Paul Yock, MD

Abstract

OBJECTIVES: The aim of this study was to evaluate the Sparrow sirolimus-eluting stent (Sparrow-SES) against the Sparrow bare-metal stent (Sparrow-BMS) and conventional balloon-expandable bare-metal stent (BMS: Driver/Micro-Driver(®) stent, Medtronic Vascular, Santa Rosa, CA). BACKGROUND: The Sparrow(®) stent (Biosensors International, Singapore) consists of a guide wire-based, self-expandable, ultra-thin nitinol stent. The performance of this device with sirolimus in a fully biodegradable polymer has not been determined. METHODS: A total of 74 patients were included in this intravascular ultrasound (IVUS) sub-study of the CARE II trial, which was a prospective, randomized, multicenter trial in the treatment of single de novo native coronary artery lesions in vessels ranging from 2.0 mm to 2.75 mm in diameter (Sparrow-SES: n = 31, Sparrow-BMS: n = 22, BMS: n = 21). RESULTS: Stent volume index (VI) was significantly increased 8-month later in Sparrow-SES and Sparrow-BMS, but not in BMS (4.0±1.0 to 4.6±1.0 mm(3) /mm, p<0.0001, 4.0±0.6 to 4.4±0.8 mm(3) /mm, p<0.05, and 5.2±1.0 to 5.1±0.9 mm(3) /mm, p=0.421, respectively). % neointimal obstruction in Sparrow-SES was significantly smaller than those in Sparrow-BMS and BMS at follow-up (17.6±9.4 vs. 36.2±13.8 and 39.9±11.1%, p<0.001). Sparrow-SES showed a mean 15% stent expansion and good suppression of neointimal proliferation, resulting in a significantly lower percentage of change in lumen VI during follow-up period (Sparrow-SES: -6.2±16.2%, Sparrow-BMS: -30.4±11.6%, BMS: -40.4±10.0%, p<0.001). CONCLUSIONS: The self-expanding Sparrow-SES demonstrated chronic stent expansion, good suppression of neointimal proliferation and resulted in a more preserved lumen in stented small vessels compared with the Sparrow-BMS and conventional balloon expandable BMS. © 2013 Wiley Periodicals, Inc.

View details for DOI 10.1002/ccd.24867

View details for Web of Science ID 000328631400007

View details for PubMedID 23413202

Abstract

The Stanford Biodesign Program began in 2001 with a mission of helping to train leaders in biomedical technology innovation. A key feature of the program is a full-time postgraduate fellowship where multidisciplinary teams undergo a process of sourcing clinical needs, inventing solutions and planning for implementation of a business strategy. The program places a priority on needs identification, a formal process of selecting, researching and characterizing needs before beginning the process of inventing. Fellows and students from the program have gone on to careers that emphasize technology innovation across industry and academia. Biodesign trainees have started 26 companies within the program that have raised over $200 million and led to the creation of over 500 new jobs. More importantly, although most of these technologies are still at a very early stage, several projects have received regulatory approval and so far more than 150,000 patients have been treated by technologies invented by our trainees. This paper reviews the initial outcomes of the program and discusses lessons learned and future directions in terms of training priorities.

View details for DOI 10.1007/s10439-013-0761-2

View details for Web of Science ID 000323736800002

View details for PubMedID 23404074

Abstract

Head and neck (H&N) radiation therapy (RT) can induce irreversible damage to the salivary glands thereby causing long-term xerostomia or dry mouth in 68%-85% of the patients. Not only does xerostomia significantly impair patients' quality-of-life (QOL) but it also has important medical sequelae, incurring high medical and dental costs. In this article, we review various measures to assess xerostomia and evaluate current and emerging solutions to address this condition in H&N cancer patients. These solutions typically seek to accomplish 1 of the 4 objectives: (1) to protect the salivary glands during RT, (2) to stimulate the remaining gland function, (3) to treat the symptoms of xerostomia, or (4) to regenerate the salivary glands. For each treatment, we assess its mechanisms of action, efficacy, safety, clinical utilization, and cost. We conclude that intensity-modulated radiation therapy is both the most widely used prevention approach and the most cost-effective existing solution and we highlight novel and promising techniques on the cost-effectiveness landscape.

View details for DOI 10.1016/j.oooo.2013.02.017

View details for PubMedID 23643579

Abstract

The aim of this study was to evaluate a new fully automated lumen border tracing system based on a novel multifrequency processing algorithm.We developed the multifrequency processing method to enhance arterial lumen detection by exploiting the differential scattering characteristics of blood and arterial tissue. The implementation of the method can be integrated into current intravascular ultrasound (IVUS) hardware.This study was performed in vivo with conventional 40-MHz IVUS catheters (Atlantis SR Pro™, Boston Scientific Corp, Natick, MA) in 43 clinical patients with coronary artery disease. A total of 522 frames were randomly selected, and lumen areas were measured after automatically tracing lumen borders with the new tracing system and a commercially available tracing system (TraceAssist™) referred to as the "conventional tracing system." The data assessed by the two automated systems were compared with the results of manual tracings by experienced IVUS analysts.New automated lumen measurements showed better agreement with manual lumen area tracings compared with those of the conventional tracing system (correlation coefficient: 0.819 vs. 0.509). When compared against manual tracings, the new algorithm also demonstrated improved systematic error (mean difference: 0.13 vs. -1.02 mm(2) ) and random variability (standard deviation of difference: 2.21 vs. 4.02 mm(2) ) compared with the conventional tracing system.This preliminary study showed that the novel fully automated tracing system based on the multifrequency processing algorithm can provide more accurate lumen border detection than current automated tracing systems and thus, offer a more reliable quantitative evaluation of lumen geometry.

View details for DOI 10.1002/ccd.23274

View details for Web of Science ID 000315339400004

View details for PubMedID 21805600

View details for DOI 10.1053/j.gastro.2012.12.009

View details for Web of Science ID 000314716300012

View details for PubMedID 23246636

Abstract

Exaggerated neointimal hyperplasia is considered as the primary mechanism for increased restenosis in patients with diabetes mellitus (DM) treated with bare-metal stent. However, the vessel response in DM and non-DM treated with different drug-eluting stents (DES) has not been systematically evaluated.We investigated 3D intravascular ultrasound (postprocedure and 6 to 9 months) in 971 patients (267 with DM and 704 without DM) treated with sirolimus- (n=104), paclitaxel- (n=303), zotarolimus- (n=391), or everolimus- (n=173) eluting stents. Volumetric data were standardized by length as volume index (VI). At postprocedure, lumen VI at the stented segment was significantly smaller in DM than in non-DM, whereas vessel VI was similar between the 2 groups. At follow-up, neointimal obstruction and maximum cross-sectional narrowing (neointimal area/stent area) were not significantly different between the 2 groups with no interaction for the DES type. Consequently, lumen VI was smaller in DM than in non-DM at follow-up. In the reference segments, residual plaque burden at postprocedure was significantly greater in DM than in non-DM, although change in lumen VI was similar between the 2 groups. The arterial responses at the reference segments also showed no interaction for the DES type.DM and non-DM lesions showed similar vessel response in both in-stent and reference segments regardless of the DES type. In the DES era, the follow-up lumen in DM patients seems to be determined primarily by the smaller lumen at postprocedure rather than exaggerated neointima within the stent or plaque proliferation at the reference segments.

View details for DOI 10.1161/CIRCINTERVENTIONS.111.962878

View details for Web of Science ID 000313576500014

View details for PubMedID 23149332

Abstract

The Sparrow stent system (Biosensors International) consists of a self-expanding, ultra-thin nitinol stent mounted within a 0.014? guidewire designed for small or tortuous coronary lesions. We compared the intravascular ultrasound (IVUS) findings between the novel self-expanding sirolimus-eluting stent (Sparrow-SES) and a conventional balloon-expandable sirolimus-eluting stent (Cypher-SES) in patients with small coronary disease.We examined 14 lesions treated with the Sparrow-SES from CARE II, compared with 22 small vessel lesions treated with Cypher-SES. IVUS examination was performed post-procedure and 8 months later. Volumetric data were standardized by length as volume index (VI; mm³/mm).While baseline stent VI trended smaller in Sparrow-SES, follow-up stent VI became similar between the 2 groups due to a significant increase of stent VI in self-expanding Sparrow-SES during the follow-up period. At 8 months, Sparrow-SES showed greater neointima than Cypher-SES (0.8 ± 0.6 mm³/mm vs 0.2 ± 0.2 mm³/mm; P<.001). However, the decrease in lumen VI was only 0.3 ± 0.7 mm³/mm in Sparrow-SES, as compared to 0.1 ± 0.3 mm³/mm in Cypher-SES (P=.259), since the late loss due to neointimal hyperplasia was partly counterbalanced by the chronic stent expansion in Sparrow-SES.While 8-month follow-up of Sparrow-SES revealed greater amounts of neointimal hyperplasia compared with conventional Cypher-SES, chronic stent expansion preserved the lumen by increasing stent volume. This novel, guidewire-based, self-expanding stent system designed to be delivered through complex anatomies may be useful to treat patients with small-caliber coronary lesions by offering sufficient lumen preservation at follow-up.

View details for Web of Science ID 000311028600014

View details for PubMedID 23043031

Abstract

To determine the feasibility and efficacy of applying an established innovation process to an active academic interventional radiology (IR) practice.The Stanford Biodesign Medical Technology Innovation Process was used as the innovation template. Over a 4-month period, seven IR faculty and four IR fellow physicians recorded observations. These observations were converted into need statements. One particular need relating to gastrostomy tubes was diligently screened and was the subject of a single formal brainstorming session.Investigators collected 82 observations, 34 by faculty and 48 by fellows. The categories that generated the most observations were enteral feeding (n = 9, 11%), biopsy (n = 8, 10%), chest tubes (n = 6, 7%), chemoembolization and radioembolization (n = 6, 7%), and biliary interventions (n = 5, 6%). The output from the screening on the gastrostomy tube need was a specification sheet that served as a guidance document for the subsequent brainstorming session. The brainstorming session produced 10 concepts under three separate categories.This formalized innovation process generated numerous observations and ultimately 10 concepts to potentially to solve a significant clinical need, suggesting that a structured process can help guide an IR practice interested in medical innovation.

View details for DOI 10.1016/j.jvir.2011.12.029

View details for Web of Science ID 000302396300009

View details for PubMedID 22464713

Abstract

This study investigated the spatial and temporal remodeling of blood vessel wall microarchitecture and cellular morphology during abdominal aortic aneurysm (AAA) development using immunofluorescent array tomography (IAT), a high-resolution three-dimensional (3D) microscopy technology, in the murine model. Infrarenal aortas of C57BL6 mice (N=20) were evaluated at 0, 7, and 28 days after elastase or heat-inactivated elastase perfusion. Custom algorithms quantified volume fractions (VF) of elastin, smooth muscle cell (SMC) actin, and adventitial collagen type I, as well as elastin thickness, elastin fragmentation, non-adventitial wall thickness, and nuclei amount. The 3D renderings depicted elastin and collagen type I degradation and SMC morphological changes. Elastin VF decreased 37.5% (p<0.01), thickness decreased 48.9%, and fragmentation increased 449.7% (p<0.001) over 28 days. SMC actin VF decreased 78.3% (p<0.001) from days 0 to 7 and increased 139.7% (p<0.05) from days 7 to 28. Non-adventitial wall thickness increased 61.1%, medial nuclei amount increased 159.1% (p<0.01), and adventitial collagen type I VF decreased 64.1% (p<0.001) over 28 days. IAT and custom image analysis algorithms have enabled robust quantification of vessel wall content, microstructure, and organization to help elucidate the dynamics of vascular remodeling during AAA development.

View details for DOI 10.1369/0022155411433066

View details for Web of Science ID 000299481300001

View details for PubMedID 22140132

Abstract

Inconsistent results in outcomes have been observed between the genders after drug-eluting stent implantation. The aim of this study was to investigate gender differences in neointimal proliferation for the Endeavor zotarolimus-eluting stent (ZES) and the Driver bare-metal stent (BMS). A total of 476 (n = 391 ZES, n = 85 BMS) patients whose volumetric intravascular ultrasound analyses were available at 8-month follow-up were studied. At 8 months, neointimal obstruction and maximum cross-sectional narrowing (CSN) were significantly lower in women than in men receiving ZES (neointimal obstruction 15.5 ± 9.5% vs 18.2 ± 10.9%, p = 0.025; maximum CSN 30.3 ± 13.2% vs 34.8 ± 15.0%, p = 0.007). Conversely, these parameters tended to be higher in women than in men receiving BMS (neointimal obstruction 36.3 ± 15.9% vs 27.5 ± 17.2%, p = 0.053; maximum CSN 54.3 ± 18.6% vs 45.6 ± 18.3%, p = 0.080). There was a significant interaction between stent type and gender regarding neointimal obstruction (p = 0.001) and maximum CSN (p = 0.003). Multivariate linear regression analysis revealed that female gender was independently associated with lower neointimal obstruction (p = 0.027) and maximum CSN (p = 0.004) for ZES but not for BMS. Compared to BMS, ZES were independently associated with a reduced risk for binary restenosis in both genders (odds ratio for women 0.003, p = 0.001; odds ratio for men 0.191, p <0.001), but the magnitude of this risk reduction with ZES was significantly greater in women than men (p = 0.015). In conclusion, female gender is independently associated with decreased neointimal hyperplasia in patients treated with ZES. The magnitude of risk reduction for binary restenosis with ZES is significantly greater in women than in men.

View details for DOI 10.1016/j.amjcard.2011.05.019

View details for Web of Science ID 000295863200002

View details for PubMedID 21784390

Abstract

Recently, universities in the United States and abroad have developed dedicated educational programs in life science technology innovation. Here, we discuss the two major streams of educational theory and practice that have informed these programs: design thinking and entrepreneurship education. We make the case that the process of innovation for new medical technologies (medtech) is different from that for biopharmaceuticals and outline the challenges and opportunities associated with developing a discipline of medtech innovation.

View details for DOI 10.1126/scitranslmed.3002222

View details for Web of Science ID 000292982600001

View details for PubMedID 21775665

Abstract

The influence of donor-transmitted coronary atherosclerosis (DA) on plaque progression during the first year after cardiac transplantation (Tx) is unknown.Serial 3-dimensional intravascular ultrasound (IVUS) studies were performed within 8 weeks (baseline; BL) and at 1 year after Tx in 38 recipients. On the basis of maximum intimal thickness (MIT) at BL, recipients were divided into DA group (DA+; MIT?0.5 mm, n=23) or non-DA group (DA-; MIT<0.5 mm, n=15). Plaque, lumen, and vessel volume indexes were calculated by volume/measured length (mm/mm) in the left anterior descending artery. Univariate and multivariate regression analyses were attempted to reveal clinical predictors of change in coronary dimensions.During the first year after Tx, plaque volume index increased significantly in DA+ group, but did not change in DA- Group (DA+, 3.0±1.5 to 4.1±1.5 mm/mm, P<0.0001: DA-, 1.2±0.4 to 1.3±0.5 mm/mm, P=0.53). In both groups vessel volume index decreased significantly (DA+, 16.3±3.6 to 14.6±3.3 mm/mm, P=0.003: DA-, 13.5±4.1 to 12.0±3.3 mm/mm, P=0.01), as did lumen volume index (DA+, 13.2±3.1 to 10.5±2.7 mm/mm, P<0.0001: DA-, 12.2±3.7 to 10.7±3.0 mm/mm, P=0.004). Univariate and multivariate regression analyses revealed that DA was one of the strongest predictors for plaque progression.DA was associated with significant plaque progression during the first year after Tx, and in conjunction with negative remodeling, may be an important determinant of cardiac allograft vasculopathy.

View details for DOI 10.1097/TP.0b013e31821ab91b

View details for Web of Science ID 000291430500019

View details for PubMedID 21512436

View details for DOI 10.1007/s12195-011-0165-z

View details for Web of Science ID 000290959200016

Abstract

To assess the efficacy of the sirolimus-eluting stent when implanted in smaller caliber vessels using three-dimensional intravascular ultrasound (IVUS) analysis.One hundred and twenty-three patients (69 sirolimus-coated Bx Velocity and 54 control) who underwent successful three-dimensional IVUS at follow up comprised this IVUS substudy from the SIRIUS (SIRolImUS-coated Bx Velocity stent in the treatment of patients with de novo coronary artery lesions) population. To evaluate the impact of vessel size, 2 groups were created using QCA reference vessel diameter (RVD; large vessel group: RVD>/=2.75 mm and small vessel group: RVD<2.75 mm).Sirolimus-eluting stents significantly reduced neointimal hyperplasia by the same relative magnitude within the stent in small vessels as well as in large vessels. Although sirolimus-eluting stents had favorable effects on lumen area at stent edges in larger vessels, the effect was less in smaller vessels, especially at the proximal edge. IVUS-detected adverse vessel response, such as late-acquired incomplete apposition, did not increase in smaller vessels even with relatively higher dose exposure.Sirolimus-eluting stents showed inhibition of neointimal hyperplasia in small vessels compared to bare metal stents with no increase of vascular complications.

View details for DOI 10.1016/j.ijcard.2008.08.006

View details for Web of Science ID 000273613300004

View details for PubMedID 18804877

Abstract

Preprocedual C-reactive protein (CRP) has been reported to correlate with in-stent restenosis following bare-metal stent implantation. The aim of this study was to investigate the impact of preprocedural inflammation on neointimal hyperplasia assessed by intravascular ultrasound (IVUS) following everolimus-eluting stent (EES) implantation.We identified 134 patients meeting the following criteria: 1) patients treated with EES; 2) those with stable or unstable angina; and 3) patients available for high-sensitivity (hs)-CRP before the procedure and volumetric IVUS analysis at follow up. We divided the patients into two groups on the basis of hs-CRP levels (< 3 or > or = 3 mg/L) before the procedure and compared IVUS parameters. Volume index (volume/length) was calculated for vessel (VVI), plaque (PVI), neointima (NIV), stent (SVI), and lumen (LVI). Percent neointimal volume (%NIV) was calculated as (NIV/SVI) x 100. Cross-sectional narrowing (CSN) was defined as neointimal area divided by stent area (%).There was no significant difference in VVI, PVI, or LVI at either baseline or 8-month follow up between the two groups. At 8-month follow up, there was also no significant difference in %NIV (4.93 +/- 5.66% vs. 4.98 +/- 5.25% p = 0.959) and maximum %CSN (16.81 +/- 13.62% vs. 18.14 +/- 13.91%; p = 0.608) as well as VVI, PVI, and LVI between the two groups. Furthermore, hs-CRP did not correlate with %NIV (r = 0.044; p = 0.610) and maximum %CSN (r = 0.086, p = 0.321) at follow up. There was no significant difference in incidence of late-acquired incomplete stent apposition between the two groups (1.2% vs. 0%; p = 0.512).Our results suggest that preprocedural inflammation does not affect neointimal hyperplasia following EES implantation.

View details for Web of Science ID 000284807300002

View details for PubMedID 19966361

Abstract

The aim of this study was to compare the vessel response between zotarolimus-eluting stents (ZES) and paclitaxel-eluting stents (PES) using intravascular ultrasound.The ENDEAVOR IV (Randomized Comparison of Zotarolimus- and Paclitaxel-Eluting Stents in Patients With Coronary Artery Disease) trial was a randomized controlled study of zotarolimus-eluting, phosphorylcholine-coated, cobalt-alloy stents for the treatment of de novo coronary lesions compared with using PES for the same treatment.Data were obtained from patients with serial (baseline and 8-months follow-up) intravascular ultrasound analysis available (n = 198). Volumetric analysis was performed for vessel, lumen, plaque, stent, and neointima. Cross-sectional narrowing (given as percentage) was defined as neointimal area divided by stent area. Neointima-free frame ratio was calculated as the number of frames without intravascular ultrasound-detectable neointima divided by the total number of frames within the stent. Subsegment analysis was performed at every matched 1-mm subsegment throughout the stent.At follow-up, the ZES group showed significantly greater percentage of neointimal obstruction (16.6 +/- 12.0% vs. 9.9 +/- 8.9%, p < 0.01) and maximum cross-sectional narrowing (31.8 +/- 16.1% vs. 25.2 +/- 14.9%, p < 0.01) with smaller minimum lumen area than the PES group did. However, the incidence of maximum cross-sectional narrowing >50% was similar in the 2 groups. Neointima-free frame ratio was significantly lower in the ZES group. In overall analysis, whereas the PES group showed positive remodeling during follow-up (13.7 +/- 4.2 mm(3)/mm to 14.3 +/- 4.3 mm(3)/mm), the ZES group showed no significant difference (12.7 +/- 3.6 mm(3)/mm to 12.9 +/- 3.5 mm(3)/mm). In subsegment analysis, significant focal positive vessel remodeling was observed in 5% of ZES and 25% of PES cases (p < 0.05).There were different global and focal vessel responses for ZES and PES. Both drug-eluting stents showed a similar incidence of lesions with severe narrowing despite ZES having a moderate increase in neointimal hyperplasia compared with neointimal hyperplasia in PES. There was a relatively lower neointima-free frame ratio in ZES, suggesting a greater extent of neointimal coverage. (The ENDEAVOR IV Clinical Trial: A Trial of a Coronary Stent System in Coronary Artery Lesions; NCT00217269).

