Evolution of percutaneous balloon aortic valvuloplasty in the treatment of patients with aortic stenosis.

Symptomatic, severe aortic stenosis (AS) is associated with a dismal prognosis with conservative management only; the mortality rate is >50% at two years with medical treatment alone. In 1986, Cribier first introduced the percutaneous balloon aortic valvuloplasty (BAV) concept in patients with acquired severe AS. The initial enthusiasm surrounding this technique, touted as an alternative to surgical aortic valve replacement (SAVR) in older patients with AS, waned with subsequent large registries, which showed failure of the procedure to alter the natural history of calcific AS and its associated procedural morbidity. For many years BAV has been used as palliative treatment for short-term symptom relief in elderly, non-surgical patients. The timely surge in transcatheter aortic valve replacement (TAVR) rejuvenated and resurrected the dormant field of BAV. By its use to predilate the stenosed valve for easier delivery of the prosthesis, valvuloplasty now plays an integral role in the majority of TAVR procedures. BAV is successfully used as a bridge to SAVR and TAVR with better outcomes and is used as a standalone treatment for symptom relief in high-risk patients and for temporary stabilization of hemodynamically unstable patients. BAV can be used as a selection tool to determine if the patient will benefit from valve replacement if they have other comorbidities, such as severe pulmonary hypertension, severe lung disease, very poor ejection fraction, or frailty.

Saphenous vein graft interventions: strategies and devices to minimize distal embolization.

Percutaneous coronary intervention of degenerated saphenous vein grafts remains relatively high risk when compared to native vessel interventions, despite advances in pharmacotherapy and embolic protection. This article discusses the phenomenon of distal embolization that seems to plague saphenous vein graft interventions, reviews device-based strategies for embolic protection, and offers a perspective on the utility of percutaneous saphenous vein graft intervention in both elective and acute settings.

Glycoprotein IIb/IIIa inhibitors and bivalirudin in patients undergoing percutaneous coronary intervention.

Percutaneous coronary intervention (PCI) is currently the standard of care for patients presenting with acute coronary syndrome (ACS), as well those patients with "stable" angina who have failed medical therapy in whom PCI is an acceptable alternative to surgical revascularization. The aim of adjunctive antiplatelet and antithrombotic therapy during PCI is to alleviate the risks associated with platelet activation and aggregation, iatrogenic plaque rupture, and thrombus formation during. The aim of this review is to summarize the evidence that has emerged from the randomized studies comparing a strategy combining heparin and a glycoprotein IIb/IIIa inhibitor (GPI) with that of bivalirudin in patients undergoing elective and urgent PCI.

Percutaneous revascularization in women with coronary artery disease: we've come so far, yet have so far to go.

Coronary artery disease (CAD) has traditionally been thought of as a disease that predominantly affects men. Women, however, are more likely than men to die from a myocardial infarction (MI). In this article, the data on access to cardiovascular care, treatment of stable and unstable coronary disease, and outcomes in women undergoing percutaneous coronary intervention (PCI) will be reviewed. Despite increased awareness of heart disease in women, and improved outcomes after PCI, women with MI have more mortality and delays to treatment than men. Women with CAD have symptoms that differ from men with CAD. Improved understanding of the symptoms of CAD in women by patients and health care providers may improve treatment and outcomes in women with CAD.

A critical appraisal of the safety and efficacy of drug-eluting stents.

Drug-eluting stents (DESs) have largely demonstrated their superiority to bare-metal stents (BMSs) with respect to in-stent restenosis. Since the US Food and Drug Administration (FDA) approved the first DES in 2003, there has been a significant increase in the use of these devices. They are used in 70-80% of all stent procedures worldwide. Nevertheless, safety concerns stemming from reports of increased risk of late stent thrombosis (ST) and myocardial infarction (MI) have tempered the enthusiasm that the advent of these stents originally generated. New generation DESs with novel polymers, antiproliferative drugs, and improved platforms are now approved and available for use. In this review we provide a critical appraisal, based on published clinical data, of the safety and efficacy of various DESs.

Emergence of the concept of platelet reactivity monitoring of response to thienopyridines.

