confluence Transcatheter aortic valve implantation (TAVI): an example of how to organise a TAVI programme

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1 issue two january 10 confluence concepts and opinions in invasive cardiology Transcatheter aortic valve implantation (TAVI): an example of how to organise a TAVI programme EDITOR-IN-CHIEF Christian W Hamm (germany) EDITORIAL BOARD Rossella Fattori (ITALY) Anthony Gershlick (UK) Henning KelbÆk (denmark) Irene Lang (AUSTRIA) Chaim Lotan (ISRAEL) Vincent Riambau (SPAIN) Alec Vahanian (france) Arnoud van t Hof (the netherlands) Thomas walther (Germany) Franz Weidinger (austria) Indications for stent grafts in type B aortic dissection The future of coronary stent design The management of ACS: interview with Irene Lang Highlights from TCT 2009 Supported by an unrestricted educational grant from Medtronic, Inc

2 Dear colleagues, EDITOR-IN-CHIEF Christian W Hamm Happy New Year and welcome to the second issue of Confluence: concepts and opinions in invasive cardiology. Previously, Piazza and colleagues discussed the huge potential for TAVI procedures in the future. In this issue, Prof ten Berg and his colleagues provide a fascinating insight into their very own TAVI programme in the Netherlands. In their article, they describe the decision-making process they use to identify the most suitable candidate patients for TAVI and how they coordinate these procedures with a dedicated multidisciplinary team. In addition, this issue includes discussion on the management of type B aortic dissection by Prof Nienabar and Dr Akin and a review of the latest advancements in coronary stent design by Prof Radke and Dr Regar. As part of our regular features we talk to Prof Irene Lang about the management of ACS and Drs Holger Nef and Helge Möllmann provide meeting highlights from this year s TCT. We hope that you continue to enjoy Confluence and, importantly, find it a valuable resource. Your opinion is important to us, so please let us know what you think of this issue and what you would like to see in future issues by ing us at confluence@axon-com.com or by returning the freepost comments card included in this issue. Contents Original article Transcatheter aortic valve implantation (TAVI): an example of how to organise a TAVI programme 3 J M ten Berg, B Swinkels, E G Mast, R Heijmen, T de Kroon Expert opinion Indications for stent grafts in type B aortic dissection 10 I Akin, CA Nienaber Review article The future of coronary stent design 16 E Regar, PW Radke Interview The management of ACS: interview with Irene Lang 21 Christian W Hamm Meeting report Highlights from TCT H M Nef, H Möllmann 2

3 original article Transcatheter aortic valve implantation (TAVI): an example of how to organise a TAVI programme J M ten Berg R Heijmen As the population ages, aortic valve stenosis becomes more prevalent. Patients who are symptomatic due to aortic valve stenosis have a severely diminished life expectancy and are, therefore, candidates for surgical aortic valve replacement. 1 That said, many of these patients (estimated up to one-third) do not undergo surgery, mainly because of the presence of severe comorbidities and the associated surgical risk. 2 This group of high-risk patients may be candidates for the recently developed transcatheter aortic valve implantation (TAVI) strategies In this article, we describe the decision-making process and how we perform the procedure in our clinic with a focus on the multidisciplinary approach we use. Catheter laboratory equipment Following thorough training in a skills lab and onsite support from a demonstrator (in the first 10 cases), we started to perform TAVI with the transfemoral approach using the CoreValve system (Medtronic Inc, Minneapolis, MN, USA) in June Since then, our TAVI programme has expanded to also include the SAPIEN valve (Edwards Lifesciences, Irvine, CA, USA) using the transapical approach. In our clinic, both operators (interventional cardiologist and cardiothoracic surgeon) were trained to use the CoreValve and the SAPIEN systems and both were trained in all the necessary associated procedures, including puncture techniques, valve crossing, valve placement etc. The only procedure solely performed by the cardiothoracic surgeon is the placement of the left anterolateral mini-thoracotomy. To help facilitate these procedures, we are currently developing a new, fully equipped, hybrid operating room at our facility. Until this is complete, we perform these procedures in the catheterisation laboratory, as the use of fluoroscopy is crucial. Patient selection The selection of patients who are candidates for TAVI is very important. The decisionmaking process needs to be done within a multidisciplinary team, consisting of interventional cardiologists, cardiothoracic surgeons, echocardiographers, and dedicated cardiac anaesthesiologists. Initially, patient Baseline requirements for evaluation in the heart team Clinical data (e.g. severity of symptoms, NYHA class) Data on co-morbidities (e.g. renal function and lung disease [FEV 1 ]) Life expectancy > 1 year TTE to evaluate the severity of the aortic valve stenosis as well as mitral valve disease. If needed, low-dose dobutamine echo to exclude pseudo aortic valve stenosis Recent (< 1 year) coronary and left ventricular angiogram Pulmonary pressure based on invasive measurement or echocardiography Visualization of the aorta ascendens (angiography or CT) STS score and EuroSCORE Additional requirements for evaluation in the transcatheter valve team Measurement of annulus size initially by TEE Visualisation of size, calcification and tortuosity of iliac and femoral arteries Calcification of the aortic arch (angiography, CT angiogram, MR angiogram) jurriën M TEN BERG ben swinkels GIJS MAST Department of Cardiology robin HEIJMEN TOM de kroon Department of Cardiothoracic Surgery St Antonius Hospital, Nieuwegein, the Netherlands Table 1 Requirements for evaluation KEY CT, computed tomography; FEV 1, forced volume vital capacity; MR, magnetic resonance; NYHA, New York Heart Association; STS, Society of Thoracic Surgeons; EuroSCORE, European System for Cardiac Operative Risk Evaluation; TTE, transthoracic echocardiography; TEE, transoesophageal echocardiography 3

4 fig. 1 SAPIEN device fig. 2 CoreValve device data (including regional and extra-regional referrals) are discussed in the heart team (Table 1). Following this, and only when considered unsuitable for conventional aortic valve surgery, patients are referred to the transcatheter valve team. This team consists of two interventional cardiologists and two cardiothoracic surgeons who decide on the suitability of TAVI as well as the best approach (transfemoral or transapical; see Table 1 for additional requirements). All candidates for TAVI are seen in the outpatient clinic by an interventional cardiologist or cardiothoracic surgeon as well as an anaesthesiologist from the team to assess the life expectancy and the frailty of the patient, and to discuss with the patient and his/her family the risks associated with the procedure. At the same time, it is also important to highlight that surgery, in the event of complications during TAVI, is not an option for patients who have been previously denied surgery. In patients with cerebral disease (e.g. Alzheimer s disease), the evaluation from a neurologist and/or geriatrician is also taken into consideration. Throughout the decision-making process we do not follow strict criteria based on the STS score or EuroSCORE alone. 11,12 These scores were not developed for high-risk aortic valve replacement in patients (most high-risk patients were excluded from the original scores STS or EuroSCORE) and they can overestimate the actual mortality. Importantly, they do not include factors such as severe pulmonary fibrosis, a porcelain aorta or the frailty of the patient. Therefore, we consider a range of factors in the decision-making process and consider clinical judgment of the utmost importance. In addition, we do not accept patients for TAVI purely based on the personal preference of the patient. Which TAVI valve to use There are currently two valves commercially available: the balloon-expandable SAPIEN device which comes in two sizes (23 mm valve for annulus sizes up to 21 mm, and 26 mm valve for annulus sizes up to 25 mm; Figure 1) and the CoreValve system, consisting of a self-expanding valved frame which also comes in two sizes (26 mm stent for annulus sizes up to 23 mm, and 29 mm stent for annulus sizes up to 27 mm; Figure 2). As the CoreValve frame anchors in the ascending aorta, it should not be larger than 45 mm. The selection of the TAVI valve and the approach (transfemoral or transapical) is based on size, calcification and tortuosity of the femoral and iliac arteries, the calcification 4

