Andrew Holden, associate professor of Radiology, Auckland University School of Medicine, Auckland, New Zealand, has been involved in the investigation of several endovascular devices for the treatment of abdominal aortic aneurysms and peripheral arterial disease. He spoke to Vascular News about his career in radiology and interventional radiology, memorable cases and interests outside medicine. He also explained why he considers off-the-shelf fenestrated grafts, bioresorbable scaffolds and an aneurysm sealing system advances in interventional medicine.
When did you decide you wanted a career in medicine? Why radiology and later, interventional radiology?
I only decided to do medicine in my last year of high school. I did not come from a medical family and to be honest, I applied for medicine only because it seemed the hardest university course to get in to and that appealed to my competitive spirit! I was attracted to radiology because it was a dynamic and rapidly changing specialty but I missed patient contact and procedural based medicine. Interventional radiology offered both of those things.
Who has inspired you in your career and what advice of theirs do you remember today?
I was fortunate in my radiology training to win a research competition that enabled me to spend some time with Dr Ken Thomson in Melbourne, Australia. Ken (who happens to be a fellow kiwi) not only gave me insight into how to practise intervention to the highest standard but also demonstrated that valuable research can be performed “down under”. Two interventionalists that made a big impression on me early in my career were Dr Barry Katzen and Dr Michael Dake. Not only have they pioneered many procedures and treatments but have emphasised the importance of interventional radiologists being clinically skilled.
Can you please tell us about the first interventional procedure you performed?
This was a superficial femoral artery angioplasty. In those days, digital subtraction angiography had only just been introduced and delivery systems were much larger than they are today but the basic techniques remain the same.
What have been your most memorable clinical cases?
As a fellow, I was lucky enough to get involved in the first bifurcated endograft procedures with Michael Lawrence-Brown and David Hartley in Perth, Western Australia. That locally made endograft was to become the Cook TriFlex device and developing that device and procedure was a great experience. Since then, I have been involved in many “first-in-man” device trials that are always exciting. Performing complex interventions during conference “live case” transmissions is always challenging but memorable. Having said that, I still find performing acute interventions successfully in life-threatening situations to be the most rewarding clinical cases.
How do you see the endovascular field developing in the future? Do you believe in an end to the turf wars between endovascular specialists?
At the moment, we still see geographic variations in who performs interventions including surgery, cardiology and radiology backgrounds. Fortunately, these boundaries are becoming blurred and we are seeing the endovascular specialist slowly evolve. I have always thought that “turf wars” are more about physician’s egos than optimum patient outcomes and I have tried to apply two principles throughout my career. Firstly, patient outcomes are optimised if a team approach is used, combining the skills and perspectives of multiple specialties. In my own practice, a close relationship with Dr Andrew Hill and his vascular surgical colleagues at Auckland Hospital has been pivotal to my practice. Secondly, the best physician to do a procedure is the physician with the training and skills to best do the job, irrespective of their background.
In your opinion, what is the role of off-the-shelf fenestrated endografts for juxtarenal/pararenal aneurysms?
There is a need for “off-the-shelf” fenestrated endografts so that patients with juxtarenal aneurysms can be treated easily and in a timely manner. This is particularly relevant in symptomatic aneurysms but ideally could be applied to the vast majority of juxtarenal aneurysm anatomies. I was fortunate to be involved in the “first-in-man” cases using the Endologix Ventana “off-the-shelf” FEVAR device. This device was very easy to use and acute performance was excellent. Unfortunately, there were some long-term durability issues encountered and ongoing clinical trials were suspended until device modifications were made. I am pleased to see that these modifications are being made, after which Ventana will be back in clinical use. It is reasonable to say that developing a fenestrated EVAR device that is robust but can treat a wide range of anatomies has proved challenging for all companies in this space but good progress has been made.
You have been investigating the use of a drug-eluting bioresorbable stent for the superficial femoral artery. What results have you seen and how do you think this device will be used in the future?
