Pacing as a Treatment for Reflex-Mediated (Vasovagal, Situational, or Carotid Sinus Hypersensitivity) Syncope: A Systematic Review for the 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society
Objectives: To determine, using systematic review of the biomedical literature, whether pacing reduces risk of recurrent syncope and relevant clinical outcomes among adult patients with reflex-mediated syncope.
Methods: MEDLINE (through PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (through October 7, 2015) were searched for randomized trials and observational studies examining pacing and syncope, and the bibliographies of known systematic reviews were also examined. Studies were rejected for poor-quality study methods and for the lack of the population, intervention, comparator, or outcome(s) of interest.
Results: Of 3188 citations reviewed, 10 studies met the inclusion criteria for systematic review, including a total of 676 patients. These included 9 randomized trials and 1 observational study. Of the 10 studies, 4 addressed patients with carotid sinus hypersensitivity, and the remaining 6 addressed vasovagal syncope. Among the 6 open-label (unblinded) studies, we found that pacing was associated with a 70% reduction in recurrent syncope (relative risk [RR]: 0.30; 95% confidence interval [CI]: 0.15–0.60). When the 2 analyzable studies with double-blinded methodology were considered separately, there was no clear benefit (RR: 0.73; 95% CI: 0.25–2.1), but confidence intervals were wide. The strongest evidence was from the randomized, double-blinded ISSUE-3 (Third International Study on Syncope of Uncertain Etiology) trial, which demonstrated a benefit of pacing among patients with recurrent syncope and asystole documented by implantable loop recorder.
Conclusions: There are limited data with substantive evidence of outcome ascertainment bias, and only 2 studies with a double-blinded study design have been conducted. The evidence does not support the use of pacing for reflex-mediated syncope beyond patients with recurrent vasovagal syncope and asystole documented by implantable loop recorder.
- AHA Scientific Statements
- Evidence Review Committee
- reflex syncope
- vasovagal syncope
Table of Contents
Search Strategy e125
Eligibility Criteria e125
Methods of Review e125
Statistical Analysis e125
Study Selection e126
Study Results e126
Studies Addressing Carotid Sinus Hypersensitivity Syncope e126
Studies Addressing Vasovagal Syncope e126
Notable Studies Excluded From Systematic Review e127
Risk of Bias e127
Synthesis of Results e127
Summary of Evidence e127
Figures and Tables
Figure 1. PRISMA Diagram e128
Table 1. Summary of Included Studies e129
Figure 2A. Forest Plot of Meta-Analysis of Recurrent Syncope (Unblinded Studies) e133
Figure 2B. Forest Plot of Meta-Analysis of Recurrent Syncope (Double-Blinded Studies) e133
Figure 3. Forest Plot of Meta-Analysis of Mortality Rate e133
Appendix 1. Evidence Review Committee Relationships With Industry and Other Entities (Relevant) e135
Reflex-mediated (vasovagal, situational, or carotid sinus hypersensitivity) syncope is common, occurring at least once in more than 40% of women and nearly one third of men by age 60 years,1–3 and can be associated with cardioinhibitory bradycardia. Studies have presented mixed results in terms of the benefits of pacemakers in patients with reflex-mediated syncope, with some suggesting benefit4–9 and others suggesting either no benefit or unclear benefit.10–15 A 2007 systematic review found significant heterogeneity and concern about an “expectation effect,” a form of outcome ascertainment bias based on the awareness of the presence of a pacemaker in unblinded trials, when no benefit was seen in double-blinded trials.16 A 2010 systematic review by the United Kingdom’s National Institute for Health and Care Excellence (NICE)17 concluded that there was low-quality evidence with significant heterogeneity that potentially demonstrated a benefit of pacing. A separate 2013 review published by the Cochrane Library18 concluded that current evidence does not support pacemaker implantation in this population. None of these reviews, however, included more recently published studies.
In support of the “2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope,”19 and in alignment with the “ACC/AHA Clinical Practice Guideline Methodology Summit Report,”20 the present Evidence Review Committee (ERC) sought to determine whether the evidence from randomized trials and observational studies suggests that pacemaker therapy reduces risk of recurrent syncope and other relevant outcomes over a minimum of 1 year of follow-up among adults with reflex-mediated syncope.
