Post-infarction ventricular septal defect: percutaneous or surgical management in the UK national registry.

AIMS: Post-infarction ventricular septal defect (PIVSD) is a mechanical complication of acute myocardial infarction (AMI) with a poor prognosis. Surgical repair is the mainstay of treatment, although percutaneous closure is increasingly undertaken. METHODS AND RESUTS: Patients treated with surgical or percutaneous repair of PIVSD (2010-2021) were identified at 16 UK centres. Case note review was undertaken. The primary outcome was long-term mortality. Patient groups were allocated based upon initial management (percutaneous or surgical). Three-hundred sixty-two patients received 416 procedures (131 percutaneous, 231 surgery). 16.1% of percutaneous patients subsequently had surgery. 7.8% of surgical patients subsequently had percutaneous treatment. Times from AMI to treatment were similar [percutaneous 9 (6-14) vs. surgical 9 (4-22) days, P = 0.18]. Surgical patients were more likely to have cardiogenic shock (62.8% vs. 51.9%, P = 0.044). Percutaneous patients were substantially older [72 (64-77) vs. 67 (61-73) years, P < 0.001] and more likely to be discussed in a heart team setting. There was no difference in long-term mortality between patients (61.1% vs. 53.7%, P = 0.17). In-hospital mortality was lower in the surgical group (55.0% vs. 44.2%, P = 0.048) with no difference in mortality after hospital discharge (P = 0.65). Cardiogenic shock [adjusted hazard ratio (aHR) 1.97 (95% confidence interval 1.37-2.84), P < 0.001), percutaneous approach [aHR 1.44 (1.01-2.05), P = 0.042], and number of vessels with coronary artery disease [aHR 1.22 (1.01-1.47), P = 0.043] were independently associated with long-term mortality. CONCLUSION: Surgical and percutaneous repair are viable options for management of PIVSD. There was no difference in post-discharge long-term mortality between patients, although in-hospital mortality was lower for surgery.

Outcomes of Cardiac Screening in Adolescent Soccer Players.

BACKGROUND: Reports on the incidence and causes of sudden cardiac death among young athletes have relied largely on estimated rates of participation and varied methods of reporting. We sought to investigate the incidence and causes of sudden cardiac death among adolescent soccer players in the United Kingdom. METHODS: From 1996 through 2016, we screened 11,168 adolescent athletes with a mean (±SD) age of 16.4±1.2 years (95% of whom were male) in the English Football Association (FA) cardiac screening program, which consisted of a health questionnaire, physical examination, electrocardiography, and echocardiography. The FA registry was interrogated to identify sudden cardiac deaths, which were confirmed with autopsy reports. RESULTS: During screening, 42 athletes (0.38%) were found to have cardiac disorders that are associated with sudden cardiac death. A further 225 athletes (2%) with congenital or valvular abnormalities were identified. After screening, there were 23 deaths from any cause, of which 8 (35%) were sudden deaths attributed to cardiac disease. Cardiomyopathy accounted for 7 of 8 sudden cardiac deaths (88%). Six athletes (75%) with sudden cardiac death had had normal cardiac screening results. The mean time between screening and sudden cardiac death was 6.8 years. On the basis of a total of 118,351 person-years, the incidence of sudden cardiac death among previously screened adolescent soccer players was 1 per 14,794 person-years (6.8 per 100,000 athletes). CONCLUSIONS: Diseases that are associated with sudden cardiac death were identified in 0.38% of adolescent soccer players in a cohort that underwent cardiovascular screening. The incidence of sudden cardiac death was 1 per 14,794 person-years, or 6.8 per 100,000 athletes; most of these deaths were due to cardiomyopathies that had not been detected on screening. (Funded by the English Football Association and others.).

Observation of Patients' 3D Printed Anatomical Features and 3D Visualisation Technologies Improve Spatial Awareness for Surgical Planning and in-Theatre Performance.