Clinical trials have demonstrated the beneficial impact of clopidogrel in preventing major adverse cardiovascular events (MACE), particularly in patients undergoing percutaneous coronary intervention (PCI). The concept of biological clopidogrel resistance emerged with the finding of persistent platelet activation despite clopidogrel therapy in some patients. Further, a link between biological clopidogrel resistance and thrombotic recurrence after PCI was observed and a threshold of platelet reactivity (PR) for thrombotic events was suggested. Consistently, in recent trials, enhanced PR inhibition translated into a reduction in the rate of MACE after PCI. This review aims to present the emergence of the concept of PR monitoring in patients undergoing PCI following recent advances in this field.

Intravascular ultrasound guidance in drug-eluting stent deployment.

The role of routine intravascular ultrasound (IVUS) guidance during percutaneous coronary intervention (PCI) in the bare metal stent era remains controversial. The potential to reduce revascularization was reported without impacting non-fatal myocardial infarction and death. Drug-eluting stents (DES) have realized improved clinical results in patients undergoing PCI but are not free of restenosis and are limited by thrombosis, particularly in more complex lesion types. Stent under-expansion, malposition, and incomplete lesion coverage have been identified as the key mechanisms of DES failure. The identification of these features on IVUS and their subsequent treatment may lead to improved clinical outcomes. Though a clinical benefit is intuitive, results from randomized trials are still needed to justify routine IVUS guided DES implantation. The Authors provide a review of the currently available evidence pertaining to the potential clinical benefit of IVUS guidance in DES implantation.

How to approach drug-eluting stent restenosis.

Drug-eluting stents (DES) have been a major advance in percutaneous coronary intervention reducing restenosis and repeat revascularization. The application of DES to the treatment of complex lesion and patient subsets has resulted in significant rates of DES restenosis or failure. Though predominantly focal, substantial rates of non-focal DES restenosis are being observed. Non-focal disease most likely represents a resistant process that will remain a therapeutic challenge. An understanding of the causative mechanical and biological factors is essential for the prevention and treatment of DES restenosis. Robust data relating to the treatment efficacy for this problem is lacking. At present, repeat DES or vascular brachytherapy appear to the best available options. Evidence from randomized controlled trials and large registries is required to establish a formal treatment approach. We provide guidelines based on current available evidence.

Intracoronary photodynamic therapy reduces neointimal growth without suppressing re-endothelialisation in a porcine model.

OBJECTIVE: To examine the effects of intracoronary PhotoPoint photodynamic therapy (PDT) with a new photosensitiser, MV0611, in the overstretch balloon and stent porcine models of restenosis. METHODS: 28 pigs were injected with 3 mg/kg of MV0611 systemically 4 h before the procedure. Animals were divided into either the balloon overstretch injury (BI) group (n = 19) or the stented group (n = 9). After BI, a centred delivery catheter was positioned in the artery to cover the injured area, and light (532 nm, 125 J/cm(2)) was applied to activate the drug (n = 10). Control arteries (n = 9) were not activated by light. In the stented group, the drug was light activated before stent deployment. Serial sections of vessels were processed 14 days after treatment in the BI group and 30 days after treatment in the stented group for histomorphometric or immunohistochemical analysis. RESULTS: Intracoronary PDT significantly reduced intimal thickness in both BI and stented arteries (about 65%: 0.22 (SEM 0.05) mm v 0.62 (0.05) mm, p < 0.01; and about 26%: 0.40 (0.04) mm v 0.54 (0.04) mm, p < 0.01, respectively). PDT increased luminal area by

Have we solved the problem of late thrombosis?

Late thrombosis (angiographic total occlusion associated with an acute coronary syndrome) is potentially a life-threatening complication after intracoronary radiation therapy. This review is intended to explore the pre-clinical and clinical evidence for late thrombosis, discuss the etiology, and provide guidelines for future management. Although we have gained a greater understanding of this complex entity, further research is required to curtail late thrombosis rates.

Clinical outcomes of compromised side branch (stent jail) after coronary stenting with the NIR stent.

