There was no difference in the prevalence of restricted posterior mitral leaflet mobility among the three groups (p = 0.19). CONCLUSIONS: The small increase in prevalence of minor degrees of AR and MR in patients treated with two to three months of Dexfen previously reported is no longer present three to five months after discontinuation of medication. These data suggest that the degree of regurgitation observed in patients who used Dexfen for a relatively short duration does not progress over time.

Specificity of Doppler echocardiography for the assessment of changes in valvular regurgitation: comparison of side-by-side versus serial interpretation.

OBJECTIVES: We sought to determine the specificity of two different methods for assessing change in aortic (AR), mitral (MR) and tricuspid (TR) valvular regurgitation. BACKGROUND: Echocardiographic imaging with Doppler is the standard noninvasive diagnostic tool for assessing valvular structure and function. Change can be assessed using either independent evaluations (serial) or using a side-by-side comparison. METHODS: Subjects were from the placebo arm of a randomized, double-blind, clinical trial. Three echocardiograms over 10 months were performed. An initial and three-month echocardiogram were read as independent groups, blinded to all parameters except sequence. The initial and 10-month echocardiograms were read side-by-side, blinded to all parameters including sequence. RESULTS: Two hundred nineteen predominantly healthy, obese, white, middle-aged women had initial and three-month echocardiograms (acquisition interval 105 +/- 28 days) evaluated by the serial method (mean 167 +/- 61 days between interpretations). The same subjects had the initial and 10-month studies (acquisition interval 303 +/- 27 days) compared side-by-side. The specificity of the serial versus side-by-side method for determining change in MR grade was 55.8% versus 93.2% (p < 0.001); TR: 63.8% versus 97.6% (p < 0.001) and AR: 93.7% versus 97.6 (p = 0.08). Notably, most of the change occurred in a range (none versus physiologic/mild) that has limited clinical significance. Furthermore, the percentage of echocardiograms interpreted as nonevaluable was lower with the side-by-side method for MR (5.0% vs. 16.0%, p = 0.06), TR (4.6% vs. 15.5%, p < 0.001) and AR (4.1% vs. 12.3%, p = 0.002). CONCLUSIONS: The side-by-side method of assessing change in valvular regurgitation appears to be the more reliable method with a higher specificity and minimal data loss.

Optimal stage duration in dobutamine stress echocardiography.

OBJECTIVES: This study attempted to determine the benefit of a 5-min dobutamine stress echocardiographic stage versus a 3-min stage in a canine model. BACKGROUND: Dobutamine stress echocardiography, as currently performed, uses a variety of different protocols. Among the many aspects of dobutamine stress echocardiographic protocols that vary is stage duration. Because dobutamine has specific pharmacodynamics, it is possible that stages of different durations may have different cardiovascular effects. METHODS: Paired dobutamine stress echocardiograms were obtained in 10 open chest instrumented dogs. The stage duration for the initial dobutamine stress echocardiogram was randomly allocated to either 3 or 5 min, and all hemodynamic and echocardiographic variables were allowed to return to baseline before the second dobutamine stress echocardiogram was obtained using the alternative stage duration. At each stage, heart rate, systolic blood pressure, coronary flow, myocardial wall thickness and left ventricular cavity area were recorded. Cavity obliteration, hypotension, ventricular tachycardia or a maximal dose of 40 micrograms/kg body weight per min served as the dobutamine stress echocardiographic end point. RESULTS: At baseline, no difference was detected between the 3- or 5-min protocols for heart rate, systolic blood pressure, rate-pressure product, coronary blood flow, wall thickness or percent area change. Heart rate, systolic blood pressure and coronary flow increased more by the 10-micrograms/kg per min dose with the 5-min protocol than with the 3-min protocol. The dobutamine stress echocardiographic end points were achieved at a lower dobutamine dose (15.0 +/- 4.1 vs. 11.0 +/- 2.1 micrograms/kg per min [mean +/- SD], p = 0.01) with the longer stage duration. CONCLUSIONS: In this canine model, a longer stage produced a greater hemodynamic effect at a lower peak dose. Thus, extending stage duration in clinical dobutamine stress echocardiography may achieve equivalent physiologic stress at lower doses and contribute to the optimization of dobutamine stress echocardiographic protocols.

Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia.

OBJECTIVES: We tested the hypothesis that intramyocardial injection of autologous bone marrow (ABM) promotes collateral development in ischemic porcine myocardium. We also defined, in vitro, whether bone marrow (BM) cells secrete vascular endothelial growth factor (VEGF) and macrophage chemoattractant protein-1 (MCP-1). BACKGROUND: The natural processes leading to collateral development are extremely complex, requiring multiple growth factors interacting in concert and in sequence. Because optimal angiogenesis may, therefore, require multiple angiogenic factors, we thought that injection of BM, which contains cells that secrete numerous angiogenic factors, might provide optimal therapeutic angiogenesis. METHODS: Bone marrow was cultured four weeks in vitro. Conditioned medium was assayed for VEGF and MCP-1 and was added to cultured pig aortic endothelial cells (PAEC) to assess proliferation. Four weeks after left circumflex ameroid implantation, freshly aspirated ABM (n = 7) or heparinized saline (n = 7) was injected transendocardially into the ischemic zone (0.2 ml/injection at 12 sites). Echocardiography to assess myocardial thickening and microspheres to assess perfusion were performed at rest and during stress. RESULTS: Vascular endothelial growth factor and MCP-1 concentrations increased in a time-related manner. The conditioned medium enhanced, in a dose-related manner, PAEC proliferation. Collateral flow (ischemic/normal zone X 100) improved in ABM-treated pigs (ABM: 98 +/- 14 vs. 83 +/- 12 at rest, p = 0.001; 89 +/- 18 vs. 78 +/- 12 during adenosine, p = 0.025; controls: 92 +/- 10 vs. 89 +/- 9 at rest, p = 0.49; 78 +/- 11 vs. 77 +/- 5 during adenosine, p = 0.75). Similarly, contractility increased in ABM-treated pigs (ABM: 83 +/- 21 vs. 60 +/- 32 at rest, p = 0.04; 91 +/- 44 vs. 36 +/- 43 during pacing, p = 0.056; controls: 69 +/- 48 vs. 64 +/- 46 at rest, p = 0.74; 65 +/- 56 vs. 37 +/- 56 during pacing, p = 0.23). CONCLUSIONS: Bone marrow cells secrete angiogenic factors that induce endothelial cell proliferation and, when injected transendocardially, augment collateral perfusion and myocardial function in ischemic myocardium.

Determination of aortic valve area in valvular aortic stenosis by direct measurement using intracardiac echocardiography: a comparison with the Gorlin and continuity equations.

OBJECTIVES: This study sought to 1) show that intracardiac echocardiography can allow direct measurement of the aortic valve area, and 2) compare the directly measured aortic valve area from intracardiac echocardiography with the calculated aortic valve area from the Gorlin and continuity equations. BACKGROUND: Intracardiac echocardiography has been used in the descriptive evaluation of the aortic valve; however, direct measurement of the aortic valve area using this technique in a clinical setting has not been documented. Despite their theoretical and practical limitations, the Gorlin and continuity equations remain the current standard methods for determining the aortic valve orifice area. METHODS: Seventeen patients underwent intracardiac echocardiography for direct measurement of the aortic valve area, including four patients studied both before and after valvuloplasty, for a total of 21 studies. Immediately after intracardiac echocardiography, hemodynamic data were obtained from transthoracic echocardiography and cardiac catheterization. RESULTS: Adequate intracardiac echocardiographic images were obtained in 17 (81%) of 21 studies. The average aortic valve area (mean +/- SD) determined by intracardiac echocardiography for the 13 studies in the Gorlin analysis group was 0.59 +/- 0.18 cm2 (range 0.37 to 1.01), and the average aortic valve area determined by the Gorlin equation was 0.62 +/- 0.18 cm2 (range 0.31 to 0.88). The average aortic valve area determined by intracardiac echocardiography for the 17 studies in the continuity analysis group was 0.66 +/- 0.23 cm2 (range 0.37 to 1.01), and that for the continuity equation was 0.62 +/- 0.22 cm2 (range 0.34 to 1.06). There was a significant correlation between the aortic valve area determined by intracardiac echocardiography and the aortic valve area calculated by the Gorlin (r = 0.78, p = 0.002) and continuity equations (r = 0.82, p < 0.0001). CONCLUSIONS: In the clinical setting, intracardiac echocardiography can directly measure the aortic valve area with an accuracy similar to the invasive and noninvasive methods currently used. This study demonstrates a new, quantitative use for intracardiac echocardiographic imaging with many potential clinical applications.

