Beyond angioplasty: novel developments in interventional cardiology.

Two specific areas in interventional cardiology have, until recently, remained problematic. First is the emerging issue of the so-called 'no option' patient, considered untreatable by conventional percutaneous coronary intervention (PCI) or surgery. Second is the long-standing dilemma of restenosis following PCI. Strategies addressing these two critical areas have been the subject of intense research efforts recently. Several important breakthroughs are being made in the important areas of novel revascularization techniques, antirestenotic agents and stent-based delivery methods. It is conceivable that these novel developments will soon mean that a broader range of patients can be treated, and that the issue of restenosis will now be seriously challenged.

Significant atheromatous debris following uncomplicated vein graft direct stenting: evidence supporting routine use of distal protection devices.

We present the case of an angiographically uncomplicated direct stent vein graft intervention in which the Percusurge embolization containment device was used. We performed histological examination of the resulting debris and observed massive particulate atheromatous material. This case illustrates the severity of distal embolization that can go clinically unnoticed after direct stenting and also supports the routine use of distal protection devices for vein graft intervention.

Adjunctive pharmacotherapy for coronary stenting.

The use of coronary stents improves the outcomes of percutaneous coronary intervention (PCI). This has led to a rapid increase in their use. Coronary stenting is not without problems and is complicated by both early ischemic events and late restenosis. The combination of anticoagulation with unfractionated heparin (UFH) and the use of antiplatelet agents including aspirin, thienopyridines, and glycoprotein IIb/IIIa inhibitors has led to a major reduction in early ischemic events after stenting. Low molecular weight heparin (LMWH) and direct thrombin inhibitors have a number of theoretical advantages over UFH. Their role as an adjunct to coronary stenting is still under investigation. Trials of systemic pharmacotherapy aimed at reducing in-stent restenosis have been consistently disappointing. Preliminary results of stents coated with agents that inhibit neointimal proliferation are extremely promising. The results of ongoing phase III trials of these coated stents are eagerly awaited.

The use of mechanical devices as adjuncts to intracoronary stenting.

A number of mechanical adjuncts to intracoronary stenting are now available to the interventional cardiologist. These devices have assisted in the development of a safer and more effective stenting practice. Intravascular ultrasound-guided stenting has been shown to reduce the rate of subacute thrombosis and subsequent restenosis. It allows a greater appreciation of lesion structure and severity so that an appropriate intervention strategy can be devised. Debulking techniques may allow the optimal deployment of stents so that restenosis is reduced; however, the results of large randomized studies are still awaited. The use of thrombectomy and distal embolization protection devices is emerging as a safer alternate to stenting alone in difficult patient subsets, such as those with thrombus-laden lesions and degenerated vein grafts. Doppler and pressure wires may be useful in determining optimal stent deployment and predict subsequent patient outcomes. An understanding of the indications and limitations of these devices is of increasing importance to the interventional cardiologist as the coming decade threatens to yield an impressive array of high-tech innovations.

Percutaneous in situ coronary venous arterialization: report of the first human catheter-based coronary artery bypass.

Diffuse coronary artery disease is frequently untreatable by coronary artery bypass or angioplasty. Many such "no-option" patients have been subjects for trials of angiogenesis using growth factor manipulation or laser injury. We think these novel revascularization strategies are limited by insufficient inflow to putative areas of new microvasculature and thus seek a more mechanical solution. We report the use of a catheter-based system for arterializing the adjacent anterior cardiac vein in a patient with chronic total occlusion of the left anterior descending coronary artery. A composite catheter system (phased-array ultrasound imaging system mounted on a catheter with extendable nitinol needle) was used to deliver an exchange-length intracoronary guidewire from the proximal left anterior descending coronary artery into the parallel anterior interventricular vein. Using standard angioplasty techniques, a fistula was then constructed from the proximal artery to the coronary vein using a self-expanding connector. The proximal vein was blocked with a novel self-expanding "blocker," thus precluding "steal" through the coronary sinus and forcing retroperfusion of the anterior wall. The procedure was completed without complication, and a follow-up angiogram at 3 months confirmed continued patency of the arteriovenous connection. This patient, who had severe angina before the procedure, has been asymptomatic for 12 months. Percutaneous in situ venous arterialization may be an effective therapy for diffuse, "untreatable" coronary disease by supplying a robust inflow of arterialized blood via retroperfusion to severely ischemic myocardium.

Balloon deflection technique: A method to facilitate entry of a balloon catheter into a deployed stent.

The entry of an angioplasty balloon into a coronary stent is occasionally difficult due to poorly expanded stent struts or calcified tissue blocking balloon passage. We describe a simple technique using a second guidewire and balloon to facilitate entry into the stent. Cathet. Cardiovasc. Intervent. 51:312-313, 2000.

Percutaneous transmyocardial laser revascularisation for severe angina: the PACIFIC randomised trial. Potential Class Improvement From Intramyocardial Channels.