Acute side-branch (SB) compromise or occlusion stent jail after native coronary stenting is a matter of concern. Attempts at maintaining SB patency can be a technical challenge. The purpose of this study was to determine the clinical impact of SB compromise or occlusion in patients undergoing stenting of parent vessel lesions. We evaluated in-hospital and long-term clinical outcomes (death, Q-wave myocardial infarction, and repeat revascularization rates at 6 months) in 318 consecutive patients undergoing NIR stent implantation across an SB. Based on independent angiographic analysis, 218 (68.6%) patients had no poststent SB compromise, 85 (26.7%) patients had narrowed SB (> 70% narrowing, without total occlusion), and 15 (4.7%) patients had an occluded SB after stent implantation. The baseline patient and lesion characteristics were similar between the groups. Procedural success was 100%. Patients with SB occlusion had a higher stents/lesion ratio (P < 0.006). Side-branch occlusion was associated with higher in-hospital ischemic complications (Q-wave myocardial infarction, 7%; non-Q-wave myocardial infarction, 20%; P < 0.05) compared to patients with SB compromise or normal SB. At 6-month follow-up, there was a trend for more myocardial infarctions in the group with SB occlusion during the index procedure (Q-wave myocardial infarction, 7% vs. 1% in the narrowed and 0% in normal SB; P = 0.09). However, late target lesion revascularization and mortality were similar in the three groups (P = 0.91). SB occlusion after parent vessel stenting is associated with more frequent in-hospital Q-wave and non-Q-wave myocardial infarctions. However, with the NIR stent, side-branch compromise or occlusion does not influence late (6 month) major adverse events, including death, myocardial infarction, or need for repeat revascularization.

Comparative efficacy of gamma-irradiation for treatment of in-stent restenosis in saphenous vein graft versus native coronary artery in-stent restenosis: An intravascular ultrasound study.

BACKGROUND: We used serial volumetric (post-irradiation and follow-up) intravascular ultrasound (IVUS) to compare the effectiveness of gamma-irradiation ((192)Ir) in saphenous vein graft (SVG) versus native coronary artery in-stent restenosis (ISR). METHODS AND RESULTS: The study population consisted of 47 patients with native coronary artery ISR from WRIST (Washington Radiation for In-Stent Restenosis Trial) and 31 patients with SVG ISR (12 from the WRIST and 19 from SVGWRIST). After irradiation and at 6-month follow-up, stent, lumen, and intimal hyperplasia (IH, stent minus lumen) areas were measured every 1 mm. ISR length was similar in the 2 groups (29+/-12 versus 29+/-14 mm, P=0.9). Post-intervention measurements of stent (280+/-154 versus 324+/-270 mm(3), P=0.4), lumen (184+/-91 versus 214+/-172 mm(3), P=0.3), and IH (96+/-77 versus 109+/-119 mm(3), P=0.5) volumes were similar in the 2 groups. The post-intervention minimum lumen cross sectional areas tended to be smaller in native artery ISR lesions (4.7+/-1.7 versus 5.4+/-1.6 mm(2), P=0.11). During follow-up, there was a slight increase in IH volume (9+/-38 mm(3)) in native artery ISR lesions and a slight decrease in IH volume in SVG ISR lesions (-9+/-32 mm(3), P=0.0463). There was also a slight decrease in minimum lumen area in the native artery ISR lesions versus a slight increase in minimum lumen area in the SVG ISR lesions (-0.8+/-1.7 versus 0.2+/-1.1, P=0.0087). As a result, the follow-up minimum lumen area in native artery lesions was smaller than in SVG ISR lesions (4.1+/-2.1 mm(2) versus 5.6+/-2.2 mm(2), P=0.0067). CONCLUSION: gamma-Irradiation with (192)Ir brachytherapy appears to be as effective in SVGs as it is in native artery ISR lesions.

Effects of 32P radioactive stents on in-stent restenosis in a double stent injury model of the porcine coronary arteries.

BACKGROUND: The major limitation of coronary stenting remains in-stent restenosis, due to the development of neointimal proliferation. Radioactive stents have demonstrated the ability to reduce this proliferation in the healthy nonatherosclerotic porcine animal model. However, inhibition of tissue proliferation in the in-stent restenotic lesion in a porcine model is not well characterized. The objective of this study was to examine the efficacy and safety of the 32P radioactive stent for the treatment of in-stent restenosis in a double stent injury model of the porcine coronaries. METHODS AND MATERIALS: Eighteen coronary arteries in 9 pigs underwent nonradioactive stent (8 mm in length) implantation. Thirty days after the initial stent implantation, a 32P radioactive stent (18 mm in length) with an activity of 0 and 18 microCi was implanted to cover the initial stent. The swine were killed 30 days after the second stent implantation. Histomorphometric analysis was performed for vessel area (VA), stent strut area (SSA), intimal area (IA), and lumen area (LA). RESULTS: Injury scores, VA, SSA, and LA were similar among the control and radiated groups. Neointimal formation was significantly reduced after placement of radioactive stents as compared to control in both the overlapped (0.93 +/- 0.12 vs. 1.31 +/- 0.51 mm(2), p < 0.05) and nonoverlapped segments (1.14 +/- 0.21 vs. 1.91 +/- 1.04 mm(2), p < 0.05). The smooth muscle cell index in the neointima was reduced. Intimal fibrin was increased in the radiated group as compared to the control (p < 0.01 respectively). CONCLUSIONS: 32P radioactive stents may be safe and effective in reducing neointimal formation leading to in-stent restenosis. Longer follow-up will be required to examine whether these positive findings can be maintained.