Contrasting patterns of autonomic dysfunction in patients with mitral valve prolapse and panic attacks.

Both mitral valve prolapse (MVP) and panic attacks have been reported to be associated with autonomic dysfunction, but previous studies have been limited by the lack of clear separation between patients with MVP and those with panic attacks and the use of noncomparable control subjects. Accordingly, heart rate and blood pressure responses to deep breathing, five minutes' quiet standing, and the Valsalva maneuver were studied in age- and cardiac symptom-matched groups of 33 control subjects, 66 patients with MVP, 20 patients with panic attacks, and 17 patients with both MVP and panic attacks. Compared with control subjects, patients with MVP exhibited more syncope (13 of 66, or 20 percent, versus none of 33, or 0 percent; p less than 0.01), more orthostatic hypotension during quiet standing (11 of 66, or 17 percent, versus one of 33, or 3 percent; p less than 0.01), loss of the normal decrease with age in vagally-mediated heart rate variability during deep breathing (r = 0.13, p = NS versus r = -0.44, p = 0.01), and lower 24-hour epinephrine excretion (6.1 +/- 0.7 versus 11.0 +/- 2.7 micrograms; p less than 0.01). In contrast, patients with panic attacks had greater increases than control subjects or patients with MVP without panic attacks in heart rate, mean blood pressure, and the product of heart rate and mean blood pressure during each minute of quiet standing and during the early strain phase of the Valsalva maneuver. These findings indicate that autonomic dysfunction occurs both in patients with MVP and in those with panic attacks in comparison with symptomatic control subjects, but that the patterns of abnormality differ. Patients with MVP exhibit decreased effectiveness of responses to orthostatic stress, reduced epinephrine excretion, and abnormal vagal tone, whereas patients with panic attacks have heightened cardiovascular responses to postural and positive intrathoracic pressure stresses.

The contribution of "mechanical" problems to in-stent restenosis: An intravascular ultrasonographic analysis of 1090 consecutive in-stent restenosis lesions.

OBJECTIVES: Serial intravascular ultrasonographic (IVUS) studies have shown that in-stent restenosis is the result of intimal hyperplasia (IH). However, routine preintervention IVUS imaging has suggested that many restenotic stents were inadequately deployed. The purpose of this IVUS study was to determine the incidence of mechanical problems contributing to in-stent restenosis (ISR). METHODS: Between April 1994 and June 2000, 1090 patients with ISR were treated at the Washington Hospital Center. All underwent preintervention IVUS imaging. IVUS measurements included proximal and distal reference lumen areas and diameters; stent, minimum lumen, and IH (stent minus lumen) areas; and IH burden (IH/stent area). RESULTS: In 49 ISR lesions (4.5%), there were morphologic findings that contributed to the restenosis. These were termed mechanical complications. Examples include (1) missing the lesion (eg, an aorto-ostial stenosis), (2) stent "crush," and (3) having the stent stripped off the balloon during the implantation procedure. Excluding mechanical complications, stent underexpansion was common. In 20% of the ISR cases the stents had a cross-sectional area (CSA) at the site of the lesion <80% of the average reference lumen area. Twenty percent of lesions had a minimum stent area <5.0 mm(2) and an additional 18% had a minimum stent area of 5.0 to 6.0 mm(2). Twenty-four percent of lesions had an IH burden <60%. CONCLUSION: Mechanical problems related to stent deployment procedures contribute to a significant minority of ISR lesions (approximately 25%).

