Research Needs and Priorities for Catheter Ablation of Atrial Fibrillation: A Report from a National Heart, Lung, and Blood Institute Virtual Workshop

Abstract

Catheter ablation has brought major advances in the management of patients with atrial fibrillation (AF). As evidenced by multiple randomized trials, AF catheter ablation can reduce the risk of recurrent AF and improve quality of life. In some studies, AF ablation significantly reduced cardiovascular hospitalizations. Despite the existing data on AF catheter ablation, numerous knowledge gaps remain in relation to this intervention. This report is based on a recent virtual workshop convened by the National Heart, Lung, and Blood Institute to identify key research opportunities in AF ablation. We outline knowledge gaps related to emerging technologies, the relationship between cardiac structure and function and the success of AF ablation, patient subgroups in whom clinical benefit from ablation varies, and potential platforms to advance clinical research in this area. This report also considers the potential value and challenges of a sham ablation randomized trial. Prioritized research opportunities are identified and highlighted to empower relevant stakeholders to collaborate in designing and conducting effective, cost-efficient, and transformative research to optimize the use and outcomes of AF ablation.

Introduction to the Series

Atrial fibrillation (AF) continues to be the most common, clinically significant arrhythmia in adults, affecting millions of people nationally and internationally.¹ With the aging of the population and worrisome trends in selected cardiovascular risk factors, the population burden of AF is expected to increase over the coming decades. In addition, existing and newer monitoring technologies are making it more feasible to identify additional patients with undiagnosed AF.^2–5 Given the negative impact that AF can have on health outcomes by increasing the risks of ischemic stroke, heart failure (HF), myocardial infarction, kidney disease, cognitive impairment, impaired quality of life, and death¹, effective and more personalized management strategies are needed.⁶

The National Heart, Lung and Blood Institute (NHLBI) has consistently recognized and supported efforts to advance population, clinical, and basic science research in AF.⁷ In 2008 the NHLBI convened an expert panel to identify gaps and to recommend research strategies focused on improving AF prevention.⁸ To engage the scientific community in identifying contemporary research priorities and opportunities in AF, the NHLBI recently initiated a series of webinar-based workshops. With the rapid expansion in the techniques and use of AF catheter ablation in the past two decades,⁹ along with the recent publication of the NHLBI-sponsored Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial,¹⁰ the first workshop in the series, held on March 12, 2019, had an overall theme of advancing research to optimize the use and outcomes of AF catheter ablation.

This report summarizes five specific areas in AF catheter ablation that were the focus of the workshop: 1) emerging technologies, 2) how cardiac structure and function influence the success of AF ablation, 3) subgroups of AF patients who may benefit more or less from ablation, 4) platforms to advance clinical research, and 5) whether a sham ablation randomized trial could be conducted in the United States.

Mechanisms of AF

Mechanisms of AF are not fully understood. AF is generally triggered by premature atrial contractions originating from the pulmonary veins. How AF is perpetuated is debated, but the following mechanisms have been proposed: multiple wavelets, a single localized focal source, a reentrant source, and rotors.¹¹ Also, atrial remodeling and autonomic and neurohormonal factors contribute to the pathogenesis of AF. A better understanding of these mechanisms in individual patients would allow better selection of treatments including the best ablation strategy.¹²

Emerging Technologies in AF Ablation

Several technologies have recently emerged that have the potential to transform the approach to AF catheter ablation.¹³ These include novel mapping technologies that look for focal sources of AF (e.g., rotors) and specific electrogram signatures and characteristics that might identify optimal ablation targets. Other emerging technologies include more effective catheters (e.g., those with compliant cryoablation balloons); new catheter-based energy delivery such as electroporation; novel energy delivery systems such as gamma radiation, carbon particle, and photon external ablation; and systems designed to assess real-time effectiveness of ablation. There are also adjunctive technologies to enhance the safety of the ablation procedure, such as performing AF ablation on uninterrupted anticoagulation and the availability of contact force monitoring. New technology has also resulted in improved systems for monitoring esophageal temperature and moving the esophagus away from ablation sites. Finally, technologies that may lead to improved prediction of successful ablation are being identified. These include imaging techniques (e.g., magnetic resonance imaging), to identify the extent of scar, and noninvasive electrical mapping.