Improved spatial awareness is vital in anatomy education as well as in many areas of medical practice. Many healthcare professionals struggle with the extrapolation of 2D data to its locus within the 3D volume of the anatomy. In this chapter, we outline the use of touch as an important sensory modality in the observation of 3D forms, including anatomical parts, with the specific neuroscientific underpinnings in this regard being described. We explore how improved spatial awareness is directly linked to improved spatial skill. The reader is offered two practical exercises that lead to improved spatial awareness for application in exploring external 3D anatomy volume as well as internal 3D anatomy volume. These exercises are derived from the Haptico-visual observation and drawing (HVOD) method. The resulting cognitive improvement in spatial awareness that these exercises engender can be of benefit to students in their study of anatomy and for application by healthcare professionals in many aspects of their medical practice. The use of autostereoscopic visualisation technology (AS3D) to view the anatomy from DICOM data, in combination with the haptic exploration of a 3D print (3Dp) of the same stereoscopic on-screen image, is recommended as a practice for improved understanding of any anatomical part or feature. We describe a surgical innovation that relies on the haptic perception of patients' 3D printed (3Dp) anatomical features from patient DICOM data, for improved surgical planning and in-theatre surgical performance. Throughout the chapter, underlying neuroscientific correlates to haptic and visual observation, memory, working memory, and cognitive load are provided.

Percutaneous Device Closure of Paravalvular Leak: Combined Experience From the United Kingdom and Ireland.

BACKGROUND: Paravalvular leak (PVL) occurs in 5% to 17% of patients following surgical valve replacement. Percutaneous device closure represents an alternative to repeat surgery. METHODS: All UK and Ireland centers undertaking percutaneous PVL closure submitted data to the UK PVL Registry. Data were analyzed for association with death and major adverse cardiovascular events (MACE) at follow-up. RESULTS: Three hundred eight PVL closure procedures were attempted in 259 patients in 20 centers (2004-2015). Patient age was 67±13 years; 28% were female. The main indications for closure were heart failure (80%) and hemolysis (16%). Devices were successfully implanted in 91% of patients, via radial (7%), femoral arterial (52%), femoral venous (33%), and apical (7%) approaches. Nineteen percent of patients required repeat procedures. The target valve was mitral (44%), aortic (48%), both (2%), pulmonic (0.4%), or transcatheter aortic valve replacement (5%). Preprocedural leak was severe (61%), moderate (34%), or mild (5.7%) and was multiple in 37%. PVL improved postprocedure (P<0.001) and was none (33.3%), mild (41.4%), moderate (18.6%), or severe (6.7%) at last follow-up. Mean New York Heart Association class improved from 2.7±0.8 preprocedure to 1.6±0.8 (P<0.001) after a median follow-up of 110 (7-452) days. Hospital mortality was 2.9% (elective), 6.8% (in-hospital urgent), and 50% (emergency) (P<0.001). MACE during follow-up included death (16%), valve surgery (6%), late device embolization (0.4%), and new hemolysis requiring transfusion (1.6%). Mitral PVL was associated with higher MACE (hazard ratio [HR], 1.83; P=0.011). Factors independently associated with death were the degree of persisting leak (HR, 2.87; P=0.037), New York Heart Association class (HR, 2.00; P=0.015) at follow-up and baseline creatinine (HR, 8.19; P=0.001). The only factor independently associated with MACE was the degree of persisting leak at follow-up (HR, 3.01; P=0.002). CONCLUSION: Percutaneous closure of PVL is an effective procedure that improves PVL severity and symptoms. Severity of persisting leak at follow-up is independently associated with both MACE and death. Percutaneous closure should be considered as an alternative to repeat surgery.

Transforming musculoskeletal anatomy learning with haptic surface painting.

Anatomical body painting has traditionally been utilized to support learner engagement and understanding of surface anatomy. Learners apply two-dimensional representations of surface markings directly on to the skin, based on the identification of key landmarks. Esthetically satisfying representations of musculature and viscera can also be created. However, established body painting approaches do not typically address three-dimensional spatial anatomical concepts. Haptic Surface Painting (HSP) is a novel activity, distinct from traditional body painting, and aims to develop learner spatial awareness. The HSP process is underpinned by previous work describing how a Haptico-visual observation and drawing method can support spatial, holistic, and collaborative anatomy learning. In HSP, superficial and underlying musculoskeletal and vascular structures are located haptically by palpation. Transparent colors are then immediately applied to the skin using purposive and cross-contour drawing techniques to produce corresponding visual representations of learner observation and cognition. Undergraduate students at a United Kingdom medical school (n = 7) participated in remote HSP workshops and focus groups. A phenomenological study of learner perspectives identified four themes from semantic qualitative analysis of transcripts: Three-dimensional haptico-visual exploration relating to learner spatial awareness of their own anatomy; cognitive freedom and accessibility provided by a flexible and empowering learning process; altered perspectives of anatomical detail, relationships, and clinical relevance; and delivery and context, relating to curricular integration, session format, and educator guidance. This work expands the pedagogic repertoire of anatomical body painting and has implications for anatomy educators seeking to integrate innovative, engaging, and effective learning approaches for transforming student learning.