5 of the aortic arch and the size of the annulus. If the size of the peripheral arteries is < 7 mm or if they are heavily calcified or tortuous, the apical approach is chosen. If the annulus size (measured by transesophageal echocardiogram [TEE] in a 3-chamber view; Figure 3) is > 25 mm, a CoreValve stent-valve prosthesis is chosen. In exceptional cases where the peripherals are < 6 mm and the annulus size is > 25 mm, a subclavian approach with the CoreValve stent-valve prosthesis is chosen. As the size of the delivery catheters will decrease in the near future (CoreValve 16 Fr and SAPIEN 18 Fr), the decision of which route to use and what valve to place may also change. The procedure: which approach to use? Transfemoral approach The procedures are performed in a catheterisation laboratory as optimal fluoroscopy during the procedure is crucial. A cardiologist and a catheter-skilled cardiothoracic surgeon conduct all procedures together (cover picture). They perform all steps of the procedure such as puncture of the femoral artery, valve crossing and placement of the valve in an alternating pattern. All procedures are performed under general anaesthesia administered by one of the dedicated anaesthesiologists in the team. In all patients, the TEE is used to help guide valve placement. The femoral artery is punctured (we do not use echoguidance) and a Prostar device (Perclose Inc., Menlo Park, CA, USA) is inserted. Then, using fluoroscopy to guide, an 18 Fr sheath is placed following administration of heparin (monitored at an activated clotting time [ACT] of 250 seconds). A final sizing of the annulus is performed by TEE before the CoreValve is loaded in the delivery catheter. A temporary balloon-tipped pacemaker lead is placed, via the jugular vein, in the right ventricular apex. Balloon dilatation (size of the balloon based on the size of the annulus) is performed under rapid pacing (180 bpm) to avoid slippage of the balloon. Maximal deployment (expansion) of the balloon has to be obtained (no residual waste). Balloon dilatation is performed just before the valve is successfully loaded to keep the time between valve dilatation and CoreValve frame placement to a minimum and prevent risk of haemodynamic deterioration of the patient. Valve placement is based on angiographic markers (calcium in the sinus, pigtail in the right coronary sinus) and echo markers making sure that the stent lands just above the base of the anterior mitral leaflet (Figure 4). At this point, we try to place the CoreValve as high within the left ventricular outflow tract as possible (max 6 mm below the annulus) to avoid high grade conduction abnormalities. Aortic valve LV Left ventricle PMVL Left atrium Annulus (=24 mm) AMVL LA CoreValve Right ventricle Aortic valve Ascending aorta fig. 3 TEE 3-chamber view fig. 4 TEE CoreValve 5

6 regurgitation is evaluated using TEE and angiography. Balloon dilatation of the stent with a bigger balloon is only performed if more than moderate regurgitation persists beyond 10 minutes after placement. In most cases, balloon dilatation of the CoreValve is not necessary as the regurgitation decreases over time due to the radial force of the device. After an uncomplicated procedure, the patient is usually extubated within 60 minutes. A permanent pacemaker is placed in all patients who develop any high-grade atrioventricular (AV) block the day after the procedure. TEE is performed the day after placement and patients stay in intensive care for at least 24 hours. They are admitted for at least 3 days to capture late complications such as conduction abnormalities. After discharge, all patients are seen in the outpatient clinic by one of the cardiologists at 6 weeks, 3, 6 and 12 months, and yearly thereafter; transthoracic echocardiography (TTE) is performed at each visits. Transapical approach In contrast to the transfemoral route, during a transapical procedure fluoroscopy is usually limited to a fixed position perpendicular to the aortic annulus displaying all relevant areas together due to the short distance between apex and annulus. Since there are no available data showing a benefit for either approach, we randomly assign our patients to increase our experience in both techniques, unless circumstances preclude the transfemoral or transapical route. Such circumstances include peripheral vascular disease, atheromatous aortic arch, severe chronic obstructive pulmonary disease, open wound or the aortic annulus size. Similar to the transfemoral approach, this procedure is performed by both the cardiothoracic surgeon and interventional cardiologist working closely together. The patient is placed under general anaesthetic with normal ventilation (i.e. no single lung ventilation is required). At first, TEE is used to measure the aortic annulus size and to ensure that it will, at least, accommodate the largest available valve size (aortic annulus < 24.5 mm for the 26 mm SAPIEN valve). Once confirmed, the appropriate valve is unpacked and prepared for implantation. A left anterolateral mini-thoracotomy is placed in the fifth intercostal space. Using minimal rib spreading, the apex of the left ventricle can be palpated. If required, the next intercostal space can be opened through the same skin incision. The pericardium is cut longitudinally and traction sutures are placed, which also can be used to distract the apex downwards to optimise exposure. In the case of a redo procedure, intrapericardial adhesions should be cleared at the apex. Using palpation of the anterior septum, the left anterior descending artery can be determined and a location is chosen slightly lateral and anterior to the true apex. Two purse-string sutures (Prolene 2-0, large needle) with interrupted Teflon pledgets are carefully placed sufficiently deep without penetrating the ventricular cavity. There is limited additional space for temporary epicardial pacemaker leads, so we prefer to use a transjugular venous lead. Prior to valve introduction, the haemodynamic response to rapid pacing is tested. Following administration of 5000 IU of heparin (aim ACT 250 seconds), a pigtail catheter is introduced transfemorally and positioned in the right coronary sinus. In the case of poor left ventricular function, a transvenous guidewire can be placed in advance to allow immediate cannulation for temporary extracorporeal support when needed. Next, the apex is punctured and a 6 Fr sheath is placed inside the ventricle followed by a stiff guidewire across the aortic valve and aortic arch towards the abdominal aorta. We prefer to skip the 14 Fr sheath used for balloon dilatation, and 6

7 introduce the 26 Fr transapical delivery sheath immediately to reduce blood loss while exchanging the various sheaths. The largebore sheath is adequately de-aired. Angiography clearly illustrates the aortic root and the C-arm is positioned accordingly. Next, balloon valvuloplasty (diameter, 20 mm) is performed during rapid ventricular pacing. The loader containing the crimped valve, the orientation of which is thoroughly checked, is introduced carefully and positioned in the annulus. During rapid pacing, the balloon is inflated halfway, followed by angiography. Any necessary position changes can still be made, after which the balloon is fully expanded and the valve placed. TEE, as well as angiography, is employed to assess valve function immediately, and again within the next half hour. When considered adequate, the apical sheath is removed and the apex securely closed using the purse-string sutures. We prefer to use rapid pacing, and hence temporary haemodynamic cessation, while closing the apex to prevent accidental tearing with potential dramatic consequences. Following standard closure of the thoracotomy, leaving one intrapleural drain, the patient is usually extubated within 1 hour. Results Between June 2007 and September 2009, a total of 95 patients were referred to our team to evaluate the possibility of a percutaneous Baseline characteristics of TAVI patients (n=73) Values are presented as mean ± SD or n (%) Mean age (yrs) 81.1 ± (9.6) 85 < (31.5) 80 < (21.9) < (37.0) Male 29 (39.7) Logistic EuroSCORE 22.0 ± 15.2 Standard EuroSCORE 10 ± 3 STS score 6.6 ± 6.2 History of: Ischaemic stroke 5 (6.8) Recent myocardial infarction* 0 (0.0) Old myocardial infarction** 12 (16.4) PCI 23 (31.5) Balloon aortic valve plasty 6 (8.2) CABG 21 (28.8) Re-CABG 3 (4.1) Biological AVR 1 (1.4) Cardiac surgery*** 22 (30.1) Body mass index (kg/m 2 ) 27 ± 5 NYHA Class I 0 (0.0) II 1 (1.4) III 59 (80.8) IV 13 (17.8) Hypertension (n; %) 29 (39.7) Severe pulmonary hypertension 15 (20.5) Peripheral arterial disease 15 (20.5) Carotid disease 7 (9.6) Paroxysmal atrial fibrillation 6 (8.2) Chronic/permanent atrial fibrillation 13 (17.8) Chronic lung disease 21 (28.8) Serum creatinine (µmol/l/mg/dl) 108 ± 46 / 1.2 ± 0.5 Dialysis 0 (0.0) Type 1 diabetes 4 (5.5) Type 2 diabetes 11 (15.1) Aortic annulus size (mm) TTE 21.8 ± 1.6 TEE 22.8 ± 1.6 Transfemoral approach 56 (76.7) (all CoreValve) Transapical approach 17 (23.3) (all SAPIEN) CoreValve prosthesis size 26 mm 33 (45.2) 29 mm 23 (31.5) SAPIEN prosthesis size 23 mm 2 (2.7) 26 mm 15 (20.5) Table 2 Baseline characteristics of TAVI patients (n=73) KEY TAVI, transcatheter aortic valve implantation; PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft; EuroSCORE, European System for Cardiac Operative Risk Evaluation; AVR, aortic valve replacement; NYHA, New York Heart Association; STS, Society of Thoracic Surgeons; TTE, transthoracic echocardiography; TEE, transoesophageal echocardiography. * 6 weeks before TAVI; **> 6 weeks before TAVI; ***Requiring opening of the pericardium; Systolic pulmonary artery pressure > 60 mmhg; Claudication, surgical or percutaneous intervention to the extremities, excluding carotid disease; Transient ischaemic attack, carotid endarterectomy, carotid occlusion or > 50% carotid stenosis. 7