Several knowledge gaps have been delineated in relation to emerging technologies, including identifying the best approach to safely and expeditiously achieve permanent pulmonary vein isolation in a single procedure. Moreover, it remains unknown if ablating additional targets will improve the outcomes of ablation of persistent and longstanding persistent AF. Better approaches to defining the structural and electrical substrates of AF are being developed. Similarly, a large amount of research is focused on developing new tools that allow creation of permanent transmural lesions. The combination of (1) better defined ablation strategies and targets as well as (2) better tools to safely create durable and permanent ablation lesions could lead to further improvement in outcomes following AF ablation (Figure 1).

Figure 1:

Emerging Technologies in AF Ablation

The following prioritized research opportunities were identified

1. Develop a more complete understanding of AF mechanisms using a robust experimental AF model that can be translated into defining mechanisms in individual patients to guide decision-making for catheter ablation.

2. Create a clinical research network that a) can efficiently conduct studies to compare the effectiveness of ablation lesion sets using new technologies and b) can significantly lower the cost of pilot and pivotal clinical studies of emerging technologies.

3. Create an open source large dataset of high-resolution electrograms and electroanatomic mapping tied to clinical and patient-centered outcomes to permit a comparison of novel versus conventional mapping approaches to the identification of successful ablation strategies and lesion sets using advanced analytic methods (e.g., machine learning/deep learning methods and applications).

How Do Cardiac Structure and Function Influence the Success of AF Ablation?

Many studies have shown a significant reduction in AF burden and improvement in symptoms and quality of life as well as cardiovascular outcomes in patients with symptomatic AF following catheter ablation.^{14, 15} In the Catheter Ablation versus Standard Conventional Therapy in Patients with Left Ventricular Dysfunction and Atrial Fibrillation (CASTLE-AF) trial among adults with HF with reduced ejection fraction (HFrEF) and who were intolerant of or unwilling to take antiarrhythmic medications, catheter ablation resulted in a significant reduction in HF hospitalizations and mortality.¹⁵ In the CABANA trial of older adults with symptomatic AF, catheter ablation led to significant reduction in cardiovascular hospitalizations and AF recurrences, and significant improvement in quality of life. However, there was no improvement in survival or a composite outcome of death, disabling stroke, serious bleeding, or cardiac arrest.¹⁰ More data are needed on the effect of AF catheter ablation on these hard clinical outcomes especially in relation to how cardiac structure and function influence the success of AF ablation.

Structural heart disease including left atrial enlargement, fibrosis, and stiffness, and left ventricular hypertrophy and reduced compliance have been associated with lower success of AF ablation. ^16–18 Trials like CABANA may help elucidate how each of these abnormalities impacts response to ablation, and how the aggregate of these pathologies influences success of ablation.

It is noteworthy that experts recommend defining “successful ablation” as freedom from symptomatic or asymptomatic atrial arrhythmia lasting for >30 seconds within 1 year of follow-up.⁹ However, this definition may underestimate the real potential net benefit of AF ablation because many patients who do not meet this definition have a significant reduction in arrhythmia burden and improvement in quality of life and heart function.¹⁹ While standardizing the definition of “successful ablation” is not within the scope of this paper, investigators are encouraged to define it clearly at the inception of any future study.

