Current Status
During a September 2022 celebration of the 35th anniversary of the first Maze procedure, I was asked if I thought that the Maze procedure would still be around in 35 more years. My immediate answer was “No, of course not!.” However, after thinking about that reflexive answer for a few seconds, I added, “But if you had asked me that question 35 years ago, I would have given you the same answer!”
Before the introduction of the surgical Maze procedure, the only way to treat patients with atrial fibrillation (AF) with any degree of success was with drugs. Interestingly, more than 95% of all patients with AF are still treated with drugs. Although the Maze procedure proved to be highly successful, it was too invasive to be used routinely as a first-line therapy for patients with drug-refractory AF. The introduction of catheter ablation for AF by Haïssaguerre and coworkers in 1998 provided a far less invasive intervention to treat patients with AF, but as might be expected, it proved to be substantially less effective than the more invasive surgical Maze procedure. The disappointing results of catheter ablation for the persistent forms of AF (see Chapter 31 ) led to the ablation of wider areas of the atrium, irrigated catheters, contact-force catheters, cryoballoon catheters, and new guidance systems such as stereotaxis and the Hanson robot. Unfortunately, none of those developments resulted in more than a marginal improvement in the results of catheter ablation for AF. Because the surgical Maze procedure was too invasive to be used routinely, surgeons developed minimally invasive surgical procedures, totally thoracoscopic off-pump approaches, and robotic procedures, but even these less invasive surgical procedures were deemed by most cardiologists to be too invasive to be the first-line therapy for stand-alone AF. A combination of the suboptimal results of catheter ablation for persistent AF and the refinement of off-pump thoracoscopic surgical techniques eventually resulted in the introduction of “hybrid procedures” in which both thoracoscopic surgery and catheter ablation are used to treat the more complex forms of stand-alone AF. Overall, thoracoscopic–catheter hybrid procedures have proven to be superior to catheter ablation for the treatment of patients with long-standing persistent AF (LSpAF).
It was hoped that the continued improvement in clinical electrophysiological mapping systems would improve the interventional results of AF ablation, and certainly, the systems that are now available are far better than the ones we developed in the mid-1980s. However, the ability to perform real-time mapping to identify and ablate complex fragmented atrial electrogram (CFAE) sites, extrapulmonary vein rotors, automatic foci, and micro-reentrant foci has had little effect on the results of catheter ablation for AF and no effect whatsoever on its surgical ablation. Ironically, despite the availability of these sophisticated mapping systems, the two proven interventional procedures for AF treatment remain pulmonary vein isolation (PVI) and the Maze procedure, neither of which requires electrophysiologic mapping. Mapping systems are currently used primarily as a confirmation tool to document the integrity of lesions created around the pulmonary veins (PVs). However, when they have been used to “map guide” the catheter ablation of AF, the clinical results have not improved. Indeed, the STAR AF 2 trial demonstrated no difference in the clinical results of PVI alone versus PVI and additional ablation lines versus PVI and CFAE ablation based on map guidance. Because the multiple extra-pulmonary vein ablation lines of the Maze procedure clearly improve the results of surgical ablation over surgical PVI alone, it seems apparent that the STAR AF 2 trial primarily demonstrated the futility of trying to map guide AF ablation and the difficulty of creating contiguous, uniformly transmural lesions reliably with a catheter. The study confirmed a statement made to me previously on at least two separate occasions by Michel Haïssaguerre that “Trying to create a line of conduction block with the tip of a catheter is like trying to cut off the corner of a sheet of paper with a straight pin. It is possible, but it is very difficult” ( Fig. 52.1 ).
Photograph of Professor Michel Haïssaguerre (left) and the author (right) at a private dinner in Bordeaux, France, in November 2013. It was at this dinner that Haïssaguerre lamented how difficult it was for interventional electrophysiologists to create a contiguous, uniformly transmural linear lesion in the atrium with the tip of a catheter. (Photo taken by Prof. Meleze Hoccini).