8 Table 3 Echocardiographic data of patients 1 week before and 1 week after TAVI (n=73) KEY TAVI, transcatheter aortic valve implantation; PAP, pulmonary artery pressure Table 4 Complications after TAVI KEY TAVI, transcatheter aortic valve implantation intervention. Patients were referred from 25 centres in the Netherlands and from two centres outside the Netherlands. Of these, 13 patients were considered surgical candidates; 11 patients were operated on and two died while on the waiting list. In five patients, only balloon angioplasty was performed as these patients were considered unsuitable for TAVI due to a severely compromised clinical condition. Two of these patients died early after balloon angioplasty. In 73 patients, TAVI was performed. The clinical and echocardiographic characteristics of the patients at baseline, and one week prior to Echocardiographic data of patients 1 week before and 1 week after TAVI (n=73) Values are presented as mean ± SD or n (%) Before TAVI After TAVI Left ventricular ejection fraction 50% 49 (67.1) 54 (74.0) 30 < 50% 16 (21.9) 11 (15.1) < 30% 8 (11.0) 3 (4.1) Unknown 0 (0.0) 5 (6.8) Left ventricular hypertrophy No 5 (6.8) 5 (6.8) Mild 27 (37.0) 31 (42.5) Moderate 30 (41.1) 20 (27.4) Severe 11 (15.1) 9 (12.3) Unknown 0 (0.0) 8 (11.0) Maximum gradient (mmhg) 73.6 ± ± 8.4 Unknown 0 (0.0) 6 (8.2) Aortic valve area (cm 2 ) 0.69 ± ± 0.9 Unknown 0 (0.0) 69 (94.5) Aortic regurgitation No 30 (41.1) 32 (43.8) Mild 32 (43.8) 32 (43.8) Moderate 10 (13.7) 5 (6.8) Severe 1 (1.4) 0 (0.0) Unknown 0 (0.0) 4 (5.5) Systolic PAP (mmhg) 44.5 ± ± 12.1 Unknown 5 (6.8) 31 (42.5) and one week following TAVI are summarised in Tables 2 and 3, respectively. The number of patients who died, suffered an ischaemic stroke, or underwent pacemaker implantation because of third-degree AV block after TAVI are summarised in Table 4, and the causes of death in Table 5. Conclusions TAVI is a new treatment option for those symptomatic patients who are not surgical candidates or in whom the risk of complications during conventional surgery is deemed to be too high. As ongoing trials will Complications after TAVI Values are presented as n (%) Complication Death Transfemoral Transapical approach approach (n=56) (n=17) During TAVI 0 (0.0) 0 (0.0) Within 30 days from TAVI / in hospital 8 (14.3) 2 (11.8) Within 30 days from TAVI or later if still in hospital 8 (14.3) 2 (11.8) Ischaemic stroke During TAVI 1(1.8) 0 (0.0) Within 30 days from TAVI / in hospital 6 (10.7) 0 (0.0) Within 30 days from TAVI or later if still in hospital 6 (10.7) 0 (0.0) Pacemaker implantation During TAVI 0 (0.0) 0 (0.0) Within 30 days from TAVI / in hospital 16 (28.6) 1 (5.9) Within 30 days from TAVI or later if still in hospital 16 (28.6) 1 (5.9) 8

9 Cause of death (< 30 days from TAVI or later if still in hospital) Cause of death Transfemoral Transapical Values are presented approach approach as n (%) (n=56) (n=17) Heart failure 0 (0.0) 1 (5.9) Multiple organ failure 0 (0.0) 1 (5.9) Myocardial infarction 1 (1.8) 0 (0.0) Ischaemic stroke 4 (7.1) 0 (0.0) Sepsis 1 (1.8) 0 (0.0) Pneumonia 1 (1.8) 0 (0.0) Ischaemic colitis 1 (1.8) 0 (0.0) demonstrate positive results of using TAVI in high-risk patients, even more patients will become candidates for this procedure. To obtain optimal results, the selection of candidate patients is crucial and we consider it essential that this is done in a multidisciplinary team including cardiologists, cardiothoracic surgeons and dedicated cardiac anaesthesiologists. In addition, the procedure itself should always be performed by the same multidisciplinary team, leading to a better overall outcome. Our results, thus far, are promising and comparable to those from recently presented registries, suggesting that our approach in performing TAVI is a valid one. Table 5 Cause of death (< 30 days from TAVI or later if still in hospital) KEY TAVI, transcatheter aortic valve implantation Address for correspondence J. M ten Berg MD, PhD, FACC, FESC. Department of Cardiology, St. Antonius Hospital, PO Box 2500, 3435 CM Nieuwegein, the Netherlands berg03@antoniusziekenhuis.nl DISCLOSURES: The opinions and factual claims herein are solely those of the authors and do not neccesarily reflect those of the publisher, editor-in-chief, editorial board and supporting company. RH is a consultant to Medtronic, Inc. JtB, BS, EGM, and TdDK have no relevant disclosures. REFERENCES 1 Nkomo VT et al. Burden of valvular heart diseases: a population-based study. Lancet 2006;368(9540): Lung B et al. Decision-making in elderly patients with severe aortic stenosis: why are so many denied surgery? Eur Heart J 2005;26(24): Cribier A et al. Early experience with percutaneous transcatheter implantation of heart valve prosthesis for the treatment of end-stage inoperable patients with calcific aortic stenosis. J Am Coll Cardiol 2004;43(4): Grube E et al. Percutaneous implantation of the CoreValve self-expanding valve prosthesis in high-risk patients with aortic valve disease: the Siegburg first-in-man study. Circulation 2006;114(15): Grube E et al. Percutaneous aortic valve replacement for severe aortic stenosis in high-risk patients using the second- and current third-generation self-expanding CoreValve prosthesis: device success and 30-day clinical outcome. J Am Coll Cardiol 2007;50(1): Chiam PT, Ruiz CE. Percutaneous transcatheter aortic valve implantation: assessing results, judging outcomes, and planning trials: the interventionalist perspective. JACC Cardiovasc Interv 2008;1(4): Webb JG et al. Percutaneous aortic valve implantation retrograde from the femoral artery. Circulation 2006;113(6): Webb JG et al. Percutaneous transarterial aortic valve replacement in selected high-risk patients with aortic stenosis. Circulation 2007;116(7): Ye J, Cheung A et al. Six-month outcome of transapical transcatheter aortic valve implantation in the initial seven patients. Eur J Cardiothorac Surg 2007;31(1): Vahanian A et al. Transcatheter valve implantation for patients with aortic stenosis: a position statement from the European Association of Cardio-Thoracic Surgery (EACTS) and the European Society of Cardiology (ESC), in collaboration with the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2008;29(11): Nashef SA et al. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 1999;16(1): Shroyer AL et al. The Society of Thoracic Surgeons: 30-day operative mortality and morbidity risk models. Ann Thorac Surg 2003;75(6): ; discussion Let us know what you think of this issue us at confluence@axon-com.com or return the freepost comments card included in this issue. Your feedback is important to us! 9

10 expert opinion I Akin C A Nienaber Indications for stent grafts in type B aortic dissection ibrahim akin christoph a nienaber Department of Medicine, Divisions of Cardiology, Pulmology and Intensive Care Unit, University Hospital, Rostock, Germany Aortic dissection is an uncommon, but highly lethal condition, with an estimated annual incidence of 20 cases per million. 1-3 Around 0.5% of all patients with chest or back pain suffer from aortic dissection or its precursors. 4 Men are found to suffer from acute aortic dissection twice as often as women with 60% of dissection cases classified as proximal (type A) and 40% as distal (type B according to the Stanford classification). 1 Dissection of the ascending aorta is associated with a mortality rate of 1 2% per hour within the first 24 hours, resulting in a mortality rate of up to 50 74% within the first 2 weeks. 1 An uncomplicated acute type B dissection is less frequently lethal, with survival rates in medically treated patients of 89% at 1 month, 84% within 1 year, and up to 80% within 5 years. 1,5 However, patients with acute or late complications including malperfusion syndrome with renal failure, visceral or leg ischaemia, or contained rupture require urgent repair, especially when you consider a mortality rising to 20% at day 2 and 25 50% within 1 month. 1 Similar to type A dissection, advanced age, rupture, shock and malperfusion are important independent predictors of early mortality in type B dissection. 6 While almost every patient with a type A dissection should be managed by open surgery, endovascular concepts have Abbreviations CT EUROSTAR TEVAR PETTICOAT INSTEAD Computed tomography EUROpean collaborators on Stent graft Techniques for abdominal aortic Aneurysm Repair Thoracic endovascular aortic repair Provisional extension to induce complete attachment Investigation of stent grafts in patients with type B aortic dissection emerged as an alternative to manage aortic dissections, mainly distal thoracic aortic dissection. Conversely, for proximal dissection, endovascular approaches (thoracic endovascular aortic repair [TEVAR]) remain anecdotal for localised pathologies in patients unfit for open repair. This article summarises results and recommendations for endovascular management of patients with type B aortic dissection. Indications for TEVAR in type B aortic dissection The natural course of aortic dissection is determined by two elements: early complications and chronic events. Early complications comprise any kind of malperfusion syndrome, persistent pains or aortic rupture, while late events are proximal progress or documented false lumen expansion with the risk for late rupture. Once a patient survives the first 2 weeks after impact of dissection, the dissection is, by definition, chronic. Acute and chronic dissections may both require similar medical treatment with primarily blood pressure control, but even acute dissections can be complicated or uncomplicated. The feasibility and relative safety of TEVAR in descending thoracic aorta has already been established as an alternative to surgical treatment of type B aortic dissection. 2,3, But due to the lack of both, randomised controlled trials and long-term follow-up data, the indications for endovascular strategies remain to be fully defined for dissection (Table 1). There is clear observational evidence 2,3, that depressurisation and shrinkage of the false 10

