Harry C. Lowe

Coronary in-stent restenosis: Current status and future strategies

In-stent restenosis (ISR) is a novel pathobiologic process, histologically distinct from restenosis after balloon angioplasty and comprised largely of neointima formation. As percutaneous coronary intervention increasingly involves the use of stents, ISR is also becoming correspondingly more frequent. In this review, we examine the available studies of the histology and pathogenesis of ISR, with particular reference to porcine and other animal models. An overview of mechanical treatments is then provided, which includes PTCA, directional coronary atherectomy and high speed rotational atherectomy. Radiation-based therapies are discussed, including a summary of current problems associated with this modality of treatment. Finally, novel strategies for the prevention of ISR are addressed, including novel developments in stents and stent coatings, conventional drugs, nucleic acid-based drugs and gene transfer. Until recently, limited pharmacologic and mechanical treatment options have been available for both treatment and prevention of ISR. However, recent advances in gene modification and gene transfer therapies and, more particularly, in local stent-based drug delivery systems make it conceivable that the incidence of ISR will now be seriously challenged.

Intravascular Modalities for Detection of Vulnerable Plaque Current Status

Abstract—Progress in the diagnosis, treatment, and prevention of atherosclerotic coronary artery disease is dependent on a greater understanding of the mechanisms of coronary plaque progression. Autopsy studies have characterized a subgroup of high-risk, or vulnerable, plaques that result in acute coronary syndromes or sudden cardiac death. These angiographically modest plaques share certain pathologic characteristics: a thin, fibrous cap, lipid-rich core, and macrophage activity. Diagnostic techniques for vulnerable-plaque detection, including serologic markers and noninvasive and invasive techniques, are needed. Recent advances in intravascular imaging have significantly improved the ability to detect high-risk, or vulnerable, plaque in vivo by using various features of plaque vulnerability as methods of identification. The characteristic anatomy of a thin, fibrous cap overlying a lipid pool has promoted high-resolution imaging, such as intravascular ultrasound, optical coherence tomography, and intracoronary magnetic resonance. The lipid-rich core is identifiable by angioscopically detected color changes on the plaque surface or by its unique absorption of energy, or “Raman shift,” of its cholesterol core, driving coronary spectroscopy. Finally, temperature heterogeneity arising at foci of plaque inflammation has prompted the development of intracoronary thermography. In this review, we will discuss these techniques, their relative advantages and limitations, and their potential clinical application.

The porcine coronary model of in-stent restenosis: Current status in the era of drug-eluting stents

Drug‐eluting stents are revolutionizing interventional cardiology. Sirolimus‐eluting stents are in widespread clinical use, associated with well‐documented remarkably low restenosis rates, and a number of other agents appear promising in clinical trials. These human studies have been preceded by numerous animal studies, foremost among them the pig coronary model of in‐stent restenosis (ISR). The histologic response to porcine coronary stenting was described over a decade ago. Porcine stenting studies now provide examinations not only of histology, but also mechanisms of action, toxicity, and biocompatibility. This review therefore examines the current status of this porcine coronary model of ISR. Contemporary methods of pig coronary stenting are discussed. The morphometric, cellular, and molecular analyses of the responses to stent injury are then described. Finally, recent pig coronary drug‐eluting stent studies are examined, with a discussion of their advantages, limitations, and possible future modifications. Catheter Cardiovasc Interv 2003;60:515–523.

Transient Left Ventricular Apical Ballooning

A 69-year-old woman presented with acute onset of chest pain and diffuse ST-segment elevation suggesting ischemia (Figure 1). The creatine phosphokinase–MB was elevated, and in view of ongoing chest discomfort, she was referred for urgent cardiac catheterization. nnnnFigure 1. Twelve-lead ECG showing normal sinus …

Toward a new blood vessel

Strategies to treat atherosclerotic coronary artery disease include coronary artery bypass grafting (CABG), in which grafts are used to bypass atherosclerotic vessels and restore blood flow to the ischemic myocardium. The grafts used include healthy arteries or veins harvested from a separate site. Results with arterial grafts have been superior to venous grafts; promoting the practice of total arterial revascularization using only arterial grafts. Suitable arterial grafts, however, are scarce and harvest procedures add to morbidity and cost. Tissue engineering combines the principles of engineering with life sciences for the development of biological substitutes and restore, maintain or improve tissue function. Advances in this field have included the development of tissue-engineered blood vessels, with the potential to serve as arterial grafts, conduits or fistulae. This review describes the history of tissue engineering arteries, the techniques used, and progress to date. The source of cells and the future direction of this field are explored.