View details for DOI 10.1016/j.jcin.2009.05.015

View details for Web of Science ID 000278971500011

View details for PubMedID 19695548

Abstract

To evaluate the feasibility of reporter gene imaging in implanted human mesenchymal stem cells (MSCs) in porcine myocardium by using clinical positron emission tomography (PET)-computed tomography (CT) scanning.Animal protocols were approved by the Institutional Administrative Panel on Laboratory Animal Care. Transduction of human MSCs by using different doses of adenovirus that contained a cytomegalovirus (CMV) promoter driving the mutant herpes simplex virus type 1 thymidine kinase reporter gene (Ad-CMV-HSV1-sr39tk) was characterized in a cell culture. A total of 2.25 x 10(6) transduced (n = 5) and control nontransduced (n = 5) human MSCs were injected into the myocardium of 10 rats, and reporter gene expression in human MSCs was visualized with micro-PET by using the radiotracer 9-(4-[fluorine 18]-fluoro-3-hydroxymethylbutyl)-guanine (FHBG). Different numbers of transduced human MSCs suspended in either phosphate-buffered saline (PBS) (n = 4) or matrigel (n = 5) were injected into the myocardium of nine swine, and gene expression was visualized with a clinical PET-CT. For analysis of cell culture experiments, linear regression analyses combined with a t test were performed. To test differences in radiotracer uptake between injected and remote myocardium in both rats and swine, one-sided paired Wilcoxon tests were performed. In swine experiments, a linear regression of radiotracer uptake ratio on the number of injected transduced human MSCs was performed.In cell culture, there was a viral dose-dependent increase of gene expression and FHBG accumulation in human MSCs. Human MSC viability was 96.7% (multiplicity of infection, 250). Cardiac FHBG uptake in rats was significantly elevated (P < .0001) after human MSC injection (0.0054% injected dose [ID]/g +/- 0.0007 [standard deviation]) compared with that in the remote myocardium (0.0003% ID/g +/- 0.0001). In swine, myocardial radiotracer uptake was not elevated after injection of up to 100 x 10(6) human MSCs (PBS group). In the matrigel group, signal-to-background ratio increased to 1.87 after injection of 100 x 10(6) human MSCs and positively correlated (R(2) = 0.97, P < .001) with the number of administered human MSCs.Reporter gene imaging in human MSCs can be translated to large animals. The study highlights the importance of co-administering a "scaffold" for increasing intramyocardial retention of human MSCs.

View details for DOI 10.1148/radiol.2513081616

View details for Web of Science ID 000268362900015

View details for PubMedID 19366903

Abstract

Sirolimus-eluting stents (SES) have been shown to reduce intimal hyperplasia (IH) within the stent. Although angiographic studies have suggested focal distribution of IH, these data are limited by its spatial resolution and the minimal amount of IH. Therefore, the exact distribution pattern of SES IH remains unclear. Ninety-six SIRIUS trial patients who underwent SES (51) or bare metal stent (45) implantation and three-dimensional IVUS at 8 months follow-up were enrolled. Neointimal area (stent-lumen area) was obtained at every 0.5-mm interval throughout the stented segment. The length of each stent with IVUS-detectable neointima was determined and divided by the stented length in each case to normalize the data. Even with IVUS, IH was detectable in very limited SES stented segments (median 8% of total stented length) compared to the diffuse nature of IH within BMS with only 5 stented lesions having segments free from IH. In 25% (13 of 51) of patients, no IH was detectable within whole SES stented segments. In conclusion, SES has reduced not only the total amount of IH, but also limited the distribution. These data suggest that local conditions (heterogeneity of biological responses of particular plaques, pharmacokinetics, or their combination) may play a role in IH following SES implantation.

View details for DOI 10.1016/j.ijcard.2008.01.054

View details for Web of Science ID 000266884600020

View details for PubMedID 18571251

View details for DOI 10.1115/1.3148836

View details for Web of Science ID 000283763700004

Abstract

The aim of this study was to evaluate the intraoperative fluorescence imaging (IFI) system in the real-time assessment of graft patency during off-pump coronary artery bypass graft.Intraoperative fluorescence imaging is an intraoperative angiography-like imaging modality using fluorescent indocyanine green excited with laser light. Recently, assessment of graft patency using the IFI system was introduced into clinical use. The feasibility and efficacy of IFI technology in off-pump coronary artery bypass graft has not been systematically compared with other conventional diagnostic modalities.Patients undergoing off-pump coronary artery bypass graft received IFI analysis, intraoperative transit time flowmetry, and postoperative X-ray angiography. In off-line IFI analysis, the graft washout was classified based on the number of heartbeats required for indocyanine green washout: fast washout (15 beats).A total of 507 grafts in 137 patients received IFI analysis. Of all the IFI analyses, 379 (75%) grafts were visualized clearly up to the distal anastomosis. With regard to anastomosis location, anterior location was associated with a higher percentage of fully analyzable images (90%). More than 80% of images were analyzable, irrespective of graft type. Six grafts with acceptable transit time flowmetry results were diagnosed with graft failure by IFI, which required on-site graft revision. All revised grafts' patency was confirmed by post-operative X-ray angiography. Conversely, 21 grafts with unsatisfactory transit time flowmetry results demonstrated acceptable patency with IFI. Graft revision was considered unnecessary in these grafts, and 20 grafts (95%) were patent by post-operative X-ray angiography. Compared with slow washout, fast washout was associated with a higher preoperative ejection fraction, use of internal mammary artery grafts, and anterior anastomosis location.The IFI system enables on-site assessment of graft patency, providing both morphologic and functional information. This technique may help reduce procedure-related, early graft failures in off-pump bypass patients.

View details for DOI 10.1016/j.jcmg.2008.12.028

View details for Web of Science ID 000287653200013

View details for PubMedID 19442948

Abstract

The coverage, cost, and quality problems of the U.S. health care system are evident. Sustainable health care reform must go beyond financing expanded access to care to substantially changing the organization and delivery of care. The FRESH-Thinking Project (www.fresh-thinking.org) held a series of workshops during which physicians, health policy experts, health insurance executives, business leaders, hospital administrators, economists, and others who represent diverse perspectives came together. This group agreed that the following 8 recommendations are fundamental to successful reform: 1. Replace the current fee-for-service payment system with a payment system that encourages and rewards innovation in the efficient delivery of quality care. The new payment system should invest in the development of outcome measures to guide payment. 2. Establish a securely funded, independent agency to sponsor and evaluate research on the comparative effectiveness of drugs, devices, and other medical interventions. 3. Simplify and rationalize federal and state laws and regulations to facilitate organizational innovation, support care coordination, and streamline financial and administrative functions. 4. Develop a health information technology infrastructure with national standards of interoperability to promote data exchange. 5. Create a national health database with the participation of all payers, delivery systems, and others who own health care data. Agree on methods to make de-identified information from this database on clinical interventions, patient outcomes, and costs available to researchers. 6. Identify revenue sources, including a cap on the tax exclusion of employer-based health insurance, to subsidize health care coverage with the goal of insuring all Americans. 7. Create state or regional insurance exchanges to pool risk, so that Americans without access to employer-based or other group insurance could obtain a standard benefits package through these exchanges. Employers should also be allowed to participate in these exchanges for their employees' coverage. 8. Create a health coverage board with broad stakeholder representation to determine and periodically update the affordable standard benefit package available through state or regional insurance exchanges.

View details for Web of Science ID 000265117600008

View details for PubMedID 19258550

Abstract

Recently, the type 2 diabetes medication, rosiglitazone, has come under scrutiny for possibly increasing the risk of cardiac disease and death. To investigate the effects of rosiglitazone on the diabetic heart, we performed cardiac transcriptional profiling and imaging studies of a murine model of type 2 diabetes, the C57BL/KLS-lepr(db)/lepr(db) (db/db) mouse.We compared cardiac gene expression profiles from three groups: untreated db/db mice, db/db mice after rosiglitazone treatment, and non-diabetic db/+ mice. Prior to sacrifice, we also performed cardiac magnetic resonance (CMR) and echocardiography. As expected, overall the db/db gene expression signature was markedly different from control, but to our surprise was not significantly reversed with rosiglitazone. In particular, we have uncovered a number of rosiglitazone modulated genes and pathways that may play a role in the pathophysiology of the increase in cardiac mortality as seen in several recent meta-analyses. Specifically, the cumulative upregulation of (1) a matrix metalloproteinase gene that has previously been implicated in plaque rupture, (2) potassium channel genes involved in membrane potential maintenance and action potential generation, and (3) sphingolipid and ceramide metabolism-related genes, together give cause for concern over rosiglitazone's safety. Lastly, in vivo imaging studies revealed minimal differences between rosiglitazone-treated and untreated db/db mouse hearts, indicating that rosiglitazone's effects on gene expression in the heart do not immediately turn into detectable gross functional changes.This study maps the genomic expression patterns in the hearts of the db/db murine model of diabetes and illustrates the impact of rosiglitazone on these patterns. The db/db gene expression signature was markedly different from control, and was not reversed with rosiglitazone. A smaller number of unique and interesting changes in gene expression were noted with rosiglitazone treatment. Further study of these genes and molecular pathways will provide important insights into the cardiac decompensation associated with both diabetes and rosiglitazone treatment.

View details for DOI 10.1371/journal.pone.0002609

View details for Web of Science ID 000264065800015

View details for PubMedID 18648539

Abstract

The purpose of this study was to evaluate optical coherence tomography (OCT) for detecting small degrees of in-stent neointima (ISN) after stent implantation compared with intravascular ultrasound (IVUS).The importance of detecting neointimal coverage of stent struts has grown with the appreciation of the increased risk for late stent thrombosis after drug-eluting stent (DES) implantation. Intravascular ultrasound, the current standard for evaluating the status of DES, lacks the resolution to detect the initial neointimal coverage. Optical coherence tomography has greater resolution but has not yet been compared with IVUS in vivo with histological correlation for validation.Intravascular ultrasound and OCT were performed with motorized pullback imaging in 6 pigs across 33 stents, 1 month after implantation. Each pig was euthanized, and histological measurements of vessel, stent, and lumen dimensions were performed in 3 sections of each stent. A small degree of ISN was defined as occupying <30% of the stent area measured with histology. The IVUS, OCT, and histological assessment of ISN were compared in matched cross-sections of the stents with a small degree of ISN.Eleven stents had a small degree of ISN (average ISN area: 1.26 +/- 0.46 mm(2), and percent area obstruction: 21.4 +/- 5.2%). Compared with histology, the diagnostic accuracy of OCT (area under the receiver operating characteristic curve [AUC] = 0.967, 95% confidence interval [CI] 0.914 to 1.019) was higher than that of IVUS (AUC = 0.781, 95% CI 0.621 to 0.838).Optical coherence tomography detects smaller degrees of ISN more accurately than IVUS and might be a useful method for identifying neointimal coverage of stent struts after DES implantation.

View details for DOI 10.1016/j.jcin.2007.12.007

View details for Web of Science ID 000207586100011

View details for PubMedID 19463295

Abstract

While only few data exist correlating cardiovascular risk factors with volumetric measurements of coronary atheroma burden in patients with coronary artery disease, a recent report using intravascular ultrasound (IVUS) demonstrated independent predictors of atherosclerotic burden in a native coronary artery with relatively mild narrowing (20-50% diameter stenosis by visual estimation). The purpose of this study was to examine whether cardiovascular risk factors can predict atherosclerotic burden at severely narrowing segments (>50% diameter stenosis).Patients who met the criteria (high-quality, automated pull-back IVUS images of severely narrowing segments prior to intervention) were identified from the IVUS database of the Cardiovascular Core Analysis Laboratory at Stanford University. Using commercially available planimetry software, lumen and vessel inside external elastic membrane areas were manually traced at every 0.5-mm interval in diseased segments. Using Simpson's method, vessel, lumen, and plaque (vessel minus lumen) volumes were calculated, and average area was calculated as volume data divided by length. Percent plaque volume was computed as plaque volume divided by vessel volume. Multiple linear regression analysis with backward selection was used to determine the risk factors for atherosclerotic burden.For percent plaque volume, diabetes or hypertension were predictors of more severe disease. For average plaque area, male gender or diabetes were predictors of more severe disease. These variables were also independent predictors in multivariate regression models.Male gender, hypertension, and diabetes are also strong independent predictors of atherosclerotic burden in coronary disease patients, though analyzed segments and disease severity were different.

View details for DOI 10.1016/j.ijcard.2006.11.194

View details for Web of Science ID 000253546900022

View details for PubMedID 17350700

View details for DOI 10.1016/j.jacc.2007.08.063

View details for Web of Science ID 000252908600013

View details for PubMedID 18237691

Abstract

The objective of this study is to evaluate the predictive value of the index of microcirculatory resistance (IMR) in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).Despite adequate epicardial artery reperfusion, a number of patients with STEMI have a poor prognosis because of microvascular damage. Assessing the status of the microvasculature in this setting remains challenging.In 29 patients after primary PCI for STEMI, IMR was measured with a pressure sensor/thermistor-tipped guidewire. The Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade, TIMI frame count, coronary flow reserve, and ST-segment resolution were also recorded.The IMR correlated significantly with the peak creatinine kinase (CK) (R = 0.61, p = 0.0005) while the other measures of microvascular dysfunction did not. In patients with an IMR greater than the median value of 32 U, the peak CK was significantly higher compared with those having values 32 U compared with

View details for DOI 10.1016/j.jacc.2007.08.062

View details for Web of Science ID 000252908600007

View details for PubMedID 18237685

Abstract

We previously reported that negative remodeling, not plaque progression, correlated with lumen loss during the first year after cardiac transplantation and that cytomegalovirus antibody seropositivity correlated with increased negative remodeling and greater lumen loss. Whether these findings persist between years 1 and 2 after transplantation is unknown.Serial 3-dimensional intravascular ultrasound analysis in the left anterior descending coronary artery was performed in 30 cardiac transplant recipients at year 1 and 2 after transplantation. Vessel, lumen, and plaque area were determined at 0.5-mm axial intervals in the first 50 mm of the left anterior descending coronary artery, and volumes were computed using Simpson's method. Univariate and multivariate regression analyses were performed to identify clinical predictors of change in coronary dimensions.Although mean vessel area did not change (13.6+/-3.4 to 13.4+/-3.3 mm/mm(3), P=0.45), mean plaque area increased (3.4+/-2.3 to 3.8+/-2.2 mm/mm(3), P=0.012), resulting in significant mean lumen area loss (10.3+/-2.5 to 9.6+/-2.3 mm/mm(3), P=0.016). However, the degree of luminal change strongly correlated with the degree of change in vessel size (R=0.81, P<0.0001), but not with change in plaque amount (R=-0.19, P=0.32). In fact, in 57% of the patients who demonstrated lumen loss, negative remodeling contributed more to lumen loss than did plaque progression. Diabetes at 2 years was the only significant independent clinical predictor of plaque progression and lumen loss.Despite significant plaque progression, negative remodeling correlated with coronary lumen loss between years 1 and 2 after cardiac transplantation.

View details for DOI 10.1097/01.tp.0000285987.27033.65

View details for Web of Science ID 000251030600006

View details for PubMedID 17998863

Abstract

Zotarolimus-eluting phosphorylcholine-coated cobalt-chromium alloy Driver stents (ZES) demonstrated significant reductions in target lesion revascularization rate with few apparent adverse events compared with bare metal stents (BMS; uncoated Driver stents) in a prospective, multicenter, double-blind, randomized controlled trial in de novo coronary lesions. The aim of this study was to examine detailed vascular responses to ZES compared with BMS using serial intravascular ultrasound analysis. A total of 343 patients (ZES n = 178, BMS n = 165) were enrolled in this formal, prespecified intravascular ultrasound substudy of the Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic AVE Zotarolimus-Eluting Driver Coronary Stent in de Novo Native Coronary Artery Lesions (ENDEAVOR II), a prospective, multicenter, double-blind, randomized controlled trial to compare ZES and BMS in de novo native coronary artery lesions. Quantitative and qualitative intravascular ultrasound analyses were performed postprocedurally and at 8-month follow-up in stented and reference segments. ZES showed significantly less neointima, with a larger lumen than BMS at 8 months (percentage neointimal volume 17.6 +/- 10.1% vs 29.4 +/- 17.2%, p <0.0001; maximum percentage neointimal area 32.9 +/- 13.0% vs 47.6 +/- 18.6%, p <0.0001; minimum luminal area 4.9 +/- 1.6 vs 4.0 +/- 1.7 mm(2), p <0.0001) and no unfavorable edge effect. In the 18-mm single stents, ZES showed evenly inhibited neointima compared with BMS. Neither persistent stent-edge dissection nor late-acquired incomplete stent apposition was observed in either group. In conclusion, ZES showed evenly inhibited neointima with no apparent adverse vascular response in stented and reference segments at 8 months compared with BMS.

View details for DOI 10.1016/j.amjcard.2007.04.016

View details for Web of Science ID 000249226100013

View details for PubMedID 17719326

Abstract

Recurrent restenosis may occur after drug-eluting stent implantation for in-stent restenosis (ISR) of bare metal stents (BMSs), especially in areas involving drug-eluting stent gaps.To investigate the details of neointimal progression and luminal narrowing after the treatment of ISR using sirolimus-eluting stents (SESs), serial intravascular ultrasound analysis was performed in 65 patients with ISR at postintervention and at 6-month follow-up. The total stented segment was categorized into 3 compartments: new SES (N), new SES and old BMS overlap (N/O), and old BMS (O). In each of the 190 compartments, serial intravascular ultrasound parameters were analyzed at the cross section of the maximum change in neointimal area (delta neointimal area) from postintervention to follow-up or the minimum lumen area at follow-up if delta neointimal area was 0. Minimum lumen area in each compartment was also investigated serially.At postintervention, lumen area was the smallest in compartment N/O (N 5.8 +/- 1.5, N/O 5.1 +/- 1.3, O 6.0 +/- 1.4 mm2, P = .005). Not only the average of maximum delta neointimal area (N 0.2 +/- 0.4, N/O 0.2 +/- 0.4, O 0.8 +/- 1.0 mm2, P < .0001) but also the frequency of minimum lumen area decreasing from > or = 4.0 mm2 at postintervention to < 4.0 mm2 at follow-up (N 4.0%, N/O 5.1%, O 23.5%, P = .012) was the largest in compartment O.Neointimal progression and consequent luminal narrowing tend to occur where BMS is uncovered with SES in treatment of ISR, even in the absence of an obvious stenosis at postintervention.

View details for DOI 10.1016/j.ahj.2007.04.023

View details for Web of Science ID 000248511000025

View details for PubMedID 17643589

Abstract

Cardiac allograft vasculopathy (CAV) is a progressive process involving the epicardial and microvascular coronary systems. The timing of the development of abnormalities in these 2 compartments and the correlation between changes in physiology and anatomy are undefined. The invasive evaluation of coronary artery anatomy and physiology with intravascular ultrasound, fractional flow reserve, coronary flow reserve, and the index of microcirculatory resistance (IMR) was performed in the left anterior descending coronary artery during 151 angiographic evaluations of asymptomatic heart transplant recipients from 0 to >5 years after heart transplantation (HT). There was no angiographic evidence of significant CAV, but during the first year after HT, fractional flow reserve decreased significantly (0.89 +/- 0.06 vs 0.85 +/- 0.07, p = 0.001), and percentage plaque volume derived by intravascular ultrasound increased significantly (15.6 +/- 7.7% to 22.5 +/- 12.3%, p = 0.0002), resulting in a significant inverse correlation between epicardial physiology and anatomy (r = -0.58, p <0.0001). The IMR was lower in these patients compared with those > or =2 years after HT (24.1 +/- 14.3 vs 29.4 +/- 18.8 units, p = 0.05), suggesting later spread of CAV to the microvasculature. As the IMR increased, fractional flow reserve increased (0.86 +/- 0.06 to 0.90 +/- 0.06, p = 0.0035 comparing recipients with IMRs < or =20 to those with IMRs > or =40), despite no difference in percentage plaque volume (21.0 +/- 11.2% vs 20.5 +/- 10.5%, p = NS). In conclusion, early after HT, anatomic and physiologic evidence of epicardial CAV was found. Later after HT, the physiologic effect of epicardial CAV may be less, because of increased microvascular dysfunction.