I have been principal investigator in the STANCE trial using the Stanza scaffold produced by 480 Biomedical. This is a self-expanding scaffold for the superficial femoral artery that is fully resorbed by 15 months. The STANCE trial showed the scaffold performed well acutely with excellent scaffold to vessel wall apposition and no significant residual stenosis. As with all bioresorbable stents, restenosis during the resorption period due to neointimal hyperplasia has been observed and so I am delighted to be co-principal investigator with Dr Iris Baumgartner of the SPRINT trial using a drug-eluting version of this Stanza scaffold. This device has an additional paclitaxel/polymer coating that provides controlled drug release. We have started to recruit into the SPRINT trial. The femoropopliteal arterial segment has proved challenging for nitinol self-expanding stents with restenosis and stent fracture being problematic. Bioresorbable vascular scaffolds have been keenly anticipated in this vascular territory.
How many cases of endovascular aneurysm sealing have you performed so far and what have the outcomes been? Are you treating patients who would not be suited for EVAR?
To date, we have performed approximately 60 endovascular aneurysm sealing (EVAS) procedures using the commercially available Endologix Nellix system at Auckland Hospital. We have had 100% procedural success with no aneurysm related mortality or morbidity. We have had one secondary intervention (1.7%) for a type Ib endoleak, easily managed by a covered stent extension. We have had no persistent endoleak of any type, including type II endoleak. We are treating patients within the published instructions for use that include a proximal neck length ≥10mm and an iliac artery diameter.
Results from the CORAL study recently presented showed no benefit of stenting over medical therapy alone for renal artery stenosis. How do you interpret the data from this study?
The NEJM report of the CORAL trial has only recently become available and I have not had an opportunity to evaluate subgroup analysis in any depth. I have been critical of the ASTRAL trial because it was not designed assuming clinical equipoise between medical therapy versus angioplasty and stenting for renal artery stenosis. Investigators enrolled patients in whom they were uncertain if endovascular intervention would benefit. This implies if a site was convinced the patient would benefit from intervention, they did not enrol that patient. Other limitations were variability in stenosis severity, a lack of independent core laboratory adjudication and high complication rates after endovascular treatment.
I consider the CORAL trial to have superior trial design and Auckland Hospital was a significant contributor to this trial. While I am disappointed that the results are very similar to ASTRAL, it is time to accept that two major randomised controlled trials have failed to show a benefit for renal artery revascularisation over medical therapy for all comers with atherosclerotic renal artery stenosis. Renal artery intervention is now likely to be reserved for limited indications including patients with critical renal artery stenosis and severe or resistant hypertension, fibromuscular dysplasia or a recent decline in renal function.
In the treatment of peripheral arterial disease, how do you use angioplasty alone, stents, drug-eluting balloons, atherectomy etc?
In the iliac arteries, our approach is to primary stent most lesions except very simply stenosis, particularly if they are external iliac artery lesions. In the common iliac artery, we almost exclusively use balloon expandable stents and prefer covered stents in occlusive lesions and to reconstruct the aortic bifurcation (CERAB technique).
Below the inguinal ligament, our initial approach is angioplasty although we do primarily use drug-eluting stents in the femoropopliteal segment for complex lesions (intermediate length lesions and chronic total occlusions) and those with sub-optimal results post-angioplasty. I would like to use drug-eluting balloons more frequently but due to cost constraints, we tend to restrict their use to restenosis cases or patients at a high risk of restenosis. A primary drug-eluting balloon approach would mean we would use bare metal stents as bail out. For long superficial femoral lesions (≥20cm), we favour self-expanding covered stents (eg. Gore Viabahn) as patency appears to be independent of lesion length. For bulky, calcified lesions, we debulk with atherectomy devices, particularly in “no stent” zones such as the common femoral and popliteal arteries. We are also integrating the high radial resistant Supera stent into our practice for these lesions.
In the tibial and pedal arteries, we primarily use angioplasty with drug-eluting balloons reserved for restenosis and drug-eluting stents as bailout for sub-optimal angioplasty in the proximal tibial arteries. We are considering bioresorbable vascular scaffolds for this indication.
You also have an interest in technologies for the treatment of hepatic tumours. How has interventional radiology helped patients with this condition?
Interventional radiology has a role in the management of primary and secondary hepatic malignant tumours. Percutaneous thermal ablation techniques (radiofrequency and microwave) can completely treat these lesions in a minimally invasive way offering the opportunity for cure. In patients with more extensive hepatic disease, in whom ablation, resection or transplantation is not possible, transarterial chemoembolisation (TACE) can prolong patient survival. We have been involved in clinical trials performing TACE with drug-eluting beads.