11 Surgical Type A aortic dissection Acute type B dissection complicated by: Retrograde extension into the ascending aorta Dissection in fibrillinopathies (e.g. Marfan syndrome, Ehlers-Danlos syndrome) Medical Uncomplicated acute type B dissection Stable isolated aortic arch dissection Chronic type B dissection (under evaluation) Interventional Unstable acute type B dissection: Malperfusion Rapid expansion (> 1 cm/year) Critical diameter (> 5.5 cm) Refractory pain Aortic dissection due to blunt chest trauma Hybrid procedure for extended type A aortic dissection lumen is beneficial in acute dissection, ideally followed by complete thrombosis of the false lumen and remodeling of the entire dissected aorta (Figure 1). Similar to historically accepted indications for surgical intervention, scenarios such as malperfusion syndrome, intractable pain rapidly expanding false lumen to a total diameter over 55 mm or signs of imminent rupture are accepted indications for TEVAR in type B dissection. 7 Even in some cases of retrogradely extended distal dissections, stent-graft treatment of the descending thoracic aorta can also be performed as a single primary step or as a staged secondary step after initial surgical repair of the proximal part of the aorta or the arch; 2,3 the surgical part may include an elephant trunk or transposition of arch vessels to allow extended landing zone for endovascular completion of such a hybrid approach. In the case of a localised retrograde type A dissection originating from an entry tear in the descending thoracic aorta, this entry can sometimes be sealed by a transfemoral stent-graft with subsequent remodeling of the entire dissected aorta. With TEVAR, paraplegia was documented in 0.8%, but, is obviously associated with extensive coverage of the aorta beyond 20 cm and with the use of multiple stent grafts, or in previously replaced infrarenal aortic aneurysm. 2,3 Table 1 Distribution of differential therapeutic strategies in aortic dissection 2,3 fig. 1 A) Type B dissection originating from the aortic arch B) One year followup evaluation after TEVAR revealed a thrombosed false lumen and a normalisation of the true lumen diameter A B 11

12 fig. 2 A) Malperfusion of distal aorta by occlusive type B dissection B) Stent-graft placement in the true lumen of the proximal descending aorta re-established flow to the abdomen and legs Complicated acute type B aortic dissection While patients with stable acute type B dissection should be managed medically, about 30 42% of acute type B aortic dissection are complicated, as evidenced by haemodynamic instability or peripheral vascular ischaemia. 8 Among other complications, acute lower limb and visceral ischaemia have been reported in 30 50%; malperfusion syndrome occurs frequently in cases of distally extended dissections and may lead to death in 50 85% if left untreated. 5,9 During necropsy of 18 patients with type B dissection, full compression of the true lumen with aortic obstruction was evident in 56%. 10 Once diagnosed, these complications require emergent therapeutic action; despite a wide array of open surgical strategies, surgical mortality for patients with acute aortic dissection complicated by renal ischaemia has been reported in 50%, and, in the case of impaired mesenteric perfusion, even up to 88%. 2,3,11 Different treatment strategies, however, may impact on survival; in 571 patients with acute type B aortic dissection, 390 (68.3%) were treated medically; among complicated cases, 59 (10.3%) underwent standard open surgery, and 66 (11.6%) were treated with an endovascular approach. 12 In complicated cases, in-hospital mortality was significantly lower with TEVAR (10.6%) than after open surgery (33.9%; p=0.002), approaching the survival rate of medically treated uncomplicated type B dissection. Therefore, stent-graft repair is an attractive alternative to surgical repair for correcting ischaemic complications. 13 Usually, TEVAR-mediated sealing of the entry site in the descending thoracic aorta results in thrombosis of the false lumen and redirection of flow to the true lumen, normalising distal vessel perfusion and restoring branch vessel patency (Figure 2). 12 The PETTICOAT concept takes the idea even further by extending A B 12

13 the stent-graft scaffold distally with opencell bare metal stents. For instance, if malperfusion persists after coverage of the primary entry tear, additional distal open stents were deployed until distal malperfusion is corrected. 14 With this concept, aortic fenestration maneuvers or branch vessel revascularisation with uncovered stents are usually not needed and obsolete. The EUROSTAR/United Kingdom registry represents a large series of patients subjected to TEVAR, including 131 patients with aortic dissection (5% proximal, 81% distal and 14% not classified), of which 57% presented with symptoms of rupture, aortic expansion, or side branch occlusion, all considered complicated dissection. Although meaningful long-term data are still lacking, technical success was achieved in 89%, at the expense of a 30-day mortality of 8.4%. 15 A series of patients at the Arizona Heart Institute, comprising 40 patients (23 acute and 17 chronic) treated with TEVAR for complicated distal aortic dissection, enjoyed a technical success in 95%. There was one perioperative death due to iliac rupture and one case of paraplegia, while 15 patients (38%) experienced transient post-procedural complications frequently of a transient renal or pulmonary nature; 1-year survival was 85%. Of the patients available for follow-up CT, 97% (30 of 31 patients) exhibited a stable or decreasing aortic diameter and no rupture during the observational period, justifying the conclusion that thoracic aortic stent grafting obviously stabilised the aorta and decreased the incidence of late expansion and rupture. 16 Such observations were confirmed in a metaanalysis in patients subjected to TEVAR for aortic dissection. 17 Procedural success was obtained in 98.2% of 609 cases, with an in hospital surgical conversion rate of 2.3% and mortality rate of 5.2%. Complications such as retrograde extension of the dissection into the ascending aorta were reported in 1.9%, with neurological complications in 2.9%. Both 30-day mortality rate and in-hospital complications were more frequent with TEVAR for acute complicated aortic dissection than in patients with chronic aortic dissections (9.8% vs. 3.2%, and 21.7% vs. 9.1% respectively; p<0.05). Interestingly, a comparison between endovascular treatment of complicated type B aortic dissection with medical therapy of uncomplicated type B dissections in 56 patients, with follow-up of 18.1±16.9 months, reported similar outcomes in both groups, with better remodelling of the descending thoracic aorta in the stent-graft group; no paraplegia and no differences in the 5-year survival rate (86.3% in both groups) were found. 18 Chronic type B aortic dissection The evolution from acute to chronic dissection involves progressive fibrosis and hardening of the intimal flap. In addition, more intimal tears are reported in chronic versus acute type B aortic dissection. Average growth rate of chronically dissected distal aorta is estimated to range from cm per year depending on both the initial aortic diameter and the state of hypertension. 19 Unfortunately, long-term outcomes of medical therapy alone is suboptimal, with a reported 50% mortality at 5 years and delayed expansion of the false lumen in 20 50% of patients at 4 years. 1,20 Expansion of the false lumen over 4 cm in diameter and persistent perfusion of the false lumen are considered predictors of aortic rupture and death. 21,22 There is consensus that TEVAR should be considered when aortic diameter exceeds mm, there is an increase of recurrent thoracic pain, or in the presence of uncontrolled blood pressure and rapid growth of the dissecting aneurysm (> 1 cm per year; Figure 3). Nienaber et al prospectively evaluated stent-graft management in 12 patients with chronic type B dissection and compared the results with 12 matched surgical controls. 23 Proximal 13

