Milestone Case in the focusAF Study:Interview with David Haines, MD

Describe high intensity focused ultrasound (HIFU) ablation for the treatment of atrial fibrillation (AF). How long has this technology been available? The primary goal of ablation with ultrasound is to heat tissue through ultrasound energy transmissions. The use of ultrasound is a little different than radiofrequency in that it utilizes ultrasonic waves, which result in mechanical rather than electromagnetic heating. Ultrasound has significant advantages over other kinds of tissue heating, primarily because ultrasound is minimally absorbed by blood, which is relatively transparent. As a result, the ultrasound enters right through blood, comes in contact with the tissue, and is converted into the tissue heating at that point. Therefore, it is a very favorable form of energy for ablating tissue in the circulating blood pool. The HIFU aspect is especially interesting in that the energy comes from a central ultrasound source on the shaft of the catheter within the balloon, and is radiated out in a radial fashion from that point. In order to project the ultrasound in a forward direction in a circle around the vein, the ProRhythm catheter employs a double-balloon design. The inner balloon is filled with saline to transmit the ultrasound energy; the outer balloon is filled with CO₂ gas. When the ultrasound hits the fluid/gas interface, it is reflected. ProRhythm designed the interface between the inner and outer balloons in a parabolic shape, so just as a mirror can reflect and focus light on a pinpoint the ultrasound energy is similarly focused by the reflection off the parabolic surface and converges at a design-specified focal distance from the balloon, which is about 2 to 4 millimeters. The advantage is that one can position the balloon catheter at the orifice of the pulmonary vein (PV) and initiate ultrasound energy transmission; the ultrasound passes through any interposed blood, meaning that you don't have to press the balloon up into firm contact with the tissue. The energy emanates from the balloon, goes through the blood, and then directly heats the tissue. The way that ProRhythm has designed the balloon is to create a circular pattern of ablation, which is well-suited for isolation of the pulmonary vein. What is the purpose of the focusAF study? How did you become involved with this study? The purpose of the focusAF study is to test the safety and efficacy of ProRhythm Inc.'s HIFU ablation system in the treatment of patients with paroxysmal atrial fibrillation. I've been an investigator in the field of atrial fibrillation and catheter ablation for a long time, so I was fortunate enough to be approached by the company and by the original investigators to be a participant in this trial. Why are permanent and persistent AF cases excluded from this study? It seems that paroxysmal atrial fibrillation is initiated from focal triggers, as originally described by Dr. Haissaguerre. It has also been demonstrated that over 90% of those triggering foci emanate from the pulmonary vein musculature or the transition tissue at the PV-LA junction. Therefore, I believe all people who are actively involved in EP have moved toward pulmonary vein isolation as the primary goal in the treatment of patients with paroxysmal atrial fibrillation. Patients with persistent or permanent atrial fibrillation most likely have that rhythm due to an abnormal myocardium and/or abnormal electrophysiologic properties of the atrial tissue outside the pulmonary veins. When conventional ablation is used to treat these persistent and permanent AF patients, we've found that PV isolation alone is usually not sufficient to treat their condition; usually some degree of substrate modification is required as well. Some researchers, including Dr. Nademanee, have proposed PV isolation is not even necessary in chronic and persistent patients, but rather, we need to be targeting abnormal regions of AF conduction and to substrate modification (i.e., ablating in lines, ablating to eliminate areas of complex fractionated electrograms, and ablating areas of high frequency and high rate). That type of ablation and targeting is not currently within the scope of the design of the catheter or the trial, although certainly in the future, non-pulmonary vein substrate modification will be a goal. However, in the focusAF study, PV isolation is the target, and is best applied to paroxysmal patients only. Describe the first patient case using HIFU. How is that patient doing today? Has there been any recurrence of AF? The patient was a 65-year-old female who had had about a year and a half history of very frequent paroxysmal AF. She had underlying hypertension and mild left atrial enlargement. We thought she would be a suitable candidate for the procedure. She did extremely well during and immediately after the procedure, and had no adverse complications. She was monitored overnight and was discharged the following day. This case was done very recently, so I cannot comment on efficacy yet. In fact, I believe that until you've followed a patient for at least six months, comments on efficacy are not appropriate. Therefore, I can state that this case was acutely successful; however, we will have to wait until the trial is over in order to determine what the long-term efficacy of the technology will be. Was there a learning curve associated with using this technology? Yes. Dr. Nakagawa at the University of Oklahoma is one of the principal investigators of the trial as well as one of the individuals who has been involved with the development of the technology. He performed training for all of the investigators, so each one of us involved in the trial traveled to Oklahoma City and spent a day in the animal lab learning about the system, and then had hands-on practice with the system in an experimental animal. I believe this was extremely important, because even though one can read about a device and handle it outside the body, actually using it in vivo is important to understand all of the details that one needs to attend to in order to perform the procedure safely and effectively in patients. For my first case, Dr. Nakagawa traveled to Michigan to advise me, and had many useful comments throughout the case. However, the device is relatively easy to use, it performed as was described, and was actually a fairly straightforward procedure. Therefore, I had no difficulty at all using the device during that first case. How many patients have been treated so far in this study at Beaumont since this first patient? That was our first case so far in the focusAF study. We have three more patients who have consented, and we are just waiting completion of some pre-randomization testing and scheduling for subsequent cases. What do you find promising about the HIFU technology? If successful, how will high intensity focused ultrasound change the treatment and outlook of AF? At the present time, pulmonary vein isolation with conventional catheters is very time- and labor-intensive, and takes a great deal of experience to do the procedure efficiently and successfully. Therefore, I believe that the only people who should be doing AF ablations are those who have had significant training and experience; this would be a difficult procedure for the standard ablating electrophysiologist to just pick up. What the HIFU balloon promises is a much easier, faster and what we hope ultimately is a more effective procedure that will allow an anatomically-based ablation to be performed by operators who may be somewhat less experienced but see the same good results that we've been seeing in our patients. Ultimately, I believe HIFU will help these procedures be quicker, be equally or more effective than conventional approaches, and have a good safety profile as well. How many ablations are performed each year at Beaumont? Also, what percentage of AF patients are treated with pharmacology versus using ablation? Presently we perform about 650 ablations per year. Of those, about 150 are atrial fibrillation ablations. Of the AF patients that we see, about half of them ultimately go on to ablation therapy, and about half are treated with other approaches, including rate or rhythm control. However, like many AF ablation specialists, I see a highly selected population of AF patients; for example, those patients who are referred to me at our Atrial Fibrillation Center tend to be younger patients with structurally normal hearts, as opposed to average AF patients who tend to be older and have underlying hypertensive or myopathic heart disease. Are you taking part in any other clinical trials in EP at Beaumont? If so, briefly list and describe. Yes, we have many. Presently we are initiating a single-center randomized trial of catheter versus surgical ablation for patients with persisting and chronic atrial fibrillation; this is about to get under way. In addition, there are a number of advanced AF ablation technologies that are in varying stages of clinical testing, and we're involved in some of those protocols as well. Is there anything else you'd like to add? Yes. I think that the field of AF ablation is evolving rapidly, and I believe we're getting acceptable results. In particular, I describe this procedure to my patients as a good procedure, although not yet a great procedure. Good because when it works, we render patients free from arrhythmia and free from need of anti-arrhythmic drugs. However, when it doesn't work, it is disappointing to both physician and patient alike. There also continues to be concern about the occurrence of rare but potentially serious procedure-related complications. However, I think that the new ablation technology such as ProRhythm's HIFU catheter may shift that equation and turn a good procedure into a great procedure, so we are looking forward to continuation of the trial and see what results we get.