The Clinical Connection: How a Doctor's Idea Becomes a Product

Kristine Fuimaono, Group Manager, Research and Development Biosense Webster, Inc. Professor Michel Haissaguerre, MD, Adjoint Centre Hospitalier Universitaire de Bordeaux
Kristine Fuimaono, Group Manager, Research and Development Biosense Webster, Inc. Professor Michel Haissaguerre, MD, Adjoint Centre Hospitalier Universitaire de Bordeaux
Electrophysiology (EP) is one of the most rapidly developing fields in medicine today. One of the reasons is the continuing development of advanced products that substantially improve the lives of both clinicians and patients. In the midst of this rapid development, it is tempting to ask: Where do all these product ideas come from? Interestingly enough, many of them come from you, the practitioners in the field. The inspiration for a great new EP product often comes from a clinician struggling to solve a recurrent problem in his or her own practice. Sometimes the clinician identifies a clinical need for which there is currently no solution. On other occasions, the clinician recognizes a need and also develops an idea for a product to fulfill the need. The idea begins to move forward when the clinician explains the problem and perhaps a potential solution to a company with relevant expertise. Then begins a process of collaboration and development, often producing a breakthrough product that advances the field in meaningful ways. A Call from Professor Haissaguerre Recognizing the need to develop a product that could reliably create linear lesions in the left atrium, Professor Haissaguerre contacted Biosense Webster, Inc. in February 1998. Kristine Fuimaono, a senior product engineer at the time, was one of the first people at Biosense Webster to talk to Professor Haissaguerre about developing his highly specialized product idea. Biosense Webster was already aware of efforts to create linear lesions in the left atrium, and quickly sent several senior executives to Bordeaux to meet with Professor Haissaguerre. After brainstorming for several days, they returned to their research laboratories with a handful of rough sketches and a general idea of how to solve the problem. These early sketches led to the first round of prototypes. (Figure 1) When initial prototypes were ready, Professor Haissaguerre and several of his colleagues traveled to California to meet with the product engineers at Biosense Webster. The collaborative team worked together to evaluate the first prototypes and, based on their analysis, the product engineers went back to the lab and developed a second set of prototypes. BWI product engineers then brought these new prototypes to Bordeaux for evaluation. The team unanimously agreed that it was time to conduct animal studies with the new prototypes. Animal Studies Lead to a New Perspective At the time of these first animal studies, current thought in the clinical arena was beginning to switch from the atrium to the pulmonary veins as the anatomical source of atrial fibrillation. Clinicians were beginning to recognize that the cause of a great number of atrial fibrillation events, particularly paroxysmal atrial fibrillation, was coming from the pulmonary veins and not the atrium. There seemed to be a number of foci in the pulmonary veins that more or less spontaneously triggered these electrical stimuli. Researchers were working diligently to identify these foci and develop methods to block the signals emitted from them. This often involved very long procedures, during which the clinical team would either wait for an atrial fibrillation event to occur or attempt to trigger one. With all of this in mind, the combined team conducting animal experiments began to rethink the experimental strategy. An alternative approach developing a method for entering the pulmonary veins and creating a circular burn there seemed more logical than trying to perfect a method for creating linear burns in the atrium. This change of strategy stimulated additional discussions, brainstorming, and product ideas that ultimately developed into a third set of prototypes. Now the team was focused on an ablation product that would be able to make curvilinear burns in the pulmonary veins instead of linear burns in the atrium. These prototypes were tested and perfected, but further animal studies led to another important discovery. A Change of Direction As soon as experiments started in the pulmonary veins, the team realized how valuable it would be to have a diagnostic product to accurately map the pulmonary anatomy. This would greatly facilitate making effective circular burns there. That is when the focus shifted from an ablation product to a diagnostic product. The BWI product engineers then developed a fourth set of prototypes for a diagnostic product that would be able to map the physical and electrical environment of the pulmonary veins as a first step toward accurate and effective ablation. When the BWI engineers returned to Bordeaux with the new prototypes, everyone on the team felt that this new tool could be a major step forward. In fact, the new diagnostic product has led to an important new understanding of paroxysmal atrial fibrillation. (Figure 2) Human Studies Lead to Important Insights After animal studies to refine the new prototypes were completed, the new diagnostic product, now called the LASSO Catheter, was approved for human clinical studies at C.H.U. Haut-Leveque, with Professor Haissaguerre as chief clinical researcher. These early human trials produced a series of significant findings that have transformed the treatment of paroxysmal atrial fibrillation. (Figure 3) It was beginning to be recognized in the EP field that a significant amount of paroxysmal atrial fibrillation emanates from foci in the pulmonary veins; a great deal of time and effort had been devoted to locating and blocking these foci. Research has proven that the impulses emanating from these foci follow pathways into the atrium and then induce atrial fibrillation there. By accurately mapping the pulmonary anatomy, the LASSO Catheter enabled the clinician, for the first time, to identify the sleeves of myocardium that extend into the pulmonary veins and provide the conduits for these pathways. Ablating across these sleeves of myocardium, the clinician could then effectively prevent any aberrant signal from entering the atrium. So, instead of ablating in the atrium or tracking down individual foci in the pulmonary veins, the LASSO Catheter enabled the clinician to map and then block the potential electrical pathways from the pulmonary veins to the atrium. Early mapping of the pulmonary veins showed that the myocardial sleeves that extend into the pulmonary veins are variable not only from patient to patient, but also within the same patient. For example, some veins may have these muscle sleeves all the way around while others may have them only a quarter of the way around or even less. Thus, effective treatment depends upon accurate mapping that pinpoints the exact location of all anatomical variables. Researchers then realized that it would only be necessary to ablate the myocardial sleeves, and not the entire pulmonary circumference. So by mapping the vein before ablating, the danger of injuring vascular tissue could be avoided while still providing a total electrical block. The procedure itself was also simplified because it was no longer necessary to trigger or await atrial fibrillation in order to treat it. Actually, it was better to treat the patient during relatively normal conditions. By ablating the pathways instead of individual foci, the clinician can avoid the potential emergence of additional foci after the ablation of the most active ones. Some clinicians think that these foci may be created by stretching of the myocardium that extends into the pulmonary veins, causing certain cells to begin functioning differently from an electrical point of view. If that indeed is the case, then there would very likely be additional cells adjacent to the target foci that could begin emitting fibrillation-triggering signals after the target foci are eliminated. Therefore, the clinical goal is to eliminate the pathway for these signals, and not to determine how many foci there are or exactly where they are. (Figure 4) A Pulmonary Mecca During the human trials, and even afterward, Professor Haissaguerre s hospital was a training and discovery center for the new product and the new procedure. The LASSO Catheter grew in popularity and became associated with leading opinion leaders, as famous clinicians traveled to Bordeaux to observe the procedure. Professor Haissaguerre and his colleagues have now shared their knowledge and experience with many clinicians from all over the world and therefore have substantially reduced the learning curve for their fellow electrophysiologists. With several years of clinical experience, both the product and the procedure have fundamentally changed the treatment of paroxysmal atrial fibrillation It s Just the Beginning Electrophysiology is a dynamic and rapidly developing field. From its inception, EP has been a partnership of clinicians and manufacturers working side-by-side to develop products that solve specific, real-world problems. It is this ongoing partnership, this collaboration, that keeps product development relevant to the needs of the clinician and, ultimately, maximally beneficial to the patient. It is a success story in the making, and many chapters remain to be written.