BACKGROUND: Percutaneous transmyocardial laser revascularisation (PTMR) is a proposed catheter-based therapy for refractory angina pectoris when bypass surgery or angioplasty is not possible. We undertook a randomised trial to assess the safety and efficacy of this technique. METHODS: 221 patients with reversible ischaemia of Canadian Cardiovascular Society angina class III (61%) or IV (39%) and incomplete response to other therapies were recruited from 13 centres. Patients were randomly assigned PTMR with a holmium:YAG laser plus continued medical treatment (n=110) or continued medical treatment only (n=111). The primary endpoint was the exercise tolerance at 12 months. Analyses were by intention to treat. FINDINGS: 11 patients died and 19 withdrew; 92 PTMR-group and 99 medical-treatment-group patients completed the study. Exercise tolerance at 12 months had increased by a median of 89.0 s (IQR -15 to 183) with PTMR compared with 12.5 s (-67 to 125) with medical treatment only (p=0.008). On masked assessment, angina class was II or lower in 34.1% of PTMR patients compared with 13.0% of those medically treated. All indices of the Seattle angina questionnaire improved more with PTMR than with medical care only. By 12 months there had been eight deaths in the PTMR group and three in the medical treatment group, with similar survival in the two groups. INTERPRETATION: PTMR was associated with increased exercise tolerance time, low morbidity, lower angina scores assessed by masked reviewers, and improved quality of life. Although there is controversy about the mechanism of action, and the contribution of the placebo effect cannot be quantified, this unmasked study suggests that this palliative procedure provides some clinical benefits in the defined population of patients.

Stent placement for non-STRESS/BENESTENT lesions: a critical review.

Stenting lesions with favorable characteristics as required for inclusion in the STRESS/BENESTENT trials have yielded superior results to that of PTCA alone. Results for less favorable lesions such as in small vessels, diffuse disease, ostial disease, and saphenous vein grafts are less well established. This review seeks to analyze available data for stent placement in this subset of non-STRESS/BENESTENT lesions.

Inhibition of restenosis with beta-emitting radiotherapy: Report of the Proliferation Reduction with Vascular Energy Trial (PREVENT).

BACKGROUND: Intracoronary gamma- and beta-radiation have reduced restenosis in animal models. In the clinical setting, the effectiveness of beta-emitters has not been studied in a broad spectrum of patients, particularly those receiving stents. METHODS AND RESULTS: A prospective, randomized, sham-controlled study of intracoronary radiotherapy with the beta-emitting (32)P source wire, using a centering catheter and automated source delivery unit, was conducted. A total of 105 patients with de novo (70%) or restenotic (30%) lesions who were treated by stenting (61%) or balloon angioplasty (39%) received 0 (control), 16, 20, or 24 Gy to a depth of 1 mm in the artery wall. Angiography at 6 months showed a target site late loss index of 11+/-36% in radiotherapy patients versus 55+/-30% in controls (P:<0.0001). A low late loss index was seen in stented and balloon-treated patients and was similar across the 16, 20, and 24 Gy radiotherapy groups. Restenosis (>/=50%) rates were significantly lower in radiotherapy patients at the target site (8% versus 39%; P:=0.012) and at target site plus adjacent segments (22% versus 50%; P:=0.018). Target lesion revascularization was needed in 5 radiotherapy patients (6%) and 6 controls (24%; P:<0.05). Stenosis adjacent to the target site and late thrombotic events reduced the overall clinical benefit of radiotherapy. CONCLUSIONS: beta-radiotherapy with a centered (32)P source is safe and highly effective in inhibiting restenosis at the target site after stent or balloon angioplasty. However, minimizing edge narrowing and late thrombotic events must be accomplished to maximize the clinical benefit of this modality.

Final results of the Can Routine Ultrasound Influence Stent Expansion (CRUISE) study.

BACKGROUND: 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. METHODS AND RESULTS: 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%). CONCLUSIONS: These data suggest that ultrasound guidance of stent implantation may result in more effective stent expansion compared with angiographic guidance alone.

Determinants of coronary remodeling in transplant coronary disease: a simultaneous intravascular ultrasound and Doppler flow study.

