Nieves Gonzalo

Interventional cardiology is a rapidly evolving field, offering the opportunity to learn procedures with immediate and life-changing results for patients. This is what has attracted Nieves Gonzalo (Clinico San Carlos University Hospital, Madrid, Spain) to the specialism, and why she believes it will continue to draw in future generations of physicians. Recently appointed as a course director for EuroPCR, Gonzalo also serves as a deputy editor of EuroIntervention, and as a co-chair of the European Association of Percutaneous Cardiovascular Interventions (EAPCI) Scientific Documents and Initiatives Committee. She tells Cardiovascular News about her career to date, research priorities, and the importance of representation.

Why did you choose to become a doctor and why, in particular, did you choose to specialise in interventional cardiology?

When I was in high school I loved biology and I was fascinated by the complexity of interactions that allow life to exist. Medicine was the perfect opportunity to continue learning about this and to apply this knowledge to improve lives. I decided to study cardiology because I found heart physiology enthralling and the specialty provided so many opportunities from diagnosis to treatment, and from the beginning, interventional cardiology was the choice for me. The possibility of performing a procedure that generates immediate results for the patient—for example primary percutaneous coronary intervention (PCI)—is extremely rewarding.

Who were the biggest influences on your early career?

I did my cardiology training at Hospital Clinico San Carlos (Madrid, Spain) and all of my colleagues in the interventional cardiology department were extremely supportive. The chief of interventional cardiology at that moment was a woman—Rosana Hernández— and she was a great inspiration. My mentor Javier Escaned, together with Manel Sabate, encouraged me to go abroad for a fellowship at the Thoraxcenter in Rotterdam (The Netherlands) with Patrick Serruys and this widened my view, helping me to incorporate research as a central aspect of my career. In Rotterdam, I worked very closely with Evelyn Regar to develop my thesis on optical coherence tomography (OCT) when the technique was starting out.

What has been the most important development in interventional cardiology during your career?

The most important developments in interventional cardiology during my career have been the incorporation of primary PCI (a lifesaving strategy), the invention of drug-eluting stents (DES) that have tremendously improved the long-term success of PCI, and the incorporation of intracoronary physiology and imaging techniques that have changed the way in which we perform PCI, providing a new insight into the pathophysiology of coronary heart disease. The other big development has been transcatheter aortic valve implantation (TAVI), another lifesaving procedure that has provided a new opportunity for many patients who did not have options before and is contributing to offer less invasive treatments for many others.

What has been the biggest technological disappointment?

The biggest disappointment for me was polymeric bioresorbable scaffolds. I worked intensively on the initial phase of the ABSORB studies during my fellowship in Rotterdam and the initial results were promising. We were all thrilled with the possibility of treating atherosclerotic disease without the need for a permanent metallic cage, it was a pity when larger trials revealed significant problems that precluded their clinical application. I still hope, however, that the concept will be revived. There are so many potential advantages for the future, especially with an ageing population that will probably require repeated interventions throughout their lives.

What are your current research priorities?

My current research priorities are focused on treatment of complex coronary disease, a growing problem as we treat older patients with multiple comorbidities. In this regard, strategies to improve treatment of calcific lesions are going to be key to improve the long-term results of our interventions. I am also very interested in the treatment of restenosis, which is much more challenging in the context of DES, especially with the development of neoatherosclerosis. Another field of interest and research is the relation between physiology and atherosclerotic plaque morphology and the treatment of left main disease.

What are the key unanswered questions around the field that future research should prioritise?

There is currently a renewed interest in the search for high-risk plaques to be able to detect them before they rupture and generate an event. I think this is an important field where intracoronary imaging techniques and potentially non-invasive imaging technologies can provide new insights and help us move toward preventing events instead of treating them. The incorporation of artificial intelligence (AI) will probably be important, especially in plaque characterisation and development of new physiological indices derived from invasive and non-invasive technologies. PCI guidance based on physiology, and imaging and impact on future events as compared with other treatment strategies, is another important area to be addressed. The concept of leaving nothing behind when treating coronary disease—either with bioresorbable devices or drug coated balloons—will also be relevant in future research.

What has been the most important paper published in the past year?

One of the most interesting papers published in the last year for me has been the long-term results of SYNTAX II. The paper demonstrated that applying a complete contemporary percutaneous revascularisation strategy incorporating heart team discussion, imaging and physiology to guide and optimise PCI can yield optimal clinical results in multivessel disease, making it competitive with more invasive strategies.

What are the current challenges facing women seeking to enter the interventional cardiology field, and how can these be overcome?