Leukocyte telomere length is associated with high-risk plaques on virtual histology intravascular ultrasound and increased proinflammatory activity.

OBJECTIVE: Leukocyte telomere length (LTL), a marker of cellular senescence, is inversely associated with cardiovascular events. However, whether LTL reflects plaque extent or unstable plaques, and the mechanisms underlying any association are unknown. METHODS AND RESULTS: One hundred seventy patients with stable angina or acute coronary syndrome referred for percutaneous coronary intervention underwent 3-vessel virtual histology intravascular ultrasound; 30 372 mm of intravascular ultrasound pullback and 1096 plaques were analyzed. LTL was not associated with plaque volume but was associated with calcified thin-capped fibroatheroma (OR, 1.24; CI, 1.01-1.53; P=0.039) and total fibroatheroma numbers (OR, 1.19; CI, 1.02-1.39; P=0.027). Monocytes from coronary artery disease patients showed increased secretion of proinflammatory cytokines. To mimic leukocyte senescence, we disrupted telomeres and binding and expression of the telomeric protein protection of telomeres protein-1, inducing DNA damage. Telomere disruption increased monocyte secretion of monocyte chemoattractant protein-1, IL-6, and IL-1ß and oxidative burst, similar to that seen in coronary artery disease patients, and lymphocyte secretion of IL-2 and reduced lymphocyte IL-10. CONCLUSIONS: Shorter LTL is associated with high-risk plaque morphology on virtual histology intravascular ultrasound but not total 3-vessel plaque burden. Monocytes with disrupted telomeres show increased proinflammatory activity, which is also seen in coronary artery disease patients, suggesting that telomere shortening promotes high-risk plaque subtypes by increasing proinflammatory activity.

Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: a prospective, randomized control trial.

BACKGROUND: Myocyte necrosis as a result of elective percutaneous coronary intervention (PCI) occurs in approximately one third of cases and is associated with subsequent cardiovascular events. This study assessed the ability of remote ischemic preconditioning (IPC) to attenuate cardiac troponin I (cTnI) release after elective PCI. METHODS AND RESULTS: Two hundred forty-two consecutive patients undergoing elective PCI with undetectable preprocedural cTnI were recruited. Subjects were randomized to receive remote IPC (induced by three 5-minute inflations of a blood pressure cuff to 200 mm Hg around the upper arm, followed by 5-minute intervals of reperfusion) or control (an uninflated cuff around the arm) before arrival in the catheter laboratory. The primary outcome was cTnI at 24 hours after PCI. Secondary outcomes included renal dysfunction and major adverse cardiac and cerebral event rate at 6 months. The median cTnI at 24 hours after PCI was lower in the remote IPC compared with the control group (0.06 versus 0.16 ng/mL; P=0.040). After remote IPC, cTnI was <0.04 ng/mL in 44 patients (42%) compared with 24 in the control group (24%; P=0.01). Subjects who received remote IPC experienced less chest discomfort (P=0.0006) and ECG ST-segment deviation (P=0.005) than control subjects. At 6 months, the major adverse cardiac and cerebral event rate was lower in the remote IPC group (4 versus 13 events; P=0.018). CONCLUSIONS: Remote IPC reduces ischemic chest discomfort during PCI, attenuates procedure-related cTnI release, and appears to reduce subsequent cardiovascular events.

Focused Multisensory Anatomy Observation and Drawing for Enhancing Social Learning and Three-Dimensional Spatial Understanding.