View details for DOI 10.1016/j.amjcard.2007.01.039

View details for Web of Science ID 000247121700024

View details for PubMedID 17531589

Abstract

Coronary culprit lesions with plaque rupture (PR) have been treated with different coronary interventions. However, it is unknown whether the presence of PR affects the restenotic process after coronary intervention. One hundred forty-two patients undergoing coronary bare metal stent implantation were enrolled in the present retrospective analysis. Case selection was based on availability of intravascular ultrasound (IVUS) and quantitative coronary angiographic examinations at baseline (before and after intervention) and at follow-up. Serial comparative analyses included qualitative and quantitative features of the culprit lesion and reference segments. PR was defined as an intraplaque cavity in communication with the lumen in the presence of a residual, disrupted cap. Patients were categorized according to the presence/absence of PR. Pre-interventional IVUS detected PR in 54 patients (38%). Baseline patient demographics were similar between the +PR and -PR groups. Quantitative IVUS analysis showed higher rates of positive remodeling and larger vessel and plaque areas in the +PR compared with -PR lesions (p <0.001 for all). At follow-up (7.2 +/- 2.6 months), no statistically significant difference was observed between the 2 groups in quantitative coronary angiographic or IVUS measurements. In conclusion, culprit lesions with PR exhibited larger plaque mass and higher rates of positive remodeling at preintervention IVUS examination. However, when treated with bare metal stents, the absence/presence of preintervention PR was not found to affect the rate or severity of in-stent restenosis in these culprit lesions.

View details for DOI 10.1016/j.amjcard.2006.12.067

View details for Web of Science ID 000246715900010

View details for PubMedID 17493467

Abstract

Recent sirolimus-eluting stent (SES) studies have suggested higher rates of restenosis in non-left anterior descending (LAD) artery lesions. The aim of this study was to evaluate differential vessel response (LAD versus non-LAD) to SES implantation using serial intravascular ultrasound (IVUS). A total of 94 patients who underwent SES implantation and serial (post-PCI and 8 months) 3-dimensional IVUS were enrolled from our database. Volumetric analysis was performed throughout the stent as well as the adjacent reference segment (up to 5 mm). Volume index (volume/length) was calculated for vessel (VVI), lumen (LVI), and plaque (PVI). Cross-sectional narrowing (CSN) was defined as neointimal area divided by stent area (%). With respect to the in-stent segment, VVI, PVI, and LVI at post-PCI were not significantly different between the LAD (n = 41) and non-LAD (n = 53) lesions. At follow up, however, maximum CSN was significantly greater in the non-LAD lesions (18.3 +/- 15.2% versus 12.2 +/- 10.0%; p = 0.029). At the proximal reference segment, the non-LAD lesions showed a significantly greater LVI decrease than the LAD lesions (p <0.05), primarily due to mild vessel shrinkage observed in the non-LAD lesions. There were no significant differences at the distal reference segment between the LAD and non-LAD lesions. This detailed IVUS analysis suggests that there are minimal differences in the vessel responses following SES implantation. These findings may have potential implications for mechanical and pharmacokinetic properties of next-generation drug-eluting stent technology.

View details for PubMedID 17404402

Abstract

Whether gender affects long-term outcomes after bare metal stent implantation remains controversial. The aim of this study was to examine the impact of gender on neointimal hyperplasia in a large cohort of patients after stent implantation using 3-dimensional intravascular ultrasound. Lumen and stent areas were manually traced at 0.5-mm intervals throughout the stented segment. Using Simpson's method, lumen, stent, and neointimal (stent - lumen) volumes were calculated and standardized by stent length. Women were older, presented more often with hyperlipidemia or hypertension, and had smaller reference vessel diameter and mean stent area, compared with men. Although neointimal hyperplasia and neointimal thickness in women were similar to that in men, the percentage of neointimal hyperplasia (neointimal area divided by stent area) was higher in women due to the smaller stent area. After adjusting for stent area, the percentage of neointimal hyperplasia did not differ by gender. In conclusion, the results of this study indicate that neointimal hyperplasia after bare metal stent implantation in women is similar to that seen in men. Despite the similarity in outcome, there are several gender-specific differences in baseline characteristics.

View details for DOI 10.1016/j.amjcard.2006.09.094

View details for Web of Science ID 000244514500014

View details for PubMedID 17293191

Abstract

A direct coronary stenting technique using drug-eluting stents may decrease drug-eluting stent efficacy due to possible damage to the surface coating of the stent. The DIRECT is a multicenter, prospective, nonrandomized trial designed to evaluate the direct stenting strategy for the sirolimus-eluting Bx-Velocity stent compared with the historical control (SIRIUS trial, stenting with predilation). Volumetric and cross-sectional intravascular ultrasound analyses at 8-month follow-up were performed in 115 patients (DIRECT n= 64, control n = 51). Patient and lesion characteristics were comparable between groups. The DIRECT group achieved an equivalent uniform expansion index, defined as minimum stent area/maximum stent area x 100, compared with the control group (65.9 +/- 11.7 vs 63.1 +/- 12.7, p = NS). At 8-month follow-up, vessel, stent, lumen, and neointimal volume index (volume in cubic millimeters/length in millimeters) and percent neointimal volume were similar between the DIRECT and control groups (vessel volume index 13.9 +/- 4.40 vs 15.0 +/- 3.83; stent volume index 6.83 +/- 2.02 vs 6.94 +/- 2.04; lumen volume index 6.71 +/- 2.04 vs 6.81 +/- 2.07; neointimal volume index 0.14 +/- 0.24 vs 0.16 +/- 0.23; percent neointimal volume 3.73 +/- 6.97 vs 3.14 +/- 5.32, p = NS for all). In addition, in-stent neointimal hyperplasia distribution was significantly smaller near the distal stent edge (0.22 vs 0.098 mm(3)/mm, p = 0.01 for an average neointimal volume index within 3 mm from the distal stent edge). In conclusion, direct coronary stenting with the sirolimus-eluting Bx-Velocity stent is equally effective in terms of uniform stent expansion and long-term quantitative intravascular ultrasound results compared with conventional stenting using predilation. This strategy appears to be associated with less neointimal hyperplasia near the distal stent edge.

View details for DOI 10.1016/j.amjcard.2006.06.046

View details for Web of Science ID 000242595300010

View details for PubMedID 17126651

Abstract

Current surgical care and technology has evolved over the centuries from the interplay between creative surgeons and new technologies. As both fields become more specialized, that interplay is threatened. A 2-year educational fellowship is described which teaches both the process and the discipline of medical/surgical device innovation. Multi-disciplinary teams (surgeons, engineers, business grads) are assembled to educate a generation of translators, who can bridge the gap between scientific and technologic advances and the needs of the physician and the patient.

View details for PubMedID 17055962

Abstract

The purpose of this study was to identify potential predictors, including clinical, procedural, angiographic, and intravascular ultrasound (IVUS) parameters, for recurrent in-stent restenosis (ISR) following beta-radiation 90Strontium/Yttrium (90Sr/Y) in a large multicenter trial.Although adjunct brachytherapy reduces recurrent ISR after primary catheter-based intervention, recurrence of stenosis after brachytherapy still occurs.We analyzed 185 IVUS cohort patients in the STent And Restenosis Therapy (START) 40/20 trial where a 40-mm, 90Sr/Y, radioactive source train was exclusively used for treatment of ISR to be treatable with a 20-mm balloon.Thirty-nine patients underwent target lesion revascularization. Preliminary univariate analysis showed that age, smoking, balloon/artery ratio, geographic miss, minimum lumen diameter, and diameter stenosis at baseline were associated with target lesion revascularization, while none of IVUS variables were (minimum lumen area, minimum stent area, or residual plaque burden). The multivariate logistic regression analysis showed that younger age, lower balloon/artery ratio, and presence of geographic miss were independent predictors of target lesion revascularization.Even with adjunct beta-radiation therapy, initial mechanical optimization, such as appropriate balloon sizing and positioning, may be critical for the prevention of recurrent ISR.

View details for PubMedID 17020560

Abstract

Bifurcation lesions remain a challenging lesion subset, even in the era of drug-eluting stents. The aim of this study was to investigate the longitudinal remodeling pattern and cross-sectional plaque location of bifurcation lesions. Seventy-four preintervention intravascular ultrasound studies of left anterior descending bifurcation lesions were analyzed, in which the lesion was located proximal (type A, n=32) or distal (type B, n=42) to the side branch. Vessel area and plaque area at the lesion (VAlesion and PAlesion) and at the reference site (VAreference and PAreference) were measured. The remodeling ratio was defined as VAlesion/VAreference, and the vessel compensation ratio was defined as (VAlesion-VAreference)/(PAlesion-PAreference). The geometric center of the lumen at the lesion site was identified, and the lesion site was divided into circumferential equal arcs to compare the cross-sectional distribution of percentage plaque area (100x[PAlesion/VAlesion]) between the 2 groups. The remodeling ratio (1.03+/-0.15 vs 0.94+/-0.14, p=0.01) and the vessel compensation ratio (0.0+/-0.36 vs -0.37+/-0.61, p<0.01) were significantly greater in type A than in type B lesions. The circumferential distribution pattern of percentage plaque area was significantly different between the groups (analysis of variance p<0.005), with greater percentage plaque area for the vessel wall opposite from the side branch in type B lesions (46.3+/-18.0% vs 54.6+/-15.4%, type A vs type B lesions, p<0.05). In conclusion, these results suggest that a major side branch may affect longitudinal lesion remodeling as well as the circumferential location of atherosclerotic plaque.

View details for DOI 10.1016/j.amjcard.2006.01.073

View details for Web of Science ID 000239185300011

View details for PubMedID 16828591

Abstract

Investigating changes in coronary physiology that occur after cardiac transplantation has been challenging. Simultaneous and independent assessment of the epicardial artery by measuring fractional flow reserve (FFR) and of the microvasculature by calculating the index of microvascular resistance (IMR) with a single coronary pressure wire may be useful.Twenty-five asymptomatic patients with normal coronary angiograms underwent FFR, thermodilution-derived IMR and coronary flow reserve (CFR) and intravascular ultrasound (IVUS) evaluation soon after cardiac transplantation and 1 year later.FFR significantly worsened (0.90 +/- 0.05 at baseline to 0.85 +/- 0.06 at 1 year, p = 0.004). FFR correlated strongly with percent plaque volume as measured by IVUS (r = -0.58, p < 0.0001). IMR improved significantly (29.2 +/- 15.9 at baseline to 19.3 +/- 7.6 units at 1 year, p = 0.007). CFR increased, but not significantly (2.6 +/- 1.4 at baseline to 3.2 +/- 1.2 at 1 year, p = not significant). Diabetes and donor heart ischemic time independently predicted baseline IMR. Treatment with rapamycin independently predicted FFR at 1 year.New coronary physiologic measures, FFR and IMR, show that epicardial artery physiology worsens and correlates with anatomic changes, whereas microvascular physiology improves during the first year after cardiac transplantation. CFR, the traditional method for evaluating coronary circulatory physiology, did not identify these changes.

View details for DOI 10.1016/j.healun.2006.03.003

View details for Web of Science ID 000239019700003

View details for PubMedID 16818118

Abstract

The use of longer radioactive seed trains to avoid geographic miss may lead to greater radiation exposure to distal vasculature due to the natural tapering of coronary arteries. The aim of this study was to use IVUS-based dosimetric analysis to evaluate the effect of beta-radiation on angiographically normal, noninjured distal segments.We analyzed 17 in-stent restenosis cases (stent length: 20 +/- 8 mm) treated with a 40 mm 90Sr/Y source train. The prescribed dose was 18.4 Gy (reference less than or equal to 3.3 mm) or 23 Gy (reference > 3.3 mm) at 2 mm from the source. Noninjured, but fully radiated, distal reference sites were determined by angiography. Based upon the three-dimensional vessel contours obtained at baseline, the minimum dose delivered to 90% of plaque volume (Dv90) was determined. Vessel, plaque and lumen volumes and Dv90 were computed in every 2 mm subsegment (n = 52).On average, no significant serial change was observed in plaque area (5.0 +/- 2.5 mm3/mm post-treatment to 5.6 +/- 3.1 mm3/mm at 8-month follow up; p = 0.09), vessel area (10.2 +/- 3.7 to 10.3 +/- 4.0 mm3/mm; p = 0.84), or lumen area (5.2 +/- 2.0 to 4.7 +/- 1.8 mm3/mm; p = 0.19). Subsegment analysis, however, revealed a wide range of dose distribution, with a significant positive correlation between Dv90 and plaque increase (p = 0.008), as well as vessel change (p < 0.001), representing dose-dependent positive vessel remodeling following beta radiation. Consequently, no significant relationship was observed between Dv90 and lumen change.Detailed IVUS-based dosimetric analysis demonstrated that beta radiation promoted positive remodeling, preventing lumen loss despite a mild increase in plaque mass on angiographically normal, noninjured distal segments.

View details for PubMedID 16816435

Abstract

To examine the influence of vessel wall calcium on neointimal hyperplasia (NIH) following bare metal stent (BMS) and drug-eluting stent (DES) implantation.While procedural complications with coronary stenting in calcified lesions are well reported, little is known about subsequent NIH on plaque calcium following either BMS or DES implantation.In the Study to COmpare REstenosis Rate between QueST and QuaDDS-QP2 (SCORE) trial, 6 months follow-up volumetric intravascular ultrasound data were available for 41 lesions (BMS, 19; DES, 22). NIH thicknesses on superficial, deep, and noncalcified plaque were calculated at every 0.5 mm intervals over the stented segment. Calcified and less-calcified cross-sections were defined as those containing arcs of plaque calcium > or = 90 degrees and < 90 degrees , respectively.In BMS, mean NIH thickness on both superficial (0.24 +/- 0.23 mm) and deep calcium (0.25 +/- 0.21 mm) was significantly smaller than that of noncalcified plaque (0.31 +/- 0.22 mm) (P < 0.0005). NIH area was significantly smaller in calcified cross-sections compared to less-calcified cross-sections (2.1 +/- 1.2 mm2 vs. 3.1 +/- 1.9 mm2, P < 0.0001). While in contrast, in DES, mean NIH thickness was similar, irrespective of the presence or location of calcium (0.03 +/- 0.05 mm vs. 0.03 +/- 0.06 mm vs. 0.03 +/- 0.05 mm, superficial vs. deep vs. noncalcified plaque, P = NS). NIH area was also similar between calcified and less-calcified cross-sections (0.3 +/- 0.6 mm2 vs. 0.3 +/- 0.6 mm2, P = NS).These results suggest that while plaque calcium may influence NIH following BMS implantation, NIH suppression using DES does not appear to be affected by the presence or location of calcium.

View details for DOI 10.1002/ccd.20708

View details for Web of Science ID 000238082300005

View details for PubMedID 16649232

Abstract

This study examined whether coronary focal vasospasm occurs in a nonuniform distribution within the coronary tree and whether a longitudinal plaque distribution pattern is present in patients with vasospastic angina using 3-dimensional intravascular ultrasound analysis. Of 121 patients with clinically suspected angina without fixed stenosis in the coronary arteries, vasospasm was provoked in 82 patients with 92 lesions (42 focal, 50 diffuse) by intravenous ergonovine maleate injection. Most focal vasospasms occurred in the proximal third of the coronary arteries (proximal 28, mid 8, distal 6, p <0.01), corresponding to the historical high-risk zones for acute coronary occlusion. More plaque burden also existed in the proximal third of the coronary arteries in patients with focal vasospasm.

View details for DOI 10.1016/j.amjcard.2005.11.073

View details for Web of Science ID 000237483100012

View details for PubMedID 16635604

Abstract

Previous long-term (>1 year) studies have suggested that saphenous vein bypass grafts (SVGs) undergo vascular remodeling similar to native coronary arteries. However, early morphologic stages of SVG remodeling have not been characterized in vivo.Thirty SVGs were studied 12 months after implantation using an intravascular ultrasound automated pullback system. Intravascular ultrasound images were analyzed between 10 and 60 mm from the tip of the guide. Lumen area (LA), intima area (IA), and vessel area (VA, defined as the area within the outer border of a hypoechoic intimal layer) were computed at 3 cross sections: the minimum LA (MLA) site and the proximal and distal reference sites. Area changes (Delta) were calculated as the MLA site minus the average of the reference sites.In this cohort, 70% of the MLA sites had a smaller VA than the average references. On average, MLA sites had significantly smaller VA (9.7 +/- 2.9 vs 10.7 +/- 3.2 mm2, P < .01) and larger IA (2.5 +/- 2.1 vs 1.2 +/- 1.3 mm2, P < .01) than at the reference sites. The relative contribution of DeltaVA (-1.0 +/- 1.4 mm2) and DeltaIA (1.3 +/- 1.3 mm2) to lumen compromise (-2.3 +/- 1.4 mm2) were 43% and 57%, respectively. On the other hand, simple linear regression analysis revealed a significant positive correlation between DeltaIA and DeltaVA (y = -1.7 + 0.52x, r = 0.50, P < .01).Within the first year, the mechanism of lumen compromise in SVG is a combination of negative remodeling and intimal hyperplasia. Positive remodeling is seen in a minority of cases. However, the direction and extent of remodeling correlated with change in intimal thickness.

View details for DOI 10.1016/j.ahj.2005.05.011

View details for Web of Science ID 000236353900027

View details for PubMedID 16504641

Abstract

Diabetes mellitus is an independent predictor of restenosis after percutaneous coronary intervention. The pattern of restenosis after bare metal stent implantation in diabetic patients was examined with 3-dimensional intravascular ultrasound analysis. Lumen and stent were manually traced at every 0.5-mm interval in stented segments. Using Simpson's method, stent, luminal, and neointimal (stent minus lumen) volumes were calculated and average area was calculated as volume data divided by length. To measure the cross-sectional and longitudinal severities of luminal encroachment by the neointima, percent neointimal area (neointimal area divided by stent area) and neointimal hyperplasia 50 (IH50) (defined as percent stent length with percent neointimal area >50%) were calculated. In 278 patients (68 with diabetes and 210 without diabetes), there was a significantly higher percentage of maximal percent neointimal area with significantly longer percent stent length that was severely encroached by the neointima in diabetic patients. Diabetic patients showed a more heterogenous pattern of the neointima after bare metal stenting, resulting in longer high-grade obstruction segments. This may have important implications for stent design and pharmacokinetic properties of next-generation drug-eluting technology for this complex patient subset.

View details for DOI 10.1016/j.amjcard.2005.08.067

View details for Web of Science ID 000235265400009

View details for PubMedID 16442392

Abstract

To assess whether asymmetric stent expansion affects suppression of neointimal hyperplasia after sirolimus-eluting stent implantation, 64 patients in the SIRolImUS-coated Bx Velocity stent trial who underwent single 18-mm stent implantation and 3-dimensional intravascular ultrasonography at 8-month follow-up were enrolled. To assess the longitudinal stent asymmetric expansion, 2 cross sections with a maximal/minimal stent area were chosen in each patient. To assess for tomographic stent asymmetric expansion, stent eccentricity was determined by dividing the minimum stent diameter by the maximum stent diameter. At the 2 cross sections with a maximal/minimal stent area, a sirolimus-eluting stent reduced neointimal hyperplasia significantly with no interaction between the treatment and stent areas. A sirolimus-eluting stent also significantly reduced neointimal hyperplasia in the concentric and eccentric stent groups.

