Therapeutic interventions for enhancing collateral development by administration of growth factors: basic principles, early results and potential hazards.

The importance of spontaneously developing collateral vessels to supplement perfusion of tissue rendered ischemic by vascular obstruction was recognized many years ago. However, it was not until potent angiogenesis factors were identified, purified, and produced in sufficient quantities, that the field began its rapid development. In the early 1990s it was first shown that basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) proteins could actually stimulate collateral flow.

Catheter-based plasmid-mediated transfer of genes into ischemic myocardium using the pCOR plasmid.

Background: Direct transfer of genes holds promise for the sustained delivery of therapeutic proteins to treat cardiovascular diseases. This can be accomplished by several approaches, including use of adenoviral vectors and naked plasmid DNA vectors. We previously demonstrated achieval of effective delivery of genes into the myocardium with a left ventricular-guided catheter-based approach using an adenoviral vector.

Mechanical Approaches for Myocardial Angiogenesis.

Because angiogenesis appears to be a fundamental mechanism associated with direct myocardial revascularization (DMR) procedures, it seems natural to combine the overall field of DMR with angiogenesis therapy. Such myocardial treatment strategy can thus be termed "mechanical approach for myocardial angiogenesis." In this article, we review the myocardial response to various ablative energy sources in order to explore data indicative for angiogenesis in response to mechanical myocardial injury, or by using hybrid approaches, combining energy sources with proangiogenic pharmacotherapy.

Optimally deployed stents in the treatment of restenotic versus de novo lesions.

Results from earlier trials performed before the implementation of optimal stent deployment techniques suggest that stenting for restenotic lesions may be associated with a higher risk of restenosis when compared with de novo lesions. The aim of this study was to compare the short- and long-term outcome of optimal stent deployment in restenotic versus de novo lesions. In all, 1,865 consecutive patients with 2,707 de novo lesions and 489 patients with 633 restenotic lesions underwent intravascular ultrasound-guided optimal stent deployment.

Prognostic value of recurrent episodes of creatine kinase-MB elevation following repeated catheter-based coronary interventions.

Creatine kinase-MB (CK-MB) enzyme elevations were shown to affect cardiac prognosis following percutaneous coronary interventions (PCIs). This study examined whether recurrent episodes of CK-MB elevation following repeated PCIs may be associated with a cumulative adverse prognostic risk. We studied 767 consecutive patients (age, 64 +/- 11 years; 69% male) who underwent two consecutive PCI procedures on two separate hospitalizations (mean interval, 121 +/- 110 days).

Clinical outcomes following "rescue" administration of abciximab in patients undergoing percutaneous coronary angioplasty.

Pre-intervention administration of abciximab in patients at "high risk" for coronary angioplasty has been shown to reduce acute and long-term cardiac outcomes. The role of intra-procedural ("rescue") administration of abciximab has not been fully elucidated. We assessed the clinical outcomes associated with rescue administration of abciximab during complex percutaneous coronary interventions.

Short- and intermediate-term clinical outcomes from direct myocardial laser revascularization guided by biosense left ventricular electromechanical mapping.

Background: Direct myocardial revascularization (DMR) has been examined as an alternative treatment for patients with chronic refractory myocardial ischemic syndromes who are not candidates for conventional coronary revascularization. Methods and Results-We used left ventricular electromagnetic guidance in 77 patients with chronic refractory angina (56 men, mean age 61+/-11 years, ejection fraction 0.48+/-0.

Percutaneous transmyocardial laser revascularization: overview of US clinical trials.

Data from four surgical trials of laser transmyocardial revascularization (TMR) show pain reductions of at least two classes occurred among 25-76% of patients, significantly greater than with optimal medical therapy. The safety and feasibility of percutaneous TMR (PTMR) was proved in multiple uncontrolled registry studies. With PTMR in two randomized trials enrolling about 550 patients, improvements were found among 45% and 66% of patients as compared with 13% for best medical therapy.

Immediate effect of Biosense guided percutaneous direct myocardial revascularization with holmium:yttrium aluminium garnet laser on myocardial contractility assessed by transesophageal echocardiography.

Objective: To evaluate immediate changes in left ventricular wall motion in patients treated using Biosense direct myocardial revascularization laser system.

Methods: Regional wall motion in 10 patients undergoing catheter-based direct myocardial revascularization using a holmium:yttrium aluminium garnet laser was assessed by transesophageal echocardiography before and immediately after the procedure.

Results: Mild deterioration in wall-motion score occurred rarely for only three of 160 (1.

Current perspectives on interventional treatment strategies in diabetic patients with coronary artery disease.

Diabetes mellitus has a negative impact on mortality and morbidity following catheter-based coronary procedures as well as coronary artery bypass surgery. Increased restenosis remains the main limitation of catheter-based coronary intervention among diabetes mellitus in addition to accelerated atherosclerosis lesion progression in other untreated coronary sites. Determinants such as excess restenosis, high atherosclerosis burden, lesion complexity, small target vessel size, and accelerated coronary atherosclerosis in remote sites may favor the surgical strategy in most cases of diabetic multivessel disease.