The concept that multisensory observation and drawing can be effective for enhancing anatomy learning is supported by pedagogic research and theory, and theories of drawing. A haptico-visual observation and drawing (HVOD) process has been previously introduced to support understanding of the three-dimensional (3D) spatial form of anatomical structures. The HVOD process involves exploration of 3D anatomy with the combined use of touch and sight, and the simultaneous act of making graphite marks on paper which correspond to the anatomy under observation. Findings from a previous study suggest that HVOD can increase perceptual understanding of anatomy through memorization and recall of the 3D form of observed structures. Here, additional pedagogic and cognitive underpinnings are presented to further demonstrate how and why HVOD can be effective for anatomy learning. Delivery of a HVOD workshop is described as a detailed guide for instructors, and themes arising from a phenomenological study of educator experiences of the HVOD process are presented. Findings indicate that HVOD can provide an engaging approach for the spatial exploration of anatomy within a supportive social learning environment, but also requires modification for effective curricular integration. Consequently, based on the most effective research-informed, theoretical, and logistical elements of art-based approaches in anatomy learning, including the framework provided by the observe-reflect-draw-edit-repeat (ORDER) method, an optimized "ORDER Touch" observation and drawing process has been developed. This is with the aim of providing a widely accessible resource for supporting social learning and 3D spatial understanding of anatomy, in addition to improving specific anatomical knowledge.

Patent Foramen Ovale Closure: State of the Art.

Patent foramen ovale (PFO) is a common abnormality affecting between 20% and 34% of the adult population. For most people, it is a benign finding; however, in some people, the PFO can open widely to enable paradoxical embolus to transit from the venous to arterial circulation, which is associated with stroke and systemic embolisation. Percutaneous closure of the PFO in patients with cryptogenic stroke has been undertaken for a number of years, and a number of purpose-specific septal occluders have been marketed. Recent randomised control trials have demonstrated that closure of PFO in patients with cryptogenic stroke is associated with reduced rates of recurrent stroke. After a brief overview of the anatomy of a PFO, this article considers the evidence for PFO closure in cryptogenic stroke. The article also addresses other potential indications for closure, including systemic arterial embolisation, decompression sickness, platypnoea-orthodeoxia syndrome and migraine with aura. The article lays out the pre-procedural investigations and preparation for the procedure. Finally, the article gives an overview of the procedure itself, including discussion of closure devices.

Remote ischaemic pre-conditioning does not attenuate ischaemic left ventricular dysfunction in humans.

AIMS: Remote ischaemic pre-conditioning (RIPC) reduces distant tissue ischaemia reperfusion injury. We tested the hypothesis that RIPC would protect the left ventricle (LV) from ischaemic dysfunction and stunning. METHODS AND RESULTS: Forty-two patients with single vessel coronary disease and normal LV function were prospectively recruited. Twenty patients had repeated conductance catheter assessment of LV function during serial coronary occlusions with/without RIPC and a further 22 patients underwent serial dobutamine stress echocardiography and tissue Doppler analysis with/without RIPC. Remote ischaemic pre-conditioning was induced by three 5 min inflations of a blood pressure cuff around the upper arm. RIPC did not diminish the degree of ischaemic LV dysfunction during coronary balloon occlusion (Tau, ms: 59.2 (2.8) vs. 62.8 (2.8), P = 0.15) and there was evidence of cumulative LV dysfunction despite RIPC [ejection fraction (EF), %: 54.3 (5.8) vs. 44.9 (3.7), P = 0.03]. Remote ischaemic pre-conditioning did not improve contractile recovery during reperfusion (EF, %: 51.7 (3.6) vs. 51.5 (5.7), P = 0.88 and Tau, ms: 55.6 (2.8) vs. 56.0 (2.0), P = 0.85). A neutral effect of RIPC on LV function was confirmed by tissue Doppler analysis of ischaemic segments at peak dobutamine (V(s), cm s(-1) control: 8.2 (0.4) vs. RIPC 8.1 (0.4), P = 0.43) and in recovery. CONCLUSION: RIPC does not attenuate ischaemic LV dysfunction in humans.

How Haptics and Drawing Enhance the Learning of Anatomy.