View details for DOI 10.1016/j.amjcard.2005.07.044

View details for Web of Science ID 000233509900012

View details for PubMedID 16275187

Abstract

To study the interaction of the sirolimus-eluting stent and vessel margins, we analyzed the intravascular ultrasound parameters in 317 edges of 167 stents having 18 edge stenoses at 8 months of follow-up from the SIRIUS trial. Of the baseline parameters, a larger reference percentage of plaque area and a larger edge stent area/reference minimum lumen area were associated with edge stenosis in the sirolimus-eluting stent cohort compared with the incidence of edge stenosis in the bare metal stent cohort. Thus, full lesion coverage and matching the stented segment properly to the adjacent segment using intravascular ultrasound guidance may improve sirolimus-eluting stent implantation efficacy further.

View details for DOI 10.1016/j.amjcard.2005.06.066

View details for Web of Science ID 000233343500015

View details for PubMedID 16253592

Abstract

The effect of lesion characteristics on neointimal hyperplasia after sirolimus-eluting stent implantation was examined in 45 patients who underwent successful preinterventional intravascular ultrasound. There were no differences in neointimal hyperplasia between the moderate/severe calcified lesion group (calcium arc >120 degrees ) and the non/mild calcified lesion group or between the positive vessel remodeling group (external elastic membrane area at the minimal lumen area site larger than that at the proximal reference site) and negative vessel remodeling group. No correlation between preinterventional plaque burden and neointimal hyperplasia was found. In patients who have coronary artery disease, sirolimus-eluting stents continue to demonstrate striking suppression of neointimal proliferation, irrespective of lesion characteristics previously associated with greater restenotic risk.

View details for DOI 10.1016/j.amjcard.2005.06.063

View details for Web of Science ID 000233343500012

View details for PubMedID 16253589

Abstract

We sought to identify the frequency of incomplete stent apposition (ISA) in sirolimus-eluting stents (SES) and clarify its findings and clinical sequelae.Late-acquired ISA has been reported in bare-metal stents (BMS) and brachytherapy and recently in drug-eluting stents. However, the characteristics of late ISA in SES have not been clarified.From the SIRIUS trial, a randomized, multicenter study comparing SES and BMS, serial qualitative intravascular ultrasound (IVUS; at stent implantation and eight-month follow-up) was available in 141 patients (BMS: n = 61; SES: n = 80). The IVUS images were reviewed for the presence of ISA.Incomplete stent apposition at follow-up was observed in 19 patients (BMS: n = 6 [9.8%]; SES: n = 13 [16.3%]; p = NS). Among these, 12 had ISA after intervention and at follow-up (persistent ISA). Late-acquired ISA was seen in the remaining seven cases, all from the SES group (BMS: n = 0; SES: n = 7 [8.7%]; p < 0.05). In late-acquired ISA, there was an increase in external elastic membrane area (after intervention: 16.2 +/- 2.7 m2; follow-up: 18.9 +/- 3.6 mm2; p < 0.05). The location of stent-vessel wall separation was primarily at the stent edges in persistent ISA cases, whereas late-acquired ISA in SES occurred mostly in the mid portion of the stent. There were no negative clinical events reported for any ISA cases at 12-month clinical follow-up.Late ISA was observed in 8.7% of patients after SES implantation. There were no negative clinical events associated with this IVUS finding at 12-month clinical follow-up; however, careful long-term follow-up will be necessary.

View details for DOI 10.1016/j.jacc.2005.05.068

View details for Web of Science ID 000231991600009

View details for PubMedID 16168282

Abstract

Several clinical studies are evaluating the therapeutic potential of delivery of various progenitor cells for treatment of injured hearts. However, the actual fate of delivered cells has not been thoroughly assessed for any cell type. We evaluated the short-term fate of peripheral blood mononuclear cells (PBMNCs) after intramyocardial (IM), intracoronary (IC), and interstitial retrograde coronary venous (IRV) delivery in an ischemic swine model.Myocardial ischemia was created by 45 minutes of balloon occlusion of the left anterior descending coronary artery. Six days later, 10(7) 111indium-oxine-labeled human PBMNCs were delivered by IC (n=5), IM (n=6), or IRV (n=5) injection. The distribution of injected cells was assessed by gamma-emission counting of harvested organs. For each delivery method, a significant fraction of delivered cells exited the heart into the pulmonary circulation, with 26+/-3% (IM), 47+/-1% (IC), and 43+/-3% (IRV) of cells found localized in the lungs. Within the myocardium, significantly more cells were retained after IM injection (11+/-3%) compared with IC (2.6+/-0.3%) (P<0.05) delivery. IRV delivery efficiency (3.2+/-1%) trended lower than IM infusion for PBMNCs, but this difference did not reach significance. The IM technique displayed the greatest variability in delivery efficiency by comparison with the other techniques.The majority of delivered cells is not retained in the heart for each delivery modality. The clinical implications of these findings are potentially significant, because cells with proangiogenic or other therapeutic effects could conceivably have effects in other organs to which they are not primarily targeted but to which they are distributed. Also, we found that although IM injection was more efficient, it was less consistent in the delivery of PBMNCs compared with IC and IRV techniques.

View details for DOI 10.1161/CIRCULATIONAHA.104.526749

View details for Web of Science ID 000231741600023

View details for PubMedID 16159808

Abstract

Adjacent reference vessel response to smaller lumens at stented segments was examined with 3-dimensional intravascular ultrasound analysis. In 128 patients after bare metal stent implantation, minimal lumen area (MLA) within the stent and average lumen area at distal/proximal adjacent reference segments (5 mm) were obtained at baseline and follow-up. In the smaller in-stent MLA group (MLA <3 mm2), lumen area decreased significantly at the distal edge compared with the larger in-stent MLA group (MLA > or =3 mm2), although no significant difference was seen at the proximal edge. In-stent lumen patency may influence vascular responses at adjacent reference segments after bare metal stent implantation.

View details for DOI 10.1016/j.amjcard.2005.03.079

View details for Web of Science ID 000231057000011

View details for PubMedID 16054461

Abstract

We assessed the predictive value of minimum stent area (MSA) for long-term patency of sirolimus-eluting stents (SES) implantation compared to bare metal stents (BMS).Although MSA is a consistent predictor of in-stent restenosis, its predictive value in BMS is still limited because of biologic variability in the restenosis process.From the SIRolImUS (SIRIUS) trial, 122 cases (SES: 72; BMS: 50) with complete serial intravascular ultrasound (IVUS) (baseline and 8-month follow-up) were analyzed. Postprocedure MSA and follow-up minimum lumen area (MLA) were obtained. Based on previous physiologic studies, adequate stent patency at follow-up was defined as MLA >4 mm(2).In both groups, a significant positive correlation was observed between baseline MSA and follow-up MLA (SES: p < 0.0001, BMS: p < 0.0001). However, SES showed higher correlation than BMS (0.8 vs. 0.65) with a higher regression coefficient (0.92 vs. 0.59). The sensitivity and specificity curves identified different optimal thresholds of MSA to predict adequate follow-up MLA: 5 mm(2) for SES and 6.5 mm(2) for BMS. The positive predictive values with these cutoff points were 90% and 56%, respectively.In this SIRIUS IVUS substudy, SES reduced both biologic variability and restenosis, resulting in increased predictability of long-term stent patency with postprocedure MSA. In addition, SES had a considerably lower optimal MSA threshold compared to BMS.

View details for DOI 10.1016/j./jacc.2004.01.044

View details for Web of Science ID 000221715800006

View details for PubMedID 15172398

Abstract

Temperature heterogeneity along the inner surface of an artery may be a surrogate marker of impending plaque rupture and has been associated with an increased likelihood of future coronary events. Initial studies using catheter-based thermographic devices have demonstrated that the changes in temperature are subtle, while the effects of coronary flow on measured temperature have not yet been examined. A novel guidewire-based system (ThermoCoil, Imetrx) designed to measure surface temperature in coronary arteries was used to study the effects of heat source intensity and flow on measured temperature. An in vitro model of a focal, eccentric, heat-generating lesion demonstrated that a guidewire-based system can detect changes in surface temperature with a precision of less than 0.08 degrees C. In this model, temperature measurements increased linearly with source temperature and decreased with increases in flow by an exponent of -0.33 (P < 0.001 for both). Flow rates and heat source properties can significantly influence the measurement and interpretation of thermographic data. The incorporation of 2D thermographic images may contribute further to the characterization of metabolically active plaques likely to cause acute coronary syndromes.

View details for DOI 10.1002/ccd.10750

View details for Web of Science ID 000221856000016

View details for PubMedID 15170716

Abstract

The effect of epicardial artery stenosis on myocardial microvascular resistance remains controversial. Recruitable collateral flow, which may affect resistance, was not incorporated into previous measurements.In an open-chest pig model, distal coronary pressure was measured with a pressure wire, and the apparent minimal microvascular resistance was calculated during peak hyperemia as pressure divided by flow, measured either with a flow probe around the coronary artery (R(micro app)) or with a novel thermodilution technique (apparent index of microcirculatory resistance [IMR(app)]). These apparent resistances were compared with the actual R(micro) and IMR after the coronary wedge pressure and collateral flow were incorporated into the calculation. Measurements were made at baseline (no stenosis) and after creation of moderate and severe epicardial artery stenoses. In 6 pigs, 189 measurements of R(micro) and IMR were made under the various epicardial artery conditions. Without consideration of collateral flow, R(micro app) (0.43+/-0.12 to 0.46+/-0.10 to 0.51+/-0.11 mm Hg/mL per minute) and IMR(app) (14+/-4 to 17+/-7 to 20+/-10 U) increased progressively and significantly with increasing epicardial artery stenosis (P<0.001 for both). With the incorporation of collateral flow, neither R(micro) nor IMR increased as a result of increasing epicardial artery stenosis.After collateral flow is taken into account, the minimum achievable microvascular resistance is not affected by increasing epicardial artery stenosis.

View details for DOI 10.1161/01.CIR.0000128669.99355.CB

View details for Web of Science ID 000221477800004

View details for PubMedID 15136503

Abstract

Delivery of angiogenic factors to ischemic myocardium remains a practical challenge. We evaluated the efficiency and efficacy of delivery of fibroblast growth factor-2 (FGF-2) protein via high-pressure retrograde injection into the anterior interventricular vein (AIV) in a porcine model of chronic myocardial ischemia. Labeled FGF-2 protein was delivered to the myocardium of three pigs via the AIV and the left anterior descending (LAD) coronary artery in three others. At 1 hr, the amount of protein in the left ventricle and the LAD region was quantified. Copper stents were implanted in the LAD of 25 pigs, resulting in chronic myocardial ischemia. At 4 weeks, microsphere-derived myocardial blood flow was assessed at rest and during pacing. In eight pigs (AIV FGF), FGF-2 protein (6 microg/kg) was delivered via high-pressure retrograde injection into the AIV. Six pigs (intracoronary FGF) received the same amount of FGF-2 by intracoronary delivery. Five pigs (AIV saline) received a placebo injection into the AIV and six pigs (control) served as controls. Four weeks later, myocardial blood flow was reassessed. At 1 hr, significantly more FGF remained in the left ventricle (1.3 vs. 0.82 microg; P < 0.04) and in the LAD region (1.2 vs. 0.64 microg; P = 0.03) after AIV compared to intracoronary delivery. Four weeks after treatment, resting LAD blood flow (normalized to right ventricular flow) improved slightly in the AIV FGF and intracoronary FGF arms (1.32-1.37 for both; P = 0.11), while it decreased significantly in the AIV saline (1.32-1.23; P = 0.02) and the control arms (1.32-1.19; P = 0.0004). Pacing LAD blood flow decreased significantly in the control arm (1.30-1.23; P < 0.05), but did not change significantly in the other three arms. High-pressure retrograde injection into the AIV may represent an efficient and effective means for delivering angiogenic factors to ischemic myocardium.

View details for DOI 10.1002/ccd.10790

View details for Web of Science ID 000220022500027

View details for PubMedID 14988909

Abstract

The use of directional coronary atherectomy (DCA) in current practice has been limited. The SilverHawk System is a newly developed plaque excision device that aims to overcome the drawbacks of prior DCA platforms. The device was evaluated in a porcine coronary model and in a series of patients. Procedural variables along with outcomes were reviewed. Quantitative angiography (QCA) was performed and excised tissue fragments were weighed and examined histologically. In porcine cases, pretreatment MLD increased from 0.51 +/- 0.26 to 2.36 +/- 0.59 mm postdebulking and 19.9 +/- 7.6 mg of tissue was retrieved. In human cases, pretreatment MLD increased from 0.8 +/- 0.4 to 2.2 +/- 0.5 mm postdebulking and 15.2 +/- 7.8 mg of tissue was retrieved without complications. These data show that the SilverHawk System may offer significant utility in treating a wide variety of complex coronary lesions.

View details for DOI 10.1002/ccd.10727

View details for Web of Science ID 000187802300008

View details for PubMedID 14696157

View details for DOI 10.1161/01.CIR.0000093680.47862.F8

View details for Web of Science ID 000186628300025

Abstract

Late incomplete stent apposition was observed in 2.4% of the 412 stented segments studied by serial intravascular ultrasound analyses. Most of these phenomena and all late vessel expansions with incomplete stent apposition developed in vessels in which lesions were treated by atherectomy before stenting, suggesting a potential association between mechanical injury from debulking and these phenomena.

View details for Web of Science ID 000186638600019

View details for PubMedID 14609603

Abstract

Current treatment for acute myocardial infarction (AMI) focuses on reestablishing blood flow (reperfusion). Paradoxically, reperfusion itself may cause additional injury to the heart. We previously found that delta-protein kinase C (deltaPKC) inhibition during simulated ischemia/reperfusion in isolated rat hearts is cardioprotective. We focus here on the role for deltaPKC during reperfusion only, using an in vivo porcine model of AMI.An intracoronary application of a selective deltaPKC inhibitor to the heart at the time of reperfusion reduced infarct size, improved cardiac function, inhibited troponin T release, and reduced apoptosis. Using 31P NMR in isolated perfused mouse hearts, we found a faster recovery of ATP levels in hearts treated with the deltaPKC inhibitor during reperfusion only.Reperfusion injury after cardiac ischemia is mediated, at least in part, by deltaPKC activation. This study suggests that including a deltaPKC inhibitor at reperfusion may improve the outcome for patients with AMI.

View details for DOI 10.1161/01.CIR.0000101682.24138.36

View details for Web of Science ID 000186475200003

View details for PubMedID 14597593

Abstract

Thermodilution coronary flow reserve (CFRthermo) is a new technique for invasively measuring coronary flow reserve (CFR) with a coronary pressure wire and is based on the ability of the pressure transducer to also measure temperature changes. Whether CFRthermo correlates well enough with absolute flow-derived CFR (CFRflow) to replace Doppler wire-derived CFR (CFRDoppler) remains unclear.In an open-chest pig model, CFRthermo was measured in the left anterior descending (LAD) artery and compared with CFRDoppler and CFRflow, measured with an external flow probe placed around the LAD. In 9 pigs, CFR was measured simultaneously by all 3 means in the normal LAD and after creation of an epicardial LAD stenosis. To determine the added effect of microvascular disease, measurements of flow reserve were also performed after disruption of the coronary microcirculation with embolized microspheres. Intracoronary papaverine (20 mg) was used to induce hyperemia. In a total of 61 paired measurements, CFRthermo correlated strongly with the reference standard CFRflow (r=0.85, P<0.001). CFRDoppler correlated less well with CFRflow (r=0.72, P<0.001). Bland-Altman analysis showed a closer agreement between CFRthermo and CFRflow.CFRthermo correlates better with CFRflow than does CFRDoppler.

View details for DOI 10.1161/01.CIR.0000099521.31396.9D

View details for Web of Science ID 000186340900005

View details for PubMedID 14568891

Abstract

The utility of measuring fractional flow reserve (FFR) to assess cardiac transplant arteriopathy has not been evaluated. Measuring coronary flow reserve (CFR) as well as FFR could add information about the microcirculation, but until recently, this has required two coronary wires. We evaluated a new method for simultaneously measuring FFR and CFR with a single wire to investigate transplant arteriopathy.In 53 cases of asymptomatic cardiac transplant recipients without angiographically significant coronary disease, FFR and thermodilution-derived CFR (CFRthermo) were measured simultaneously with the same coronary pressure wire in the left anterior descending artery and compared with volumetric intravascular ultrasound (IVUS) imaging. The average FFR was 0.88+/-0.07; in 75% of cases, the FFR was less than the normal threshold of 0.94; and in 15% of cases, the FFR was < or =0.80, the upper boundary of the gray zone of the ischemic threshold. There was a significant inverse correlation between FFR and IVUS-derived measures of plaque burden, including percent plaque volume (r=0.55, P<0.0001). The average CFRthermo was 2.5+/-1.2; in 47% of cases, CFRthermo was < or =2.0. In 14%, the FFR was normal (> or =0.94) and the CFR was abnormal (<2.0), suggesting predominant microcirculatory dysfunction.FFR correlates with IVUS findings and is abnormal in a significant proportion of asymptomatic cardiac transplant patients with normal angiograms. Simultaneous measurement of CFR with the same pressure wire, with the use of a novel coronary thermodilution technique, is feasible and adds information to the physiological evaluation of these patients.

View details for DOI 10.1161/01.CIR.0000091116.84926.6F

View details for Web of Science ID 000185624500027

View details for PubMedID 12963639

Abstract

Intravascular brachytherapy may cause "exaggerated" vessel remodeling with late incomplete apposition in segments that have little disease, which are exposed to higher radiation doses. The long-term clinical impact of this finding is unclear.

View details for DOI 10.1016/S0002-9149(03)00728-8

View details for Web of Science ID 000185060700017

View details for PubMedID 12943881

Abstract

A relatively simple, invasive method for quantitatively assessing the status of the coronary microcirculation independent of the epicardial artery is lacking.By using a coronary pressure wire and modified software, it is possible to calculate the mean transit time of room-temperature saline injected down a coronary artery. The inverse of the hyperemic mean transit time has been shown to correlate with absolute flow. We hypothesize that distal coronary pressure divided by the inverse of the hyperemic mean transit time provides an index of microcirculatory resistance (IMR) that will correlate with true microcirculatory resistance (TMR), defined as the distal left anterior descending (LAD) pressure divided by hyperemic flow, measured with an external ultrasonic flow probe. A total of 61 measurements were made in 9 Yorkshire swine at baseline and after disruption of the coronary microcirculation, both with and without an epicardial LAD stenosis. The mean IMR (16.9+/-6.5 U to 25.9+/-14.4 U, P=0.002) and TMR (0.51+/-0.14 to 0.79+/-0.32 mm Hg x mL(-1) x min(-1), P=0.0001), as well as the % change in IMR (147+/-66%) and TMR (159+/-105%, P=NS versus IMR % change), increased significantly and to a similar degree after disruption of the microcirculation. These changes were independent of the status of the epicardial artery. There was a significant correlation between mean IMR and TMR values, as well as between the % change in IMR and % change in TMR.Measuring IMR may provide a simple, quantitative, invasive assessment of the coronary microcirculation.

View details for DOI 10.1161/01.CIR.0000080700.98607.D1

View details for Web of Science ID 000183887100004

View details for PubMedID 12821539

Abstract

We sought to document whether a physiologic change in gender has any effect on coronary arterial size.The coronary arteries are smaller in women, even after correction for body surface area (BSA). These differences may contribute to adverse clinical outcomes after coronary artery bypass graft surgery and myocardial infarction in women. In male and female transsexuals, pharmacologic doses of estrogens and androgens significantly influence vascular diameter. Thus, gender differences in the coronary vasculature may be a reflection of the hormonal environment.In 86 patients who had undergone orthotopic heart transplantation, serial intravascular ultrasound studies of the proximal left anterior descending coronary artery (LAD) were analyzed. Changes in vessel area (VA) over the first or second post-transplant year were recorded, and comparisons were made between donor hearts that were transplanted in a patient of the same gender and those that were transplanted in a patient of the opposite gender.Vessel area of the proximal LAD increased over time in all patient groups. In hearts transplanted within the same gender and in male donor hearts transplanted to female recipients, the change was small and not significant. However, in hearts transplanted from female donors to male recipients, there was a substantial and highly significant increase in LAD VA (median 16.13 to 17.88 mm(2); p = 0.01). This increase was not explained by confounding due to changes in BSA or left ventricular wall thickness.This pattern of arterial remodeling early after heart transplantation supports a link between host gender and coronary arterial size.