The ERC partnered with Doctor Evidence, LLC (DRE) to conduct a systematic review addressing the question: What is the effectiveness of pacemaker therapy in patients with vasovagal, carotid sinus, or situational syncope in adults? This systematic review complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement21 and with recommendations of the “ACC/AHA Clinical Practice Guideline Methodology Summit Report.”20
Searches were conducted on October 7, 2015, in PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials and included all studies published from inception of the databases to the date of the search. Synonyms of “syncope” and “pacemaker” (Table 1 footnotes) were used in the searches. References of published systematic reviews were also searched to identify any additional studies.
Randomized controlled trials (RCTs) and observational studies were selected for inclusion if they compared the use of all types of pacemakers programmed “ON” with pacemakers programmed “OFF” or no pacemaker (including medical therapy or usual care alone) for adult patients at least 18 years of age with vasovagal, carotid sinus, or situational syncope. Studies were included if they had a minimum follow-up of at least 1 year and were conducted in the ambulatory, outpatient, or community-based settings. Studies had to be published and in English to be included in the review. The outcomes of interest included syncope recurrence (primary outcome), falls, all-cause mortality, hospitalization due to cardiovascular causes, other symptoms attributable to the underlying condition (such as presyncope, injury, and quality of life), and adverse events resulting in an intervention.
Methods of Review
A medical librarian screened the titles and abstracts of studies against predefined selection criteria by using a software environment that allows for color coding of relevant key words and ranking of titles on the basis of key words. A second medical librarian performed quality control using the aforementioned tools. The chief medical officer and a methodologist reviewed all included and excluded abstracts, managed any discrepancies between librarians, and dealt with studies of uncertain eligibility. Members of the ERC (L.Y.C., P.A.N., A.L.M., D.J.S., and V.T.) were divided into pairs and performed dual independent review of full-text articles in the DOC Library software platform. Disagreements were resolved through discussion between the 2 reviewers and then by the ERC Chair (P.D.V.). Two DRE methodologists performed independent quality assessment of the included studies using the Cochrane Collaboration Risk of Bias Tool for RCTs22 and the Newcastle-Ottawa Scale for cohort studies.23 Disagreements were resolved by a third methodologist. Data extraction took place in the DOC Data 2.0 software platform, with a standard template used for predefined data points. The first author was contacted in the case of a single study10 for which more information was needed, but the data were no longer available for analysis. Included studies were single-extracted by a member of the DRE team of evidence analysts, with each study verified against the source article by a quality control analyst (single extraction with sequential quality control). Discrepancies were resolved by the DRE project methodologist and/or chief medical officer. Subsequent dataset-level quality control (to identify outliers and ensure consistency of data across studies) was performed by a DRE audit specialist. A DRE ontology specialist managed the naming of outcomes on the basis of author-named outcomes and relevant definitions.
When at least 4 studies included analyzable outcomes, meta-analyses were performed in DOC Data 2.0 with the integrated R statistical package Metafor and random-effects models.24 RCTs were analyzed separately from observational studies because of differences in study design. A statistical test for heterogeneity was also performed for each outcome, and funnel plots were examined for the presence of publication bias, but there was not convincing evidence that publication bias was present. Out of concern for the possibility that outcome ascertainment bias (on the presence/absence of blinding to intervention [pacing] status) could be present, analyses were stratified by blinding status. To test for statistical evidence that study blinding status modified the apparent association of pacing with reduction in recurrent syncope, random-effects meta-regression was performed.
After removing duplicates, a total of 3188 titles were screened (2563 from EMBASE, 1638 from Medline, and 138 from Cochrane), and 40 of these were found to be relevant for full-text review (Figure 1). Each of these was reviewed by 2 ERC members, with a third member providing adjudication in cases of discordance. After full-text review, 10 studies,4,6,7,9–14,25 including a total of 676 adult patients with vasovagal, situational, and/or carotid sinus hypersensitivity syncope, that compared pacing to pacing off (or no pacemaker) and had at least 1 year of follow-up were included in the systematic review.
