Ashok Seth

Revascularization of a thrombosed, previously stented aorto‐renal graft using combined directional atherectomy and AngioJet thrombectomy

We report an interesting case with bilateral PTFE aorto‐renal grafts of which one graft underwent balloon angioplasty and stenting for proximal stenosis. Combined debulking by AngioJet thrombectomy and Simpsons directional atherectomy was performed within the stent following reocclusion of the graft 9 months later. Cathet. Cardiovasc. Intervent. 46:85–88, 1999.

“Anti-healing” versus “pro-healing”

The Drug Eluting Stent (DES) has revolutionized the treatment of obstructive and symptomatic coronary artery disease by decreasing restenosis. It is gratifying to see complex and multiple lesions, long lesions in small vessels, bifurcation lesions, and total occlusions looking ‘‘pristine and frozen in time’’ even years after DES implantation—which we rarely saw in Bare Metal Stent (BMS) era 10 years ago. However, the initial ‘‘mass euphoria’’ of 0% restenosis in the RAVEL study has sobered down over the last six years as we keep encountering a new set of complications in our daily practice—that occasional patient with aneurysmal dilatation at the site of DES implantation; the patient who discontinues dual antiplatelet therapy two years later for a noncardiac surgery and has an acute MI; worse still, a patient who four years after DES implantation has extremely late stent thrombosis (VLST) and MI despite continuing dual antiplatelet therapy. While debates, with evidence and counter evidence, rage regarding the long-term safety of DES, we all realize that a small and definite risk of sudden and unforeseen VLST continues to remain with our patients for years following DES implantation. We are no more overjoyed; we wish we could do things differently and are looking for answers? VLST following DES is an interplay of numerous factors: procedure and operator-related, lesion-related, patient-related, antiplatelet therapy-related, stentand polymer-related. But the most consistently and persistently prevalent factor is the ‘‘anti-healing’’ property of DES. Following intimal vascular injury due to stent implantation, the nature heals the vessel wall by reforming a robust and functional endothelium covering the stent and the injured segment. Sirolimus and Paclitaxel while suppressing smooth muscle cell migration and neointimal proliferation to decrease restenosis, also suppress endothelial cells and inhibit re-endotheliazation. They are therefore ‘‘anti-healing’’. The nonendothelized stent struts could predispose to thrombosis even many years later [1]. For the same reason, newer generation of DES using different ‘‘anti-healing’’ drugs, irrespective of new polymer or stent platforms, would continue to create similar safety concerns over many years till proven otherwise. In this issue of CCI, Miglionico et al. publish their experience of a novel and radically opposing approach; ‘‘pro-healing’’ using endothelial progenitor cell (EPC) antibody coated Genous R Stent (Orbus Neich, Fort Lauderdale, Florida). This stainless steel bio-engineered stent is coated with antibodies specific to CD34 and thus captures the circulating EPCs derived from bone marrow. The EPCs are responsible for natural intimal healing and accelerate the process of re-endotheliazation over the stent thus providing protection against thrombosis as well as hopefully decreasing restenosis. In this single center prospective registry, 93 Genous R Stent were implanted in 80 patients who were at high risk for stent thrombosis or restenosis. Majority patients received dual antiplatelet therapy for 2 months only. Over a mean follow up of 14 months, there was no stent thrombosis. The 8-month angiographic restenosis rate in prospectively defined 31 patients subgroups was 19% and late loss was 0.88 mm—although only 5% of patients had ischaemia driven TLR. Keeping in mind the relatively large vessels treated (mean reference vessel diam: 3.3 mm) and that two third patients had 18 mm stents; the results of this relatively small registry may not look impressive. Other perspective registries using the Genous R stent have demonstrated excellent safety profile in the intermediate term with low TLR’s. The HEALING II Study (Healthy Endothelial Accelerated Lining Inhibitors Neointimal Growth) enrolled 63 patients in 10 European Centers who received Genous R stent followed by one month of dual antiplatelet therapy. The mean lesion length was 9.83 mm. The 9 month TLR (6.3%) and MACE (7.9%) was unchanged at 18 months. There was no sub acute or late stent thrombosis. Interestingly there was a regression of late

Another “nail in the coffin” for protection devices in acute MI?