View details for DOI 10.1016/S0735-1097(03)00246-8

View details for Web of Science ID 000182631800019

View details for PubMedID 12742295

Abstract

Most patients come to the catheterization laboratory without prior functional tests, which makes the cost-effective treatment of patients with intermediate coronary lesions a practical challenge.We developed a decision model to compare the long-term costs and benefits of 3 strategies for treating patients with an intermediate coronary lesion and no prior functional study: 1) deferring the decision for percutaneous coronary intervention (PCI) to obtain a nuclear stress imaging study (NUC strategy); 2) measuring fractional flow reserve (FFR) at the time of angiography to help guide the decision for PCI (FFR strategy); and 3) stenting all intermediate lesions (STENT strategy). On the basis of the literature, we estimated that 40% of intermediate lesions would produce ischemia, 70% of patients treated with PCI and 30% of patients treated medically would be free of angina after 4 years, and the quality-of-life adjustment for living with angina was 0.9 (1.0 = perfect health). We estimated the cost of FFR to be 761 dollars, the cost of nuclear stress imaging to be 1093 dollars, and the cost of medical treatment for angina to be 1775 dollars per year. The extra cost of splitting the angiogram and PCI as dictated by the NUC strategy was 3886 dollars by use of hospital cost-accounting data. Sensitivity and threshold analyses were performed to determine which variables affected our results.The FFR strategy saved 1795 dollars per patient compared with the NUC strategy and 3830 dollars compared with the STENT strategy. Quality-adjusted life expectancy was similar among the 3 strategies (NUC-FFR = 0.8 quality-adjusted days, FFR-STENT = 6 quality-adjusted life days). Compared with the FFR strategy, the NUC strategy was expensive (>800,000 dollars per quality-adjusted life year gained). Both screening strategies were superior to (less cost, better outcomes) the STENT strategy. Sensitivity analysis indicated that the NUC strategy would only become attractive (<50,000 dollars/quality-adjusted life years compared with FFR) if the specificity of nuclear stress imaging was >25% better than FFR. Our results were not altered significantly by changing the other assumptions.In patients with an intermediate coronary lesion and no prior functional study, measuring FFR to guide the decision to perform PCI may lead to significant cost savings compared with performing nuclear stress imaging or with simply stenting lesions in all patients.

View details for DOI 10.1016/S0002-8703(03)00072-3

View details for Web of Science ID 000183258300020

View details for PubMedID 12766748

Abstract

Treatment with antiproliferative drugs via coated stents appears to be a promising approach to both mechanically remodel target lesions and biologically reduce neointimal hyperplasia. Drug-eluting stents can maximize local drug effects and minimize the potential for systemic toxic effects. The purpose of this review is to describe the effects of a lipophilic microtubular inhibitor, paclitaxel, a strong antiproliferative agent under clinical investigation, and to define the vascular response to taxol-based eluting stents by intravascular ultrasound.

View details for PubMedID 12612382

Abstract

We investigated whether neointimal regrowth is related to the mechanism of acute lumen gain during the treatment of in-stent restenosis (ISR) lesions both with and without adjunct intravascular brachytherapy. From the WRIST (Washington Radiation for In-Stent Restenosis Trial) cohort, 54 ISR patients ((192)Ir, 29; placebo, 25) were treated with nonrepeat stenting percutaneous interventions (excimer laser, rotational atherectomy, and/or balloon angioplasty) prior to (192)Ir or placebo therapy. Using Simpson's method, serial volumetric intravascular ultrasound (IVUS) analyses (pre- and posttreatment and 6-month follow-up) were analyzed to obtain stent, lumen, and intimal hyperplasia (IH) volumes that were then adjusted for stent length to create stent, lumen, and IH volume indexes. In the placebo group, the acute reduction of neointima (1.6 +/- 1.4 mm(3)/mm) was counteracted by intimal regrowth (2.1 +/- 1.7 mm(3)/mm). The amount of intimal regrowth correlated directly with the intimal reduction due to the intervention (r = 0.76; P < 0.001), but not with the amount of additional stent expansion. In the (192)Ir-treated group, intimal regrowth was significantly less than in the placebo group (-0.3 +/- 0.1 vs. 2.1 +/- 1.7 mm(3)/mm; P < 0.001) despite a similar initial intimal reduction (1.3 +/- 0.9 vs. 1.6 +/- 1.4 mm(3)/mm; P = NS). No correlation was found between intimal reduction at the time of the procedure and intimal regrowth in the (192)Ir group. In this study, neointimal regrowth following treatment of ISR lesions correlates directly with the extent of acute intimal volume reduction, but not with the extent of additional stent expansion. This relation is not seen in ISR segments treated with radiation, where intimal regrowth is substantially inhibited.

View details for DOI 10.1002/ccd.10405

View details for Web of Science ID 000182814600005

View details for PubMedID 12552537

Abstract

Deep vessel wall injury is believed to affect vessel dimension following coronary intervention. The cutting balloon is designed to treat coronary artery stenoses with dilatation and surgical incisions, thereby reducing excess vessel injury. This study examines the effect of deep vessel wall injury on acute and late coronary arterial response after cutting balloon angioplasty. Serial volumetric intravascular ultrasound (IVUS) analyses were performed in 63 lesions treated with cutting balloon angioplasty alone. Before intervention, the longitudinal range of the lesion segment that included the smallest lumen area (LA) was determined as LA <4 mm(2) and/or LA stenosis >60%. The exact corresponding site at postintervention and follow-up was aligned using peri- and intravascular landmarks. Average vessel area (VA), plaque area (PA), and LA were measured. Lesion segments were categorized as with or without deep vessel wall injury, which was defined as the presence of plaque/vessel wall fracture extending to the sonolucent (medial) layer. Before intervention, the lesion vessel size of deep injury group was smaller than that of the nondeep injury group (p <0.05 for average VA and PA), whereas average lesion LA, lesion length, and reference vessel size did not differ. Immediately after cutting balloon angioplasty, the deep injury group showed a significant increase in VA (p <0.0001) and a lesser decrease in PA (p <0.01) compared with the nondeep injury group. During follow-up, the increase of VA tended to be greater in the deep injury group than in the nondeep injury group (p = 0.06), whereas the change of PA did not differ. Consequently, LA decrease was less in the deep injury group than in the nondeep injury group (p <0.05). From these results, it is suggested that deep vessel wall injury tends to occur in lesions with relatively small size and such lesions show favorable vessel response after cutting balloon angioplasty.

View details for Web of Science ID 000180201000002

View details for PubMedID 12505563

Abstract

The Helixcision system is a novel 6 Fr-compatible catheter designed to debulk tissue for in-stent restenosis lesions. The purpose of this study was to determine the efficacy and feasibility of this new system for removing neointimal hyperplasia. A total of 32 in-stent restenosis lesions in 32 patients were treated with helixcision followed by balloon angioplasty. Debulking efficacy was assessed with serial baseline intravascular ultrasound (IVUS) in a subset of 18 lesions. To investigate longitudinal efficacy, 3D analysis was also performed in 12 lesions with automated pullback to calculate average cross-sectional areas across the stent. Prior to procedure, the angiographic reference diameter was 2.60 +/- 0.46 mm. Immediately after procedure, minimum lumen diameter improved from 0.84 +/- 0.33 to 2.19 +/- 0.41 mm (P < 0.0001). IVUS showed a significant reduction of intimal area (IA) after helixcision (from 4.95 +/- 2.04 to 2.88 +/- 1.48 mm(2); P < 0.001). Adjunctive balloon angioplasty further improved lumen area (LA) mainly by stent expansion rather than IA reduction at the site of minimum lumen area. The degrees of IA reduction and LA improvement were closely similar in volumetric analysis. Thirty-day and 6-month clinical follow-up were available in 97% (n = 31) and 72% (n = 23) of the enrolled patients, respectively. At 30-day follow-up, no major adverse cardiac event was reported except for periprocedural CK elevation in two patients (6%). Target legion revascularization within 6 months was performed in six patients (26%). Preliminary results of helixcision indicate that this system is safe and feasible for the treatment of in-stent restenosis. The concordant results between 2D and 3D IVUS analyses suggest that this unique technology can achieve uniform longitudinal debulking throughout the stent. The long-term outcomes appeared to be favorable, considering the relatively diffuse lesion morphology.

View details for DOI 10.1002/ccd.10352

View details for Web of Science ID 000182814400006

View details for PubMedID 12455079

Abstract

Several studies have shown that mechanisms for lumen enlargement following conventional balloon angioplasty (BA) consist of plaque reduction and vessel expansion. To assess the mechanisms of lumen enlargement after Cutting Balloon (CB) angioplasty, intravascular ultrasound images were analyzed in 180 lesions (89 CB and 91 BA). External elastic membrane (EEM) cross-sectional area (CSA), lumen CSA, and plaque plus media (P+M) CSA were measured before and after angioplasty. In the CB group, lower balloon pressure was utilized (P < 0.0001). DeltaP+M CSA was significantly larger (P = 0.02) and deltalumen CSA showed a trend toward being larger (P = 0.07) compared to BA group. For noncalcified lesions, CB resulted in a larger deltaP+M CSA (P < 0.05) and a smaller deltaEEM CSA (P = 0.10) than BA. For calcified lesions, deltalumen CSA was significantly larger in the CB group (P < 0.05) without significant differences in deltaEEM CSA and deltaP+M CSA. Dissections complicated with calcified lesions were associated with larger deltalumen CSA for the CB group. In conclusion, for noncalcified lesions, CB achieves similar luminal dimensions with larger plaque reduction and less vessel expansion compared to BA. On the other hand, for calcified lesions, the CB achieves larger lumen gain, especially in lesions with evidence of dissections.

View details for DOI 10.1002/ccd.10344

View details for Web of Science ID 000182814400002

View details for PubMedID 12455075

View details for Web of Science ID 000179262600027

View details for PubMedID 12423727

Abstract

Previous studies have demonstrated that the mechanism of acute lumen enlargement after balloon angioplasty is a combination of vessel expansion and plaque redistribution, but not plaque compression. The purpose of this study was to clarify, from a three-dimensional aspect, the vascular response to cutting balloon angioplasty.Serial intravascular ultrasound (IVUS) studies, including pre- and post-intervention, were performed in 36 native coronary lesions treated with the cutting balloon device. External elastic membrane (EEM), lumen, and plaque + media cross-sectional area were measured at 16-frame intervals (30 frames = 1 mm) over a lesion length of 16 mm with the center on the smallest pre-intervention lumen area. Volumetric calculations were based on Simpson's rule.EEM volume (261.16 +/- 89.59 vs. 279.59 +/- 85.92 mm3; p < 0.01) and lumen volume (106.48 +/- 37.83 v.s. 133.72 +/- 36.57 mm3; p < 0.01) significantly increased after cutting balloon angioplasty. Furthermore, the plaque + media volume throughout the lesion changed significantly after cutting balloon angioplasty (154.68 +/- 63.36 vs. 145.87 +/- 59.20 mm3; p < 0.01). The change in lumen volume correlated strongly with the change in EEM volume (r = 0.75; p < 0.01), but poorly with the change in plaque + media volume (r = 0.08; p = 0.64). Less longitudinal plaque redistribution was also observed throughout the vessel after angioplasty.The results of this study indicate that the predominant mechanism of lumen enlargement from cutting balloon angioplasty is vessel expansion, although total plaque mass reduction and longitudinal plaque redistribution do occur.

View details for Web of Science ID 000180010800003

View details for PubMedID 12517054

Abstract

Observations from previous intracoronary radiation therapy trials noted a considerable discrepancy between the prescribed radiation dose and the dose actually delivered. The aims of this study were to investigate the effect of actual delivered dose on vascular changes and to test the appropriateness of the current dose prescription.Serial volumetric intravascular ultrasound (IVUS) analysis was performed in 30 in-stent restenosis cases treated with a 40-mm (90)Sr/Y source train. The fixed dose was prescribed at 2 mm from the centerline of the source train (18.4 Gy at 2 mm for reference diameter < or =3.35 mm and 23 Gy for diameter > or =3.36 mm). Only stent segments with full radiation coverage and device injury were enrolled and divided into 2-mm-long subsegments (n=202). D(S90)EEM (the minimum dose absorbed by 90% of the external elastic membrane surface) was calculated as the delivered dose corresponding to each segment, assuming that the radiation catheter occupied the same position in the vessel as the IVUS catheter. Mean D(S90)EEM of 23.5+/-5.82 Gy (range 12.3 to 41.7 Gy) was delivered to these subsegments. Overall, intimal hyperplasia volume remained constant from postintervention to follow-up (2.23+/-1.10 to 2.32+/-1.09 mm3/m; P=NS). Regression analysis revealed there was no correlation between delivered dose intensity and changes in intimal hyperplasia volume. No particular dose-dependent complications were appreciated in this delivered dose range.The current dose-prescription protocol of (90)Sr/Y radiation to native in-stent restenosis lesions may provide substantial inhibition of neointimal reproliferation regardless of the actual delivered dose intensity.

View details for DOI 10.1161/01.CIR.0000036367.17043.03

View details for Web of Science ID 000179046600017

View details for PubMedID 12403663

Abstract

Catheter-based vascular interventions have been in development worldwide for several decades, leading to remarkable progress in device technology. Mechanical interventional devices, such as angioplasty balloons, atherectomy devices, and stents, were invented and have contributed greatly to the treatment of atherosclerotic vascular stenosis. However, mechanical approaches do not effectively prevent subsequent intimal growth. Recently, several biological approaches, including radiation therapy and drug-eluting stents, have shown striking inhibition of intimal growth. These significant results are likely to change the treatment strategy in the field of interventional cardiology. Furthermore, additional catheter-based technologies for vascular interventions are presently being evaluated. These latest technologies designed to prevent intimal proliferation include intravascular sonotherapy, cryotherapy, photoangioplasty, and soft X ray. To date, intravascular sonotherapy has proven its efficacy in animal studies and safety in human studies. Cryotherapy, the application of cold thermal energy during angioplasty, enhances the acute effects of conventional dilation while decreasing the likelihood of restenosis. Photoangioplasty has a unique property based on its selective mechanism of action to treat atheromatous plaque. Soft X ray systems provide convenient device handling and well-controlled radiation dose. Some of these technologies may play an important role in vascular interventions in the near future.

View details for PubMedID 12440180

Abstract

Inhibition of neointimal tissue growth has been demonstrated in preliminary human feasibility studies with a stent-based polymer sleeve delivering 7-hexanoyltaxol. The Study to COmpare REstenosis rate between QueST and QuaDS-QP2 (SCORE) trial is a human, randomized, multicenter trial comparing 7-hexanoyltaxol (QP2)-eluting stents (qDES) with bare metal stents (BMS) in the treatment of de novo coronary lesions. The purpose of this substudy was to evaluate the acute expansion property and long-term neointimal responses of qDES compared with BMS as assessed by intravascular ultrasound (IVUS).A total of 122 (qDES 66, BMS 56) patients were enrolled into the IVUS substudy. All IVUS images (immediately after the procedure and at 6-month follow-up) were analyzed at an independent core laboratory in a blind manner. At baseline, qDES achieved stent expansion similar to BMS. At follow-up, qDES showed reduced neointimal growth by 70% at the tightest cross section and by 68% over the stented segment (P<0.0001 for both), resulting in a significantly larger lumen in qDES than in BMS. Unlike intracoronary brachytherapy, there was no evidence of negative edge effects, unhealed dissections, or late stent-vessel wall malapposition over the stented and adjacent references segments in either group.Detailed IVUS analysis revealed that qDES had comparable acute mechanical and superior long-term biological effects to BMS. Although the long-term benefits and limitations of this technology require further investigation, the reduction in neointimal thickenings demonstrated that local delivery of 7-hexanoyltaxol through polymer sleeves augments conventional mechanical treatment of atherosclerotic disease.

View details for Web of Science ID 000178385700012

View details for PubMedID 12356631

Abstract

Arterial remodeling has been shown to be responsible for lumen narrowing after nonstent interventions.To examine the impact of deep vessel wall injury (DI) after balloon angioplasty on the subsequent vessel remodeling process, we performed serial intravascular ultrasound (IVUS) analysis in 47 native coronary artery lesions that underwent balloon angioplasty. An IVUS study was performed before and after balloon angioplasty and repeated at follow-up. Vessel and lumen area were measured at the narrowest site before intervention. Plaque area was calculated as vessel area minus lumen area. DI was defined as the presence of plaque/vessel wall fracture deep in the medial layer (sonolucent zone by IVUS) after angioplasty.After angioplasty, DI was present in 18 (38%, DI group) and absent in 29 (62%, non-DI group) of lesions. During follow-up, changes in vessel area in the DI group were significantly larger than in the non-DI group (P =.007). There were no significant differences in changes in plaque area. A trend toward greater late lumen loss was observed in the non-DI group (P =.05). In the DI group, changes in lumen area correlated better with changes in vessel area (r = 0.81, P <.0001) than with changes in plaque area (r = 0.32, P =.20). However, in the non-DI group, changes in lumen area correlated with changes in plaque area (r = -0.55, P =.002), but not with changes in vessel area (r = 0.30, P =.11).Deep vessel wall injury after balloon angioplasty is associated with the magnitude of the subsequent vessel remodeling process. The differences in the remodeling process may have implications regarding adjunctive therapies to prevent restenosis after balloon angioplasty.

View details for DOI 10.1067/mhj.2002.122282

View details for Web of Science ID 000177501400022

View details for PubMedID 12177652

Abstract

Radiofrequency intravascular ultrasound (IVUS-RF) analysis, as an extension of conventional IVUS imaging, may provide more accurate plaque discrimination. Thirty-two autopsy atherosclerotic coronary arteries were investigated. Corresponding sectors in different plaques were matched by histologic and RF analysis. Histologic analysis utilized the American Heart Association plaque classification. The backscattered ultrasound RF signal was analyzed by fast-Fourier transform, providing the underlying frequency components of its power spectrum. The normalized backscattered signal power (in decibels [dB]) for frequencies between 15.3 and 40.3 MHz was then measured for plaque discrimination. Advanced/complicated plaque types showed a higher signal power at all frequencies than early/intermediate lesion types (p <0.001 to p = 0.005). Discrimination of advanced/complicated lesion types was best at 15.3 MHz, with a cut-off point of 2.5 dB (sensitivity 93%, specificity 79%), and second best at 17.6 MHz (sensitivity 87%, specificity 71%, cut-off point 1.9 dB). With conventional IVUS, plaque discrimination was weaker; the best sensitivity for diagnosing early/intermediate lesion types was reached for "soft plaque" (sensitivity 63%, specificity 73%). Compared with conventional IVUS, IVUS-RF can discriminate between advanced/complicated and early/intermediate coronary atherosclerotic lesions with relatively high sensitivity and specificity in vitro.

View details for Web of Science ID 000176635000005

View details for PubMedID 12088773

Abstract

Re-stenting of in-stent restenosis (ISR) improves acute angiographic results. Methods and Results- Volumetric intravascular ultrasound analysis was performed in 70 ISR lesions that received either placebo (n=36) or (192)Ir radiation (n=34). ISR lesions treated by re-stenting were divided into 3 groups: old stent not re-stented (A), old/new stent overlap (B), and new stent only (C). ISR lesions treated without re-stenting were categorized as D. In placebo patients, postintervention lumen volume index (LVI) was significantly greater in re-stented segments B and C than in non-re-stented segment A (P<0.05).At follow-up, however, LVI was similar in all 4 segments secondary to the increased intimal hyperplasia (IH) reaccumulation within the re-stented segments. In patients treated with (192)Ir radiation, LVI was maintained from baseline to follow-up only in non-re-stented segments A and D. Conversely, there was a significant decrease in LVI in re-stented segments B and C (P<0.05). Qualitatively, 79% of patients in the irradiated group had stent struts with undetectable neointimal versus only 27% in the placebo group (P<0.001). Coefficient of variation of IH reaccumulation was greater in re-stented segments of (192)Ir patients (B=57.3% and C=58.9%) than in re-stented segments in placebo patients (B=27.3% and C 26.8%) and non-re-stented segments in irradiated patients.Additional lumen gain from re-stenting ISR lesions is counteracted by exaggerated neointimal proliferation in placebo patients. Maximum effectiveness and safety of radiation can be achieved for ISR lesions when treated without re-stenting. Thus, regardless of supplementary intravascular brachytherapy, repeat stenting strategies provided little long-term advantage.