Despite the large volume of existing studies of AF ablation, several gaps in knowledge remain about the potential effect of cardiac structure and function on the likelihood of success of AF ablation. Some studies have shown that the reduction in AF burden that results from AF ablation improves left ventricular ejection fraction and HF symptoms in patients with reduced ejection fraction attributed to ischemic or non-ischemic cardiomyopathy.²⁰ It is less certain whether similar benefits might be observed in patients with HF with preserved ejection fraction (HFpEF). While several studies have suggested that outcomes in patients with HFpEF may be improved with AF catheter ablation, these studies were limited by the small sample size and their observational study design.^21–23 AF ablation may result in or worsen left atrial non-compliance which, in turn, may lead to a reduction in forward flow and the development of pulmonary hypertension, right ventricular dysfunction, tricuspid insufficiency, and right atrial enlargement. Thus, more definitive studies are needed to delineate the impact of AF ablation on outcomes in patients with HFpEF.

The correlation between the degree of atrial dilation and fibrosis and successful ablation of AF is poorly understood. Also, how the specific components of structural heart disease (e.g., left atrial structure/function, left ventricular structure, etc.) impact the success of AF ablation and the likelihood of recurrence requires further investigation. Neurocardiac interactions such as the role of neural networks in the generation and maintenance of AF should be studied. While ganglionic plexus ablation may improve the success of pulmonary vein isolation, studies to date have been small and the vast majority lacked randomization of treatment options.²⁴ Knowledge gaps in understanding AF mechanisms and AF ablation in individuals with cardiac structural remodeling or HF must be filled to optimize the outcomes of patients with AF. Potential clinical and translational studies to address these knowledge gaps are outlined in Figure 2.

Figure 2:

How Cardiac Structure and Function Influence the Success of AF Ablation

The following research opportunities were identified

1. Determine the role and safety profile of AF catheter ablation in patients with HFpEF and/or left atrial scar with special emphasis on clarifying the relationship between left atrial scar and non-compliance that may be worsened with ablation, and the occurrence and/or elimination of AF.

2. Create the necessary datasets to enable machine learning/deep learning-based research that can identify cardiac structure and function-related features predicting procedural and clinical outcomes after AF catheter ablation.

3. Understand the impact of ablation of the ganglion plexus on the outcomes of AF ablation and study neural hormonal contributions to the success of AF ablation.

Are There Subgroups of Patients Who Benefit Less from AF Ablation?

Identification of patient subgroups that are less likely to benefit from AF ablation can highlight areas in which future research might lead to better AF ablation outcomes. Such subgroups include patients with persistent or long-standing persistent AF, left atrial dilation with extensive atrial scarring and fibrosis, and other forms of structural heart disease such as hypertrophic cardiomyopathy²⁵ (for which atrial wall thickness may limit the effectiveness of ablation) or valvular heart disease (for which hemodynamic forces may reduce the success of maintaining sinus rhythm).¹⁷ Patients with obesity, metabolic syndrome, and/or sleep apnea have higher AF recurrence rates after ablation, and targeting these potentially reversible risk factors may improve the success of ablation.²⁶ Other subgroups include patients who can benefit from ablation but are considered at higher risk for peri-procedural complications. These include older patients, women, and those with HF or a higher risk of ischemic stroke.²⁷ Finally, genetic susceptibility to AF may also impact the success of AF ablation.²⁸

Gaps in knowledge about patient subgroups who may benefit less from AF ablation relate to the following areas

1. Persistent and long-standing persistent AF: What upstream pathways, biomarkers, genomic or various “-omics” data might be targeted to prevent AF progression and improve ablation success and lead to more precision in the timing and selection of therapeutic options? The definition of successful ablation in patients with persistent or long-standing persistent may need to be refined from the current consensus-based standard of 30 seconds of recurrent AF to correctly identify patients in whom these approaches are clinically effective.

2. Large atrial size and fibrosis: What strategies can be implemented to improve ablation outcomes in patients with large atrial size or large scar burden?

3. Higher risk of complications: What are the best techniques and the best ablation energy modality that can improve ablation safety? How can AF ablation risks be reduced?