Pathologic validation of a new method to quantify coronary calcific deposits in vivo using intravascular ultrasound.

Current methods of calcium quantification by intravascular ultrasound (IVUS) measure the arc of calcium using the cross-sectional image at the lesion and at the reference site while neglecting calcium elsewhere. Calcium at these sites may not adequately represent the extent of total epicardial coronary calcium. We devised a new method to quantify calcium as a percentage of the coronary luminal surface. This study examines whether this new method accurately reflects coronary calcium determined by histology. Seventeen postmortem coronary arteries were pressure-fixed and imaged by IVUS using a motorized pullback device. Total plaque-luminal circumferential length and calcified plaque-luminal circumferential length were measured from serial cross-sectional IVUS images every 1 mm. With use of Simpson's method, the total plaque and calcified plaque surface area was then calculated. Histologic sections were stained with hematoxylin-eosin and Movat pentachrome at 3-mm intervals. Calcium was independently quantified by planimetry under light microscopy. Histologic analysis (n = 253 sections) revealed a wide range of calcium (0 to 47 mm2; mean 12 +/- 16 mm3). The IVUS-derived calcified plaque surface area was 17 +/- 23 mm2), which represented 3.1 +/- 4.1% (range 0% to 13.9%) of the total plaque surface area. The histologic and IVUS quantification of calcium by this method was strongly related (r = 0.84, p <0.0001), which was an improvement over current 2-dimensional measures of calcium arc (r = 0.41, p = 0.18). Calculation of calcified plaque surface area from sequential IVUS images appears to accurately reflect the degree of total coronary calcification.

Effect of preintervention plaque burden on subsequent intimal hyperplasia in stented coronary artery lesions.

We sought to determine if axial and circumferential distribution of plaque before stenting determines the axial and circumferential distribution of subsequent intimal hyperplasia (IH). We studied 22 patients with a single Palmaz-Schatz stent implanted in a native coronary artery, who underwent intravascular ultrasound (IVUS) imaging before intervention, after stenting, and at 6-month follow-up. For each lesion, 7 locations were analyzed: proximal and distal reference, proximal and distal edge of the stent, proximal and distal location within the body of the stent, and the articulation. Pre- and postintervention and follow-up image slices were precisely aligned and analyzed for pre- and postintervention plaque area and follow-up IH area and thickness. The location of maximal IH area was at or adjacent to the location of maximal preintervention plaque in 17 of 22 of the patients (77%). Similiarly, the circumferential distribution of IH at follow-up paralleled the eccentricity pattern of the native plaque burden in 69% (24 of 35 slices). Using multivariant analysis, the strongest predictor of IH was preintervention plaque area (p = 0.001). IH accumulates axially and circumferentially preferentially at the site of maximal preintervention plaque.

Assessment of coronary plaque with optical coherence tomography and high-frequency ultrasound.

This study compares the ability of intravascular optical coherence tomography (OCT) and high-frequency intravascular ultrasound (IVUS) to image highly stenotic human coronary arteries in vitro. Current imaging modalities have insufficient resolution to perform risk stratification based on coronary plaque morphology. OCT is a new technology capable of imaging at a resolution of 5 to 20 microm, which has demonstrated the potential for coronary arterial imaging in prior experiments. Human postmortem coronary arteries with severely stenotic segments were imaged with catheter-based OCT and IVUS. The OCT system had an axial resolution of 20 microm and a transverse resolution of 30 microm. OCT was able to penetrate and image near-occlusive coronary plaques. Compared with IVUS, these OCT images demonstrated superior delineation of vessel layers and lack of ring-down artifact, leading to clearer visualization of the vessel plaque and intima. Histology confirmed the accuracy and high contrast of vessel layer boundaries seen on OCT images. Thus, catheter-based OCT systems are able to image near-occlusive coronary plaques with higher resolution than that of IVUS.

Serial volumetric intravascular ultrasound analysis of the efficacy of beta irradiation in preventing recurrent in-stent restenosis.