View details for DOI 10.1161/01.CIR.0000018949.39445.40

View details for Web of Science ID 000175927500011

View details for PubMedID 12034650

Abstract

To determine whether intramural administration of L-arginine reduces intimal thickening after optimal Palmaz-Schatz stent deployment in humans, 50 patients with native coronary artery disease who received a single Palmaz-Schatz stent were enrolled in this pilot study. Patients were randomized into 2 treatment groups: an L-arginine group (n = 25) and a saline group (n = 25). After stent deployment, L-arginine (600 mg/6 ml) or saline (6 ml) was locally delivered via the Dispatch catheter (Scimed) over 15 minutes. Serial angiography and intravascular ultrasound examinations (motorized pull-back at 0.5 mm/s) were performed before and after the procedure, and at 6-month follow-up. Measurements of stent area, lumen area, and neointimal area were computed within the stents at 1-mm intervals, by technicians who were blinded to the treatment assignment. Using Simpson's rule, stent, plaque, and lumen volumes, neointimal volume within the stent, and percent neointimal volume were measured before and after the procedure, and at 6-month follow-up. The 6-month volume data in quantitative coronary ultrasound showed that neointimal volume in the L-arginine group was significantly less than in the saline group (25 vs 39 mm(3); p = 0.049). Similarly, percent neointimal volume was significantly less in the L-arginine group at 6-month follow-up (17 +/- 13% vs 27 +/- 21%; p = 0.048). Thus, these results showed that local delivery of L-arginine reduces in-stent neointimal hyperplasia in humans, indicating that this approach may be a novel strategy to prevent in-stent restenosis.

View details for Web of Science ID 000173816400001

View details for PubMedID 11835911

Abstract

Acute myocardial infarction is a frequent cause of sudden death, and is typically initiated by the rupture of coronary artery plaques. The likelihood and severity of rupture are influenced by the plaque structures and components. Radiofrequency (RF) intravascular ultrasound (US) (IVUS-RF) measurements extend current IVUS imaging techniques and may eventually enable the in vivo identification of these features. However, IVUS-RF measurements are affected by the transducer's instantaneous position in the vessel. Specifically, backscattered intensity (BI) decreases as either the distance between the tissue and the transducer increases, or as the beam's angle of incidence on the tissue increases. IVUS-RF data were acquired from seven disease-free coronary arteries in vitro. The 0-dB level for BI was defined as the peak intensity of the reflection from a stainless-steel flat reflector at each distance. The baseline BI measured in adventitial tissue was -32.5 dB (at 0 degrees, 0 mm) with angle and distance dependencies of -0.172 dB/ degrees and -3.37 dB/mm. In contrast, the BI from combined intima and media was -38.2 dB with dependencies of -0.111 dB/ degrees and -4.46 dB/mm (p < 0.05 for all three parameters). Acknowledging and compensating for these effects may allow IVUS-RF to develop into a rapidly deployable tool for the clinical detection of vulnerable plaques and to monitor coronary artery disease progression and regression.

View details for Web of Science ID 000174317900009

View details for PubMedID 11879955

Abstract

To investigate whether intravascular ultrasound provides additional information regarding the prediction of stent thrombosis, a retrospective multicentre registry was designed to enrol patients with stent thrombosis following stent deployment under ultrasound guidance.A total of 53 patients were enrolled (mean age 61+/-9 years) with stable angina (43%), unstable angina (36%), and post-infarct angina (21%) who underwent intracoronary stenting. The majority had balloon angioplasty alone prior to stenting (94%) with 6% also undergoing rotational atherectomy. The indication for stenting was elective (53%), suboptimal result (32%) and bailout (15%). There were 1.6+/-0.8 stents/artery with 87% undergoing high-pressure dilatation (> or =14 atmospheres). The minimum stent area was 7.7+/-2.8 mm(2)with a mean stent expansion of 81.5+/-21.9%. Overall, 94% of cases demonstrated one abnormal ultrasound finding (stent under-expansion, malapposition, inflow/outflow disease, dissection, or thrombus). Angiography demonstrated an abnormality in only 32% of cases (chi-square=30.0, P<0.001). Stent thrombosis occurred at 132+/-125 h after deployment. Myocardial infarction occurred in 67% and there was an overall mortality of 15%.On comparison with angiography, the vast majority of stents associated with subsequent thrombosis have at least one abnormal feature by intravascular ultrasound at the time of stent deployment.

View details for DOI 10.1053/euhj.2001.2707

View details for Web of Science ID 000173390100009

View details for PubMedID 11785994

Abstract

The purpose of this study was to assess the impact of pre-intervention arterial remodeling on subsequent vessel behavior following balloon angioplasty.Positive arterial remodeling before intervention has been shown to have a negative impact on the clinical outcome after nonstented coronary interventional procedures. However, the mechanism of interventions in coronary vessel geometry over time is less well characterized.Serial (pre-, post- and follow-up) intravascular ultrasound analysis was performed in 46 native coronary lesions. Positive remodeling (PR) was defined as vessel area (VA) at the target lesion greater than that of average reference segments. Intermediate or negative remodeling (IR/NR) was defined as VA at the target lesion less than or equal to that of average reference segment. Remodeling index was defined as VA at the target lesion site divided by that of average references.Pre-interventional PR and IR/NR were present in 21 (46%) and 25 (54%) of 46 patients, respectively. At follow-up, the change in plaque area was similar between the two groups (1.3 +/- 2.1 vs. 1.2 +/- 2.1 mm(2), p = 0.840). Lesions with PR showed a significantly smaller change in VA than those with IR/NR (-0.2 +/- 2.5 vs. 1.4 +/- 2.3 mm(2), p = 0.03). As a result, late lumen loss was significantly larger in lesions whose pre-intervention configuration exhibited PR (-1.5 +/- 1.8 vs. 0.2 +/- 1.6 mm(2), p = 0.002).Lesions with PR appear to have less capacity to compensate for further plaque growth after balloon angioplasty and thus show a proportional increase in late lumen loss. This may in part explain the less favorable clinical outcomes of positively remodeled lesions.

View details for Web of Science ID 000172458000035

View details for PubMedID 11738307

Abstract

Adjunctive balloon dilatation strategy has been shown to improve optimal stent deployment. As improvements in current stent designs evolve, less adjunctive balloon dilatation may be needed. However, few data currently exist to support this practice. We evaluated 88 native coronary lesions treated with single stent implantation (Nir, Tristar or S670). Serial intravascular ultrasound was performed after successful stent deployment and again after adjunctive balloon dilatation. To investigate further the precise expansion characteristics of the stents, serial volumetric intravascular ultrasound analyses were performed in 40 patients with automated pullback. After adjunctive balloon dilatation, minimal stent area increased significantly, from 6.4 +/- 2.1 to 7.4 +/- 2.2 mm(2) (p <0.001). Volumetric analysis showed a corresponding increase in stent volume index (6.6 +/- 1.8 to 7.5 +/- 2.0 mm(3)/mm, p <0.001). In the analysis of cross sections at 0.5-mm axial intervals, the percentage of cross sections, where stent area was > or =80% of the average reference lumen area, increased from 51% to 78% (p <0.001). Similarly, the percentage of cross sections, where stent area was > or =90% of the average reference lumen area, increased from 29% to 56% (p <0.001) with postdilatation. Postdeployment high- pressure balloon dilatation improved minimal stent area and volumetric expansion throughout the stented segment.

View details for Web of Science ID 000172412300006

View details for PubMedID 11703954

Abstract

Determination of fractional flow reserve (FFR) has been proposed as a means to assess stent deployment. In this prospective, multicenter trial, we evaluate the use of FFR to optimize stenting by comparing it with standard intravascular ultrasound (IVUS) criteria.Eighty-four stable patients with isolated coronary lesions underwent coronary stent deployment starting at 10 atm and increased serially by 2 atm until the FFR was >/=0.94 or 16 atm was achieved. IVUS was then performed. FFR was measured with a coronary pressure wire with intracoronary adenosine to induce hyperemia. The diagnostic characteristics of an FFR <0.94 to predict suboptimal stent expansion by IVUS, defined in both absolute and relative terms, were calculated. Over a range of IVUS criteria, the highest sensitivity, specificity, and predictive accuracy of FFR were 80%, 30%, and 42%, respectively. Receiver operator characteristic analysis defined an optimal FFR cut point at >/=0.96; at this threshold, the sensitivity, specificity, and predictive accuracy of FFR were 75%, 58%, and 62%, respectively (P=0.03 for comparison of predictive accuracy, P=0.01 for concordance between FFR and IVUS). The negative predictive value was 88%. Significantly better diagnostic performance was achieved in a subgroup that received higher doses (>30 microgram) of intracoronary adenosine during pressure measurements, suggesting that FFR might be overestimated in the other group.A fractional flow reserve <0.96, measured after stent deployment, predicts a suboptimal result based on validated intravascular ultrasound criteria; however, an FFR >/=0.96 does not reliably predict an optimal stent result. Higher doses of intracoronary adenosine than previously used to measure FFR improve these results.

View details for Web of Science ID 000171828700011

View details for PubMedID 11602494

View details for Web of Science ID 000170090500020

View details for PubMedID 11472713

Abstract

The aim of this study was to use serial intravascular ultrasound (IVUS) to evaluate the long-term effect of stent-based 7-hexanoyltaxol (QP2, a taxane analogue) delivery on neointimal tissue growth within the stent and on vessel dimensions at the adjacent reference segments.Serial IVUS analyses (immediately after intervention and at follow-up at 8.3 months) were performed in 15 native coronary lesions treated with the QuaDS-QP2 stent. IVUS measurements were performed at 8 cross-sections in each target segment (4 cross-sections within the stent and 2 cross-sections in each reference segment). At baseline, no significant plaque protrusion or thrombus was detected in the target segment. Mild incomplete stent apposition and edge dissection were observed in one and two cases, respectively. Percent expansion of the stent (minimum stent area/average reference lumen area) was 96.0+/-21.7%. At follow-up, mean neointimal area within the stent was 1.2+/-1.3 mm(2), and mean cross-sectional narrowing (neointimal area/stent area) was 13.6+/-14.9%. At the vessel segments immediately adjacent to the stent, a significant increase in plaque area (1.9+/-2.6 mm(2), P=0.001) was observed, but vessel area remained unchanged. However, no patients showed clinically significant in-stent or edge restenosis (diameter stenosis >/=50%) during the follow-up period.The first human experience with the new drug-delivery stent showed a minimal amount of neointimal proliferation in the stented segment. Late lumen loss at the reference sites adjacent to the stent was acceptable and predominantly due to plaque proliferation.

View details for Web of Science ID 000170116200003

View details for PubMedID 11468196

Abstract

Vessel remodeling is an important mechanism of late lumen loss after nonstent coronary interventions. However, its impact on in-stent restenosis has not been systematically investigated.Serial volumetric intravascular ultrasound analyses (poststent and follow-up) were performed in 55 lesions treated with a balloon-expandable stent (ACS MultiLink) using standard stent deployment techniques. The vessel volume (VV), lumen volume (LV), and volume bordered by the stent (SV) were measured using Simpson's method. The volume of plaque and neointima outside the stent (peri-stent volume, PSV) and volume of neointima within the stent (intrastent volume) were also measured. The change of each parameter during the follow-up period (follow-up minus poststent) was calculated and then divided by SV to normalize these values (designated as percent change [%]). As expected, %PSV directly correlated with %VV (P<0.0001, r=0.935), with no significant SV. A highly significant inverse correlation was seen between %PSV and the percent change of intrastent volume (P<0.0001, r=0.517). Consequently, %LV significantly correlated with peri-stent remodeling, as measured by %VV (P<0.0001, r=0.602).Positive remodeling of the vessel exterior to a coronary stent occurs to a variable degree after stent implantation. There is a distinct trade-off between positive remodeling and in-stent hyperplasia: in segments in which the degree of peri-stent remodeling is less, intrastent neointimal proliferation is greater and accompanied by more significant late lumen loss.

View details for Web of Science ID 000168583700002

View details for PubMedID 11331251

Abstract

Intimal hyperplasia and subsequent in-stent restenosis remain a major limitation after stent implantation. In vitro cell culture studies show that low-frequency, noncavitational ultrasound energy may impact smooth muscle cell proliferation. Accordingly, we assessed the efficacy of intravascular sonotherapy treatment on intimal hyperplasia in a swine stent model.After balloon injury, biliary stents (Johnson & Johnson) were implanted in the femoral arteries of 14 swine. A total of 48 stented sites were randomized to sonotherapy or sham treatment using a custom-built, 8-French catheter intravascular sonotherapy system (URX, PharmaSonics Inc). After stent deployment, ultrasound energy (700 KHz) was applied to the treatment group for up to 5 minutes. Smooth muscle cell proliferation was assessed using bromodeoxyuridine histology preparation (BrdU) at 7 days in 28 stented sites. At 28 days, the neointimal thickness and the ratio of neointimal/stent area (percent stenosis) was calculated by histomorphometric quantification in 20 stented sites. At 7 days, percent of BrdU staining was significantly reduced in the sonotherapy group compared with the sham group (24.1+/-7.0% versus 31.2+/-3.0%, P<0.05). At 28 days, percent stenosis was significantly less in the sonotherapy group than in the sham group (36+/-24% versus 44+/-27%, P<0.05), and the mean neointimal thickness in the sonotherapy group was less than in the sham group (417+/-461 micrometer versus 643+/-869 micrometer, P=0.06).In this swine peripheral model, intravascular sonotherapy seemed to decelerate cellular proliferation and decrease in-stent hyperplasia. Therefore, intravascular sonotherapy may be an effective form of nonionizing energy to reduce in-stent restenosis.

View details for Web of Science ID 000168122300010

View details for PubMedID 11294798

Abstract

We sought to investigate the in vivo mechanical properties of a new self-expanding coronary stent (RADIUS) and, particularly, the subsequent vessel response over time.Preclinical studies have suggested that self-expanding stents may produce less vessel wall injury at initial deployment, leading to larger follow-up lumens than with balloon-expandable stents. However, the influence of the chronic stimulus from self-expanding stents on the vessel wall remains unknown.Sixty-two patients were randomly assigned to either the RADIUS self-expanding stent group (n = 32) or the Palmaz-Schatz balloon-expandable stent group (n = 30). Intravascular ultrasound was performed after stent deployment and at six-month follow-up.At follow-up, the RADIUS stents had increased 23.6% in overall volume, while the Palmaz-Schatz stents had remained unchanged. Due to the greater mean neointimal area (3.0 +/- 1.7 mm2 vs. 1.9 +/- 1.2 mm2, p = 0.02) in the RADIUS group, no significant difference in net late lumen loss was observed between the two groups. On the other hand, analysis at the peristent margins demonstrated that mean late loss was significantly smaller in the RADIUS group than it was in the Palmaz-Schatz group (0.1 +/- 2.1 mm2 vs. 1.9 +/- 2.4 mm2, p = 0.02).Serial volumetric IVUS revealed that the RADIUS stents continued to enlarge during the follow-up period. In this stent implantation protocol, this expansion was accompanied by a greater amount of neointima than the Palmaz-Schatz stents, resulting in similar late lumen loss in both configurations. In the peristent margins, however, late lumen loss was minimized with the RADIUS stents.

View details for Web of Science ID 000167901700027

View details for PubMedID 11300443

Abstract

The study was done to elucidate the relationship between baseline arterial remodeling and clinical outcome following stenting.The impact of preintervention arterial remodeling on subsequent vessel response and clinical outcome has been reported following nonstent coronary interventions. However, in stented segments, the impact of preintervention remodeling on clinical outcome has not been clarified.Preintervention remodeling was assessed in 108 native coronary lesions by using intravascular ultrasound (IVUS). Positive remodeling (PR) was defined as vessel area (VA) at the target lesion greater than that of average reference segments. Intermediate or negative remodeling (IR/NR) was defined as VA at the target lesion less than or equal to that of average reference segment. Remodeling index expressed as a continuous variable was defined as VA at the target lesion site divided by that of average reference segments.Positive remodeling was present in 59 (55%) and IR/NR in 49 (45%) lesions. Although final minimal stent areas were similar (7.76 +/- 1.80 vs. 8.09 +/- 1.90 mm2, p = 0.36), target vessel revascularization (TVR) rate at nine-month follow-up was significantly higher in the PR group (22.0% vs. 4.1%, p = 0.01). By multivariate logistic regression analysis, higher remodeling index was the only independent predictor of TVR (p = 0.02).Lesions with PR before intervention appear to have a worse clinical outcome following IVUS-guided stenting. Intravascular ultrasound imaging before stenting may be helpful to stratify lesions at high risk for accelerated intimal proliferation.

View details for Web of Science ID 000167515700010

View details for PubMedID 11263604

View details for Web of Science ID 000167636600007

Abstract

Motexafin lutetium (Lu-Tex, Antrin Injection) is a photosensitizer that selectively accumulates in atheromatous plaque where it can be activated by far-red light. The localization and retention of intra-arterially administered Lu-Tex and its efficacy following activation by endovascularly delivered light (photoangioplasty) was evaluated.Bilateral iliac artery lesions were induced in 17 rabbits by balloon denudation, followed by a high cholesterol diet. Lu-Tex distribution within the atheroma was examined (n=8) following local injection. Fluorescence spectral imaging and chemical extraction techniques were used to measure Lu-Tex levels within the atheroma and adjacent normal tissue. Photoactivation was performed 15 min following Lu-Tex administration (180 J/cm fiber at 200 mW/cm fiber). Two weeks post photoangioplasty, vessels were harvested and hematoxylin and eosin (H&E) and RAM11 (macrophages) staining was performed.Local delivery of Lu-Tex achieved immediate high concentrations within plaque (mean 40x control iliac atheroma). Mean percent plaque area in the treated segments was significantly lower than in the non-treated contralateral lesions (73 vs. 82%, P<0.01). No medial damage was observed. Quantitative analysis using RAM11 positive cells revealed significant reduction of macrophages in treated lesions in both the intima (5 vs. 22%, P<0.01) and in media (8 vs. 23%, P<0.01) compared to untreated contralateral segments.Local delivery provides high levels of Lu-Tex selectively within atheroma. Photoactivation results in a significant decrease in macrophage and a small decrease in atheroma burden without damage to the normal vessel wall.

View details for Web of Science ID 000166820000022

View details for PubMedID 11164855

View details for PubMedID 11068273

Abstract

The purpose of this study was to clarify the 3-dimensional behavior of plaque during coronary stent expansion. Serial intravascular ultrasound (IVUS) studies, preintervention, and poststenting were evaluated in 32 patients treated with a single-balloon expandable tubular stent. External elastic membrane (EEM), lumen, stent, and plaque + media cross-sectional area were measured at 1-mm intervals through the entire stent as well as proximal and distal reference segments 5 mm from the stent edge. Volumetric calculations were based on Simpson's rule. Overall, the plaque + media volume through the entire lesion did not change during stent expansion (218 +/- 51 vs 217 +/- 47 mm3, p = 0.69). However, EEM and lumen volume increased significantly (EEM volume, 391 +/- 84 vs 448 +/- 87 mm3 [p < 0.0001]; lumen volume, 173 +/- 52 vs 231 +/- 54 mm3 [p < 0.0001]). The change in lumen volume correlated strongly with the change in EEM volume (r = 0.85, p < 0.0001), but poorly with the change in plaque + media volume (r = 0.37, p = 0.03). Plaque + media volume decreased in the midstent zone (59 +/- 14 vs 53 +/- 11 mm3, p = 0.0005), and increased in the distal stent zone (40 +/- 11 vs 44 +/- 9 mm3, p = 0.003), but did not change in either the proximal stent zone or reference segments. The mechanism of stent expansion is a combination of vessel stretch and plaque redistribution, translating disease accumulation from the midstent zone to the distal stent zone.

View details for Web of Science ID 000165185500003

View details for PubMedID 11074201

Abstract

Recent advances in the treatment of heart disease, in particular cardiovascular gene therapy and therapeutic angiogenesis, highlight the need for efficient and practical local delivery methods for the heart. We assessed the feasibility of percutaneous selective coronary venous cannulation and injection as a novel approach to local myocardial drug delivery. In anesthetized swine, the coronary sinus was cannulated percutaneously and a balloon-tipped catheter advanced to the anterior interventricular vein (AIV) or middle cardiac vein (MCV). During balloon occlusion, venous injection of radiographic contrast caused regional infiltration of targeted myocardial regions. Complete AIV occlusion had no impact on LAD flow parameters. Videodensitometric analysis following venous injection showed that radiographic contrast persisted for at least 30 min. Selective regional myocardial infiltration is feasible by this approach, targeting selected myocardial beds, including the apex, anterior wall, septum, and inferoposterior wall. This novel technique has potential application for local myocardial drug or growth factor delivery. Cathet. Cardiovasc. Intervent. 51:358-363, 2000.