There are many challenges that women face when they decide to pursue a career in interventional cardiology ranging from the lack of role models and support to concerns regarding pregnancy and reconciliation of family and work life. Big efforts have been made in recent years to generate guidance to overcome these barriers and promote the incorporation of women in leading positions and I am sure they will take effect in the next generation. Promoting a meritocratic system in which gender is not an issue will bring more women into the field and will help them to reach leading roles. Equal representation in research and education is also an important aspect that needs to be considered and properly promoted.

What can interventional cardiology do to better attract young physicians into the field?

The best way to attract young physicians is to show them how fascinating this specialty is. Interventional cardiology is in continuous evolution, meaning that you always keep learning and it is impossible to get bored. From a personal point of view, it is demanding but also really rewarding, offering you a lot of options to help patients. Promoting enthusiastic young colleagues and generating a good working environment for the future is a task for every one of us.

Looking back over your career, what has been your most memorable case?

There are many cases that have been memorable especially, for example, my first case of a patient with a left main occlusion who arrived in a critical situation and was able to survive and recover after primary PCI. There is another case that we performed recently that was also transformative for me. This involved a lady with advanced renal disease, severe peripheral disease with no conventional accesses, critical left main disease with extreme calcification and very severe left ventricular (LV) function. In this case, after careful planning with computed tomography (CT) and with the help of the vascular surgeon, we were able to perform the PCI with LV support through a surgical left subclavian access that was the only route available. For me it was an example of how teamwork is going to be critical in the future as we tackle more and more complex patients and disease.

Outside of medicine, what are your hobbies and interests?

I like nature and outdoor activities. Taking care of my garden is especially relaxing for me. Also, doing exercise is essential to keep me happy. I especially enjoy spending time with my children and share with them my love for music and books.

Appointments and training

„ Director Consultant

Interventional Cardiologist, Clinico San Carlos University Hospital, Madrid, Spain

„ Fellowship, Thoraxcenter, Erasmus University Rotterdam, Rotterdam, The Netherlands

„ Doctor of Medicine, Universidad Autónoma de Madrid, Madrid, Spain

Memberships

„ European Society of Cardiology (ESC)

„ European Association of Percutaneous Cardiovascular Interventions (EAPCI)

Research

„ RIBS IV and V OCT sub-study

„ VISTA study

Appointments

„ Deputy Editor, EuroIntervention

„ EuroPCR Course Director

„ Co-chair, EAPCI Scientific Documents and Initiatives Committee)

A wealth of data underscore treatment choices for coronary DCBs

The modern field of percutaneous coronary intervention (PCI) has come to be dominated by drug-eluting stents (DES), but there are many instances in which “leaving nothing behind” in the vessel is an attractive prospect. Proponents of this approach, including Tuomas Rissanen (North Karelia Central Hospital, Joensuu, Finland), believe that using a drug-coated balloon (DCB) is an effective alternative to the stent that offers a range of benefits in selected patients.

UNDERPINNING THIS BELIEF IS A WEALTH of clinical data, including from registry-based studies, and randomised trials that inform treatment in a wide set of clinical and anatomical scenarios. Among the leading devices in the field is the paclitaxel and iopromide-coated SeQuent® Please product family (B. Braun)—widely acknowledged as the bestinvestigated DCB in the market—which has clinical evidence from more than 110 published studies, totalling more than 25,000 patients, and stretching back almost 15 years since its entry into the market.

In this interview, Rissanen discusses the clinical indications that are most suited to the use of a DCB, the studies that have been most impactful to the field, and how having a proven device backed by a wide set of data is key.

“The fundamental difference to a stent is that no foreign body material is left in the artery that may cause later problems such as stent thrombosis,” Rissanen explains, discussing what separates PCI with a DCB to stent implantation. In simple terms, the DCB delivers an antirestenotic agent directly to the lesion, usually either paclitaxel or sirolimus mixed with an excipient helping to move the drug from the balloon catheter to the vessel wall.

“Stents are very useful when the treated vessel needs mechanical support due to collapse of the vessel or significant flow-limiting dissection—in fact, stents were developed for these two purposes,” comments Rissanen. “However, when the predilatation result is good and there are no problems that would need a metallic implant, then it is best just to use a drug coated balloon catheter delivering an antirestenotic drug,” he advises.

“An advanced interventional cardiologist should absolutely have both tools in the toolbox,” Rissanen comments, pointing out that the DCB and DES offer complementary characteristics.

Predominantly the DCB has been seen as a tool for treating in-stent restenosis, where it carries a class I recommendation with evidence type A in guidelines from the European Society of Cardiology (ESC) and European Association for Cardio-Thoracic Surgery (EACTS), based largely on studies performed with the SeQuent paclitaxel and iopromide coating, including the PACCOATH ISR I and II or PEPCAD trials. However, more recently there has been an increase in interest in the use of DCBs in de novo lesions, where the therapy has been shown to be safe and effective in numerous scenarios.

