This Article Free upon publication Full Text (PDF) All Versions of this Article: 117/21/e350    most recent CIRCUALTIONAHA.108.189742v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Epstein, A. E. Articles by Sweeney, M. O. PubMed PubMed Citation Articles by Epstein, A. E. Articles by Sweeney, M. O.

(Circulation. 2008;117:e350-e408.)
© 2008 American Heart Association, Inc.

AHA Practice Guideline

ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities

A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): Developed in Collaboration With the American Association for Thoracic Surgery and Society of Thoracic Surgeons

Writing Committee: Andrew E. Epstein, MD, FACC, FAHA, FHRS, Chair^*; John P. DiMarco, MD, PhD, FACC, FAHA, FHRS^*; Kenneth A. Ellenbogen, MD, FACC, FAHA, FHRS^*; N.A. Mark Estes, III, MD, FACC, FAHA, FHRS; Roger A. Freedman, MD, FACC, FHRS^*; Leonard S. Gettes, MD, FACC, FAHA; A. Marc Gillinov, MD, FACC, FAHA^*,; Gabriel Gregoratos, MD, FACC, FAHA; Stephen C. Hammill, MD, FACC, FHRS; David L. Hayes, MD, FACC, FAHA, FHRS^*; Mark A. Hlatky, MD, FACC, FAHA; L. Kristin Newby, MD, FACC, FAHA; Richard L. Page, MD, FACC, FAHA, FHRS; Mark H. Schoenfeld, MD, FACC, FAHA, FHRS; Michael J. Silka, MD, FACC; Lynne Warner Stevenson, MD, FACC, FAHA; Michael O. Sweeney, MD, FACC^*

Key Words: ACC/AHA practice guideline • device-based therapy • implantable cardioverter-defibrillator • implantable coronary device • arrhythmia • pacemaker • pacing • cardiomyopathy

	Introduction

Top Introduction Preamble 1. Introduction 2. Indications for Pacing 3. Indications for Implantable... 4. Areas in Need... Staff References

 