4. Atypical atrial flutters and other difficult to ablate atrial arrhythmias: What are the best ablation strategies for these patients? Can a personalized approach to ablation be achieved based upon noninvasive imaging and/or noninvasive mapping?²⁹

5. Obesity, metabolic syndrome, sleep apnea: What is the role of weight reduction, bariatric surgery, and care pathways promoting healthier diet, weight loss, increased physical activity, and higher quality sleep? How can we meaningfully achieve effective risk factor reduction? (see Figure 3).

Figure 3:

Subgroups of Patients Who Benefit Less From AF Ablation

The following prioritized research opportunities were identified

1. Develop advanced imaging, electrocardiographic testing, and biomarkers with the goal of stratifying individuals for risks of complications and benefit from AF ablation.

2. Improve understanding of the underlying pathophysiology of AF, including progression from paroxysmal to persistent, and identify new upstream therapies to prevent AF progression.

3. Improve understanding of how existing technologies are used in specific patient subgroups and develop new ablation techniques and approaches that will improve the effectiveness and safety of AF ablation, especially in patients with persistent AF.

Platforms to Advance Clinical Research in AF Ablation

Larger, contemporary platforms that can generate data on AF catheter ablation more rapidly and efficiently and at a lower cost are needed. Such platforms may include a nationwide AF ablation registry, AF trial networks for traditional and pragmatic clinical trials, and implementation of standardized data elements, including harmonized outcomes,³⁰ and definitions³¹ across AF studies to promote pooled analyses. At present, there are two US-based registries of AF catheter ablation: The National Cardiovascular Data Registry (NCDR)’s AF Ablation Registry™ and a section of the Get With The Guidelines^®-AF registry. However, the limited reach of these registries has raised questions about the generalizability of their findings. A national AF ablation registry could provide important information on the characteristics and outcomes of patients undergoing AF ablation in “real-world” practice. Such a registry could also facilitate examination of long-term safety and effectiveness of AF ablation, durability of the effect of this procedure, and the incidence and predictors of rare complications. A national AF ablation registry involving health care delivery systems as well as tertiary care centers could also provide a platform in which both traditional and pragmatic clinical trials can be conducted. Embedding randomized trials within comprehensive registries would ensure that trials are pragmatic in design, enrolling patients who are similar to those who would receive the intervention in usual care settings and whose care and follow-up are in line with accepted standards.

Although a national AF ablation registry is likely to be valuable, several uncertainties remain regarding the feasibility and success of such an effort. To ensure its success, a reliable and sustainable source of funding is critical. Also, data collection should not be burdensome, and ways to leverage electronic health record systems to accurately and consistently auto-populate as many of the registry data fields as possible should be developed. Unintended consequences of data collection through a national registry should be anticipated, detected early, and addressed. While the idea of embedding traditional and pragmatic clinical trials in a national AF ablation registry is enticing, operationalizing such protocols in efficient and cost-effective ways is yet to be defined, and feasibility pilot testing will likely be needed. Establishing an AF ablation research network in the United States is likely to be helpful, as it would bring together a broad spectrum of investigators and institutions to expedite clinical research and to establish a strong infrastructure for developing, coordinating, and conducting multiple clinical protocols to improve AF ablation outcomes. Research networks related to other areas, such as HF and evaluating other cardiovascular procedures, already exist and have been effective in advancing clinical research in those areas.^32–37

The following prioritized research opportunities were identified (see Figure 4)

Figure 4:

Platforms to Advance Clinical Research in AF Ablation

1. Engage a multidisciplinary group of stakeholders to develop a strategy for establishing an innovative nationwide AF ablation registry by addressing logistical and financial challenges of engaging the medical community, identifying key incentives for participation, reducing the burden of data collection, and developing a plan to address unintended consequences.

2. Establish an AF ablation research network to conduct collaborative traditional and pragmatic randomized clinical trials as well as leverage national registries in North America to improve AF ablation outcomes. To that end, the financial challenges of this effort should be addressed, and multi-sponsorship and/or leveraging existing infrastructures, such as the Patient-Centered Clinical Research Network (PCORNet), should be explored.