Among the 10 studies meeting the inclusion criteria, there were 9 randomized trials (n=642)4,6–11,13,14 and 1 observational study (n=34).12 Among the 9 randomized trials, only 37,10,11 included a double-blinded methodology. However, only 2 of these7,11 included analyzable data involving implantation of a pacemaker in all patients but with programming pacing functions off according to random assignment with blinded ascertainment of outcomes. These 10 studies (4 vasovagal, 6 carotid sinus hypersensitivity, and 0 situational) are summarized in Table 1.
Studies Addressing Carotid Sinus Hypersensitivity Syncope
A 1992 open-label study found that at 3 years, syncope had recurred in 57% of patients randomly assigned to no pacemaker but in only 9% assigned to receive a pacemaker (P=0.0002).8 There were no differences in mortality rate between groups.
In the 2001 SAFE PACE (Syncope and Falls in the Elderly — Pacing and Carotid Sinus Evaluation) open-label randomized trial,13 syncope had recurred by 12 months among 11% of the 87 patients with a pacemaker and among 22% of the 88 patients without a pacemaker (P=0.063). Falls were substantially reduced among patients with a pacemaker (669 versus 216 falls; odds ratio: 0.42; 95% confidence interval [CI]: 0.23 to 0.75).
A 2007 unblinded randomized trial had similar results when 10% of patients randomized to receive a pacemaker had recurrence of syncope at 12 months, whereas 40% without a pacemaker had recurrent syncope (P=0.008).6
In the subsequent 2010 SAFE PACE 2 trial,10 which was a double-blinded RCT, randomly assigned patients underwent either pacemaker implantation or loop recorder implantation. There was no benefit of pacing in terms of recurrent syncope, quality of life, or cognitive function, but the act of intervention (implantation of a device) was associated with substantially lower than expected event rates in both groups after device implantation. Unfortunately, data from this study could not be included in the meta-analysis because the raw numerator/denominator data for the key outcome of recurrent syncope are no longer accessible to the investigators.
Studies Addressing Vasovagal Syncope
An open-label randomized trial in 1999 found that over a mean of 52 months of follow-up, syncope had recurred among 6 of 10 patients who were assigned to receive a pacemaker but in none of the 10 patients who did not receive a pacemaker (P<0.02).14
The 2004 SYNPACE (Vasovagal Syncope and Pacing) RCT with double-blinding included 29 patients with severe recurrent tilt-induced vasovagal syncope who underwent pacemaker implantation.11 Among these, 16 patients were assigned to DDD mode pacing with rate drop response, and 13 were assigned to pacemaker OFF (OOO mode). At a median of 23.8 months of follow-up, 8 of 15 (50%) assigned to pacing and 5 of 13 (38%) assigned to OOO mode had experienced recurrent syncope (P=0.38).
In an observational cohort study published in 2007 of 34 patients with tilt-induced asystole, researchers found that by a mean of 18.6 months of follow-up, syncope had recurred among 5 of 22 (23%) patients who received a pacemaker and among 3 of 12 (25%) who did not (P>0.05).12 Interestingly, and similar to the findings of the SAFE PACE 2 trial,10 rates of syncope were substantially lower after enrollment in both groups.
The ISSUE-3 (Third International Study on Syncope of Uncertain Etiology) trial was an RCT with double-blinding conducted in 2012.7 All of the 77 subjects with at least 3 prior syncopal episodes who were subsequently documented by implantable loop recorder to have asystole (at least 3 seconds associated with syncope or at least 6 seconds associated with presyncope) received a pacemaker. Of these, 38 were randomly assigned to DDD mode pacing with a rate drop response, and 39 were assigned to have pacing functions off. Over 2 years of follow-up, syncope recurred in 19 patients assigned to pacing “off” and in 8 of the patients assigned to DDD pacing with rate drop response (P=0.039).
In a single-blinded randomized crossover trial published in 2013, researchers implanted pacemakers in 50 patients with recurrent tilt-induced vasovagal syncope, and all received DDD pacing.9 Patients were randomly assigned to closed-loop stimulation (CLS) programmed “on” or “off,” and then after 18 months and a subsequent 1-month washout period, patients were crossed over to the other group. The authors found that there were only 2 syncopal episodes during assignment to CLS ON, but there were 15 while CLS was programmed OFF (P=0.007). Because there was no comparison group that received no pacing, this study was not included in the meta-analysis.