The effect of intracoronary radiation for the treatment of recurrent in-stent restenosis in patients with chronic renal failure.

OBJECTIVES: This study was designed to analyze the in-hospital and six-month clinical and angiographic outcomes of patients with chronic renal failure (CRF) treated with intracoronary radiation for the prevention of recurrence of in-stent restenosis. BACKGROUND: Patients with CRF are at a higher risk than the general population for accelerated atherosclerotic cardiovascular disease and for restenosis after percutaneous coronary intervention. Previous studies have shown the effectiveness of both beta and gamma radiation in preventing recurrent restenosis in patients with in-stent restenosis. METHODS: We studied the in-hospital and six-month clinical and angiographic outcomes of 118 patients with CRF and 481 consecutive patients without CRF who were treated with intracoronary radiation for the prevention of recurrence of in-stent restenosis in native coronaries and saphenous vein grafts. RESULTS: Patients with CRF were usually older, women, hypertensive and diabetic, with multivessel disease and with reduced left ventricular function. In-hospital outcome for patients with CRF was marred by a higher incidence of death, non-Q-wave myocardial infarction and major vascular and bleeding complications. At six-month follow-up, the mortality rate was higher in patients with CRF, 7.6% compared with 1.9% in non-CRF patients (p = 0.003). Restenosis, target lesion revascularization (TLR) and target vessel revascularization (TVR) rates were similar in the two groups. In patients with CRF, radiation therapy compared to placebo reduced restenosis (53.8% vs. 22.6%, p = 0.04), TLR (71.4% vs. 15.3%, p < 0.0001) and TVR (78.6% vs. 23.7%, p = 0.0002). CONCLUSIONS: Intracoronary radiation for the prevention of recurrence of in-stent restenosis achieved similar rates of restenosis and revascularization procedures in patients with and without CRF. Despite this benefit, patients with renal dysfunction continued to have significantly higher in-hospital and six-month adverse outcomes.

An intravascular ultrasound classification of angiographic coronary artery aneurysms.

The purpose of this study was to use intravascular ultrasound (IVUS) to clarify the morphology of coronary aneurysms diagnosed by angiography. Seventy-seven consecutive patients with an aneurysmal dilatation in a native coronary artery diagnosed by angiography (defined as a lesion lumen diameter 25% larger than reference) were evaluated by IVUS. IVUS true aneurysms were defined as having an intact vessel wall and a maximum lumen area 50% larger than proximal reference. IVUS pseudoaneurysms had a loss of vessel wall integrity and damage to adventitia or perivascular tissue. Complex plaques were lesions with ruptured plaque or spontaneous or unhealed dissection. Aneurysmal dilatation and reference segments were assessed using standard IVUS quantitative techniques. Twenty-one lesions (27%) were classified as true aneurysms, 3 (4%) were classified as pseudoaneurysms, 12 (16%) were complex plaques, and the other 41 (53%) were normal arterial segments adjacent to > or =1 stenosis. The maximum lumen area within the aneurysmal segment was largest for pseudoaneurysm (35.1 +/- 10.4 mm(2)), 22.1 +/- 9.9 mm(2) for true aneurysm, and similar for complex plaques (11.2 +/- 3.5 mm(2)) and normal segments with adjacent stenoses (13.8 +/- 6.4 mm(2)): analysis of variance, p <0.0001. Only one third of angiographically diagnosed aneurysms had the IVUS appearance of a true or pseudoaneurysm. Instead, most angiographically diagnosed aneurysms had the morphology of complex plaques or normal segments with adjacent stenoses.