3. Design and implement proof-of-concept studies that explore how electronic health record systems and other patient data collection technologies can be leveraged in conjunction with new data standards to conduct AF ablation-related research in larger and more diverse and representative populations.

Can a Sham Ablation RCT Be Conducted in the United States?

As mentioned previously, the intention-to-treat analysis of the CABANA trial showed that catheter ablation did not significantly improve the primary composite endpoint of death, disabling stroke, serious bleeding, or cardiac arrest.¹⁰ Given these results, some clinicians have called for randomized controlled trials of AF ablation versus a sham procedure in order to evaluate the efficacy of catheter ablation while accounting for any “placebo effect^{10, 38, 39} and reducing the high rate of treatment cross-over observed in CABANA. Interventional trials in which patients are unaware of their randomized assignment are more likely to provide conclusive answers regarding efficacy.⁴⁰ Such trials may be beneficial in definitively examining hard outcomes of AF ablation.

However, several important issues need to be addressed before a large-scale sham controlled randomized clinical trial could be conducted, especially in the United States (Figure 5). These issues and challenges generally relate to feasibility and selection of endpoints. A sham trial of AF ablation carries challenges including concerns regarding the risk of a sham procedure. While the risks of femoral venous access might be acceptable, trans-septal catheterization confers uncommon but serious risks of cardiac tamponade and thromboembolism. Additionally, some may argue that an adequate sham procedure would require intubation and general anesthesia for 3 to 4 hours as well as systemic anticoagulation, bilateral femoral access and placement of a radial arterial line. The cumulative risks of these interventions would be considerable, as would associated costs. Defining what constitutes an adequate sham AF ablation control arm is beyond the scope of this paper, but it will be essential to address prior to pursuing a sham trial.

Figure 5:

Considerations for Planning a Sham Controlled Trial in AF ablation

A fundamental question remains: does physician and patient equipoise exist such that a sham-controlled procedure is feasible to perform in the United States? The CABANA trial, which compared pharmacologic therapy with AF ablation took more than 8 years to enroll 2204 patients. A sham-controlled trial would require sufficient physician (cardiologists, primary care physicians) willingness to enroll patients and patient acceptance of randomization to AF ablation versus a sham procedure. Many U.S. cardiac electrophysiologists and cardiologists may be unwilling to enroll patients in a sham ablation randomized trial. Similarly, patients may be less likely to agree to participate in a sham-controlled trial, and the few who might be willing to do so may not be representative of the majority of patients considered eligible for AF catheter ablation. For example, patients with mild symptoms might be more agreeable to participate than patients with severe symptoms. Notwithstanding these challenges, sham-controlled trials have been successfully conducted in other fields and demonstrated the lack of efficacy of invasive procedures in relation to certain outcomes that are meaningful to patients and clinicians.^{41, 42}

Due to enrollment challenges and costs of a sham-controlled trial, these types of trials would need to focus more on outcomes such as procedural complications, recurrence of AF, AF burden, AF-related symptoms and overall and disease-specific quality of life, as they would most likely be underpowered to address definitively important clinical outcomes (e.g., all-cause and cardiovascular death, stroke, hospitalization). Consequently, data from such sham-controlled trials may not fully satisfy those who may want definitive evidence of beneficial effects of this procedure on hard outcomes.

Short of a sham-controlled trial, the evidence base supporting catheter ablation can be improved by enhancing study design features. In a 2018 review of AF and atrial flutter-related clinical trials in the ClinicalTrials.gov database, 31% were non-randomized, and 28% were single arm studies.⁴³ In addition, the use of blinding was limited to only 16% of patients, 4% of proceduralists, and 44% of event ascertainers. From a cost and pragmatic perspective, patient and proceduralist blinding is challenging. However, particularly in light of the use of less objective surrogate endpoints, ablation studies should implement blinded event ascertainment and use the most appropriate comparator groups.⁴³

The following prioritized research opportunities were identified

1. Systematically evaluate acceptance by patients and physicians and the potential feasibility of sham-controlled randomized trial protocols for AF catheter ablation, including identification of possible target populations and associated biases.