Students' engagement with two-dimensional (2D) representations as opposed to three-dimensional (3D) representations of anatomy such as in dissection, is significant in terms of the depth of their comprehension. This qualitative study aimed to understand how students learned anatomy using observational and drawing activities that included touch, called haptics. Five volunteer second year medical students at the University of Cape Town participated in a six-day educational intervention in which a novel "haptico-visual observation and drawing" (HVOD) method was employed. Data were collected through individual interviews as well as a focus group discussion. The HVOD method was successfully applied by all the participants, who reported an improvement of their cognitive understanding and memorization of the 3D form of the anatomical part. All the five participants described the development of a "mental picture" of the object as being central to "deep learning." The use of the haptic senses coupled with the simultaneous act of drawing enrolled sources of information that were reported by the participants to have enabled better memorization. We postulate that the more sources of information about an object, the greater degree of complexity could be appreciated, and therefore the more clearly it could be captured and memorized. The inclusion of haptics has implications for cadaveric dissection versus non-cadaveric forms of learning. This study was limited by its sample size as well as the bias and position of the researchers, but the sample of five produced a sufficient amount of data to generate a conceptual model and hypothesis.

Percutaneous management of paravalvular leaks.

Paravalvular leak (PVL) is a complication that occurs in 5-17% of patients after surgical prosthetic valve implantation. Whereas PVLs can be benign, some PVLs are associated with substantial morbidity and mortality. Percutaneous closure using occluders specifically designed to improve closure and reduce procedural complications has now become the first-line treatment for PVL. In this Review, we first detail the frequency and clinical consequences of PVL closure. The role of cardiac imaging in the assessment and management of PVL, including echocardiographic imaging and adjunctive techniques such as CT, is then discussed, together with important considerations for the percutaneous closure of PVL, such as access site and device selection. Finally, we summarize the clinical evidence for percutaneous closure of PVL, including large national registries from Ireland, Spain and the UK, as well as head-to-head data comparing this procedure with surgical closure.

Author Correction: Percutaneous management of paravalvular leaks.

In the version of this article initially published online, the Paravalvular Leak Device (PLD; Occlutech) was incorrectly described as having a "proximal disc that is slightly larger than the distal disc", whereas the distal disc is actually slightly larger than the proximal disc. This error has been corrected for the HTML, PDF and print versions of the article.

Patent Foramen Ovale Closure in 2019.

Patent foramen ovale (PFO) is a common abnormality affecting between 20% and 34% of the adult population. For most people it is a benign finding; however, in some the PFO can open widely, enabling a paradoxical embolus to transit from the venous to arterial circulation, which is associated with stroke and systemic embolisation. Percutaneous closure of PFO in patients with cryptogenic stroke has been undertaken for a number of years, and a number of purpose-specific septal occluders have been marketed. Recent randomised controlled trials have demonstrated that closure of PFO in patients with cryptogenic stroke is associated with reduced rates of recurrent stroke. After a brief overview of the anatomy of a PFO, this review considers the evidence for PFO closure in cryptogenic stroke. The review also addresses other potential indications for closure, including systemic embolisation, decompression sickness, platypnoea-orthodeoxia syndrome and migraine with aura. It lays out the pre-procedural investigations and preparation for the procedure. Finally, it gives an overview of the procedure itself, including discussion of closure devices.

A Giant Saphenous Vein Graft Aneurysm Treated With Percutaneous Closure.

A patient with a history of coronary artery bypass graft presented with breathlessness and was found to have an 11 × 6 cm aneurysm in a distally occluded saphenous vein graft. This case describes the investigation, heart team discussion, and percutaneous closure of the aneurysm. (Level of Difficulty: Beginner.).

Effects of Patent Foramen Ovale Closure on Obstructive Sleep Apnea Syndrome: PCOSA Study.