We compared postintervention and follow-up intravascular ultrasound findings of 25 patients from the beta-Washington Radiation for InStent restenosis Trial (in which all patients received radiation) and 75 patients from the Washington Radiation for InStent restenosis Trial (in which patients were randomized to gamma irradiation). The decrease in lumen volume was similar for beta versus gamma and less in both gamma versus placebo and beta versus placebo; the increase in intimal hyperplasia volume was similar for beta versus gamma and greater in both beta versus placebo and gamma versus placebo.

In vivo mitral valve morphology and motion in mitral valve prolapse.

Mitral leaflet morphology in mitral valve prolapse (MVP) has been suggested to be prognostically important, but in vivo valvular morphology is incompletely described in patients with MVP or in normal subjects. Accordingly, the length of both mitral leaflets and their zone of apposition, the thickness of their rough and clear zones, diastolic and systolic mitral annular diameters, and indexes of abnormal leaflet motion were measured in the parasternal long-axis echocardiographic view in 100 patients with MVP and 100 age- and sex-matched normal subjects. In both groups posterior leaflet thickness was related to age, as were anterior leaflet thickness and posterior leaflet length in patients with MVP. Compared with normal subjects, MVP patients without mitral regurgitation had thickened leaflets, elongated anterior leaflets, and large annular diameters (p < 0.0001). Patients with severe regurgitation had thicker leaflets, longer posterior leaflet and annular dimensions, and more abnormal leaflet motion than MVP patients without regurgitation. Leaflet thicknesses of different zones were supranormal in 60% to 67% and in 49% to 59% of MVP patients with and without severe regurgitation, respectively. MVP patients with regurgitation also had higher prevalences of abnormal mitral annular diameter than those without regurgitation (67% vs 29%) and > 3 mm posterior leaflet billowing into the left atrium (60% vs 34%). Thus, mitral valve size and leaflet thickness are increased in MVP patients without as well as with clinically important mitral regurgitation. The usefulness of leaflet thickening as a marker of severe MVP is limited by its high prevalence in patients with clinically mild MVP.

Intravascular ultrasonic analysis of plaque characteristics associated with coronary artery remodeling.

We sought to determine the patient and plaque characteristics associated with the different forms of arterial remodeling as seen by intravascular ultrasound (IVUS) before coronary intervention. Remodeling in response to plaque accumulation may occur in the form of compensatory enlargement and/or focal vessel contraction. Previous studies report variation in the frequency and form of arterial remodeling. We performed preintervention IVUS imaging on 169 patients. Vessels were categorized as exhibiting compensatory enlargement or focal contraction if the arterial area at the lesion was larger or smaller, respectively, than both proximal and distal reference arterial areas; otherwise the artery was considered not to have undergone significant remodeling. Calcification was assessed and noncalcified plaque density was measured by videodensitometry. Sixty-one of 169 patients (66 narrowings) (46 men and 15 women, age 56+/-11 years) had adequate reference segments. Remodeling occurred in 43 of 66 patients (65%): compensatory enlargement in 27 of 66 (41%) and focal contraction in 16 of 66 (24%). Lesions with focal contraction had significantly smaller arterial area (13.3+/-3.3 vs. 18.1+/-7.0 mm2, p = 0.02) and plaque area (9.5+/-2.8 vs 13.7+/-5.5 mm2, p<0.01). Cross-sectional stenosis was similar (71+/-9% vs. 75+/-10%, p = NS), as was plaque density (p = 0.20), eccentricity, and calcium. Patient age, gender, and lesion location were not related to the form of remodeling. Similarly, history of diabetes, hypercholesterolemia, or hypertension was not predictive. Smoking was the only risk factor associated with focal contraction (p<0.01). Thus, whereas compensatory enlargement appears to be the most common form of coronary artery remodeling, focal contraction occurs more often in smokers.

Effect of atenolol or metoprolol on arbutamine stress echocardiography in patients suspected of having coronary artery disease.

Arbutamine stress echocardiography was performed in 81 patients with suspected coronary artery disease. Arbutamine infusion, using a dedicated closed-loop delivery device, provided comparable myocardial stress in patients receiving beta-1 blockers versus those who were not.