2. Identify outcomes that would be most relevant and feasible for possible sham-controlled randomized trials of AF catheter ablation, including conducting research about whether reducing the surrogate outcome of AF burden translates into improved clinical outcomes.

3. Alternatives to sham trials should be explored, especially in countries like the United States where such trials may be difficult to conduct. In addition, robust trial designs for ablation studies, with appropriate comparator groups and blinded event ascertainment should be encouraged.

Conclusions

In many AF patients, catheter ablation is a highly effective intervention for improving AF-related symptoms, significantly reducing AF burden and cardiovascular hospitalizations, and appreciably improving quality of life. With the emergence of data supporting a role for catheter ablation in managing AF and the increasing number of people affected by AF nationally and internationally, the use of AF catheter ablation will continue to expand. Therefore, it is critical to address important knowledge gaps related to AF ablation.

Prioritized research opportunities that emerged from the recent NHLBI workshop include gaining a better understanding of the mechanisms that underlie different types of AF and AF recurrence, particularly through an experimental AF model and an open source dataset of high-resolution mapping tied to clinical and patient-centered outcomes. Additional knowledge of the impact of neurohormonal contributions and the presence of preexisting left atrial abnormalities on the success of AF ablation is needed (Table). Other research priorities relate to understanding the relationship between AF ablation, AF burden, and cardiovascular outcomes, improving the effectiveness and safety of catheter ablation through new technologies, and improved understanding of the outcomes of the procedure in real-world settings, such as through a national AF ablation registry and/or research conducted using electronic health records within health care delivery systems. Critically important is gaining an understanding of the role of AF ablation in patients with HFpEF and establishing the cause-effect relationship between ventricular dysfunction and AF, and the potential moderating role of atrial structure and function. Translational and multidisciplinary approaches are needed to identify targetable substrates and minimize the risks of AF ablation, including application of machine learning and deep learning analytic methods, integrating advanced imaging modalities, and generating multiomics datasets. Finally, consideration of different clinical trial designs and target AF populations, as well as selection of the most relevant and patient-centered clinical outcomes, are needed to further optimize and personalize the use of AF catheter ablation.

Table.

Prioritized Research Opportunities for AF Ablation

Emerging Technologies in AF Ablation

1. Develop a more complete understanding of AF mechanisms using robust experimental AF models that can be translated into defining mechanisms in individual patients to guide decision-making for catheter ablation.

2. Create a clinical research network that (1) can efficiently conduct studies to compare the effectiveness of ablation lesion sets using new technologies and (2) can significantly lower the cost of pilot and pivotal clinical studies of emerging technologies.

3. Create an open source large dataset of high-resolution electrograms and electroanatomic mapping tied to clinical and patient-centered outcomes to permit a comparison of novel versus conventional mapping approaches to the identification of successful ablation strategies and lesion sets using advanced analytic methods (e.g., machine learning and deep learning methods and applications).

How Do Cardiac Structure and Function Influence the Success of AF Ablation?

1. Determine the role and safety profile of AF catheter ablation in patients with HFpEF and/or left atrial scar with special emphasis on clarifying the relationship between left atrial scar and non-compliance that may be worsened with ablation, and the occurrence and/or elimination of AF.

2. Create the necessary datasets to enable machine learning/deep learning-based research that can identify cardiac structure and function-related features predicting procedural and clinical outcomes after AF catheter ablation.

3. Understand the impact of ablation of the ganglion plexus on the outcomes of AF ablation and study neural hormonal contributions to the success of AF ablation.

Are There Subgroups of Patients Who Benefit Less from AF Ablation?