The fact that isolation of the PVs is the main goal of catheter ablation emphasizes the misnomer of the term “catheter ablation.” The actual objective of catheter ablation for AF is not to “ablate” AF but rather to isolate as many of the PV triggers that induce AF as possible. Thus, successful PVI does not “ablate” AF but rather, it simply makes a future episode of AF less likely to be induced. On the contrary, the Maze procedure was designed specifically to ablate AF and preclude its ability to return by rendering the atria incapable of fibrillating. It seems clear that one avenue that should be pursued in the future is to refocus “catheter ablation” on the actual ablation of AF rather than on reducing the likelihood that it will be induced after intervention. However, there remain several seemingly intractable hurdles to making significant progress in catheter or surgical ablation of AF in the future despite the current universal infatuation with pulsed-field ablation (PFA) as the ultimate ablative energy source for arrhythmias (see later discussion).
Current Obstacles to Progress
Inadequate Classification System for Atrial Fibrillation Interventional Therapy
The current clinical classification parameters for AF are fundamentally different from the clinical classification systems for other heart disease because it is based on the single criterion of the duration of an AF episode. Classification systems for other structural heart diseases weigh the impact of patient demographics, symptomatology, anatomy, pathophysiology, and comorbidities. All of these factors can impact the outcomes of intervention for AF, but none of them are included in the current classification of AF. The interventional electrophysiologist (EP) and the AF surgeon are likely aware of most of these important preoperative characteristics, but they are not used to categorize the patients into groups that require different specific interventions and have different interventional goals, risks, and expectations. This is of particular importance in patients with AF because without the availability of a meaningful and clinically relevant classification of AF before intervention, the selection of the optimal interventional procedure for a given patient is more difficult to determine, and inappropriate interventional procedures can be the result. The present classification system has served noninvasive cardiologists reasonably well but not interventional EPs and arrhythmia surgeons (i.e., those who treat patients with AF by interventional means rather than with drugs).
When a patient is scheduled to undergo surgical mitral valve (MV) repair for mitral regurgitation (MR), the surgeon knows the magnitude of the preoperative MR, its likely cause, the specific anatomic abnormality of the valve, and the patient’s preoperative symptomatology, functional capacity at rest and exercise, quality of life, and relevant comorbidities that could impact the safety and efficacy of the surgery, as well as the functional characteristics of the atria and ventricles as quantitated by preoperative echocardiography and other tests. This information helps determine the optimal surgical intervention for individual patients with any type of structural heart abnormality. A similar level of the preoperative characteristics of AF should be included in a classification system for patients with AF who require catheter or surgical intervention. Such factors include age, sex, the type and duration of AF, AF burden, symptomatology, functional capacity at rest and exercise, quality of life, four-chamber cardiac function, left and right atrial sizes and volumes, the degree of left atrial fibrosis, history of transient ischemic attack or stroke or other systemic thromboembolism, and comorbidities. As noted earlier, we usually know these patient characteristics before surgery for other cardiac disorders, but none of them have anything to do with classifying the AF into paroxysmal AF (PAF), persistent AF, or LSpAF.
Currently, AF seems to be viewed as one large disease that can be divided into these three simple categories to determine the appropriate interventional procedure and to assess its outcomes. This is analogous to classifying all neoplastic disease into the simple categories of head and neck cancer, torso cancer, and limb cancer and then reporting the results of “cancer therapy” for each of those meaningless categories. AF is a spectrum of diseases that varies from simple, classic right atrial flutter to complex forms of LSpAF (see Chapter 5 ). That spectrum can be subdivided in multiple ways, and each subdivision (say, persistent AF) can be further subdivided based on such characteristics as its response to PVI alone or to a box lesion. It is imperative that a new, clinically relevant classification system be developed for AF that will help us decide on the best interventional therapy to offer each individual patient and improve our ability to determine the actual clinically relevant outcomes of our interventional procedures. Unfortunately, as pointed out throughout this book, intraoperative mapping is not currently capable of defining the optimal interventional approach for each patient.