In 2000, the VASIS (Vasovagal Syncope International Study) open-label randomized trial4 published results comparing DDI pacemaker with rate hysteresis to no pacemaker among patients with severe cardioinibitory tilt-positive vasovagal syncope (defined as asystole >3 seconds during tilt-table test). The authors found that over a mean of 3.7 years of follow-up, 1 of 19 patients (5%) with a pacemaker and 14 of 23 patients (61%) with no pacemaker (P=0.0006) had recurrence of syncope. Interestingly, repeat tilt-table testing within 15 days of enrollment (including after pacemaker implantation) demonstrated similar rates of tilt-induced syncope in both groups (59% versus 61%; P=not significant).
Notable Studies Excluded From Systematic Review
It is worth mentioning, however, that the VPS (Vasovagal Pacemaker Study)5 and the subsequent VPS II (Vasovagal Pacemaker Study II)15 were not included in the systematic review because they did not have follow-up of at least 1 year. In VPS,5 which was an open-label (unblinded) randomized trial, 54 patients were assigned to receive a pacemaker or no pacemaker. An 85% relative risk (RR) reduction was found to be associated with pacing. Because the authors were suspicious that the lack of blinding (because of the open-label study design) could result in substantive outcome ascertainment bias, they conducted the subsequent VPS II15 as a randomized trial with double-blinding; all patients were assigned to receive a pacemaker, but 48 were assigned to DDD mode, and 52 were assigned to pacing off (ODO mode). At 6 months of follow-up, no significant benefit of pacing was evident; 22 of 52 patients (42%) assigned to ODO mode and 16 of 48 (33%) assigned to DDD mode had experienced recurrent syncope (1-sided P=0.14).
Risk of Bias
The findings of VPS (Vasovagal Pacemaker Study)5 and VPS II (Vasovagal Pacemaker Study II),15 as well as the fact that after enrollment, lower than expected rates of syncope were reported in patients both with and without pacemakers,10,12 suggest the possibility that outcome ascertainment bias may be present. As such, we decided to proceed with meta-analysis for the primary outcome of recurrent syncope stratified by blinding status of the relevant studies.
Synthesis of Results
Although we considered multiple outcomes, including recurrent syncope (primary outcome), death, falls, traumatic injury, hospitalization, adverse events, and symptoms attributable to the underlying condition (eg, presyncope, quality of life), only for recurrent syncope and death were there a minimum of 4 studies with analyzable data suitable for meta-analysis.
Among the 8 studies with analyzable data for the primary outcome of recurrent syncope over at least 1 year of follow-up, only 2 were conducted with a double-blinded study design,7,11 and the remaining 6 studies (n=424) were conducted with an open-label (unblinded) design.4,6,8,12–14 Among the open-label studies, after meta-analysis using random-effects models (Figure 2A), we found an apparent 70% reduction in recurrent syncope associated with pacing (RR: 0.30; 95% CI: 0.15 to 0.60). When the open-label studies were excluded from analysis, the double-blinded studies (n=89) revealed no apparent benefit from pacing (RR: 0.73; 95% CI: 0.25 to 2.1) (Figure 2B).
Random-effects meta-regression failed to demonstrate statistically significant evidence that blinding status modified the association of pacing with outcome (beta coefficient, 0.35; 95% CI: −0.54 to 1.2; P=0.38). In the setting of only 2 studies with double-blinded study design included in the analysis, confidence intervals were quite wide.
Four studies (n=315) included data on mortality rate suitable for meta-analysis.6,8,13,14 Among these, we found no evidence that open-label pacemaker implantation was associated with reduced mortality rate (RR: 1.1; 95% CI: 0.5 to 2.4; P=0.81), but CIs were wide (Figure 3).