1. Develop advanced imaging, electrocardiographic testing, and biomarkers with the goal of stratifying individuals for risks of complications and benefit from AF ablation.

2. Improve understanding of the underlying pathophysiology of AF, including progression from paroxysmal to persistent AF, in order to identify new upstream therapies to prevent AF progression.

3. Improve understanding of how existing technologies are used in specific patient subgroups and develop new ablation techniques and approaches that will improve the effectiveness and safety of AF ablation, especially in patients with persistent AF.

Platforms to Advance Clinical Research in AF Ablation

1. Engage a multidisciplinary group of stakeholders to develop a strategy for establishing an innovative nationwide AF ablation registry by addressing logistical and financial challenges of engaging the medical community, identifying key incentives for participation, reducing the burden of data collection, and developing a plan to address unintended consequences.

2. Establish an AF ablation research network to conduct collaborative traditional and pragmatic randomized clinical trials as well as leverage national registries in North America to improve AF ablation outcomes.

3. Design and implement proof of concept studies that explore how electronic health record systems and other patient data collection technologies can be leveraged in conjunction with new data standards to conduct AF ablation-related research in larger and more diverse and representative populations.

Can a Sham Ablation Randomized Clinical Trial Be Conducted in the US?

1. Systematically evaluate acceptance by patients and physicians and the potential feasibility of sham-controlled randomized trial protocols for AF catheter ablation, including identification of possible target populations and associated biases.

2. Identify outcomes that would be most relevant and feasible for possible sham-controlled randomized trials of AF catheter ablation, including conducting research about whether reducing the surrogate outcome of AF burden translates into improved clinical outcomes.

3. Alternatives to sham trials should be explored, especially in countries like the United States where such trials may be difficult to conduct. In addition, robust trial designs for ablation studies, with appropriate comparator groups and blinded event ascertainment should be encouraged. In addition, robust trial designs for ablation studies, with appropriate comparator groups and blinded event ascertainment should be encouraged.

Non-standard Abbreviations and Acronyms

CABANA

Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation

CASTLE-AF

Catheter Ablation versus Standard Conventional Therapy in Patients with Left Ventricular Dysfunction and Atrial Fibrillation

NCDR

National Cardiovascular Data Registry

PCORNet

Patient-Centered Clinical Research Network

APPENDIX

Working Group Members

Writing Group – Contributing Authors

Sana M. Al-Khatib, MD, MHS, Duke University Medical Center; Emelia Benjamin, MD, ScD, Boston University School of Medicine; Alfred E. Buxton, MD, Harvard Medical School; Hugh Calkins, MD, Johns Hopkins University School of Medicine; Mina K. Chung, MD, Cleveland Clinic; Anne B. Curtis, MD, University at Buffalo School of Medicine and Biomedical Sciences; Patrice Desvigne-Nickens, MD, National Heart, Lung, and Blood Institute; Pierre Jais, MD, University of Bordeaux; Douglas L. Packer, MD, Mayo Clinic; Jonathan P. Piccini, MD, MHS, Duke University Medical Center; Yves Rosenberg, MD, MPH, National Heart, Lung, and Blood Institute; Andrea M. Russo, MD, Cooper University; Paul J. Wang, MD, Stanford University; Lawton S. Cooper, MD, MPH, National Heart, Lung, and Blood Institute; Alan S. Go, MD, Kaiser Permanente Northern California

Workshop Participants

Jeff S. Healey, MD, MSc, McMaster University; Mark S. Link, MD, University of Texas Southwestern; Nassir F. Marrouche, MD, University of Utah; Peter A. Noseworthy, MD, Mayo Clinic; Prashanthan Sanders, MBBS, PhD, Adelaide University; Melanie True Hills, CSP, StopAfib.org; Xiaoxi Yao, PhD, Mayo Clinic; Susan J. Zieman, MD, PhD, National Institute on Aging