The goal of primary Percutaneous Coronary Intervention (PCI) in Acute Myocardial Infarction (AMI) is to achieve maximal myocardial salvage by improving blood flow through epicardial vessels as well as through the microcirculation, thus leading to improved outcomes. This however is not always easy to achieve, given the fact that we are dealing with a ruptured soft friable plaque with overlying thrombus, which has a tendency to embolize downstream causing occlusion of the distal macro and microcirculatory bed. This may either occur spontaneously or with manipulations of wire passage and balloon predilatation; but commonly occurs after the scissoring effect of high pressure stent implantation. Thus, it is not unusual for brisk antegrade flow in the vessel to deteriorate after stent implantation to slow or no flow due to plugging of micro circulation despite normal looking and patent epicardial arteries. Recovery from this is often prolonged, with continued chest pain and non resolution of ST-T changes indicating continued myocardial damage despite return of good flow. It is therefore intuitive to believe that mechanical removal of thrombus during primary PCI prior to balloon dilatation and stent implantation could decrease the risk and extent of distal embolization and hence improve myocardial salvage. In this issue of the Journal, Korn et al. [1] have reported their study on the use of Export Aspiration System during PCI in 79 patients with acute coronary syndrome and visible thrombus and have compared it to another group of 79 historical controls with similar clinical presentation treated without export aspiration. Majority of patients in both groups had ST elevation myocardial infarction (STEMI) with TIMI 0 flow (66% vs. 77%). There was no difference in final TIMI-3 flow (69% vs. 72%), myocardial blush grade-3 (57% vs. 56%), or in hospital MACE (11.4% vs. 11.4%; even though the study was not powered for this) in the treated group versus controls. Hence the authors conclude that routine removal of visible thrombus by Export Aspiration System provides no substantial benefits. The study has limitations of being a small single centre registry rather than a randomized control trial and includes a variety of patients and clinical presentations across the spectrum of acute coronary syndrome. It also has a large number of saphenous vein graft (SVG) intervention in the treatment arm in whom export aspiration alone may not be successful without use of a distal protection device. It is however interesting that previous studies for microcirculatory protection using Guardwire Plus balloon occlusion and aspiration system [2] and Filterwire EZ–distal filter device [3] in similar settings have also not shown any angiographic or clinical benefits. These results are not just disappointing but contradict our logical hypothesis for which these trials were designed. After all both Percusurge Guardwire and FilterWire when used during PCI in SVGs, which are also complicated by similar distal embolization and slow flow, have been conclusively shown to protect the distal vascular bed by capturing and removing macroscopic grummous, cheesy, and thrombotic debris leading to decreased complication rates and MI [4,5]. So why do these devices not work in the setting of AMI? Before we put another nail in the coffin for these aspiration/distal protection devices let us put all this to reason! It stands to reason that thrombus and soft plaque embolization is not the only mechanisms affecting myocardial perfusion and microcirculatory integrity. AMI leads to endothelial dysfunction, increased platelet aggregability, vasospasm, vascular inflammation and edema, neurohormonal release; all of which predominantly affect the microcirculation. Pharmacological approaches targeted at these pathophysiological mechanisms in addition to device protection may therefore be necessary. Pretreatment of the vascular

Ectatic coronary arteries: “Experienced innovation”†

Ectatic coronary arteries (ECA) are not an infrequent finding but uncertainty exists regarding their actiology, prognosis, and therapeutic strategies. The ectatic coronary segment results in stagnation and swirling of blood as well as poor antegrade flow down the vessel. A relatively common presentation is acute coronary syndrome due to increased propensity for thrombus formation with or without distal embolization even in the absence of stenotic coronary artery disease. ECA may be considered in some ways akin to degenerated saphenous vein grafts (SVG). For patients with ECA without stenotic coronary artery disease who are asymptomatic, there is no data to support long-term oral anticoagulation. However, I have patients with triple vessel ECA who even in the absence of coronary stenosis presented with recurrent MI in different arteries over a period of follow up because of spontaneous thrombosis. It is prudent to treat such patients with oral anticoagulation in addition to aspirin. In the absence of any recommendation, the INR is usually maintained in the range of 1.5–2.5. Similar strategy may be applicable to those patients with ECA who have recurrent unstable angina without stenotic coronary artery disease. ECA patients with stenotic disease pose multiple challenges—the large vessel size and the lack of dedicated large size stents; visible or ‘‘invisible layered’’ thrombus in the ectatic segment leading to risk of macro or micro distal embolization; slow flow phenomenon; periprocedure infarctions and vessel to stent mismatch along its length. Thus new strategies and innovations are warranted on a case to case basis. Abu Fadel et al. [1] overcome this problem elegantly by the use of tapered self expanding Rx Acculink Carotid Stent in their two patients with stenotic ECA with excellent results. In the absence of evidence based approach, one can only rely on lessons learnt from treating ECA and SVG over a period of time. If large bulk of thrombus is present but is nonocclusive with TIMI III flow, it is sensible to use an IIb/IIIa receptor antagonist followed by heparin injections/oral anticoagulation for 2–6 weeks. Often the thrombus dissolves leaving behind a clear vascular bed for a better assessment of underlying stenosis and a safer intervention if necessary. If the thrombus is occlusive, then thrombosuction with or without distal protection may be necessary to restore flow and prevent distal embolization. Because of the large size of these vessels Possis Angiojet (Possis Medical) is usually more effective than thrombo aspiration catheters like Export (Medtronic) for adequate thrombus clearance. The second issue is the assessment of underlying stenosis which may not be critical but ‘‘looks so’’ in comparison to the ectatic segment. It is best to avoid ‘‘occulostenotic reflex’’ and assess the lesion by IVUS. Once intervention is decided, the following strategies may prove useful. In the 1990s, the coronary self expanding ‘‘Magic Wall Stent’’ (Boston Scientific Corporation, Maple Grove, Minnesota) was a very useful device as it could be deployed in upto 6 mm ECA’s. Subsequently, in early 2000s, the Symbiot self expanding, PTFE layered stent system (Boston Scientific Corporation) designed for vein grafts was also useful for ECAs. Its results from the open label Registry Symbiot-I in SVG were very favorable but the randomized Symbiot-II trial was disappointing. Self expanding stents are a natural choice for ECA because they can first adapt to the variations in size and contours of the ectatic segments, second they come in larger sizes, third they trap the layered thrombus behind the struts, and fourth they exert a prolonged outward radial force for improved stent apposition over a period of time. In the present case report, Dr. Abu Fadel’s approach has taken advantages of all of the above with the currently available self expanding stent (which are only available for Carotids/Peripherals). But there are other options. Learning from the experiences in SVG—one should explore the option of

