Correcting Arrhythmias: Interventional and Surgical Ablation Therapy
23 February 2017
23 February 2017
07 April 2017 (online)
Prof. Mohr has an outstanding sense of discovering exceptionally talented stallions. As soon as he would discover such talent, only a short period of time would pass before he actively stimulated inspiration among his team to integrate this talent. Soon after, a highly motivated and efficient team was created. Working day and night, while demonstrating utmost ambition to pursue innovation, this team would then passionately pursue their vision to bring this stallion through the finishing line first.
This particular gift of Prof. Mohr explains how various visions at the Leipzig Heart Center have been transformed from just being an initial idea into novel treatment concepts, which were established in clinical practice worldwide.
The evolution of rhythm surgery is a very good example for Prof. Mohr's exceptional gift and its impact on current standards and treatment approaches in cardiac surgery.
His friendship with James Cox had given him insights into the effective surgical treatment of atrial fibrillation. In the beginning of the 1990s, Cox had developed the maze operation. Back then, Cox and “his” cardiologist performed intraoperative epicardial electrical mappings and concluded from their findings that biatrial fragmentation by defined transmural cutting lines could treat atrial fibrillation. This surgery is highly effective, but at the same time also highly invasive. The procedure originally required establishing cardiopulmonary bypass as well as additional cross-clamping times of 60 minutes. Long-term follow-up over meanwhile 20 years showed success rates of more than 80% of the patients retaining sinus rhythm. In several centers, especially in the United States, this procedure is being performed as a “stand-alone” procedure and the good results have proven to be reproducible using current follow-up guidelines.
Toward the end of the 1990s, the development of percutaneous catheter ablations was only in its early beginnings. Nevertheless, successful ablation lines were neither transmural nor linear. These were also the years when minimally invasive mitral valve and later tricuspid valve surgery were successfully introduced into clinical practice at the Leipzig Heart Center. The early insights of Prof. Mohr's friend Randy Chitwood were further developed, modified, and rapidly established in clinical practice there. Prof. Mohr subsequently introduced minimally invasive surgery for the treatment of atrioventricular valves in Europe and, later on, the world.
Soon after minimally invasive valve surgery was clinically established it received recognition from rhythm specialists, ultimately leading to an exchange of ideas regarding the surgical treatment of “stand-alone” atrial fibrillation with an interdisciplinary approach. Gerd Hindricks and Hans Kottkamp, who had already developed their ideas to treat atrial fibrillation in Mannheim with Prof. Borggrefe, were keen on performing minimally invasive intraoperative endocardial ablations using high-frequency energies.
Following interdisciplinary planning of the operative setting, the first controlled prospective study Intraoperative Radiofrequency Ablation of Atrial Fibrillation (IRAAF) was designed at the Heart Center Leipzig in close collaboration between cardiac surgeons and cardiologists. A total of 130 patients with atrial fibrillation were successfully treated with an outstanding result of 90% sinus rhythm at 1-year follow-up. Unfortunately, this novel procedure was associated with several new unexpected complications. Three patients suffered from esophageal perforations with esophago- as well as broncho-atrial fistulae. Early diagnosis of this complication was challenging, as patients complained of nonspecific symptoms beginning usually a week after the ablation procedure. These included fever, chills, strokes, and signs of mediastinitis. Major concerns were expressed, and after identification of the third perforation in our cohort, we discontinued this treatment strategy and began investigating its pathomechanism in depth.   We tested all alternative energy sources which created transmural linear endo- and epicardial scars in animal models. The aforementioned complication could be reproduced when using unipolar dry high-frequency ablation ([Fig. 1]). Furthermore, we were able to demonstrate that endocardial cryoablation (argon or nitrous oxide), as well as bipolar epicardial ablation, were safe and effective.  Atrial fibrillation is not a life-threatening illness and hence life-threatening complications related to this procedure were not acceptable.
Atrial fibrillation is a widespread disease with an overall incidence of approximately 1%. It is more frequent at an advanced age and roughly 10% of the population over 80 years is afflicted. We estimate that over one million patients in Germany suffer from atrial fibrillation. Many are highly symptomatic and require treatment. Often elderly patients can be managed with adequate medical rate and rhythm control. Several patients remain challenging, including those with atrial fibrillation lasting longer than 1 year, patients with significantly enlarged left atria (over 45 mm), or with a history of several failed catheter ablations. For these patients, surgery offers a lasting option with excellent long-term results. An additional advantage to the surgical approach lies in the ability to isolate the left atrial appendage. The resection or exclusion of the left atrial appendage as part of a surgical ablation procedure reduces the risk of strokes up to fivefold, given that 90% of cardiogenic emboli originate from the left atrial appendage due to its trabeculated inner surface. The Protect-AF Study (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) could demonstrate that interventional closure of the left atrial appendage is not inferior to anticoagulation. A major surgical study Left Atrial Appendage Occlusion Study (LAAOS)-III, including over 7,000 patients, aims to validate the significance of left atrial appendage exclusion. Including isolation of the left atrial appendage as part of the maze, the operation is unequivocally indicated.