Histopathologic analysis of in-stent neointimal regression in a porcine coronary model.

Background: Animal and clinical studies have demonstrated late regression of in-stent neointima. This study was performed to identify the temporal changes in the in-stent neointimal constituents responsible for late regression.

Methods: NIR stents were implanted in porcine coronary arteries (size of stent (in mm) to size of artery (in mm) approximately equal to 1.

The "hybrid" approach for revascularisation: direct myocardial revascularisation and coronary angioplasty.

We report the cases of two patients where catheter-based laser direct myocardial revascularisation has been coupled with conventional coronary angioplasty at the same sitting using the Biosense left ventricular electromechanically guided laser procedure. In both the cases, the non-revascularizable ischaemic target zone was identified using left ventricular electromechanical mapping signals, and Ho: YAG laser channels were placed at the designated target lesion following successful coronary stenting. The results did not show any procedural complications.

Prognostic value of cardiac troponin-I levels following catheter-based coronary interventions.

This study has examined the prognostic significance of troponin-I (Tn-I) levels after catheter-based coronary interventions in coronary arteries and saphenous vein grafts lesions. Tn-I and creatine kinase-MB (CK-MB) fraction levels were measured at 6 and 18 to 24 hours after catheter-based coronary intervention in 1,129 consecutive patients with normal preintervention plasma levels of Tn-I, and CK-MB levels below the cutoff for myocardial infarction. Patients were stratified according to maximal postangioplasty Tn-I levels.

Angiographic Morphology Following Heparin and Aspirin Therapy in Patients with Acute Coronary Syndromes and Intracoronary Thrombus.

This series included 26 patients with acute myocardial infarction (15 patients) or unstable angina (11 patients), with thrombotic lesions identified by angiography and treated with intravenous heparin (mean 8 +/- 3 days, aPTT 1.5-2.5 times baseline) and aspirin (250 mg/day).

Electromechanical characterization of acute experimental myocardial infarction.

Objective: A new cardiac mapping system combines harmless magnetic field energy and tip-deflecting catheters (equipped with location sensors) to obtain real-time 3-dimensional electromechanical maps of the left ventricle endocardial surface without using x-ray fluoroscopy. This experimental study assessed electromechanical changes during acute coronary occlusion and reperfusion in a canine model.

Methods: Group 1 (n = 10) underwent coronary occlusion for 45 minutes followed by reperfusion (n = 6) and group 2 (n = 11) underwent coronary occlusion for 90 minutes.

Severe spasm of the free radial artery graft in a patient undergoing high-risk angioplasty under percutaneous cardiopulmonary support.

This report illustrates a case of percutaneous intervention in a very high-risk patient who already had three previous bypass operations and was not a suitable candidate for further surgical revascularization. Since intra-aortic balloon pump insertion was contraindicated due to the origin of a radial graft from the descending aorta, percutaneous cardiopulmonary support (CPS) was used to perform the procedure. Thus, CPS proved useful in providing adequate hemodynamic support and allowed us to use adequate amount of antispastic drugs to relieve any spasm during the procedure.

Electromagnetic guidance for catheter-based transendocardial injection: a platform for intramyocardial angiogenesis therapy. Results in normal and ischemic porcine models.

Objectives: To test the feasibility of myocardial angiogenic gene expression using a novel catheter-based transendocardial injection system.

Background: Angiogenesis has been induced by direct injection of growth factors into ischemic myocardium during open-heart surgery. Catheter-based transendocardial injection of angiogenic factors may provide equivalent benefit without need of surgery.

Use of fluorescent microspheres to localize in vivo gene transfer injection sites.

The potential for using gene therapy to treat a variety of disease states is growing rapidly. Many vector types and delivery systems have been developed that allow the optimization of protein production levels and kinetics for a given therapeutic gene product. In cases in which a transient, localized delivery of gene product is desired, any determination of the locale of transfected tissue by non-marker genes is problematic.

Procedural results and late clinical outcomes after percutaneous interventions using long (> or = 25 mm) versus short (< 20 mm) stents.

Objectives: To evaluate clinical outcomes after the use of long coronary stents.

Background: The use of long slotted-tube stents has been recently approved in the U.S.

Procedural results and intermediate clinical outcomes after multiple saphenous vein graft stenting.

Objectives: We evaluated the early and mid-term (18-month) clinical events in a consecutive series of patients undergoing a nonstaged multiple saphenous vein grafting (SVG) intervention with stents as compared with a single SVG stent procedure.

Background: Saphenous vein graft angioplasty has been limited by high rates of distal embolization, myocardial infarction, restenosis and late mortality. It is unknown whether stenting of multiple, different SVGs at the same setting is associated with higher risk.

Delivery strategies to achieve therapeutic myocardial angiogenesis.

The use of recombinant genes or growth factors to enhance myocardial collateral blood vessel function may represent a new approach to the treatment of cardiovascular disease. Proof of concept has been demonstrated in animal models of myocardial ischemia, and clinical trials are underway. Currently, it is unknown which is the safest and most effective delivery strategy to induce clinically important therapeutic angiogenic responses in ischemic myocardium.