BACKGROUND: Previous studies have shown a higher prevalence of patent foramen ovale (PFO) in patients with obstructive sleep apnea syndrome (OSAS). Right to left shunting through a PFO may be encouraged by the respiratory physiology of OSAS, contributing to the disease pathophysiology. We assessed whether PFO closure would improve respiratory polygraphy parameters compared with baseline measurements in patients with OSAS. METHODS: Twenty-six patients with newly diagnosed OSAS and a moderate-large PFO (prevalence, 18% of 143 patients screened) were referred for PFO closure. The oxygen desaturation index (ODI), apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), 6-minute walk test (6MWT), and Sleep Apnea Quality of Life Index (SAQLI) results were compared in these patients at baseline (before continuous positive pressure ventilation [CPAP]) and at 6-month follow-up (after interrupting CPAP for 1 week). RESULTS: All PFOs were safely sealed at 6 months, as confirmed by repeated transthoracic echocardiography. The ODI (44.8 [interquartile range (IQR), 31.2-63.5) vs 42.3 [IQR, 34.0-60.8]; P = 0.89) and AHI (47.9 [IQR, 31.5-65.2] vs 42.3 [IQR, 32.1-63]; P = 0.99) did not change after PFO closure nor did the 6MWT, although the ESS (13.0 [IQR, 12.0-16.8] vs 6.0 [IQR, 4.0-8.8]; P < 0.001) and the SAQLI (3.4 [IQR, 2.8-4.3] vs 4.4 [IQR, 3.9-5.3]; P < 0.001) did improve. CONCLUSIONS: The prevalence of PFO in OSAS appears to be no higher than that in the general population. Although PFO closure is safe and effective, it did not improve respiratory polygraphy measures of OSAS severity. The improvement in the ESS and SAQLI likely reflect residual benefits from CPAP.

Human vascular smooth muscle cells from restenosis or in-stent stenosis sites demonstrate enhanced responses to p53: implications for brachytherapy and drug treatment for restenosis.

The p53 tumor suppressor gene regulates growth arrest and apoptosis after DNA damage. Recent studies suggest that p53 is inactive in vascular smooth muscle cells (VSMCs) in human angioplasty restenosis, promoting VSMC accumulation and vessel stenosis. In contrast, the success of irradiation (brachytherapy) for in-stent restenosis argues that DNA-damage p53 responses are intact. We examined p53 expression and function in human VSMCs from normal vessels (n-VSMCs) and angioplasty/in-stent restenosis sites (r-VSMCs). p53 expression was uniformly low in all VSMCs and was induced by DNA damage. However, p53 induced profoundly different biological effects in r-VSMCs versus n-VSMCs, causing growth arrest and apoptosis in r-VSMCs only. In addition, dominant-negative p53 promoted cell proliferation and apoptosis in r-VSMCs but not n-VSMCs. Cytotoxic drug-- or irradiation-induced growth arrest and apoptosis in both cell types was mediated only partly by p53. In contrast, cyclin D degradation in response to DNA damage, a critical early mediator of growth arrest, was impaired in r-VSMCs, an effect that required p53. We conclude that p53 expression and function are normal or increased in r-VSMCs and may underlie the success of brachytherapy. We also identify a restenosis VSMC-specific defect in cyclin D degradation induced by DNA damage.

Results of Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) trial.

BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) is a major problem affecting 15% to 30% of patients after stent placement. No oral agent has shown a beneficial effect on restenosis or on associated major adverse cardiovascular events. In limited trials, the oral agent tranilast has been shown to decrease the frequency of angiographic restenosis after PCI. METHODS AND RESULTS: In this double-blind, randomized, placebo-controlled trial of tranilast (300 and 450 mg BID for 1 or 3 months), 11 484 patients were enrolled. Enrollment and drug were initiated within 4 hours after successful PCI of at least 1 vessel. The primary end point was the first occurrence of death, myocardial infarction, or ischemia-driven target vessel revascularization within 9 months and was 15.8% in the placebo group and 15.5% to 16.1% in the tranilast groups (P=0.77 to 0.81). Myocardial infarction was the only component of major adverse cardiovascular events to show some evidence of a reduction with tranilast (450 mg BID for 3 months): 1.1% versus 1.8% with placebo (P=0.061 for intent-to-treat population). The primary reason for not completing treatment was > or =1 hepatic laboratory test abnormality (11.4% versus 0.2% with placebo, P<0.01). In the angiographic substudy composed of 2018 patients, minimal lumen diameter (MLD) was measured by quantitative coronary angiography. At follow-up, MLD was 1.76+/-0.77 mm in the placebo group, which was not different from MLD in the tranilast groups (1.72 to 1.78+/-0.76 to 80 mm, P=0.49 to 0.89). In a subset of these patients (n=1107), intravascular ultrasound was performed at follow-up. Plaque volume was not different between the placebo and tranilast groups (39.3 versus 37.5 to 46.1 mm(3), respectively; P=0.16 to 0.72). CONCLUSIONS: Tranilast does not improve the quantitative measures of restenosis (angiographic and intravascular ultrasound) or its clinical sequelae.