Thomas Zeller, head, Department of Angiology at Universitäts—Herzzentrum Freiburg, Bad Krozingen, Germany, says that interventional angiology “almost did not exist” when he performed his first non-coronary intervention in 1996. In this interview, Zeller talks about his career, mentors, first insights from the DEFINITIVE AR trial, renal angioplasty and other of his research topics
When did you decide you wanted a career in medicine? Why cardiology and angiology?
The decision to study medicine was made a couple of months before I became a medical student at the Albert-Ludwigs-University of Freiburg. My initial plan was to become a veterinary doctor but I soon realised it would be difficult to communicate with animals. My primary intention was to pursue an education in Internal Medicine, with global knowledge and skills in this specialty. However, in 1987 I met a colleague who enjoyed the same hobby as I did—playing tennis. This colleague convinced me that cardiology would be more attractive. After over two years working in a general Internal Medicine department in a small regional hospital, in 1991 I moved to the Benedikt-Kreutz Rehabilitation Center for Heart and Circulation Diseases Bad Krozingen—now part of the University Heart Center Freiburg-Bad Krozingen to start my training as a cardiologist, and starting my invasive career in the end of 1992. However, in 1993 I participated in an exchange programme with the University Hospital Basel, Switzerland, where I stayed for six months in the angiology department. During this time, I realised that cardiovascular diseases have almost the same etiology and that the diagnostic and therapeutic tools and techniques are very similar. After returning back to Bad Krozingen in 1994 I stepwise built up a section in vascular medicine, first establishing non-invasive diagnostic pathways and, in 1996, starting with the first peripheral endovascular intervention. Nowadays, the section is established as an angiology department comprising of 26 physicians and performing almost 2,700 peripheral interventional procedures per year. The reason for moving from cardiology to angiology was a lack of qualified angiologists and an oversupply of cardiologists in Germany.
Who has inspired you in your career and what advice of theirs do you remember today?
The first person who was important in my career was my chief physician in the department of Internal Medicine in the small regional hospital in Schopfheim, Dr Fabian-Krause. He was trained in almost all fields of internal medicine and he trained me in echocardiography, right heart catheterisation and pacemaker implantation.
The next one was Dr Achim Büttner, at that time one of the most experienced interventional cardiologists in Germany and the head of the interventional cardiology department in my clinic, who convinced me to become an interventional cardiologist.
Prof Kurt Jäger from Basel was the first one who raised my interest for angiology and trained me in duplex ultrasound techniques.
During my career as an interventional angiologist I was most influenced by three people: Prof Blum, Prof Felix Mahler and Prof Giancarlo Biamino. Prof Blum and Prof Mahler were pioneers in endovascular renal artery revascularisation, the topic of my postdoctoral lecture qualification thesis. Prof Biamino is probably the interventional angiologist who changed the paradigms of endovascular therapy in Europe. By introducing laser-assisted angioplasty of long femoropopliteal lesions, he was one of the first who tried to manage such lesions non-surgically. I had the opportunity to visit him in 1997 in Berlin for one week and was very impressed with his kindness and willingness to teach me (a “nobody” in the cathlab at that time) and give me the opportunity of having some hands-on experience. As a result of this experience I built up a workshop programme in my institution teaching more than 100 physicians every year. Moreover, we established a network of experienced European endovascular centres to conduct interventional trials.
What have been your proudest moments?
My proudest moment Certainly was my first publication in a peer-reviewed journal in 2001, followed by the first publication in Circulation in 2003. An important and challenging step in my career was the nomination as associate professor at the University of Freiburg in 2009. Becoming a member of the scientific committee of TCT and of the guideline commission of the ESC were other milestones.
How has interventional angiology evolved since you began your career?
Interventional angiology almost did not exist at the time I performed my first intervention in 1996. At least in Germany, at that time, almost all interventions were performed by radiologists. Interventional tools had not yet been developed as in cardiology, eg. renal interventions had been performed through 9F guiding catheters over 0.035 inch guidewires with hand crimped stiff Palmaz stents. The interventional toolbox consisted of balloon catheters, some early stent devices and the excimer laser. Dedicated below-the-knee devices were not available.
What have been your most memorable clinical cases?
My first non-coronary intervention, which was a renal procedure; and my first carotid intervention, which was done under the proctorship of Prof Klaus Matthias, who is the inventor of this intervention; and the life-saving implantation of an endoprosthesis in a patient with a ruptured type B dissection of the thoracic aorta four hours before I had to give a lecture about the endovascular treatment of aortic dissection and aneurysm.
You criticised a supposed “selection bias” in the ASTRAL (Angioplasty and stent for renal artery lesions) trial and the effect its results had on the RADAR trial enrolment. Do you still hold the same opinion about ASTRAL?
I still believe that ASTRAL was a very biased trial. Firstly, the power calculation was based on a sample size of 1,000 patients but the study was terminated already after enrolling 806 patients. Secondly, study inclusion criteria did exclude from enrolment patients which might have had the most benefit from revascularisation—only patients with an uncertain indication for revascularisation were allowed to be enrolled. There was no proof of the haemodynamic relevance of the renal artery stenosis; more than 50% of lesions enrolled were not significant. Finally, almost 40% of the patients were lost for follow-up after two years when the primary endpoint was analysed. The only conclusion that can be drawn from ASTRAL is that one should not treat patients with an uncertain indication which are basically the ones without a clear proof of the haemodynamic relevance of the lesion.