After publishing the data of the IRAAF trial, we reestablished the program for surgical ablation in atrial fibrillation as “stand-alone” treatment as well as in concomitant procedures during valve and bypass surgery. Our data, which were based on major experimental animal laboratory studies performed at the Leipzig University and the Heart Center, have changed ablation strategies and transformed this procedure into a safe and routine approach in current surgical practice worldwide. In open-heart concomitant procedures, epicardial bipolar high-frequency energy and endocardial cryoablation (argon or nitrous oxide) are being used routinely in the treatment of paroxysmal atrial fibrillation.   This treatment approach has been included in the 2016 guidelines for the treatment of atrial fibrillation. Out of approximately 100,000 cardiac surgery patients in Germany, at present 5.5% undergo surgical ablation. This number increases to approximately 10% in specialized centers such as the Leipzig Heart Center. The majority of these ablation procedures are performed in a concomitant setting. For “stand-alone” procedures, totally endoscopic approaches without cardiopulmonary bypass using a combination of bipolar high-frequency energy with unipolar techniques are being performed.    The developments in surgical ablation were paralleled by the rapid evolution of percutaneous catheter ablations for the treatment of atrial fibrillation. Almost 40,000 percutaneous catheter ablations per year are currently performed in Germany. Based on very good success rates and published in numerous randomized studies, this treatment approach has also been included in international guidelines. As a result, invasive surgical treatment concepts of isolated atrial fibrillation have become less popular.
In the United States, Jim Egerton has developed an endoscopic surgical procedure for treating “stand-alone” atrial fibrillation avoiding the need for cardiopulmonary bypass using bipolar high-frequency energy. In Europe, this concept has been initially adopted by the Netherlands and was subsequently performed in Germany for the first time in 2009 ([Fig. 2]).
In order to introduce and establish this new endoscopic approach into clinical practice, it was essential to gain initial experience in animal models. The European Surgical Institute (ESI, training and education institute, Johnson & Johnson, Norderstedt, Germany) aided in realizing this endoscopic approach. Our center later became a renowned national training center for surgeons who intended to acquire experience to perform endoscopic ablation procedures at their hospitals. Today, a well-tailored training program preparing cardiac surgeons to safely perform this novel technique has been established.
After the first successful endoscopic ablation procedure in Germany in April 2009, many European centers followed. Numerous randomized studies, data registries, and interdisciplinary studies have been published. Thoracoscopic procedures avoiding the use of cardiopulmonary bypass have shown very good midterm results. However, there are limitations to this method. Treating the left atrium in atrial fibrillation ablation strategies is highly effective, since more than 90% of the triggers originate from there, with the majority being located near the pulmonary vein orifices. Nonetheless, in 5% of the cases, atrial fibrillation originates from the right atrium. These sites are difficult or not at all accessible thoracoscopically for the surgeon. Furthermore, the important line to the mitral valve annulus is almost impossible to reach. These are areas, however, easily accessible for percutaneous catheter ablations strategies.
These challenging patients suffering from highly symptomatic atrial fibrillation were approached in an interdisciplinary manner and a hybrid procedure was conceptualized. Again, the Benelux countries were leaders in this approach and Germany pursued closely. After initial experience with “one-stage hybrid” techniques in Belgium and the Netherlands, we established a “two-stage hybrid” technique. Based on observational studies we concluded that success rates could be increased further once electrophysiologists and cardiac surgeons collaborated together. Based on this notion, a European randomized study has been initiated, aiming to observe challenging patients with long-standing or persistent atrial fibrillation with significantly enlarged left atria (> 45 mm). This study includes two treatment arms. One arm represents surgical endoscopic ablation followed by a right and left atrial electrophysiological mapping with or without catheter ablation within the first 3 months after surgery. This is followed by a blanking period of 6 months after the index procedure and a 3-year follow-up. The second arm represents an initial catheter ablation to be later followed by further catheter ablations, if indicated, within the first 6 months after the index procedure. Randomization is performed in a 2:1 mode in favor of the surgical arm. Follow-up will be performed centrally and independently by a Central Research Organization (CRO). Leipzig and Stuttgart have been nominated as “coordinating primary investigators.” The goal of this study is not only to encourage the cooperation between electrophysiologists and cardiac surgeons but also to improve patient care and adjust current guidelines for treatment of atrial fibrillation, whether surgical or interventional. Following the slogan, “stronger together” we are seeking to improve and modify care in the interest of our patients ([Fig. 3]).
We are very proud of the initial visions which have risen from Prof. Mohr's interests, outstanding initiative, and the development and evolution of concepts by our team in Leipzig, as well as our cooperating partners nationally and internationally that have followed since. We dedicatedly aim to further improve treatment concepts for atrial fibrillation in the future.
With this, I would like to express my deepest gratitude to my teacher, role model, and dear friend, Friedrich Mohr, for allowing my participation in developments to improve concepts in treating atrial fibrillation. I am grateful for him entrusting me with this task and allowing me to accompany him through these unique opportunities.
Dear Friedrich, thank you for an exceptionally exciting, innovative, inspirational, and amicable time in Leipzig!
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