14 fig. 3 A) Type B aortic dissection with large false lumen and compromised small true lumen B) Partial thrombosis of the false lumen during the chronic phase C) Complete thrombosis of the false lumen and re-expansion of the true lumen after stent-graft placement A B C entry closure and complete thrombosis of the false lumen at 3 months were achieved in all patients. Stent-graft treatment resulted in no morbidity or mortality, whereas surgical treatment resulted in 4 deaths (33%; p=0.04) and 5 adverse events (42%; p=0.04). 23 Similar results were obtained by Kato et al in a series of 15 patients with no mortality during a follow-up of 2 years. 24 Eggebrecht et al investigated the clinical outcome of 38 patients with type B aortic dissection (10 acute and 28 chronic). Following TEVAR, results showed lower in-hospital mortality and a trend towards better 4-year survival rate in patients with chronic aortic dissection. 25 However, prophylactic implantation of stent graft in patients with chronic type B aortic dissections was not superior (in terms of mortality) to efficient medical treatment with 2 years of follow-up in the INSTEAD trial. 21 Traumatic aortic dissection Blunt aortic injury is not infrequent and 20% of cases are associated with motor vehicle accidents or deceleration trauma; prehospital mortality ranges between 80 90%. 26 Without appropriate treatment, 30% of survivors who reach the hospital die within the first 6 hours. Blunt thoracic aortic injury involves the aortic isthmus, in 55 90%, the ascending aorta or aortic arch in 10 14%, and the distal descending or abdominal aorta in 15 30%. 27 Aortic disruption is associated with other life-threatening injuries most of the time (90%), with 24% requiring major surgery before aortic repair. 27 In this scenario, with open-surgical mortality and paraplegia occurring in 20 54%, surgery is being replaced by endoluminal stent-graft therapy, with markedly lower mortality and morbidity, completely avoiding thoracotomy, single lung 14

15 ventilation and heparinisation. 26,27 Marcheix et al reported a primary success rate of 100% in 33 patients with aortic rupture with complete healing 1 month after TEVAR in all patients with complete reconstruction of the aortic wall and no residual pseudoaneurysm. 28 The diameter of the aorta shrunk over the stent-graft without any signs of paraplegia during a mean follow-up of 46 months. 28 Recently, a comparative meta-analysis reviewed outcomes of 699 patients referred for endovascular or open repair surgery after traumatic aortic transsections. With a technical success rate from open repair (96.5% vs. 98.5%; p=0.58), TEVAR (n=370) was associated with both lower periprocedural mortality (7.6% vs. 15.2%; p= 0.076) and lower incidence of paraplegia (0% vs. 5.6%; p<0.001) and stroke (0.85% vs. 5.3%; p=0.0028). 29 On aggregate, based on the available evidence, TEVAR has become a clear therapeutic option for complicated acute distal dissection, for traumatic aortic injury with impending rupture and for selected cases of chronic dissection with emerging signs of imminent late complications. Address for correspondence Christoph A. Nienaber, MD, PhD Department of Medicine I, Divisions of Cardiology, Pulmology and Intensive Care Unit, University Hospital Rostock, Rostock School of Medicine Ernst-Heydemann-Str Rostock, Germany DISCLOSURES: The opinions and factual claims herein are solely those of the authors and do not neccesarily reflect those of the publisher, editor-in-chief, editorial board and supporting company. IA and CN have no relevant disclosures. The authors have no competing interests and therefore, they have nothing to declare. REFERENCES 1 Hagan PG et al. The International Registry of Acute Aortic Dissection (IRAD). JAMA 2000;283: Erbel R et al. Diagnosis and management of aortic dissection. Eur Heart J 2001;22: Svensson LG et al. Expert consensus document on the treatment of descending thoracic aortic disease using endovascular stent-grafts. Ann Thorac Surg 2008;85:S Kodolitsch Y et al. Clinical prediction of acute aortic dissection. Arch Intern Med 2000; 160: Estrera AL et al. Outcomes of medical management of acute type B aortic dissection. Circulation 2006;114 [suppl I]: Nienaber, CA et al. Gender-related differences in acute aortic dissection. Circulation 2004;109: Nienaber CA et al Emergency stent-graft placement in thoracic aortic dissection and evolving rupture. J Card Surg 2003;18: Tsai TT et al. Long-term survival in patients with type B acute aortic dissection: Insight from the International Registry of Acute Aortic Dissection. Circulation 2006;114: Svensson LG et al. Variables predictive of outcome in 832 patients undergoing repairs of the descending thoracic aorta. Chest 1993;104(4): Roberts CS, Roberts WC. Aortic dissection with the entrance tear in the descending thoracic aorta: analysis of 40 necropsy patients. Ann Surg 1991;213: Trimarchi S et al. Role and results of surgery in acute type B aortic dissection: insights from the International Registry of Acute Aortic Dissection (IRAD). Circulation 2006;114 (1 suppl):i Fattori R et al. Complicated acute type B dissection: is surgery still the best option?: a report from the International Registry of Acute Aortic Dissection. J Am Coll Cardiol Intv 2008;1: Kische S et al. Endovascular treatment of acute and chronic aortic dissection: midterm results from the Talent Thoracic Retrospective Registry. J Thorac Cardiovasc Surg 2009;138(1): Nienaber CA et al. Provisional extension to induce complete attachment after stent-graft placement in type B aortic dissection: the PETTICOAT concept. J Endovas Ther 2006;13: Leurs L et al. Endovascular treatment of thoracic aortic diseases: combined experience from the EUROSTAR and United Kingdom Thoracic Endograft registries. J Vasc Surg 2004;40:670-9; discussion Nathanson DR et al. Endoluminal stent-graft stabilization for thoracic aortic dissection, J Endovasc Ther 2005;12(3): Eggebrecht H et al. Endovascular stent-graft placement in aortic dissection a metaanalysis. Eur Heart J 2006;27(4): Dialetto G et al. Treatment of type B aortic dissection: endoluminal repair or conventional medical therapy? Eur J Cardiothorac Surg 2005;27: Doroghazi RM et al. Long-term survival of patients with treated aortic dissection. J Am Coll Cardiol 1984;3: Williams JS. Aortic injury in vehicular trauma. Ann Thorac Surg 1994;57(3): Nienaber CA et al. Investigation of stent grafts in patients with type B aortic dissection (INSTEAD). Circulation 2009 (Epub, ahead of print) 22 Kato M et al. Determining surgical indications for acute type B dissection based on enlargement of aortic diameter during the chronic phase. Circulation 1995;92 (Suppl):II Nienaber CA et al. Nonsurgical reconstruction of thoracic aortic dissection by stent-graft placement. N Engl J Med 1999;340: Kato N, Hirano T, Shimono T, et al. Treatment of chronic aortic dissection by transluminal endovascular stent-graft placement : preliminary results. J Vasc Interv Radiol 2001;12: Eggebrecht H et al. Endovascular stent-graft treatment of aortic dissection: determinants of post-interventional outcome. Eur Heart J 2005;26: Fabian TC. Prospective study of blunt aortic injury. Multicenter Trial of the American Association for the Surgery of Trauma. J Trauma 1997;42(3): Jahromi AS et al. Traumatic rupture of the thoracic aorta: cohort study and systemic review. J Vasc Surg 2001;34: Marcheix B et al. Endovascular repair of traumatic rupture of the aortic isthmus: midterm results. J Thorac Cardiovasc Surg 2006;132(5): Tang GL et al. Reduced mortality, paraplegia, and stroke with stent graft repair of blunt aortic transsection: a modern meta-analysis. J Vasc Surg 2008;47: Let us know what you think of this issue us at confluence@axon-com.com or return the freepost comments card included in this issue. Your feedback is important to us! 15

16 review article E Regar P W Radke The future of coronary stent design Evelyn Regar Erasmus Medical Center, Rotterdam, the Netherlands Peter W Radke University Hospital Schleswig- Holstein, Lübeck, Germany The methodology in interventional cardiology has historically evolved from diagnostic coronary angiography to balloon angioplasty, to the use of bare metal stents (BMSs), to their refinement to drug-eluting stents with a durable polymer, and is now on the verge of drug-eluting stents with further developed drug delivery approaches such as reservoir technology and the use of bioresorbable polymers. Two decades ago, coronary stents were stainless steel (316L) tubes designed to prevent the acute complication of balloon angioplasty acute vessel closure. Ever since, efforts have been directed, not only to improve acute procedural outcomes, but also towards long-term outcomes and prognosis. Many lessons learned in the past are still relevant for stent design today and the future. Lessons from the past In the early days of coronary stents, development was focused on improvement of stent deliverability. Advances in this area included pre-mounted stents, self-expanding stents, reduced crossing profiles and improved flexibility. Modifications in stent design such as rotating and locking mechanisms afforded them higher flexibility when unexpanded and remarkable radial strength when expanded. When most issues of acute feasibility of stenting were resolved, long-term outcomes became the focus of attention, with in-stent restenosis presenting the major limitation of coronary stenting. It was recognised that neointimal formation and in-stent restenosis were related to patient-specific factors such as genetic predisposition or diabetes; to lesion-specific factors such as vessel caliber, lesion length or plaque burden, and to procedure-specific factors such as extent of vessel damage, residual dissections, stent length, or postprocedure minimal diameter or area. Systematic investigations gave insights into mechanisms of stent action and vessel biology. Stent expansion principles (balloonor self-expansion), geometry (number of intersections and inter-strut area), strut configuration and thickness and metal-toartery ratio are all major determinants of stent profile, flexibility, radial strength and (elastic) expansion characteristics, 1-3 polishing, ion implantation or coating as chemistry, charge, and texture. 4,5 In the late 1990s, radioactive stents were introduced based on the observation that radiation has inhibitory effects on smooth muscle cell growths. 6 However, clinical results were disappointing. 7-9 Another strategy to modify stent surface characteristics was the coating of metallic struts. However, polymer surfaces have shown conflicting results. While some have proven able to reduce protein deposition and platelet adhesion 10 others provoked severe tissue responses In clinical trials, a number of other coatings like inert polymer, 2 phosphorylcholine 14,15 or heparin 16,17 were able to reduce (sub)acute stent thrombosis rates. 18 However, these acute beneficial effects did not translate into a substantial decrease for in-stent restenosis rates. 19 In response to this, the interest in coatings has shifted towards considering coatings as vehicles for local drug delivery. Local drug delivery was hypothesised as being able to overcome the repeated failure of clinical drug studies. 20 It was a widely 16