Summary of Evidence
In this systematic review, among unblinded studies, we found evidence that pacing reduced the risk of recurrent reflex-mediated syncope; among the 2 double-blinded randomized trials, there was no apparent benefit. These findings suggest that an expectation effect exists among open-label (unblinded) studies.16 This expectation effect is a form of outcome ascertainment bias in which the knowledge of the presence of a pacemaker may lead to expectation of benefit on the part of both patients and clinicians.
When these 10 studies, comprising a total of 676 subjects, are considered, there is very limited evidence beyond small, unblinded studies to suggest a benefit of pacing in patients with reflex-mediated syncope, with 1 notable, but limited exception. The ISSUE-3 trial,7 which used a randomized, double-blinded study design, demonstrated a reduction in recurrent syncope among patients with recurrent vasovagal syncope in whom clinically relevant asystole had been documented by implantable loop recorder.
This systematic review has important limitations. Although all the studies included involved reflex-mediated syncope, the primary analysis included studies with both vasovagal syncope and carotid sinus hypersensitivity syncope, and as a result, there are challenges in interpreting the results. In addition, the limited number of studies and relatively small number of subjects constitute a limitation, but the methodological concern about outcome ascertainment bias among the majority of these studies (those without blinding) is an even greater problem. The small number of double-blinded studies (2 trials) means that the meta-regression analysis using statistical tools to determine whether the blinding status of studies modifies the apparent association of pacing with a reduction in recurrent syncope results in a coefficient with CIs so wide that meaningful interaction cannot be excluded.
There are very limited data on the benefits of pacing among patients with reflex-mediated (vasovagal, situational, and carotid sinus hypersensitivity) syncope. The apparent lower incidence of syncope observed with pacing among open-label studies, compared with the lack of benefit of pacing among the blinded studies, suggests that an expectation effect (a form of outcome ascertainment bias) may be present. Unfortunately, only 2 studies with a double-blinded study design met criteria for inclusion. The evidence does not support the routine use of pacing for reflex-mediated syncope beyond patients with recurrent syncope and asystole documented by implantable loop recorder, such as those meeting the entry criteria for the ISSUE-3 trial.7 These findings suggest that additional rigorously designed randomized trials with double-blinded study design are needed, and these studies should include sufficient sample sizes and duration of follow-up to provide enough statistical power to answer definitively the important scientific and clinical questions about the potential benefits of pacing among patients with vasovagal, situational, and/or carotid sinus hypersensitivity syncope.
ACC/AHA Task Force Members
Glenn N. Levine, MD, FACC, FAHA, Chair; Patrick T. O’Gara, MD, FACC, FAHA, Chair-Elect; Jonathan L. Halperin, MD, FACC, FAHA, Immediate Past Chair*; Sana M. Al-Khatib, MD, MHS, FACC, FAHA; Kim K. Birtcher, MS, PharmD, AACC; Biykem Bozkurt, MD, PhD, FACC, FAHA; Ralph G. Brindis, MD, MPH, MACC*; Joaquin E. Cigarroa, MD, FACC; Lesley H. Curtis, PhD, FAHA; Lee A. Fleisher, MD, FACC, FAHA; Federico Gentile, MD, FACC; Samuel Gidding, MD, FAHA; Mark A. Hlatky, MD, FACC; John Ikonomidis, MD, PhD, FAHA; José Joglar, MD, FACC, FAHA; Susan J. Pressler, PhD, RN, FAHA; Duminda N. Wijeysundera, MD, PhD
Presidents and Staff
American College of Cardiology
Richard A. Chazal, MD, FACC, President
Shalom Jacobovitz, Chief Executive Officer
William J. Oetgen, MD, MBA, FACC, Executive Vice President, Science, Education, Quality, and Publishing
Amelia Scholtz, PhD, Publications Manager, Science, Education, Quality, and Publishing
American College of Cardiology/American Heart Association
Katherine Sheehan, PhD, Director of Guidelines Operations
Lisa Bradfield, CAE, Director, Guideline Methodology and Policy
Abdul R. Abdullah, MD, Science and Medicine Advisor
Clara Fitzgerald, Project Manager, Clinical Practice Guidelines
Allison Rabinowitz, MPH, Project Manager, Clinical Practice Guidelines
American Heart Association
Steven R. Houser, PhD, FAHA, President
Nancy Brown, Chief Executive Officer
Rose Marie Robertson, MD, FAHA, Chief Science and Medicine Officer
Gayle R. Whitman, PhD, RN, FAHA, FAAN, Senior Vice President, Office of Science Operations
Jody Hundley, Production Manager, Scientific Publications, Office of Science Operations