Dubious Definition of Success or Failure of Atrial Fibrillation Interventions
Even more egregious than the shortcomings of the current AF classification system is the virtually worthless definition that is universally accepted for defining the success or failure of catheter and surgical ablation for AF. Failures of catheter and surgical ablation for AF are currently defined as a documented 30-second episode of AF that recurs more than 3 months after intervention (the “blanking period”) in a patient who is on no antiarrhythmic drugs. Yet no adverse sequelae of a 30-second burst of AF have ever been documented, and to make matters worse, no continuous loop recorder is capable of detecting a 30-second episode of AF! Thus a treatment failure in which a patient has episodes of AF lasting less than 2 minutes each could go undetected for years even though the patient’s rhythm is being monitored continuously.
Although the definitions of success or failure after surgery for valve disorders or coronary artery disease are objective and meaningful, the success or failure of catheter or surgical ablation for AF can be meaningless clinically. For example, consider a patient who has experienced AF 24 hours per day for years and then undergoes a catheter or surgical intervention. Under the current definition of procedure success or failure, after a 90-day blanking period, one documented 2-minute episode of AF is enough to designate the interventional AF procedure as a failure ( Fig. 52.2 ). This isolated episode of AF is likely asymptomatic, cannot cause tachycardia-induced cardiomyopathy, and does not increase the stroke risk, especially if the left atrial appendage has been closed or amputated, so it is of utterly no clinical importance. Nevertheless, the interventional procedure is still deemed to be a failure. Furthermore, the “failure” designation cannot be changed to a “success” later because most follow-up data are reported using Kaplan-Meier survival curves that, as the name implies, are based on an irreversible endpoint, death. In addition, the current definition of success or failure for a catheter PVI in a healthy 45-year-old patient with PAF is the same as it is for a surgical Maze procedure in a 75-year-old patient with LSpAF. This nonsensical definition of success versus failure is a major reason why it is virtually impossible to collect accurate and meaningful data on the true clinical effectiveness of either catheter ablation or surgery for AF. It is likely that both catheter and surgical ablation for AF are far more successful clinically than is currently reported. Thus in the future, it is imperative that a new classification system and a new definition of success versus failure be developed for the interventional treatment of patients with AF.
Implanted pacemaker continuous monitoring demonstrating that this patient was in atrial fibrillation (AF) 24 hours per day before having a surgical Maze procedure. He was successfully cardioverted for postoperative AF (POAF), and after a 90-day blanking period, the only episode of AF he had was asymptomatic and lasted only 2 minutes. Nevertheless, under the current definition of success or failure, his surgical procedure is classified as a “failure.”
Lack of Collaboration between Electrophysiologists and Cardiac Surgeons
In the Preface to this book, I mentioned the lag time of 10 to 20 years between the development of a surgical treatment for individual cardiac arrhythmias and the catheter ablation of these same arrhythmias. However, this sequence for the development of interventional therapy for cardiac disease is not unique to arrhythmias. For example, the first successful coronary artery bypass grafting for ischemic heart disease was performed in the mid-1960s, but the first percutaneous coronary angioplasty by a non-surgeon was not performed until in the mid-1970s. Closure of a patent ductus arteriosus (PDA) was first performed surgically in 1938, but it was more than 40 years before PDA closure could be accomplished reliably by non-surgeons. Closed MV commissurotomy was first performed for mitral stenosis in 1923 and became routine practice in 1947, but balloon mitral valvotomy by non-surgeons did not become common until some 30 years later. Similar lag times between interventional therapy by surgeons and interventional therapy by nonsurgeons existed for every congenital cardiac anomaly, mitral insufficiency, aortic stenosis, aortic insufficiency, and thoracic aortic disease. One reason why it was surgeons rather than non-surgeons who developed the first interventional procedures for all of these cardiac anomalies is that surgeons are trained to manipulate anatomy, but non-surgeons are trained to manipulate images . This gives surgeons an obvious advantage over non-surgeons in developing new interventional procedures. However, non-surgeons were the first to understand and explain the pathophysiology of disease processes in depth, especially congenital malformations, coronary artery disease, and cardiac arrhythmias. Without non-surgeons sharing this basic knowledge and including their surgical colleagues in collaborative new approaches, the development of surgical therapy for cardiac disorders would have evolved much more slowly. Thus, the evolution of interventional treatment for all cardiac disease has historically depended on a collaboration between surgeons and non-surgeons.