RADAR was the first and, to date, only trial which was designed in a way that only patients with haemodynamically relevant lesions could be enrolled. Unfortunately, study enrolment slowed done to almost zero after the publication of ASTRAL and the sponsor finally stopped his support after the enrolment of about one third of the intended study population. Basically, an analysis of the primary endpoint of the study, the difference in GFR-rate after one year between the endovascular and medical group accurately confirmed the assumption made for the power calculation. However, due to the small number of patients, this difference was not significant in favour of the stent cohort.
What are your expectations with regards to the results of the CORAL trial comparing medical therapy vs. medical therapy and stenting for renal artery stenting?
Unfortunately, this trial enrolled in the majority moderate lesions, there was no need to prove the significance of a lesion, inclusion criterion was at least 60% renal artery stenosis by angiography (no QA, eyeballing only). Thus, I do not expect any difference in outcomes between both study cohorts.
What is your experience with renal denervation and how are you making sure you select the right patients for this procedure?
With renal denervation we are still at the very beginning, still understanding this therapy. So far, it seems that all approved devices result in a modest reduction in office based blood pressure. However, therapy is still limited to patients with resistant hypertension, other indications are still investigational. In my clinical experience, the responder rate is about 60%, and 10% to 20% respond so well that medication can be reduced. I am not yet sure which technology will make the race: radiofrequency, ultrasound, radiation or local drug delivery. We will need hard endpoint trials with meaningful endpoints such as survival, stroke, hospitalisation etc.
You are a co-principal investigator in the DEFINITIVE AR (anti-restenosis) study comparing atherectomy plus drug-eluting balloon vs. drug-eluting balloon alone. What insights from this trial could you share with us at this point? When will results be presented?
The results of this pilot trial will be available in the first quarter of 2014. What we have learnt so far is that we should not be too aggressive with atherectomy if a drug-eluting balloon will be used afterwards; even small perforations or cuts through the adventitia can result in pseudoaneurysm formation. Regarding restenosis rates, we did not perform an interim analysis after six months; we are waiting for the final angiographic outcome results after one year. My expectation is that we will find a trend to a lower minimal lumen diameter for the combination therapy cohort, if we eliminate those patients who received a stent graft for sealing a pseudoaneurysm.
In your opinion, what is the best way to treat in-stent restenosis?
In-stent restenosis can be successfully treated with drug-eluting balloon balloons. If it is an in-stent reocclusion, the lesion should undergo debulking prior to drug-eluting balloon, eg. Rotarex thrombectomy, laser or directional atherectomy.
What other topics are you researching at the moment?
We are doing cost-effectiveness analyses of drug-eluting balloons and drug-eluting stents in different applications. In general, our current focus is still the evaluation of different drug-based approaches to reduce restenosis in peripheral interventions (above and below the knee). Another hot topic is identifying expanded indications for renal denervation.
What is the most interesting paper you have come across recently?
It is probably the paper about the prognostic value of elevated troponin in peripheral arterial disease patients regarding cardiovascular events (Linnemann et al. JACC 2013). Another landmark trial published this year was the randomised controlled trial comparing primary stenting with percutaneous transluminal angioplasty and stenting on indication in the popliteal artery (Rastan et al. Circulation 2013).
What skills does the interventionalist of the 21st century need to develop?
He must be familiar with different access techniques including retrograde access; he needs advanced knowledge about the unique features of dedicated guidewires; and he needs to know which device in the big toolbox will most likely result in a durable clinical benefit for the patient. In the future, reimbursement will be based on the cost-effectiveness of a particular technology. Thus, he needs to be up to date with current research results.
Outside of medicine, what are your interests?
In the rare case of time outside medicine, I like playing tennis and driving fast cars. Together with the family, I enjoy hiking and travelling around the world.
Head, Department of Angiology at Universitäts – Herzzentrum Freiburg, Bad Krozingen, Germany
1980–1985 Studies in human medicine at Albert-Ludwigs-University, Freiburg i Br, Germany
1988 Conferral of doctorate Dr med (medical doctor) at Albert-Ludwigs-University, Freiburg
2006 Postdoctoral lecture qualification, Albert-Ludwigs-University Freiburg
2009 Associate professor nomination at Albert-Ludwigs-University Freiburg
Admission medical specialist Internal Medicine
1995 Subarea term Cardiology
1996 Subarea term Angiology
2006 Admission “hypertension specialist” by the German Hypertension League (DHL)
1987–1989 Medical assistant of the Department of Internal Medicine at Klinikum Lahr
1989–1991 Medical assistant of Department of Internal Medicine at Municipal Hospital Schopfheim
1991–1993 Medical assistant at Herz-Zentrum Bad Krozingen (Prof Dr H Roskamm)
1993–1994 Medical assistant at Kantonsspital Basle, Department Angiology and Department Intensive Care
1994 Herz-Zentrum Bad Krozingen, in interventional cardiology, and constitution of Interventional Angiology Department
2002 Senior physician at Herz-Zentrum Bad Krozingen, head of the Department of Angiology
2003 Head physician, head of Department Clinical and Interventional Angiology at Herz-Zentrum Bad Krozingen, now Universitäts-Herzzentrum Freiburg, Bad Krozingen
Honours and awards
2001 Young Investigator Award, International College of Angiology
2013 Honorary Membership at the Austrian Society of Angiology
Member Guideline Commission, European Society of Cardiology
Member of Scientific Committee, Transcatheter Cardiovascular Therapeutics (TCT), EuroPCR, Leipzig Interventional Course (LINC), Resistant Hypertension Course (RHC), president-elect of the Annual Meeting of the German Society of Vascular Medicine 2015
Editorial board member, VASA, Eurointervention, Vascular Medicine, Catheterization Cardiovascular Interventions, Journal of Endovascular Therapy, Gefäßmedizin.net