BACKGROUND: Coronary remodeling plays a significant role in lumen loss in transplant allograft vasculopathy (TxCAD), but the determinants of remodeling are unknown. We assessed the relationship between remodeling and plaque topography, coronary compliance, and blood flow in TxCAD. METHODS AND RESULTS: One artery in each of 27 transplant patients was investigated with simultaneous intravascular ultrasound and coronary flow measurements (basal and hyperemic by Doppler flow wire). At 4 to 8 different cross sections (mean 5.1+/-1. 2), plaque topography (concentric or eccentric) was determined, and total vessel area, lumen area, and intimal/medial area (IMA) were measured. Mean remodeling ratio (vessel area/IMA) in eccentric lesions (E, n=28) was significantly larger than that in concentric lesions (C, n=70) (E 5.87+/-0.93 versus C 3.58+/-0.62; P<0.001), despite similar IMA (E 3.89+/-0.68 versus C 3.90+/-0.41; P=NS) and distribution of imaged segments. Remodeling ratio was consistently larger in eccentric lesions in all 3 vessel segments when analyzed separately, and mean remodeling ratio for each artery was larger in vessels with predominantly eccentric lesions. Coronary compliance ([Delta lumen area/diastolic lumen area]/Delta mean arterial pressure x 10(3)) was also significantly greater in eccentric lesions versus concentric lesions (proximal 1.00+/-0.39 versus 0.22+/-0.04; mid 0.71+/-0.17 versus 0.21+/-0.10; distal 0.43+/-0.13 versus 0. 01+/-0.08; all P<0.01). Coronary flow reserve was also significantly higher in coronary arteries with primarily eccentric lesions (E 2. 49+/-0.64 versus C 1.87+/-0.28; P<0.01). CONCLUSIONS: Vessel remodeling in transplant vasculopathy is significantly greater in eccentric lesions than in concentric lesions, possibly due to greater coronary compliance and resistive vessel function.

Clinical applications of brachytherapy for the prevention of restenosis.

Restenosis remains the bane of percutaneous coronary intervention. Local delivery of radiation, brachytherapy, is a promising therapy for the prevention of restenosis. Animal studies have suggested that brachytherapy may be an effective treatment for preventing restenosis. The type of radiation as well as the doses and delivery systems are currently under study; several clinical trials are underway. This paper reviews the biological basis, including animal studies, of intracoronary brachytherapy as well as the current data from clinical trials.

Catheter-based percutaneous myocardial laser revascularization in patients with end-stage coronary artery disease.

OBJECTIVES: This study evaluates the feasibility and safety of a catheter-based laser system for percutaneous myocardial revascularization and analyses the first clinical acute and long-term results in patients with end-stage coronary artery disease (CAD) and severe angina pectoris. BACKGROUND: In patients with CAD and intractable angina who are not candidates for either coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA), transmyocardial laser revascularization (TMR) has been developed as a new treatment that results in reduced angina pectoris and increased exercise capacity. However, surgical thoracotomy is required for TMR with considerable morbidity and mortality. METHODS: A catheter-based system has been developed that allows creation of laser channels in the myocardium from within the left ventricular cavity. Laser energy generated by a Holmium: YAG (Cardiogenesis Corporation, Sunnyvale, California) laser was transmitted to the myocardium via a flexible optical fiber capped by an optic lens. The optical fiber was maneuvered to the target area under biplane fluoroscopy through a coaxial catheter system permitting movement in three dimensions. RESULTS: Thirty-four patients with severe CAD not amenable to either CABG or PTCA and refractory angina pectoris (Canadian Cardiologic Society [CCS] Angina Scale Class III-IV) were included in the study. Ischemic regions were identified by coronary angiography and confirmed by thallium scintigraphy. The percutaneous myocardial revascularization (PMR) procedure was successfully completed in all patients. In 29 patients, one vascular territory of the left ventricle and in 5 patients, two vascular territories were treated. Eight to fifteen channels were created in each ischemic region. Major periprocedural complications were limited to an episode of arterial bleeding requiring surgical repair. There was one death early after PMR, due to a myocardial infarction (MI) in a nontreated region. Clinical follow-up at 6 months (17 patients) demonstrated significant improvement of angina pectoris (CCS class before PMR: 3.0+/-0.0, six months after PMR: 1.3+/-0.8, p<0.0001) and increased exercise capacity (exercise time on standard bicycle ergometry before PMR: 384+/-141 s, six months after PMR: 514+/-158 s, p<0.05), but thallium scintigraphy failed to show improved perfusion of the laser treated regions. CONCLUSIONS: Percutaneous myocardial revascularization is a new safe and feasible therapeutic option in patients with CAD and severe angina pectoris not amenable to either CABG or PTCA. Initial results show immediate and significant improvement of symptoms and exercise capacity but evidence of improved myocardial perfusion is still lacking.

An embolization containment device.

A coaxial catheter system for containment of distal embolization is described. Utilizing a novel 0.014" hypotube with a distal elastomeric occlusion balloon, the PercuSurge GuardWire functions as a guidewire while trapping distal embolization resulting from more proximal intervention. The particulate debris is evacuated with a single operator exchange aspiration catheter (Export catheter) prior to deflation of the distal occlusion balloon. This animal study confirmed the feasibility of concept. The system was easily delivered through tortuous coronary anatomy. The GuardWire served as an adequate rail for delivery of dilatation balloons and a multitude of stents. There was no evidence of deep wall damage from low-pressure inflation and apposition of the distal occlusion balloon.

A novel stent delivery catheter: the Intella Trinity balloon.

The Trinity catheter is a novel multiballoon device designed to facilitate stent delivery by providing for predilatation, stent deployment, and further expansion on a single shaft. The device was tested extensively in a canine model with a variety of stents before being used in a limited human feasibility trial in Europe. A description of the device and its initial human application is presented.