The evolution of mapping capabilities, surgery, and catheter ablation for cardiac arrhythmias over the past half-century has again demonstrated the importance of surgeon and non-surgeon collaboration. Cardiac surgeons will never know as much electrophysiology as cardiac EPs, but EPs are less capable of designing interventional procedures that are as effective as surgical procedures. Of course, nonsurgical interventions are far less invasive, but they are also less effective. One reason that “hybrid procedures” were developed was so that the talents unique to both surgeons and non-surgeons could be combined to solve the problem of how best to treat patients with stand-alone LSpAF. It is also the reason that the development of better interventional procedures in the future should also depend on that collaboration. Perhaps the best way of putting it from a surgeon’s standpoint is a statement that I have repeated hundreds of times over the past several decades: “An arrhythmia surgeon is only as good as his/her electrophysiologist.” This remains as true today as it was 50 years ago.
Pathways to Future Improvement
Science usually progresses in small, sequential steps and less often by complete paradigm shifts. Progress in the interventional treatment of patients with AF has been made by gradually improving the understanding of normal and abnormal electrophysiology in general and ultimately, the abnormal electrophysiology of AF. This accrued knowledge provided the scientific basis for the development of the Maze procedure as well as for the catheter ablation of AF. Near-future progress in the treatment of stand-alone AF is likely to continue its historical arc toward less invasive interventional procedures, and at least for the foreseeable future, this means catheter ablation and for a while longer, hybrid procedures. The most important areas of catheter ablation for stand-alone AF depend on the discovery or creation of new ablative energy sources and the development of more manipulative catheters that are capable of creating contiguous, uniformly transmural linear lesions anywhere inside the heart. Currently, this can be accomplished consistently only with open surgical techniques. Although the most dramatic changes in the treatment of stand-alone AF that should be expected in the near future will likely occur with catheter ablation, it is an unfortunate truth that despite 25 years of experience, millions of patients, billions of development and marketing dollars, and the demonstration of catheter ablation’s superiority over pharmacologic therapy but inferiority to surgery, only around 4% of all patients with AF undergo catheter ablation annually, and fewer than half of them are successfully ablated long term (see Chapter 31 ). One might contemplate that if a new drug had been introduced in 1998 for the treatment of patients with AF that had the same safety, efficacy, and cost profile as catheter ablation for AF, would that drug still be on the market a quarter-century later?
The Future Role of Surgery in Treating Stand-Alone Atrial Fibrillation
Although the concomitant surgical ablation of AF when performing other cardiac surgical procedures will continue to be an important part of cardiac surgery in the future, it is unlikely that surgery for stand-alone AF will ever be performed as primary therapy, even for LSpAF. Surgery has always been considered to be too invasive for the routine treatment of stand-alone AF, though minimally invasive surgical Maze procedures still yield the best results for the treatment of stand-alone LSpAF (see Chapters 17 and 28 ). If off-pump hybrid procedures can be modified so that the combination of thoracoscopic and catheter lesions create all of the lesions of a surgical Maze procedure, the results can be expected to be the same as they are currently for the on-pump minimally invasive surgical Maze procedures (see Chapter 37 ). Both robotic Maze procedures and the minimally invasive surgical Maze procedures require cardiopulmonary bypass and therefore are unlikely to ever become first-line therapy for stand-alone AF (see Chapter 16 ).
Improved Ablative Energy Sources
Before the late 1990s, only two ablative energy sources were available to treat AF, nitrous oxide (N 2 O) for cryosurgery and unipolar radiofrequency (RF) energy for catheter ablation. After Haïssaguerre and coworkers’ introduction of RF catheter ablation for the treatment of AF in 1998, both unipolar and bipolar RF surgical devices were developed to provide surgeons with the benefits of the speed and ease of use of these new devices. Soon thereafter, several other energy sources were introduced for the surgical ablation of AF, including microwave energy, laser energy, high-intensity focused ultrasound (HIFU), and argon gas cryogen. Unfortunately, none of these new energy sources could be delivered safely and reliably through a catheter, so they were used exclusively by surgeons. For a variety of reasons, microwave, laser, and HIFU energy devices were soon withdrawn from the surgical market, leaving only unipolar RF, bipolar RF, and N 2 O and argon gas as viable ablative energy sources that can be used in surgery. Unipolar RF and N 2 O cryogen have been the only available ablative energy sources for catheter ablation for several years, but recently, two new energy sources have been made available for catheter ablation: electroporation and near-critical nitrogen. Electroporation is more commonly called “pulsed-field ablation,” and near-critical nitrogen is referred to as “ultra-low-temperature cryoablation” (ULTC).