Chemoembolisation with drug-eluting beads enables the delivery of high concentrations of chemotherapeutic agents to the tumour cells while limiting systemic toxicity. We are also involved in randomised controlled trials assessing the use of selective internal radiation therapy (SIRT) using radiation emitting micro-spheres, most commonly used in colorectal metastatic disease.
What else are you researching at the moment?
We are currently involved in 15 first-in-man device trials ranging from drug-eluting balloons and stents to inferior vena cava filters. We are soon to commence a new covered balloon expandable stent trial and a drug-eluting version of the Trireme Chocolate balloon that provides a different method of angioplasty. We hope to commence an innovative new renal denervation device trial in 2014. Other interesting device trials include a procedure to bypass long femoral artery occlusions with endografts via the superficial femoral vein. A promising device we are trialling is specifically designed for calcified arterial lesions, often so challenging for current devices. The Shockwave device combines angioplasty with lithotripsy to create a procedure termed “lithoplasty”. On the imaging front, we are very interested in image modality fusion to facilitate interventions.
What is the most interesting paper you have come across recently?
I found the paper by El Batti et al titled “Type II endoleaks after endovascular repair of abdominal aortic aneurysm are not always a benign condition” (J Vasc Surg 2012;57:1291–8) an interesting paper. This paper, produced by Jean-Pierre Becquemin’s group showed (as others have done) that type II endoleak is associated with a significantly higher rate of aneurysm sac expansion that aneurysms without type II endoleak. However, the paper also showed patients with type II endoleak had a significantly higher rate of serious complications including death, rupture and open conversion as well as late type I and III endoleak. It is information such as this that confirms my excitement for an endovascular aneurysm sealing device that may prevent endoleaks of any type.
Outside of medicine, what are your interests?
I am very fortunate to have a great family and enjoy spending time with them. We have a beach house and enjoy water sports there—swimming, fishing, snorkelling, etc. I like to keep fit and have run five marathons. I enjoy hiking, golf and travelling. I am a patriotic kiwi and support New Zealand teams, especially the All Blacks!
1984 MBChB, Otago University
1996 Member of Interventional Radiological Society of Australasia (IRSA)
1996–2002 Director of Ultrasound Imaging, Auckland Hospital
2002– Director of Body Imaging and Interventional Services, Auckland City Hospital
2005– Associate Professor of Radiology, Auckland University School of Medicine
2003–2012 Examiner, FRANZCR Part 2 Examinations
1989–1993 Radiology registrar, Auckland Area Health Board
1993–1994 Staff radiologist, Middlemore Hospital
1994–1995 Senior registrar/fellow Interventional Radiology and MRI, Royal Perth Hospital
1995 Staff radiologist, Royal Perth Hospital
1996– Staff radiologist, Auckland Hospital.
1966–2001 Private radiologist, The Radiology Group, Auckland
2000–2005 Private radiologist, Ascot Radiology, Auckland
2005– Associate professor of Radiology, Auckland University School of Medicine
Completed research projects
Flexstent (Flexible Solutions) First-in-Man Stent Trial, Cardiva Champion First-in-Man Trial, Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) Trial, Bayer SHARP Trial, CRUX RETRIEVE IVC Filter Trial
Current research projects
Endologix Ventana First-in-Man Fenestrated, Endograft Trial, Engage (Medtronic) Registry, Vital Access First-in-Man Trial, Endologix Nellix First in Man Endograft Trial, Quattro Vascular Chocolate Balloon First-in-Man Trial, Abbott Xpert Tibial Stent Motion Study, Abbott ABSORB First-in-Man Trial, Tetherx Vascular Scaffold First-in-Man Trial, 480 Biomedical STANCE First-in-Man Trial, Johnson and Johnson Inception Trial, Siemens i-pilot Iliac Artery Study, Biocompatibles Drug Eluting Beads as a Bridge to Liver Transplantation, SIRTEX Sirflox Trial, Bayer SEARCH Trial, Bayer STORM Trial, Abbott LIGHT Trial, SIRT in HCC Trial