17 accepted explanation that the failure of systemic agents to significantly impact restenosis was due to insufficient achievable drug levels at the arterial lesion site. Local drug administration allows higher tissue concentrations while systemic release is minimal and may reduce the risk of remote or systemic toxicity. Early studies with numerous anti-proliferative agents showed mixed results It was concluded that it might not be sufficient to have an active drug and a metallic stent, but that a delivery vehicle must ensure drug release into the vessel in predictable concentrations and duration while being able to resist mechanical stress during stent expansion. This concept has proven successful in reducing in-stent restenosis in the landmark RAVEL 27 and the SIRIUS 27 trials, employing sirolimus (rapamycin) eluting coronary stents (SES), followed by the TAXUS (paclitaxel eluting stent [PES]) trial family The SIRIUS trial was the pivotal study evaluating SES for FDA approval. It compared SES with the Bx Velocity (Cordis Corporation, Bridgewater, NJ, USA) BMS in a total of 1,058 subjects. The primary endpoint, target vessel failure, was reached by 21% of BMS subjects versus 8.6% with SES (p<0.001). Long-term follow-up to 6 years has been completed and demonstrates preservation of clinical benefit related to reductions in target lesion failure of the SES over BMS and no differences in safety between the experimental or control arms with respect to stent thrombosis. Both SES and PES limited in-stent restenosis impressively and minimised the impact of patient- and lesion-specific factors. 32 Therefore, many lesions that had shown disappointing results when treated interventionally, such as small vessels or chronic total occlusions, were suddenly candidates for percutaneous revascularisation therapy in the beginning of the new millennium. However, soon a new enemy emerged: late-stent thrombosis. 33,34 Today, we are facing the second generation of drug-eluting stents with improved deliverability and safety likely (Figure 1). Most of them still follow the concept of metallic stent structure for vessel scaffolding, coating as a delivery vehicle and a drug as antiproliferative agent. Only recently, however, reducing the risk for late-stent thrombosis by further developed drug delivery approaches, such as the reservoir technology or the use of bioresorbable polymers, have been identified as an additional goal. The reduction of polymer exposure to the vessel wall might improve vascular healing and lower the rate of undesirable side effects, such as stent thrombosis, especially in the long term once the drug is completely eluted. To date, a number of non-inferiority trials employing drug-eluting stents with different drug and coating principles are ongoing. Future developments: technological breakthroughs Even with current drug-eluting technologies accompanied by modern pharmacological interventions, restenosis as well as late-stent thrombosis have not vanished as the most significant long-term limitations, especially in high-risk populations (i.e. insulin-dependent diabetics). In addition to the never-ending Efficacy Safety Deliverability Imaging Re-interventions Plaque sealing Individualisation Restoration of physiology 1 2 >3 fig. 1 Stent generations 17

18 challenge of improving deliverability, future developments will, therefore, aim to eliminate the risk of late-stent thrombosis and restenosis. Research is directed toward further sophistication in coating and drug delivery technology, but also toward dramatic improvement of BMSs, taking into account numerous engineering lessons from the past as well as advanced material sciences, leading to innovative materials, finally resulting in very thin struts for example. Another target for the future is the simplification of the stenting procedure with the goal of further reducing the acute risk of adverse events in high-risk patients, decreasing radiation dose to the operator and patient, and decreasing procedural time and cost. An example is the Stent-on-a-Wire (SOAW; Svelte Medical Systems, New Providence, NJ, USA) coronary stent system, consisting of a delivery system using a fixed-wire catheter platform and a cobalt chromium stent. The system has a lesion entry profile. Currently, a prospective study is being conducted to evaluate the safety and performance of the SOAW stent. Other examples include specialised stents dedicated for different lesion subsets, such as bifurcations, very long or ostial lesions. A fundamentally different strategy is seen in creating a temporary vessel prosthesis, which would scaffold the vessel wall in the acute setting to allow for adequate lumen gain, in order to alleviate angina and myocardial ischaemia. Furthermore, a system that would support the biological healing process and would disappear when vascular healing has been accomplished (as stents exert their beneficial clinical effect within a relatively narrow time frame) is another opportunity. Research into bioabsorbable technologies for stents began more than 20 years ago with the pioneering work done at Duke University. Back then, the first polylactic acid or PLAbased bioabsorbable stent was a braided, self-expanding stent. Five years later, the first balloon-expandable PLA stent was also developed at Duke. 39 Around this time, metallic stents were being developed at an accelerated rate because they solved the problem of abrupt closure with balloon angioplasty. Hence, bioabsorbable stents were put on the back burner for a while as metallic stents gained rapid acceptance and proved efficacious. Until now, a variety of biodegradable or bioabsorbable materials have been investigated, with mixed clinical results. 40,41 In the late 1990s, the Igaki-Tamai stent (Kyoto Medical Planning Ltd., Kyoto, Japan) was a self-expanding coil stent made of a poly-l-lactic (PLLA) monofilament that took between months to fully biodegrade. Clinically it showed remarkable results with both restenosis and a target lesion revascularisation rate of 10.5% at 6 months. 42 Today, very promising results are available from a clinical, first-in-man trial out to 2 years with an everolimus-eluting, bioabsorbable stent (BVS, Figure 2). Thirty patients with a single de-novo coronary artery lesion were followed up for 2 years clinically and with multiple imaging methods: multislice computed tomography (CT), angiography, intravascular ultrasound, derived morphology parameters (virtual histology, palpography, and echogenicity), and optical coherence tomography (OCT). At 2 years, the stent was completely absorbed as demonstrated by intravascular ultrasound and OCT; had vasomotion restored and restenosis prevented; and was clinically safe without cardiac deaths, ischaemia-driven target lesion revascularisations, or stent thromboses. 43,44 Metallic stents using mainly magnesium as a compound have also been used and evaluated in clinical trials with promising results (AMS stent, Figure 2). 18

19 fig. 2 Stent system examples NEVO stent Drug-filled stent (DFS) AMS (magnesium) stent BVS everolimus-eluting coronary stent system Further conceptual advancements will challenge the one size fits all philosophy of nearly all stents currently used in clinical practice. Dedicated stents for specific anatomic specifications (i.e. bifurcations or long lesions) are already in clinical use. In the near future, however, specific stents will also be available to address different clinical situations (i.e. acute coronary syndrome, diabetes) with specific restenosis and/or stent thrombosis risks and resulting requirements (i.e. high vs. low antiproliferative capacity). These will be likely accomplished by stents with multi-drug delivery and drug-specific elution characteristics as already used in clinical trials (i.e. NEVO stent system [Cordis Corporation, Bridgewater, NJ, USA]; Figure 2). Further promising approaches include the combination of innovative BMS concepts (i.e. continuous sinusoid technology) with non-polymeric drug elution controlled by organic diffusion physics ( drug-filled stent [DFS] system; [Medtronic Inc, Minneapolis, MN, USA]; Figure 2). How will the patient benefit? How will changes in coronary stent design as discussed above translate into a measurable clinical benefit for the patient? In other words, what are we accomplishing with percutaneous coronary interventions at present and what kind of progress in stent technology would lead to further significant and measurable clinical improvements? Clearly, the elementary advances in stent design (i.e. reduction of strut thickness, drug delivery) have mainly improved efficacy (reduction of restenosis) and deliverability of stents. Only recently, new developments in drug elution and polymer composition have addressed safety aspects, i.e. reduction of stent thrombosis. In the meantime, procedural aspects (i.e. high pressure implantation) and new pharmacological concepts (temporary dual-antiplatelet therapy) have significantly improved both, efficacy and safety (reduction of stent thrombosis rates) of coronary stents. As a result of 20 years in stent development, the use of stents has led to a reduction in mortality and morbidity in patients with acute coronary syndromes and to a more symptomatic and less prognostic improvement in lower-risk patients with stable coronary artery disease. These differences in treatment aims can be described as the gradient of benefit. Completely degrading polymeric or metallic stents, however, will likely represent one of the next breakthrough technologies affecting the gradient of benefit towards prognostic implications, even for stable patients if they Polymeric Nonpolymeric BMS 'backbone' Nobori NEVO No 'backbone' BVS everolimus REVA Medical AMS Degradation PROMUS CYPHER ENDEAVOR RESOLUTE XIENCE V YUKON DES ESI DES No degradation fig. 3 Stent framework 19