Pulsed-Field Ablation
Interventional EPs have embraced PFA using electroporation more enthusiastically than any ablative energy source since RF ablation was introduced more than 30 years ago. Electroporation is a biophysical technique in which trains of high-voltage electrical pulses are applied to open or enlarge physical holes in the cell membranes of the targeted tissue. The size of the pores that can be created in the cell membranes is related to the amount of current applied to the tissue.
Reversible electroporation has been used for years to treat patients with various types of cancer by opening holes in the cell membrane enough to allow anticancer drugs, genes, or DNA to be “inserted” directly into the cell itself. After this transfer is accomplished, the train of electrical impulses (electroporation) is stopped, and the holes in the cell membrane close, trapping the therapeutic drug, gene, or DNA inside the cell. Reversible electroporation does not create heat in the targeted tissue.
Irreversible electroporation destroys cells by creating holes in the cell membrane that are too large to reclose upon termination of the electroporation, so the cells quickly die and are replaced by fibrocytes. Because irreversible electroporation results in the creation of scars, it can be used to treat patients with AF. The alleged advantage of irreversible electroporation over other ablation energy sources is its safety because there is an energy zone between reversible electroporation and heat-generated irreversible electroporation where irreversible electroporation can be accomplished without heating the targeted tissue ( Fig. 52.3 ). This means that permanent atrial lesions can be created by nonthermal irreversible electroporation (or PFA). The tissues of anatomic structures adjacent to the heart, such as the esophagus and phrenic nerves, are not irreversibly ablated at the specific level of energy that is lethal for myocardial cells. Therefore, PFA is said to be a nonthermal, “myocardial-specific” ablation technique that is safer than RF or cryothermia, both of which are temperature-dependent ablative energy sources that can potentially damage surrounding structures.
A graph of the electric field of electroporation as a function of the distance from the center of the pulsed-field ablation (PFA) catheter electrode. The curved lines represent the electric field for electrode voltages from 100 volts (lower curved line) in increments of 100 volts. The three stages of (1) reversible electroporation, (2) nonthermal irreversible electroporation, and (3) thermal electroporation are designated. The objective of PFA for atrial fibrillation is to stay within the nonthermal irreversible stage. If too little energy is applied, the PFA will be reversible, and no permanent lesions will be created. If too much energy is applied, the thermal irreversible stage will be reached, and the PFA catheter will function as a heat-based ablative energy much the same as a radiofrequency catheter.
(Reproduced from Daniels CS, Rubinsky B. Cryosurgery with pulsed electric fields. PLoS One . 2011;6(11):e26219).
Although PFA is theoretically less likely to damage the phrenic nerves or the esophagus, PFA can cause several problematic side effects even if the current is maintained within the nonthermal irreversible zone. These side effects of PFA include coronary artery spasm ( Fig. 52.4 ), , which is associated with long-term neointimal hyperplasia and tunica media fibrosis in coronary arteries ( Fig. 52.5 ). Coronary artery spasm and subsequent pathological changes in coronary arteries near the site of PFA catheters has proven to be such a problem that on September 15, 2022, the device company that manufactures the PFA catheter (Farapulse–Boston Scientific, Inc.) issued an “Urgent Field Safety Notice– Product Advisory” in which the following was stated:
“The FARAWAVE PFA Catheter has not been studied clinically in the mitral isthmus or cavotricuspid isthmus areas. Ablations in areas adjacent to coronary arteries may lead to coronary artery spasm and/or injury, and the resulting myocardial injury can be fatal.”