Pharmacologic Reperfusion Therapy for Acute Myocardial Infarction

Acute myocardial infarction (MI) remains a significant problem in terms of morbidity, mortality and healthcare costs. Pharmacologic reperfusion therapies for MI are becoming increasingly complex. This review therefore places contemporary pharmacologic MI developments into perspective. An historical overview of pharmacologic reperfusion therapy for MI is provided, followed by an analysis of current limitations, treatment options, and present and likely future pharmacologic therapies. Adjunctive percutaneous and other treatments are also discussed, to clarify what is becoming a rapidly changing field.

Compassionate use of the amplatzer ASD closure device for residual postinfarction ventricular septal rupture following surgical repair

We report successful transcatheter closure of a post‐MI ventricular septal rupture acutely following unsuccessful surgical repair. Catheter closure was accomplished by the use of a 26‐mm Amplatzer atrial septal occluder. Initial attempts to close the defect with the use of 28‐mm and 33‐mm CARDIOSEAL were unsuccessful. Closure technique, immediate and long‐term follow‐up outcomes are reported. Cathet Cardiovasc Intervent 2003;59:230–233.

Histopathology of coronary in-stent restenosis following γ brachytherapy

The histopathology of in-stent restenosis (ISR) following γ brachytherapy is described. Such histology has not been reported previously. An 82 year old man presented with recurrent ISR three months after γ brachytherapy to an area of ISR within a native circumflex vessel. The recurrent ISR was treated with directional coronary atherectomy; the histopathology of this directional coronary atherectomy specimen is discussed. These histopathological examinations showed abundant extracellular matrix material. Surprisingly, there was a relatively small cellular (myofibroblastic) component, with an absence of endothelial cells and little evidence of active proliferation. ISR after γ brachytherapy may be a pathologically distinct entity.

Catheter-based ventricle-coronary vein bypass.

The goal of this study was to investigate the feasibility of a catheter‐based ventricle‐to‐coronary vein bypass (VPASS) in order to achieve retrograde myocardial perfusion by a conduit (VSTENT) from the left ventricle (LV) to the anterior interventricular vein (AIV). Percutaneous coronary venous arterialization has been proposed as a potential treatment strategy for otherwise untreatable coronary artery disease. In an acute setting, the VSTENT implant was deployed percutaneously using the VPASS procedure in five swine. Coronary venous flow and pressure patterns were measured before and after VSTENT implant deployment with and without AIV and left anterior descending artery (LAD) occlusion. In a separate chronic pilot study, the VPASS procedure was completed on two animals that had a mid‐LAD occlusion or LAD stenosis. At day 30 post‐VPASS procedure, left ventriculography and magnetic resonance imaging (MRI) were performed to assess the patency and myocardial viability of the VSTENT implants. Pre‐VSTENT implantation, the mid‐AIV systolic wedge pressure was significantly lower than LV systolic pressure during AIV blockage (46 ± 19 vs. 90 ± 16 mm Hg; P < 0.01). The VSTENT implant deployment was performed without complication and achieved equalization of the AIV and LV systolic pressures and creation of retrograde flow in the distal AIV (maximal flow velocity: 37 ± 7 cm/sec). At day 30 post‐VPASS procedure, left ventriculography showed VSTENT implant patency. MRI perfusion images demonstrated myocardial viability even with an LAD occlusion. Coronary retrograde perfusion using the VPASS procedure is feasible and may represent a potential technique for end‐stage myocardial ischemia. Catheter Cardiovasc Interv 2005.

Coronary in-stent restenosis following beta brachytherapy A histopathological examination

Two cases of in-stent restenosis of a coronary artery bypass vein graft following beta (beta) brachytheraphy are presented. Previously unreported histopathology of directed atherectomy specimens of such restenotic lesions and a discussion of their proposed significance form the basis of this report.