20 Address for correspondence Prof. Dr. Peter W. Radke Leitender Oberarzt Medizinische Klinik 2 Kardiologie, Angiologie, Internistische Intensivmedizin Universitätsklinikum Schleswig- Holstein Campus Lübeck Ratzeburger Allee 160 D Lübeck Peter.Radke@uk-sh.de are able to match the high standards set forth for safety, efficacy and deliverability by existing stents. Degradation and polymer use are, therefore, pivotal characteristics for current and future stent generations and allow classification of stents in a simplified matrix (Figure 3). The advances of future generation stents will be potentially mediated by the ease for re-interventions or re-operations, the ability for non-invasive follow-up studies using imaging technologies like coronary CT and/or magnetic resonance imaging (MRI), as well as the restoration of physiology/vascular adaptive processes (i.e. positive remodelling) and functionality (vasomotion; Figure 1). Summary Interventional cardiology has historically evolved from diagnostic coronary angiography to balloon angioplasty; from the short-term solutions through the use of BMSs to the improvement of longer-term outcomes by their refinement of drug-eluting stents. The field of percutaneous coronary interventions using stents is now set to shift the paradigm from angioplasty to vascular restoration by individualised absorbable/degradable stent technologies. Dramatic improvements in stent design will very likely translate into even better symptomatic and prognostic improvements in patients with stable or unstable coronary disease as compared to current clinical practice. DISCLOSURES: The opinions and factual claims herein are solely those of the authors and do not neccesarily reflect those of the publisher, editor-in-chief, editorial board and supporting company. ER and PR have no relevant disclosures. The authors have no competing interests and therefore, they have nothing to declare. REFERENCES 1 Lossef SV et al. Comparison of mechanical deformation properties of metallic stents with use of stress-strain analysis. J Vasc Interv Radiol 1994;5: Rogers C, Edelman ER. Endovascular stent design dictates experimental restenosis and thrombosis. Circulation 1995;91: Carter AJ et al. Stent design favorably influences the vascular response in normal porcine coronary arteries. J Invasive Cardiol 1999;11: Edelman ER et al. Gold-coated NIR stents in porcine coronary arteries. Circulation 2001;103: Wilczek KL et al. Implantation of balloon expandable copper stents in porcine coronary arteries. A model for testing the efficacy of stent coating in decrasing stent thrombogenicity. Circulation 1995;92 (Suppl): Rubin P et al. Cellular and molecular mechanisms of radiation inhibition of restenosis. Part I: role of the macrophage and platelet-derived growth factor. Int J Radiat Oncol Biol Phys 1998;40: Fischell TA, Hehrlein C. The radioisotope stent for the prevention of restenosis. Herz 1998;23: Carter AJ, Fischell TA. Current status of radioactive stents for the prevention of in-stent restenosis. Int J Radiat Oncol Biol Phys 1998;41: Albiero R et al. Edge restenosis after implantation of high activity (32)P radioactive betaemitting stents. Circulation 2000;101: Simon C et al. Protein interactions with endovascular prosthetic surfaces. J Long Term Eff Med Implants 2000;10: van Beusekom HM et al. Coronary stent coatings. Coron Artery Dis 1994;5: van Beusekom HM et al. Synthetic polymers. Semin Interv Cardiol 1998;3: van der Giessen WJ, Schwartz RS. Coated and active stents: an introduction. Semin Interv Cardiol 1998;3: Malik N et al. Phosphorylcholine-coated stents in porcine coronary arteries: in vivo assessment of biocompatibility. J Invasive Cardiol 2001;13: Whelan DM et al. Biocompatibility of phosphorylcholine coated stents in normal porcine coronary arteries. Heart 2000;83: Serruys PW et al. Heparin-coated Palmaz-Schatz stents in human coronary arteries. Early outcome of the Benestent-II pilot study. Circulation 1996;93: van der Giessen WJ et al. Heparin-coating of coronary stents. Semin Interv Cardiol 1998;3: Holmes DR et al. Polymeric stenting in the porcine coronary artery model: differential outcome of exogenous fibrin sleeves versus polyurethane-coated stents. J Am Coll Cardiol 1994;24: Serruys PW et al. Randomised comparison of implantation of heparin-coated stents with balloon angioplasty in selected patients with coronary artery disease (Benestent II) [published erratum appears in Lancet 1998 Oct 31;352(9138):1478]. Lancet 1998;352: Radke PW et al. A double-blind, randomized, placebo-controlled multicenter clinical trial to evaluate the effects of the angiotensin II receptor blocker candesartan cilexetil on intimal hyperplasia after coronary stent implantation. Am Heart J. 2006;152(4):761.e Mak KH, Topol EJ. Clinical trials to prevent restenosis after percutaneous coronary revascularization. Ann N Y Acad Sci 1997;811:255-84; discussion O'Keefe JH et al. Ineffectiveness of colchicine for the prevention of restenosis after coronary angioplasty. J Am Coll Cardiol 1992;19: Muller DW et al. Intramural methotrexate therapy for the prevention of neointimal thickening after balloon angioplasty. J Am Coll Cardiol 1992;20: de Scheerder I et al. Local angiopeptin delivery using coated stents reduces neointimal proliferation in overstretched porcine coronary arteries. J Invasive Cardiol 1996;8: de Scheerder I et al. Local methylprednisolone inhibition of foreign body response to coated intracoronary stents. Coron Artery Dis 1996;7: Lincoff AM et al. Sustained local delivery of dexamethasone by a novel intravascular eluting stent to prevent restenosis in the porcine coronary injury model. J Am Coll Cardiol 1997;29: Morice MC et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002;346: Moses JW et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med Oct 2;349(14): Tanabe K et al. TAXUS III Trial: in-stent restenosis treated with stent-based delivery of paclitaxel incorporated in a slow-release polymer formulation. Circulation 2003;107: Grube E et al. TAXUS I: six- and twelve-month results from a randomized, double-blind trial on a slow-release paclitaxel-eluting stent for de novo coronary lesions. Circulation 2003;107: Stone GW et al. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med 2004;350: Regar E et al. Angiographic findings of the multicenter randomized study with the sirolimus-eluting Bx velocity balloon-expandable stent (RAVEL): sirolimus-eluting stents inhibit restenosis irrespective of the vessel size. Circulation 2002;106: McFadden EP et al. Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy. Lancet 2004;364: Regar E et al. Incidence of thrombotic stent occlusion during the first three months after sirolimus-eluting stent implantation in 500 consecutive patients. Am J Cardiol 2004;93: Windecker S et al. Biolimus-eluting stent with biodegradable polymer versus sirolimuseluting stent with durable polymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial. Lancet 2008;372: Vranckx P et al. Biodegradable-polymer-based, paclitaxel-eluting Infinnium stent: 9-Month clinical and angiographic follow-up results from the SIMPLE II prospective multi-centre registry study. EuroIntervention 2006;2: Ostojic M et al. First clinical comparison of Nobori -Biolimus A9 eluting stents with Cypher- Sirolimus eluting stents: Nobori Core nine months angiographic and one year clinical outcomes. EuroIntervention 2008;3: van Beusekom H et al. The neointimal response to stents eluting tacrolimus from a degradable coating depends on the balance between polymer degradation and drug release. EuroIntervention 2008;4: Stack RS et al. Interventional cardiac catheterization at Duke Medical Center. Am J Cardiol 1988;62:3F-24F. 40 Erbel R et al. Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: a prospective, non-randomised multicentre trial. Lancet 2007;369: Bhargava B et al. Preclinical and early clinical experience with a biodegradable polymerbased, rapamycin-elunting Indian drug-eluting coronary stent: The Bio -Rapid study. Indian Heart J. 2008;60(3): Tamai H et al. Initial and 6-month results of biodegradable poly-l-lactic acid coronary stents in humans. Circulation 2000;102: Ormiston JA et al. A bioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial. Lancet 2008;371: Serruys PW et al. A bioabsorbable everolimus-eluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods. Lancet 2009;373:

21 interview The management of ACS: interview with Irene Lang I Lang What are the current challenges for those interventional cardiologists who treat patients with ACS? In my institution the main patient-related challenges are old age, complex lesions and risk of bleeding. Shock can also be a challenging presentation, but I don t think that there is any doubt that patients in shock due to AMI should go to the catheter lab immediately. Interventional challenges include initial thrombolysis and the timing of angiography and PCI after thrombolysis. Another dilemma, of course, is the most appropriate antiplatelet therapy and treatment paradigm. How do we block platelet activation and how do we identify responders versus nonresponders to antiplatelet therapy? Were there any specific talks or seminars at TCT or ESC this year that directly address some of these challenges? Were there other key data presented for patients with ACS? I think the NORDISTEMI data will help us address some of these challenges, in particular regarding the timing of PCI after thrombolysis. The study found that STEMI patients who live in remote areas and receive initial thrombolysis have better outcomes with an early invasive strategy involving immediate hospital transfer for angiography and PCI compared with a conservative, ischaemia-guided strategy. Reports from the ATLAS-TIMI 42, APPRAISE-2 and SEPIA studies provided some interesting new data on the role of factor Xa inhibitors, rivaroxaban, apixaban and otamixaban, respectively, as adjunctive therapies in patients with recent ACS. I think that there is some further research needed on targeted anticoagulation in ACS to help reduce the risk for bleeding. In addition, I think there have been some important new steps in atrial fibrillation shown in the RE-LY trial; although it hasn t translated into ACS yet, we can expect this soon. In the future, there will be treatments more efficacious than fondaparinux but not as aggressive as the GP IIb/IIIa inhibitors. What do you think of the current treatment options and strategies to reduce bleeding in STEMI patients and how can they be improved? The very obvious strategy would be to use bivalirudin and there has been some strong data supporting its use from the HORIZONS trial. I think, at the cost of some early thrombus, we need to move into the mode of assessing the inherent risk. We need some bleeding risk scores to better characterise this very difficult clinical disorder. Further, there should be two scores; a bleeding score and an ischaemic-risk score to allow us to assess the right course of action for each individual situation. The use of bivalirudin should be encouraged if the bleeding risk score exceeds what we can tolerate. At TCT this year, one of the interventional/surgery questions raised was Should left main PCI be a class IIa indication?. What are your thoughts? In the 2005 guidelines, PCI of unprotected left main stenosis was included as a IIb C indication. I think based on the advances within the past 4 years we are getting closer to having a class IIa indication for left main PCI, but we are not quite there yet it needs to be restricted to very well defined, or otherwise low-risk, cases. irene lang Department of Cardiology, Medical University of Vienna, Vienna, Austria KEY ACS, acute coronary syndrome; AMI, acute myocardial infarction; ESC, European Society of Cardiology; GP, glycoprotein; IVUS, intravascular ultrasound; MACE, major adverse cardiac event; NSTEMI, non-st segment myocardial infarction; OCT, optical coherence tomography; PCI, percutaneous coronary intervention; STEMI, ST segment elevation; TCT, Transcatheter Cardiovascular Therapeutics 21

22 Address for correspondence Prof. Irene Lang Department of Cardiology, Medical University of Vienna, Vienna, Austria How would you describe the evolution of antiplatelet therapy in the management of ACS? I have seen antiplatelet therapy change dramatically; initially the importance of platelets when you implant the stent was not very clear and we used to put patients on warfarin and aspirin after stent implantation. Now we know that it is not coagulation factors but platelet activation and platelet receptors that play a critical role in MACE; therefore, you need dual inhibition. I think that the use of GP IIb/ IIIa inhibitors will be overtaken by potent platelet inhibitors, and treatment will be chosen based on individual bleeding risk and the individual stenting anatomy (i.e. the location, placement, angulation and assembly of stents, and their impact on the final vascular anatomy). Pharmacogenetics will also be important in allowing us to characterise patients and individualise treatment strategies. How did the data from TRITON- TIMI 38 impact your personal clinical determination of antiplatelet therapy when it came to the treatment of a patient with UA/NSTEMI, STEMI and stent thrombosis? TRITON-TIMI 38 has raised awareness of the importance of antiplatelet treatment in high-risk situations. Stent thrombosis is a catastrophe; I think platelet inhibition and thrombosis is not an issue here, because you cannot address stent thrombosis by inhibiting platelets it is too late. With regard to NSTEMI and STEMI, TRITON-TIMI 38 has shown clearly that more potent platelet inhibition in these situations does reduce the risk of cardiac events, but that effect needs to be balanced against the increased risk for bleeding. In STEMI this increased bleeding risk disappears, as the ischaemic risk is much greater. How important is a multidisciplinary approach to managing ACS? It is very important, it involves emergency care, nurses, coronary surgeons and technical personnel and, increasingly, it requires a new group of people who manage the IVUS and OCT. I think that IVUS has a place in ACS treatment and without the technician we cannot use it. How would you like to see the guidelines improved to help those who manage patients with ACS? Thrombectomy is included in current guidelines for STEMI patients. I suspect it will eventually be incorporated into guidelines for NSTEMI as well. We need to remember that while we might get more complicated and polymorbid ACS cases in our units in Austria today compared with 5 years ago, our colleagues in Eastern Europe still see many classical cases in which thrombectomy would be ideal. That said, if thrombectomy is not in the guidelines then that is a barrier to its use, as health resources will not be allocated for its use. Nevertheless, this change has to be based on solid data on thrombectomy catheters and further research in this area is needed. Finally, a key concept is to individualise patient care and management in ACS. Guidelines should focus more on individual risk; there can t be one indication for everyone. After all, we treat the 96-yearold who comes with an occluded right coronary artery very differently from a healthy 40-year-old patient. I think this will, ultimately, improve the standard of care for the patient. DISCLOSURES: The opinions and factual claims herein are solely those of the author and do not neccesarily reflect those of the publisher, editor-in-chief, editorial board and supporting company. IL has no relevant disclosures. 22

23 meeting report Highlights from TCT 2009 H M Nef H Möllmann This year, the Transcatheter Cardiovascular Therapeutics (TCT) congress was held in San Francisco, CA, USA, from 21 25th September. As the largest global medical and scientific symposium dedicated to interventional cardiovascular medicine, it attracted almost 15,000 visitors. It's all about the patients This year s congress had a strong focus on the importance of the individual patient in treatment decisions and a multidisciplinary approach involving the entire heart team (surgeons, cardiologists, anaesthetists, nurses and technicians). Reporting results from the ongoing PARTNER trial evaluating the SAPIEN valve (Edwards Lifesciences, Irvine, CA, USA) in patients who are considered high risk for conventional open-heart valve surgery, C Miller (USA) described what he has learned from transcatheter aortic valve implantation (TAVI). Working hand in hand with (interventional) cardiologists is really stimulating intellectually. It s fun, gratifying and, ultimately, I think it s better for patients. Of course, it can be terrifying at times, but it s terrifying for both of us, he said. Key trial data As ever, TCT showcased the latest results from current trials in interventional cardiology including data from some key stent trials. SPIRIT IV is a prospective, single-blinded, multicentre clinical trial, with 3,690 patients randomised 2:1 to either the Xience V (Abbott, Abbott Park, IL, USA) stent or the Taxus Express (Boston Scientific, Natick, MA, USA) stent. This year G Stone (USA) presented results from SPIRIT IV. The primary endpoint was the rate of ischaemia-driven target lesion failure (TLF) after 1 year. At 1-year follow up, the rate of TLF was 4.2% for the Xience V group and 6.8% for the Taxus Express group (p<0.0001). Furthermore, the results showed a significant difference in ischaemia-driven target lesion revascularisation of 2.5% in the Xience V group vs. 4.6% in the Taxus Express group (p<0.001) while the rate of stent thrombosis was lower with 0.17 in the Xience V group compared with 0.85 in the Taxus group. Using the Academic Research Consortium definition of definite/probable stent thrombosis, the rates were 0.29 for Xience V and 1.10 for Taxus Express. These data suggest a newer generation of drug-eluting stents (DESs) may have benefits over firstgeneration versions. Cardiologists have used DESs off-label to treat in-stent restenosis for some time with limited clinical data to support this indication. This year, R Byrne (Germany) presented some promising data from the ISAR-DESIRE 2 study. This open-label study randomised 450 patients with sirolimus-eluting stent (SES) restenosis to the Taxus Express (paclitaxeleluting) or Cypher (Cordis Corporation, Bridgewater, NJ, USA; sirolimus-eluting) stents. Results showed no difference in late lumen loss between stents at 0.40 and 0.38 mm (p=0.75) in the Taxus and Cypher groups, respectively. Event rates for binary restenosis (20.6% vs. 19.0%, respectively) and target lesion revascularisation (14.6% vs. 16.6%, respectively) were also similar in both groups. These data suggest that treating in-stent restenosis with either Cypher or Taxus results in comparable anti-restenotic efficacy. K Volker (Germany) presented 2-year followup data from the LEADERS trial demonstrating the safety and efficacy of a biolimus A9 Holger m nef helge möllmann Kerckhoff Klinik Heart and Thorax Center, Bad Nauheim, Germany 23