|Committee Member||Employment||Consultant||Speakers Bureau||Ownership/Partnership/Principal||Personal Research||Institutional/Organizational or Other Financial Benefit||Expert Witness|
|Paul D. Varosy, Chair||University of Colorado Hospital, Clinical Cardiac EP Training Program—Associate Program Director; VA Eastern Colorado Healthcare System—Director of Cardiovascular EP||None||None||None||None||None||None|
|Lin Y. Chen||University of Minnesota Medical School— Associate Professor of Medicine||None||None||None||None||None||None|
|Amy L. Miller||Brighman and Women’s Hospital, Harvard Medical School—Assistant Professor, Cardiovascular Medicine||None||None||None||None||None||None|
|Peter A. Noseworthy||Mayo Clinic College of Medicine— Associate Professor of Medicine||None||None||None||None||None||None|
|David J. Slotwiner||New york Presbyterian Queens—Chief, Division of Cardiology; Weill Cornell Medical—Assistant Professor||None||None||None||None||None||None|
|Venkatesh Thiruganasambandamoorthy||Ottawa Hospital Research Institute— Assistant Professor, Staff Attending Physician||None||None||None||None||None||None|
This table represents the relationships of evidence review committee members with industry and other entities that were determined to be relevant to this document. These relationships were reviewed and updated in conjunction with all meetings and/or conference calls of the writing committee during the document development process. The table does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of ≥5% of the voting stock or share of the business entity, or ownership of ≥$5000 of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person’s gross income for the previous year. Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted. According to the ACC/AHA, a person has a relevant relationship IF: a) the relationship or interest relates to the same or similar subject matter, intellectual property or asset, topic, or issue addressed in the document; or b) the company/entity (with whom the relationship exists) makes a drug, drug class, or device addressed in the document or makes a competing drug or device addressed in the document; or c) the person or a member of the person’s household, has a reasonable potential for financial, professional or other personal gain or loss as a result of the issues/content addressed in the document.
* For transparency, the ERC members’ comprehensive disclosure information is available as an online supplement (http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIR.0000000000000500/-/DC1).
ACC indicates American College of Cardiology; AHA, American Heart Association; EP, electrophysiology; and HRS, Heart Rhythm Society.
The American Heart Association requests that this document be cited as follows: Varosy PD, Chen LY, Miller AL, Noseworthy PA, Slotwiner DJ, Thiruganasmbandamoorthy V. Pacing as a treatment for reflex-mediated (vasovagal, situational, or carotid sinus hypersensitivity) syncope: a systematic review for the 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2017;136:e123–e135. DOI: 10.1161/CIR.0000000000000500.
This document was approved by the American College of Cardiology Clinical Policy Approval Committee on behalf of the Board of Trustees, the American Heart Association Science Advisory and Coordinating Committee, the American Heart Association Executive Committee, and the Heart Rhythm Society Board of Trustees in January 2017.
This article has been copublished in the Journal of the American College of Cardiology and HeartRhythm.
Copies: This document is available on the World Wide Web sites of the American College of Cardiology (www.acc.org), the American Heart Association (professional.heart.org), and the Heart Rhythm Society (www.hrsonline.org). A copy of the document is available at http://professional.heart.org/statements by selecting either the “By Topic” link or the “By Publication Date” link. To purchase additional reprints, call 843-216-2533 or e-mail .
Expert peer review of AHA Scientific Statements is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit http://professional.heart.org/statements and select the “Policies and Development” link.
Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.heart.org/HEARTORG/General/Copyright-Permission-Guidelines_UCM_300404_Article.jsp. A link to the “Copyright Permissions Request Form” appears on the right side of the page.
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↵* Former Task Force member; current member during the writing effort.
- © 2017 by the American College of Cardiology Foundation, the American Heart Association, Inc., and the Heart Rhythm Society.
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