View details for Web of Science ID 000165141100027

View details for PubMedID 11066126

Abstract

The goal of the present study was to compare the use of pressure-derived myocardial fractional flow reserve for detecting ischemia with nuclear stress imaging in patients undergoing stent placement for intermediate coronary lesions. We demonstrated that myocardial fractional flow reserve detects ischemia in intermediate coronary lesions accurately when compared with nuclear stress imaging.

View details for Web of Science ID 000165096000023

View details for PubMedID 11053717

Abstract

Ultra-high-frequency (40- to 50-MHz) intravascular ultrasound (IVUS) improves image quality compared with conventional 20- to 30-MHz IVUS. However, as the frequency of IVUS increases, high-intensity backscatter from blood components may cause visual difficulties in discrimination between the lumen and arterial wall structure. The purpose of this study was to evaluate the effect of a novel blood noise reduction algorithm (BNR) on quantitative coronary ultrasound measurements.IVUS studies using a 40-MHz transducer were performed in 35 patients with coronary artery disease. A total of 620 gray-scale images (310 pairs) were processed with and without the BNR, and lumen cross-sectional area (CSA) was determined by 2 independent observers. With the BNR, the intraobserver and interobserver correlation coefficients for lumen CSA were significantly improved (0.85 to 0.99 and 0.80 to 0.98, respectively). In the 270 images (135 pairs) in which vessel wall measurements were possible, the BNR significantly improved the intraobserver and interobserver correlation coefficients for plaque plus media CSA (0.83 to 0.99 and 0.76 to 0.97, respectively), whereas no influence was observed for external elastic membrane CSA (1.00 to 1.00 and 0.99 to 0.99, respectively).This study demonstrates the feasibility of this novel algorithm to reduce blood noise, thereby enabling accurate lumen border delineation and providing reproducible measurements of both the lumen and plaque plus media CSAs. Incorporating a digital BNR may serve as an important adjunct to ultra-high-frequency IVUS imaging for improving accurate quantitative evaluation of vessel dimensions.

View details for Web of Science ID 000089593000012

View details for PubMedID 11015344

Abstract

Conventional gray-scale images of intravascular ultrasound (IVUS) cannot accurately differentiate histologic subtypes of sonolucent coronary plaques with or without a lipid core.We analyzed radiofrequency signals obtained in vitro from 24 regions of interest (ROI) of noncalcified (sonolucent) plaques in 10 atherosclerotic coronary artery specimens pressure-fixed by formalin. Radiofrequency signals were sampled with a 30-MHz IVUS catheter and digitized at 500 MHz in 8-bit resolution. The ROIs were histologically categorized into 12 plaques with a lipid core and 12 plaques without it. Integrated backscatter and statistical parameters of the radiofrequency envelope (mean/SD ratio [MSR], skewness, and kurtosis) within the ROI were calculated offline, and their ability to detect a lipid core was compared with visual analysis of the IVUS video images. In the group with lipid cores, percent area of a lipid core in each ROI was measured in a digitized histologic image by a computerized planimeter.Sensitivity and specificity of MSR, skewness, and kurtosis for lipid core detection were substantially greater than visual video image analysis (83.3% and 91.7%, 100% and 91.7%, 100% and 91.7% vs 53.3% and 71.7%). Furthermore, the parameters of integrated backscatter, MSR, skewness, and kurtosis were significantly correlated to percent of core area (r = -0.64, -0.73, 0.78, and 0.63, respectively; P<.05).Compared with IVUS video images, the parameters of radiofrequency signal analysis may be used to aid in more accurate detection and quantitative evaluation of a lipid core, which is one of the major factors of a vulnerable coronary plaque.

View details for Web of Science ID 000089692600005

View details for PubMedID 11011329

Abstract

Fractional flow reserve (FFR) is a measure of coronary stenosis severity that is based on pressure measurements obtained at maximal hyperemia. The most widely used pharmacologic stimulus for maximal coronary hyperemia is adenosine, administered either as a continuous intravenous (IV) infusion or intracoronary (IC) bolus. IV adenosine has more side effects and is more costly than IC adenosine but has a more stable and prolonged hyperemic effect.We compared the efficacy of IC and IV adenosine administration for the measurement of FFR in a multicenter trial. Fifty-two patients with 60 lesions underwent determination of FFR with both IV and IC adenosine. IV adenosine was administered as a continuous infusion at a rate of 140 microgram/kg per minute until a steady state hyperemia was achieved. IC adenosine boluses were administered at a dose of 15 to 20 microgram in the right and 18 to 24 microgram in the left coronary artery. FFR was calculated as the ratio of the distal coronary pressure (from pressure guide wire) to the aortic pressure (guide catheter) at maximal hyperemia.A total of 26 left anterior descending, 23 right, 9 left circumflex, and 3 left main coronary arteries were evaluated. Mean percent stenosis for both groups was 55.8% +/- 23.6% (range 0% to 95%), and mean FFR was 0.78 +/- 0.15 (range 0.41 to 0.98). There was a strong and linear correlation between FFR measurements with IV and IC adenosine (R = 0.978, y = 0. 032 + 0.964x, P <.001). The agreement between the 2 sets of measurements was also high, with a mean difference in FFR of -0.004 +/- 0.03. However, a small random scatter in both directions of FFR measurements was noted with 5 lesions (8.3%) where FFR with IC adenosine was higher by 0.05 or more compared with IV infusions, suggesting a suboptimal hyperemic response in these patients. Changes in heart rate and blood pressure were significantly higher with IV adenosine. Two patients with IV, but none with IC adenosine, had severe side effects (bronchospasm and severe nausea).These results suggest that IC adenosine is equivalent to IV infusion for the determination of FFR in the majority of patients. However, in a small percentage of cases, coronary hyperemia was suboptimal with IC adenosine.

View details for Web of Science ID 000089692600016

View details for PubMedID 11011341

Abstract

Current immunosuppressive protocols fail to prevent chronic rejection often manifested as graft vascular disease (GVD) in solid organ transplant recipients. Several new immunosuppressants including sirolimus, a dual function growth factor antagonist, have been discovered, but studies of drug efficacy have been hampered by the lack of a model of GVD in primates, as a prelude to clinical trials. As described earlier, we have developed a novel non-human primate model of GVD where progression of GVD is quantified by intravascular ultrasound (IVUS).Twelve cynomolgus monkeys underwent aortic transplantation from blood group compatible but mixed lymphocyte reaction-mismatched donors. To allow the development of GVD in the allograft, no treatment was administered for the first 6 weeks. Six monkeys were treated orally with sirolimus from day 45 after transplantation to day 105.Progression of GVD measured as change in intimal area from day 42 to 105 was halted in sirolimus-treated monkeys compared to untreated monkeys (P<0.001, general linear model). On day 105, the intimal area +/- SEM was 3.7+/-1.0 and 6.4+/-0.5 mm2, respectively (P<0.05, t test). The magnitude of allograft intimal area on day 105 correlated inversely with sirolimus trough levels (R2=0.67, P<0.05). Regression of the intimal area was seen in four of six sirolimus-treated monkeys, which was significantly different from the untreated monkeys (P<0.05).Our results in the first non-human primate model of GVD showed that treatment with sirolimus not only halted the progression of preexisting GVD but also was associated with partial regression. Sirolimus trough blood levels were correlated with efficacy. Therefore, sirolimus has the potential to control clinical chronic allograft rejection.

View details for Web of Science ID 000089710700014

View details for PubMedID 11014651

Abstract

It has been postulated that atherosclerotic plaque deposition is spatially related to regions of low shear in non-branching vessel segments. Intravascular ultrasound (IVUS) allows precise spatial orientation of coronary artery plaque formation in humans. The objective of this study was to test the hypothesis that coronary plaques have a higher prevalence on the myocardial side in regions that encounter low surface shear stress. IVUS allows the determination of the inner versus the outer curve of the vessel based on vascular and perivascular landmarks. We studied 30 consecutive patients pre-intervention using IVUS and measured vessel area, lumen area and plaque area (vessel-lumen area) during a motorized pullback at 1 mm intervals. Vessel segments near a side branch (within two times the diameter of the vessel) were excluded from analysis because of flow disturbances. All plaques were classified as concentric or eccentric and all eccentric plaques were further divided with respect to their spatial orientation in the vessel into quadrants: myocardial (inner curve, lower shear stress), epicardial (outer curve, higher shear stress) and lateral (two quadrants intermediate). A total of 613 cross-sections were analyzed in 14 left anterior descending, six left circumflex, and ten right coronary arteries. Plaque distribution was found to be concentric in 321 (52.4%) and eccentric in 292 (47.6%) cross sections. Of all eccentric plaques, 184 cross sections were oriented toward the myocardial side (62.6%) compared to only 54 toward the epicardial side (17.3%) and 54 in the 2 lateral quadrants (19.5%, P<0.001). No difference in plaque area (6.75+/-2.70 vs. 6.76+/-2.60 mm(2)), vessel area (15.28+/-4.73 vs. 15.35+/-4.40 mm(2)), or plaque thickness (1.26+/-0.37 vs. 1.25+/-0.43 mm) was noted between myocardial or epicardial plaques. These results suggest that atherosclerotic plaques develop more frequently on the myocardial side of the vessel wall, which may relate to lower shear stress. However, plaque size is similar on the epicardial and myocardial side.

View details for Web of Science ID 000089447700025

View details for PubMedID 10996357

Abstract

To test the hypothesis that patients with unstable coronary syndromes show accentuated compensatory vessel enlargement compared with patients with stable angina, and that this may in part be related to increased coronary artery distensibility.In 23 patients with unstable coronary syndromes (10 with non-Q wave myocardial infarction and 13 with unstable angina), the culprit lesion was investigated by intravascular ultrasound before intervention. The vessel cross sectional area (VA), lumen area (LA), and plaque area (VA minus LA) were measured at end diastole and end systole at the lesion site and at the proximal and distal reference segments. Similar measurements were made in 23 patients with stable angina admitted during the same period and matched for age, sex, and target vessel. Calculations were made of remodelling index (VA at lesion site / VA at reference site), distensibility index ([(delta A/A)/delta P] x 10(3), where delta A is the luminal area change in systole and diastole and delta P the difference in systolic and diastolic blood pressure measured at the tip of the guiding catheter during a cardiac cycle), and stiffness index beta ([ln(P(sys)/P(dias))]/(delta D/D), where P(sys) is systolic pressure, P(dias) is diastolic pressure, and delta D is the difference between systolic and diastolic lumen diameters). Positive remodelling was defined as when the VA at the lesion was > 1.05 times larger than at the proximal reference site, and negative remodelling when the VA at the lesion was < 0.95 of the reference site.Mean (SD) LA at the lesion site was similar in both groups (4.03 (1.8) v 4.01 (1. 93) mm(2)), while plaque area was larger in the unstable group (13. 29 (4.04) v 8.34 (3.6) mm(2), p < 0.001). Remodelling index was greater in the unstable group (1.14 (0.18) v 0.83 (0.15), p < 0.001). Positive remodelling was observed in 15 patients in the unstable group (65%) but in only two (9%) in the stable group (p < 0.001). Negative remodelling occurred only in two patients with unstable symptoms (9%) but in 17 (74%) with stable symptoms. At the proximal reference segment, the difference in LA between systole and diastole was 0.99 (0.66) mm(2) in the unstable group and 0.39 (0.3) mm(2) in the stable group (p < 0.001), and the calculated coronary artery distensibility was 3.09 (2.69) and 0.94 (0.83) per mm Hg in unstable and stable patients, respectively (p < 0.001). The stiffness index beta was lower in patients with unstable angina (1.95 (0.94) v 3.1 (0.96), p < 0.001).Compensatory vessel enlargement occurs to a greater degree in patients with unstable than with stable coronary syndromes, and is associated with increased coronary artery distensibility.

View details for Web of Science ID 000089145800020

View details for PubMedID 10956298

Abstract

Graft vascular disease (GVD) is an incompletely understood process and the primary cause of late allograft failure. A nonhuman primate model was established to study the progression of GVD by using serial intravascular ultrasound (IVUS).Aortic allografts were transplanted below the inferior mesenteric arteries (IMA) into 6 rhesus monkeys. Removed and re-implanted aortic segments between renal arteries, and the inferior mesenteric arteries served as autografts. IVUS was performed at days 0, 24, 52, 80, and 98 after transplantation. Vessel area (VA) and lumen area (LA) were measured from each cross-section at 0.5 mm intervals. Intimal index (II=100x (VA-LA/VA)) and corresponding vessel volumes were calculated for the whole grafts. Histologic features were assessed from autopsy samples using computerized morphometric method and a score from 0 to 3 for GVD (0=none, 3=severe).In allografts, vessel volume and luminal volume decreased significantly (P<0.05 for both) and the intimal index increased from 12% to 59% by day 98. These parameters remained unchanged in autografts. Histologic analysis of allografts showed concentric intimal hyperplasia and scattered mononuclear cell accumulations, whereas the autografts had only occasional eccentric intimal changes. The GVD-scores were significantly higher in allografts than in autografts (median 3 vs. 1, P=0.042).We introduce a nonhuman primate model of GVD that enables serial IVUS assessments of multiple parameters of GVD. Concentric intimal proliferation and decrease of vessel dimensions was observed in allografts as a consequence of alloimmunity. This is a potential new model for studying new therapies to prevent GVD or halt its progression.

View details for Web of Science ID 000088863300006

View details for PubMedID 10949182

Abstract

Intravascular ultrasound (IVUS) can assess stent geometry more accurately than angiography. Several studies have demonstrated that the degree of stent expansion as measured by IVUS directly correlated to clinical outcome. However, it is unclear if routine ultrasound guidance of stent implantation improves clinical outcome as compared with angiographic guidance alone.The CRUISE (Can Routine Ultrasound Influence Stent Expansion) study, a multicenter study IVUS substudy of the Stent Anti-thrombotic Regimen Study, was designed to assess the impact of IVUS on stent deployment in the high-pressure era. Nine centers were prospectively assigned to stent deployment with the use of ultrasound guidance and 7 centers to angiographic guidance alone with documentary (blinded) IVUS at the conclusion of the procedure. A total of 525 patients were enrolled with completed quantitative coronary angiography, quantitative coronary ultrasound, and clinical events adjudicated at 9 months for 499 patients. The IVUS-guided group had a larger minimal lumen diameter (2.9+/-0.4 versus 2.7+/-0. 5 mm, P<0.001) by quantitative coronary angiography and a larger minimal stent area (7.78+/-1.72 versus 7.06+/-2.13 mm(2), P<0.001) by quantitative coronary ultrasound. Target vessel revascularization, defined as clinically driven repeat interventional or surgical therapy of the index vessel at 9 month-follow-up, occurred significantly less frequently in the IVUS-guided group (8.5% versus 15.3%, P<0.05; relative reduction of 44%).These data suggest that ultrasound guidance of stent implantation may result in more effective stent expansion compared with angiographic guidance alone.

View details for Web of Science ID 000088486200010

View details for PubMedID 10920064

Abstract

Automated edge detection may standardize measurements among observers, providing for rapid assessment of intravascular ultrasound (IVUS) images. However, with high frequency images, enhanced blood signals make it difficult to define and trace the lumen borders. Accordingly, we evaluated a fully automated contour analysis facilitated with a blood noise reduction algorithm (BNR) for 40-MHz IVUS images in human coronary arteries of 27 patients. This algorithm is based on the principle that blood echo speckles have higher temporal and spatial variations than the arterial wall. A total of 193 paired lumen areas and 78 external elastic membrane (EEM) areas were measured and compared. Automated measurements showed good agreement with manual tracings for lumen and EEM area, with high correlation coefficients (0.945 and 0.950, respectively) and small variability (0.4 +/- 14.4% and 0.6 +/- 9.7%, respectively). This preliminary finding suggests that automated contour detection facilitated with BNR appeared to be a feasible and reliable technique for area measurements in 40-MHz IVUS imaging.

View details for Web of Science ID 000089463900009

View details for PubMedID 10996703

Abstract

The poor long-term outcome in young diabetic patients receiving stents is not well understood. The purpose of this study was to characterize the pastprocedural results of stent placement in diabetic patients using intravascular ultrasound to identify factors that might be associated with poor clinical outcome. The acute dimensions from intravascular ultrasound studies after stent deployment at 5 sites were measured from 39 coronary segments from patients with diabetes mellitus (DM) and 161 segments from nondiabetic patients (non-DM). Within these 2 groups, segments were subgrouped into young (y) and old (o) in reference to the mean study age of 64 years, forming 4 groups: yDM (n = 20), y non-DM (n = 65), oDM (n = 19), and o non-DM (n = 96). Results are reported as mean +/- 1 SD. Diabetic patients had smaller mean lumen area within the treated segment than o non-DM (8.37+/-2.59 vs. 9.11+/-3.35 mm2, p<0.01). These differences were more pronounced at the distal reference vessel lumen of yDM than y non-DM (7.6+/-2.3 vs. 10.3+/-4.5 mm2, p<0.003), and were associated with greater percent plaque area in the distal reference vessel (43.4+/-13% vs. 34.1+/-11.2%, p<0.003). In young diabetic patients undergoing elective stent placement, underexpansion of the stented segment is common, which may contribute to the relatively poor long-term outcome in these patients. We suggest that when stenting is the procedure of choice in this subgroup of high-risk patients, special attention should be given to optimizing lumen dimensions.

View details for Web of Science ID 000085650900008

View details for PubMedID 11078267

Abstract

Measurements of Doppler derived coronary flow reserve (CFR) and pressure derived fractional flow reserve (FFR) for coronary stenosis assessment depend on the induction of maximal hyperemia. Adenosine is the most widely used pharmacological agent but is expensive and poorly tolerated by some patients.The objective of this study was to test the equivalency of adenosine 5'-triphosphate (ATP) to adenosine in their ability to cause maximal hyperemia as compared with the hyperemic response of complete coronary occlusion in 6 canines. Intracoronary administration of either ATP or adenosine resulted in a significant increase in CFR (2.79+/-0.64 and 2.22+/-0.7 for 10 microgram versus 4. 65+/-1.22 and 4.25+/-0.78 for 100 microgram for ATP and adenosine, respectively, P for trend <0.001) but not reaching the level of coronary occlusion (6.35+/-2.26). Additionally, FFR and CFR were measured in 35 different stenoses using ATP, adenosine, and coronary occlusion. There was an excellent linear correlation between ATP and adenosine for both CFR (R=0.934, P<0.001) and FFR (R=0.985, P<0.001). However, hyperemia with either ATP or adenosine was less than postocclusion hyperemia, resulting in significantly different reserve measurements (CFR: 1.93+/-0.66 and 2.08+/-0.81 versus 2.35+/-0.97, P<0.001; FFR: 0.62+/-0.24 and 0.63+/-0.23 versus 0.58+/-0.2, P<0.001).1) Step up in dosage of ATP and adenosine beyond currently recommended clinical doses resulted in a significant increase in coronary hyperemia; 2) ATP was equivalent to adenosine for both CFR and FFR; and 3) complete coronary occlusion yielded a better hyperemic response than either drug, indicating that maximal hyperemia was not achieved by either pharmacological stimulus.

View details for Web of Science ID 000084957100031

View details for PubMedID 10645929

Abstract

We investigated the efficacies of sirolimus (rapamycin) and cyclosporine for inhibition of graft vascular disease (GVD) in cynomolgus monkey recipients of aortic allografts. Increases in arterial intimal thickening in the midgraft (six consecutive cross-sections) after transplantation were quantified by serial intravascular ultrasound (IVUS) from day 21 to day 105. These data enabled correlations between changes in intimal indexes [II = (intimal area/vessel area) x 100] and trough levels of sirolimus and cyclosporine to be determined. Eighteen recipients received no immunosuppression for 6 weeks to allow alloimmune injury to occur. On day 45, monkeys were treated daily with sirolimus (n = 6) or cyclosporine (n = 6); six monkeys remained untreated. II increased significantly from day 63 to day 105 in untreated monkeys and monkeys treated with cyclosporine, whereas monkeys treated with sirolimus did not have a significant increase in II (P = 0.008, P = 0.006, P = NS; paired t-test). The change in II from days 63 to 105 was significantly greater in untreated monkeys compared to sirolimus-treated monkeys (P = 0.13; one-way ANOVA, P = 0.012 Tukey's post hoc test); other post hoc pairwise comparisons were not significant. Mean sirolimus and cyclosporine levels +/- SEM were 43 +/- 7 ng/ml and 562 +/- 20 ng/ml, respectively. Sirolimus trough levels, but not cyclosporine levels, correlated inversely with changes in II from day 42 to 105 (r2 = 0.73, P = 0.03). This non-human primate study shows that inhibition of intimal thickening by sirolimus depends on trough levels and provides the rationale for clinical trials of sirolimus for the control of GVD in organ transplant recipients.