Following a crush and a kiss: Why is it lonely out there?

The bifurcation lesion has remained one of the most exciting challenges for the interventional cardiologist since the advent of angioplasty. It has tested our skills, innovation, and creativity and, despite best strategies and execution, has given uncertain outcomes. With increased realization that CPK rises related to side-branch occlusion could adversely impact outcomes, achieving a full patency of the side branch (SB) at the end of the procedure became important in the short and long term. To achieve this, numerous bifurcation techniques were developed in the bare metal stent (BMS) era, almost all of them involving placement of two stents: one in the main vessel and the other in the side branch (T-stenting, modified Tstenting, culotte, Yand V-stenting, and provisional Tstenting). However, as time went on, it became clear that one stent had better outcomes than two stents, provided the side-branch patency could be maintained by balloon dilatation alone [1]. With the drug-eluting stents (DES) being the magic bullet for all complex lesions, the enthusiasm for two-stent strategy resurfaced, only to be dampened by the results of randomized trials of sirolimus-eluting stents in bifurcation lesions. The multicenter trial demonstrated that while the 6-month outcomes were better than historical controls of the BMS era, the restenosis rate in the sidebranch stent was unacceptably high when two stents were implanted [2]. One of the limitations of the study was a nearly 50% rate of crossover from a single-stent strategy to two-stent strategy, thus contaminating the group and subsequent clinical outcomes. It was also felt that the high restenosis rate in the side branch was related to the lack of complete coverage of SB ostium. Keeping in mind the high crossover rate, it was also felt that a definitive technique using two stents and achieving good SB ostial coverage was needed. To address the crossover issue, Pan et al. [3] performed a randomized study of single stent vs. two stents in which crossover was prevented unless there was a severe persistent stenosis or flow-limiting dissection of SB (only 1 out of 47 crossed over), thus keeping the two groups pure. They still showed that single-stent strategy with SB balloon dilatation was equivalent to two-stent strategy as regards clinical outcomes and obviously simpler and more cost-effective. While for most, the pendulum swung back to singlestent strategy with provisional SB stenting; for others, innovations in two-stent strategy continued. This led to description of the crush technique, which was simpler to perform but surprisingly did not achieve the desired clinical outcomes [4]. We must compliment John Ormiston and his colleagues for developing a bench-top model to test out bifurcation strategies, the importance of which has increased in the DES era. Despite the obvious limitations of a plexiglass tube bifurcation model versus human coronary arteries, Ormiston et al. [5] had earlier provided basic insights into the optimization of the crush technique. In this issue, Ormiston et al. [6] have meticulously studied a variety of commonly used stenting and postballoon dilatation strategies with a variety of commonly used DES platforms and provide some most interesting insights. For me, this study is a landmark in bifurcation treatment strategies in the DES era. The important and unexpected observations from their present study are as follows. (a) The culotte technique followed by a final kissing balloon inflation provides good stent expansion and apposition in the main vessel and excellent scaffolding of the SB ostium, but is limited by the size of the hole created in the stent, especially for the main vessel, which for Bx Velocity platform (Cypher stent; Cordis) was only 2.5 3 3.0 mm despite using a 3.5 mm balloon at 20 atm. The technique could find favor with the Express and Liberte platforms (Taxus stent; Boston Scientific), in which the cells can be stretched to create nearly a 3.5 mm opening. (b) The following internal (reversed) crush with tubular stents, the crushed SB stent is well flattened against the main-vessel stent and still the SB ostium remains fully covered. This is in contradiction to the external crush, where following the crush the SB ostium gets uncovered and requires a final kissing balloon dilata-