“Depending on the patient and lesion characteristics, and most importantly, on the result of the predilatation of the lesion, the method that is best for the patient should be chosen,” says Rissanen. Typically, an adequate vessel preparation involves achieving less than 30% stenosis, no flow- limiting dissection, and a fractional flow reserve (FFR) of >0.8.

Rissanen offers the view that this is particularly appealing among patients that are at high-risk of bleeding, as the DCB allows the clinician to stop antithrombotic medication within a month after the procedure in stable coronary artery disease patients, without an increase in event rates. Besides DCBonly usage in standard de novo lesions, he notes that there are also anatomic scenarios for DCB-only PCI, including, for example, in complex bifurcations, where the side branch, main branch, or both branches, can be treated using a DCB.

“The advantages of DCB-only therapy over stenting in this situation are that the side branches that are in the treatment area are not that easily occluded,” Rissanen adds. “Also, the lack of metallic implant allows later positive remodelling of the vessel and of course eliminates the risk of stent thrombosis.” Additionally, in recent years this technology is gaining more traction in complex and diffuse coronary artery disease being used alongside stents to reduce the overall stent-burden.

Turning to the data supporting the use of DCB in coronary lesions, Rissanen identifies two studies— BASKET-SMALL-2 and DEBUT, both of which used SeQuent Please/NEO DCBs—as being the standout studies to have led the field. BASKET-SMALL-2, results of which were published in The Lancet in novo coronary lesions in patients with high-bleeding risk using DCB or a bare metal stent, results, published in The Lancet in 2019, showed that the DCB was superior to the stent against a primary outcome of MACE at nine months. A total of 208 patients were enrolled in the trial, with MACE having occurred in one patient (1%) in the DCB group versus 15 (14%) in the stent group.

The accumulation of data continues and according to Rissanen, of the more recent studies to influence thinking on DCBs is the 2020 publication of a metaanalysis in the Journal of the American College of Cardiology (JACC), authored by Bruno Scheller (University of Saarland, Homburg/Saar, Germany) is fundamental. This took data from 26 randomised controlled trials, including 4,590 patients, looking at paclitaxel-coated devices, and reached the conclusion that the use of paclitaxel DCBs for treatment of coronary artery disease is safe in the long term.

Outside of these landmark trials, Rissanen also points to a wealth of further research that has shaped perceptions on DCB in diverse patient populations. Among them is PEPCAD-NSTEMI, a trial that addressed DCB-only therapy in non-ST-elevation myocardial infarction (NSTEMI) patients, finding that treatment of coronary de novo lesions with DCB was non-inferior to stenting with bare metal or drugeluting stents. This was underlined in a sub-group analysis of the BASKET-SMALL 2 trial, where noninferiority to DES in acute coronary syndrome (ACS) patients, including around half with NSTEMI, was shown. Rissanen also highlights the REVELATION study, addressing a DCB-only approach in STEMI using FFR measurement as a surrogate marker.

Do these data translate into clinical practice, and should it inform decision-making when it comes to device selection? Yes, according to Rissanen. “The SeQuent Please DCB has shown consistently good clinical results in many registry-based studies and randomised clinical trials,” he comments. “These trials involve different clinical and anatomical

2018, is an open-label randomised non-inferiority trial investigating the use of DCB in small vessels, comparing 758 patients with lesions <3mm in diameter receiving either a DCB or a DES. Results of the trial demonstrated the non-inferiority of the DCB versus DES, with major adverse cardiovascular events (MACE) shown to be comparable between the two groups (7.5% for the DCB group vs. 7.3% for the DES cohort). Rissanen notes that three-year followup from the trial, published in 2020, has shown consistent and durable results, while a sub-group analysis on high-bleeding-risk patients, in particular, has highlighted the benefit of DCB versus stenting.

In DEBUT, a single-blind, randomised, noninferiority trial, examining the treatment of de scenarios and cover also more complex situations such as bifurcations, calcified lesions and even chronic total occlusions (CTOs).

“SeQuent Please DCB currently has the most clinical data to show its safety and efficacy. This is important as the patient population in the cath lab nowadays is very complex. You can trust the device that you are using in these circumstances and convince also your patient that he or she is receiving the best available treatment.”

Summing up why he chooses only to use the devices that have the best available evidence, Rissanen concludes: “In our centre we use devices based on the proven clinical data. It is both costeffective and best for the patient.”