View details for PubMedID 11112022

Abstract

Unprocessed ultrasound radiofrequency (RF) signal analysis has been shown to distinguish different tissue structures more reliably than gray-scale interpretation of conventional ultrasound images.The objective of this study was to test the feasibility of in vivo intravascular ultrasound (IVUS) RF signal analysis in an animal model of allograft rejection. Six cynomolgus monkeys underwent transplantation of 3-cm aortic allograft segments distal to the renal arteries from immunologically mismatched donors. IVUS imaging with a 30-MHz system was performed 84 to 105 days after the operation. RF signals were acquired from cross sections of the recipient and the allograft aortas in real time with a digitizer at 500 MHz with 8-bit resolution. Sixty-five cross sections and 68 regions of interest (31 in host aorta and 37 in allograft) were analyzed in the adventitial layer with a total number of 8568 vectors processed. For each region of interest, a weighted-average attenuation was calculated on the basis of the attenuation and length for each individual vector. Histological examination was performed at every cross section imaged by IVUS. When the gray-scale images of conventional IVUS scored by an independent observer were compared, no distinction between adventitia of the native aorta and allograft was possible. Analysis of the average RF backscatter power also showed no significant difference (70.32+/-3.55 versus 70.72+/-3.38 dB). However, the average attenuation of allografts was significantly lower than that of the host aortas (2.64+/-1.38 versus 4.02+/-1.16 dB/mm, P<0.001). Histology demonstrated a marked adventitial inflammatory response in all allografts, with no inflammation observed in the host aortas.In vivo IVUS tissue characterization can be performed during routine imaging. In this model of transplant vasculopathy, RF attenuation measurements were more sensitive than visual or quantitative gray-scale analysis.

View details for Web of Science ID 000083945000005

View details for PubMedID 10571969

Abstract

Iridium-192 (gamma)-radiation is effective in preventing recurrent in-stent restenosis by reducing neointimal hyperplasia as illustrated by intravascular ultrasound study and plaque area-length plot. This analytic technique will further our understanding of vessel behavior to radiant energy source both inside and outside the stented coronary artery segments.

View details for Web of Science ID 000082833300017

View details for PubMedID 10513786

View details for Web of Science ID 000081733400019

View details for PubMedID 10470481

Abstract

We tested the ability of ultrasound radiofrequency (RF) signal analysis to characterize thrombus accumulation in a Dacron graft incorporated into the exteriorized arteriovenous shunt in 3 baboons with constant blood flow for 60 min. Thrombus formation was quantified by sequential measurements of 111Indium-labeled platelet deposition. RF signals were acquired every 15 min at 2 sites in the graft, using a 2.9 Fr intravascular ultrasound catheter-based transducer (30 MHz) and digitized at 250 MHz in 8-bit resolution. Regions of interest were placed within a 0.5-mm perimeter adjacent to the graft wall. Integrated backscatter increased significantly (p < 0.001) with increasing platelet deposition. However, mean-to-standard deviation ratio of the RF envelope showed no significant change and the distribution pattern of the RF probability function remained constant and consistent with a Rayleigh scattering process. These results provide a basis for using RF analysis to monitor the time-course of thrombus formation.

View details for Web of Science ID 000080191900009

View details for PubMedID 10386731

Abstract

In this study, we summarize the role of residual plaque burden, as determined by intravascular ultrasound, on the development of restenosis following percutaneus coronary interventions. Several clinical trials have shown that the amount of residual plaque is a consistent and independent predictor of subsequent restenosis. The impact of residual plaque burden on late lumen loss is particularly augmented by negative vessel remodeling that is commonly seen after balloon angioplasty and atherectomy. However, early evidence suggests that the importance of plaque burden also applies in the context of stenting. The cotreatment of debulking may further improve the long-term outcome of stenting by maximizing an acute lumen gain with less vessel stretching, preventing stent edge problems and possibly reducing the cell source involved in the intimal hyperplastic process. Evaluation of residual plaque burden with on-line intravascular ultrasound could lead to definitive therapies via risk stratification of the treated segments.

View details for Web of Science ID 000079175800003

View details for PubMedID 10348121

View details for PubMedID 11096617

View details for Web of Science ID 000077593000033

View details for PubMedID 9865284

Abstract

The validity of quantitative coronary angiography (QCA) after stent placement has been questioned because the optical density of a metallic stent, added to the density of a contrast-filled lumen, could affect border definition. METHODS andWe deployed 3.0- and 4.0-mm Palmaz-Schatz, Wiktor, Multilink, NIR, and InStent stents in precision-cast phantoms. Central lumens of 2.0 mm were created. There was no difference between the "true" diameters of any stented lumen by both QCA and quantitative ultrasonic (QCU) measurement poststenting. QCA systematic error (SE) varied from 0.01 for the Wiktor stents to 0.14 mm for the Palmaz-Schatz stents; the random error (RE) was 0.03 to 0.14 mm. QCU SE varied from 0.05 to 0.11 mm, and RE ranged from 0.01 to 0.07 mm. At the next stage, 4.0-mm Wiktor and Palmaz-Schatz stents were deployed into the phantom lumens; 1.5-, 2.0-, 2.5- and 3.0-mm lumens were created inside the stents. QCA and QCU measurements of 1.5- to 2.5-mm residual lumens were overestimated by 0.1 to 0.3 mm. In the 3. 0-mm residual lumen within the Wiktor stent, QCA underestimated the luminal size by -0.1 mm. There was no QCA inaccuracy for a 3.0-mm lumen within the Palmaz-Schatz stent. In patients, in 25 stented segments in both the Palmaz-Schatz and Wiktor groups, there was no difference between QCA and QCU diameters.QCU is sufficiently precise for the assessment of the coronary lumen after stenting. QCA can be used as an accurate method of poststent assessment, except when a very mild recurrence within a highly opaque stent is measured. In that instance, QCA may underestimate the luminal diameter.

View details for PubMedID 9769302

Abstract

In January 1997, experts from the United States, Europe, and Japan gathered at Stanford University to review their collective experience with intracoronary and noncoronary stenting and to identify and prioritize issues requiring further clinical investigation. This report summarizes the discussions that took place during this stent summit. Knowledge of stent-tissue interaction from animal and human pathologic specimens was reviewed in the context of evolving stent designs. The relative merits of coil and slotted tubular stent designs were discussed. Stent deployment routines, including self-expansion, balloon expansion, and high-pressure delivery were debated. The potential for covered stents and coated stents was explored. Problems surrounding the routine deployment of stents were identified: small vessel disease, long lesions, bifurcation stenoses, vein graft disease, ostial disease, left main stenoses, and intrastent restenosis. The value of intravascular ultrasound, as an adjunct to stenting, was explored and debated. An algorithm for "provisional stenting" based on ultrasound criteria was developed. Noncoronary stenting of the aorta, iliacs, and carotids were discussed. Clinical applications that may lead to randomized clinical trials were identified.

View details for Web of Science ID 000076316800005

View details for PubMedID 9778060

View details for Web of Science ID 000081808900017

View details for PubMedID 10225191

Abstract

Intravascular ultrasound (IVUS) images are typically viewed and recorded in an arbitrary rotational orientation. This study was performed to validate a new method for improved orientation of sonographic vascular cross-sections.We have tested a simple technique for rotational indexing of IVUS in cases in which guiding catheters with side holes are used. Although guiding catheters are opaque to ultrasonography, the side holes transmit the beam and therefore can be easily identified. The orientation of the side holes, which is characteristic for each make of guiding catheter, can be used to determine the anatomically appropriate rotational orientation of the IVUS image. In this study images of four commercially available side-hole guiding catheters were viewed in vitro to confirm the visibility of the side holes and to characterize their orientation for purposes of rotational orientation of images. Feasibility tests of rotational orientation based on side holes were then performed in canine coronary arteries (n = 3) and in six human coronary arteries. Three serial imaging runs in each clinical case yielded a mean variability in rotational orientation of 7.5 +/- 1.5 degrees.Validation testing of the side-hole technique demonstrates the potential for consistent and anatomically appropriate orientation of intravascular ultrasound images.

View details for Web of Science ID 000074109300018

View details for PubMedID 9630112

Abstract

A variety of new devices in the field of intravascular ultrasound imaging are being designed and tested. Mechanical intravascular ultrasound (IVUS) devices with rotating transducers have been developed that allow transducer pullback with integrated longitudinal 2-dimensional displays. Recent advances in the area of imaging include (1) solid-state systems that combine ultrasound with balloon and stent placement; (2) combined imaging atherectomy devices; (3) imaging cores or guidewires; (4) forward-looking devices; (5) 3-dimensional reconstruction techniques; (6) high-frequency imaging; and (7) improved methods for characterizing tissue. Other promising approaches include magnetic resonance imaging, thermography, and optical coherence tomography. An important goal for long-term technologic improvement is visualization of lipid accumulations and fibrous caps during their early stages of development.

View details for Web of Science ID 000073005600007

View details for PubMedID 9551592

Abstract

Over the past 5 years intravascular ultrasound imaging has achieved many technical advancements both in catheter design and image quality. In addition to improved image quality that provides clear display of the endovascular structure, efficient signal penetration permits the viewing of structures beyond the artery by highlighting the perivascular structures. These perivascular landmarks, which are unique within a particular coronary segment, help provide both axial and spatial orientation during multiple imaging runs throughout a coronary artery. Orientation on the basis of veins and pericardium assists the operator to appreciate the full three-dimensional view of a particular coronary segment. This article describes several of the common perivascular structures that may be viewed from different arteries routinely imaged during coronary procedures.

View details for Web of Science ID 000071772900004

View details for PubMedID 9487465

Abstract

The AVE Micro Stent (AVE Inc., Santa Rosa, CA) is composed of helically welded 3 mm long, zigzag crowns with stent lengths from 6 to 39 mm and diameters from 2.5 to 4.5 mm. Quantitative coronary angiography and histologic analyses of acute and chronic implantation were obtained in 52 stented coronary segments of 18 dogs. Three hearts with 8 stented coronary segments were harvested after 24 hr, 3 hearts with 9 stented segments were harvested after 2 weeks, 6 hearts with 15 stented segments were harvested at 8 weeks, and 6 hearts with 20 stented segments were harvested at 24 weeks post-deployment. There were no procedural complications, deaths, or acute vessel closures. The average lumen diameter of the stented segment was largest at 2 weeks (3.3 +/- 0.3 mm). The smallest average diameters were observed at 8 weeks after the stent deployment (2.7 +/- 0.4, P < 0.05) with an increase again at 24 weeks (2.9 +/- 0.6). The pre-explant percent of stenosis was <30% in all animals. Histologically, a peak of inflammation was visible at 2 weeks; however, the extent of luminal narrowing reached its peak at 8 weeks and the lumen dimension increased somewhat at 24 weeks. The degree of intimal thickening remained relatively constant throughout the different time points (<200 microm). Overall, these data suggest that constrictive remodeling within the stented segment occurs at 8 weeks in this animal model. The later increase of the stented segment dimensions as well as higher net gain at 24 weeks compared to 8 weeks after deployment suggests that this constriction is a transitory phenomenon.

View details for Web of Science ID A1997XC51700023

View details for PubMedID 9184299

Abstract

Intravascular ultrasound has dramatically changed our view of atherosclerotic disease and has helped to define mechanisms of therapeutic interventions, providing a new rationale for selection of appropriate devices. Currently, this technology is used for sizing and orientation of commonly performed interventions such as balloon angioplasty and directional atherectomy. The information from intravascular ultrasound has also led to a dramatic change in the deployment algorithm of stents. Further improvements in catheter design and the findings from clinical trials utilizing intravascular ultrasound will help define a practical role for this new technology.

View details for PubMedID 9546978

Abstract

IVUS provides a new gold standard for visualization and measurement of coronary artery disease. Morphologic and morphometric observations by IVUS are in general considerably more detailed and accurate than those obtained by angiography. IVUS has led to new insights into the pathophysiology of coronary plaque accumulation with respect to adaptive vessel responses (remodeling) and their exhaustion (de-remodeling, shrinkage). Further technologic refinements need to focus on issues such as improvement in resolution and miniaturization of IVUS catheters to enhance the applicability of this imaging technique.

View details for PubMedID 9085748

Abstract

Intravascular ultrasound distortion errors and longitudinal reconstructions are primarily determined by the angle of curvature. The error in commonly encountered angles is relatively small.

View details for Web of Science ID A1997WG53700029

View details for PubMedID 9036768

Abstract

Stent deployment strategies have changed significantly in the past 2 yr, with "high-pressure" balloon inflations postdilatation being performed in the large majority of cases. There is currently little information about the effects of high pressure on the geometry of stent expansion and on the adjacent areas of the vessel wall. Intravascular ultrasound (IVUS) imaging is well-suited to investigate these issues, since it provides information not only about stent expansion and apposition but also about adjacent vessel-wall morphology at transition points such as the articulation site of the stent and the the stent borders. We report on the results of a cohort of 30 consecutive stent cases which were systematically examined by IVUS following high-pressure inflation. All deployments were deemed successful by angiographic inspection. However, in 6 cases, intimal disruptions or "edge tears" were noted at the stent borders by IVUS. In 5 cases, edge tears were seen to occur at the distal border, whereas in one case edge tears were seen at both the proximal and distal edges of the stent. No angiographic and sonographic parameters were different except percent plaque area at the stent margins, which was significantly higher (53 +/- 11%) in the lesions with edge tears, compared to 40 +/- 10% plaque area in the group without evidence of pocket flaps (P = 0.007). This experience suggests that intimal disruptions or "edge tears" are a relatively common occurrence following high-pressure stent deployment, and may be related to the extent of marginal dissections.

View details for Web of Science ID A1997WF28200006

View details for PubMedID 9047054

Abstract

One hundred twenty-three patients treated with high-speed rotational atherectomy (HSRA) were restudied 6.9 +/- 1.2 months later. At the follow-up, the number of focal concentric lesions increased from 32.2 percent to 63.0 percent, p<0.01, with decrease of type C lesions from 54.8 percent to 30.8 percent, p<0.05. Comparison of the degree of the net gain (NG) showed more severe baseline lesions in the high-gain group (NG >20 percent) compared with the moderate-gain group (20 percent > NG > 0 percent) and to the loss group (minimal luminal diameter [MLD] 0.8 +/- 0.4 mm vs 1.0 +/ 0.4 mm, p<0.05; and 1.2 +/- 0.5 mm; p<0.01, respectively). Highest initial gain (36.5 percent +/- 26.2 percent vs 24.5 percent +/- 18.1 percent; p<0.015; and 19.0 percent +/- 23.2 percent; p<0.001) as well as lowest late loss (1.8 percent +/- 21.7 percent vs 14.0 percent +/-18.4 percent; p<0.01 and 28.1 percent +/- 25.0 percent; p<0.01) were found in the high NG group. A higher interaction between burr and atheroma resulted in the lowest restenosis rate of 6 percent.

View details for Web of Science ID A1996UE42100002

View details for PubMedID 8721633

View details for Web of Science ID A1996VA98800006

View details for PubMedID 8853582

Abstract

Intravascular ultrasound (IVUS) imaging provides cross-sectional views of the vessel lumen; however, lumen measurements still rely on operator-dependent border delineation and time-consuming lumen tracings. We tested a new system for automated lumen border detection in IVUS images based on acoustic quantification of blood and vessel wall. In 10 rabbits, 29 segments of the aorta were imaged in vivo using a 2.9-Fr IVUS catheter. IVUS images were obtained during motorized pullbacks of aortic segments of 18 mm length. Automated measurements of lumen dimensions were compared to automated measurements of a second pullback through the same segment, lumen measurements derived from visual border tracings in IVUS images, and to quantitative angiography. The automated system showed good reproducibility: Correlations for repeated measurements of lumen area, maximal and minimal lumen diameters were r = 0.97, r = 0.91, and r = 0.93, respectively. Automated measurements also correlated well to visual image analysis (lumen area, r = 0.97; maximal lumen diameter, r = 0.89; minimal lumen diameter, r = 0.89) and to angiographic measurements (lumen area, r = 0.93; lumen diameter, r = 0.95). In 12% of the images, the automated system overestimated lumen dimensions because of weak wall signals in the presence of echolucent structures next to the wall. Signal artifacts from the IVUS catheter itself or strong blood backscatter resulted in lumen underestimation in 6% of the images. Over- and underestimation of lumen by the border detection system were often associated with eccentric catheter position. Thus, lumen measurements in vivo IVUS images can be performed using an automated border detection system based on acoustic quantification of blood and vessel wall. The system allows reproducible and accurate measurements of lumen area and diameters. (ECHOCARDIOGRAPHY, Volume 13, November 1996)

View details for PubMedID 11442974

Abstract

Seven hundred ten high speed rotational atherectomy (HSRA) procedures were performed in a single consecutive series of 656 patients. Stand alone HSRA was performed in 253 patients (35%). HSRA with adjunctive low pressure (< or = 2 ATM) balloon angioplasty (LP BA) was performed in 221 patients (31%), and HSRA with adjunctive high pressure (> or = 4 ATM) balloon angioplasty (HP BA) was performed in 236 patients (34%). Prognostically unfavorable Type B2 and C lesions dominated the study group (74.7%). Procedural success rate was 96%. Emergency coronary artery bypass surgery was performed in 1.4% of cases, Q wave myocardial infarction occurred in 3.4% and death, related to procedure, was consequent in 0.5% of cases. Incidence of flow limiting dissections was 3.1%, distal spasm was 5.3%, and "no reflow" phenomenon was 1.8%. The recent technique modifications included continuous advancer/guiding catheter infusion of the nitroglycerin-verapamil mixture, limitation of duration of lesion engagement by the burr, stepwise increase in the burr size, decrease of rotational speed, and strict control of rpm drop during lesion ablation. Evolution of the interventional technique involved trends towards decrease of the use of HP BA in conjunction with steady increase in the percentage of SA and LP BA procedures over time. These technique changes resulted in complete absence of "no reflow" in 1994, as well as a generalized decrease in overall coronary vascular reactivity from all burr passes.

View details for Web of Science ID A1995TM65600002

View details for PubMedID 8719378

Abstract

The continuous wave Doppler ultrasound signal across the left ventricular outflow tract in hypertrophic cardiomyopathy has a characteristic pattern that is in keeping with the dynamic nature of the pressure gradient in this condition. To determine the accuracy and reliability of the peak Doppler flow velocity signal for measuring the peak pressure gradient in this condition, 340 beats were analyzed from five consecutive patients studied with simultaneous continuous wave Doppler ultrasound and dual catheter pressure recordings across the left ventricular outflow tract. Each patient was studied at steady state and during physiologic and pharmacologic manipulations of the pressure gradient. Peak velocity and calculated peak gradient were determined by two independent observers who did not know the catheter measurements. In addition, 18 beats with well defined flow velocity envelopes were digitized for analysis of the magnitude, timing and contour of the instantaneous Doppler ultrasound and catheter gradients throughout systole. Peak catheter gradient in the 340 beats ranged from 12 to 245 mm Hg. The correlations between the Doppler-derived and catheter peak gradients were close (r = 0.96, SEE = 4 mm Hg for Observer 1 and r = 0.97, SEE = 11 mm Hg for Observer 2). Interobserver variability for measurement of peak flow velocity was small (mean +/- SD 0.16 +/- 0.15 m/s). An interobserver difference greater than 0.3 m/s occurred in 25 of the 340 beats analyzed. By retrospective analysis, this was due to contamination of the outflow tract signal by mitral regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)

View details for Web of Science ID A1988M853200012

View details for PubMedID 3351141