Preamble...e352

   1. Introduction...e352

      1.1. Organization of Committee...e352

      1.2. Document Review and Approval...e353

      1.3. Methodology and Evidence...e353

   2. Indications for Pacing...e356

      2.1. Pacing for Bradycardia Due to Sinus and Atrioventricular Node Dysfunction...e356

         2.1.1. Sinus Node Dysfunction...e356

         2.1.2. Acquired Atrioventricular Block in Adults...e357

         2.1.3. Chronic Bifascicular Block...e359

         2.1.4. Pacing for Atrioventricular Block Associated With Acute Myocardial Infarction...e360

         2.1.5. Hypersensitive Carotid Sinus Syndrome and Neurocardiogenic Syncope...e361

      2.2. Pacing for Specific Conditions...e362

         2.2.1. Cardiac Transplantation...e362

         2.2.2. Neuromuscular Diseases...e363

         2.2.3. Sleep Apnea Syndrome...e363

         2.2.4. Cardiac Sarcoidosis...e363

      2.3. Prevention and Termination of Arrhythmias by Pacing...e364

         2.3.1. Pacing to Prevent Atrial Arrhythmias...e364

         2.3.2. Long-QT Syndrome...e364

         2.3.3. Atrial Fibrillation (Dual-Site, Dual-Chamber, Alternative Pacing Sites)...e364

      2.4. Pacing for Hemodynamic Indications...e365

         2.4.1. Cardiac Resynchronization Therapy...e365

         2.4.2. Obstructive Hypertrophic Cardiomyopathy...e366

      2.5. Pacing in Children, Adolescents, and Patients With Congenital Heart Disease...e367

      2.6. Selection of Pacemaker Device...e369

         2.6.1. Major Trials Comparing Atrial or Dual-Chamber Pacing With Ventricular Pacing...e369

         2.6.2. Quality of Life and Functional Status End Points...e372

         2.6.3. Heart Failure End Points...e372

         2.6.4. Atrial Fibrillation End Points...e372

         2.6.5. Stroke or Thromboembolism End Points...e372

         2.6.6. Mortality End Points...e372

         2.6.7. Importance of Minimizing Unnecessary Ventricular Pacing...e372

         2.6.8. Role of Biventricular Pacemakers...e373

      2.7. Optimizing Pacemaker Technology and Cost...e373

      2.8. Pacemaker Follow-Up...e374

         2.8.1. Length of Electrocardiographic Samples for Storage...e375

         2.8.2. Frequency of Transtelephonic Monitoring...e375

   3. Indications for Implantable Cardioverter-Defibrillator Therapy...e376

      3.1. Secondary Prevention of Sudden Cardiac Death...e376

         3.1.1. Implantable Cardioverter-Defibrillator Therapy for Secondary Prevention of Cardiac Arrest and Sustained Ventricular Tachycardia...e376

         3.1.2. Specific Disease States and Secondary Prevention of Cardiac Arrest or Sustained Ventricular Tachycardia...e377

         3.1.3. Coronary Artery Disease...e377

         3.1.4. Nonischemic Dilated Cardiomyopathy...e377

         3.1.5. Hypertrophic Cardiomyopathy...e377

         3.1.6. Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy...e378

         3.1.7. Genetic Arrhythmia Syndromes...e378

         3.1.8. Syncope With Inducible Sustained Ventricular Tachycardia...e378

      3.2. Primary Prevention of Sudden Cardiac Death...e378

         3.2.1. Coronary Artery Disease...e378

         3.2.2. Nonischemic Dilated Cardiomyopathy...e379

         3.2.3. Long-QT Syndrome...e380

         3.2.4. Hypertrophic Cardiomyopathy...e380

         3.2.5. Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy...e381

         3.2.6. Noncompaction of the Left Ventricle...e381

         3.2.7. Primary Electrical Disease (Idiopathic Ventricular Fibrillation, Short-QT Syndrome, Brugada Syndrome, and Catecholaminergic Polymorphic Ventricular Tachycardia)...e382

         3.2.8. Idiopathic Ventricular Tachycardias...e383

         3.2.9. Advanced Heart Failure and Cardiac Transplantation...e383

      3.3. Implantable Cardioverter-Defibrillators in Children, Adolescents, and Patients With Congenital Heart Disease...e385

         3.3.1. Hypertrophic Cardiomyopathy...e386

      3.4. Limitations and Other Considerations...e386

         3.4.1. Impact on Quality of Life (Inappropriate Shocks)...e386

         3.4.2. Surgical Needs...e387

         3.4.3. Patient Longevity and Comorbidities...e387

         3.4.4. Terminal Care...e388

      3.5. Cost-Effectiveness of Implantable Cardioverter-Defibrillator Therapy...e389

      3.6. Selection of Implantable Cardioverter-Defibrillator Generators...e390

      3.7. Implantable Cardioverter-Defibrillator Follow-Up...e391

         3.7.1. Elements of Implantable Cardioverter-Defibrillator Follow-Up...e391

         3.7.2. Focus on Heart Failure After First Appropriate Implantable Cardioverter-Defibrillator Therapy...e392

   4. Areas in Need of Further Research...e392

Appendix 1. Author Relationships With Industry...e405

Appendix 2. Peer Reviewer Relationships With Industry...e406

Appendix 3. Abbreviations List...e408

References...e393

	Preamble

Top Introduction Preamble 1. Introduction 2. Indications for Pacing 3. Indications for Implantable... 4. Areas in Need... Staff References

 
It is important that the medical profession play a significant role in critically evaluating the use of diagnostic procedures and therapies as they are introduced and tested in the detection, management, or prevention of disease states. Rigorous and expert analysis of the available data documenting absolute and relative benefits and risks of those procedures and therapies can produce helpful guidelines that improve the effectiveness of care, optimize patient outcomes, and favorably affect the overall cost of care by focusing resources on the most effective strategies.

The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly engaged in the production of such guidelines in the area of cardiovascular disease since 1980. The American College of Cardiology (ACC)/AHA Task Force on Practice Guidelines, whose charge is to develop, update, or revise practice guidelines for important cardiovascular diseases and procedures, directs this effort. Writing committees are charged with the task of performing an assessment of the evidence and acting as an independent group of authors to develop, update, or revise written recommendations for clinical practice.

Experts in the subject under consideration have been selected from both organizations to examine subject-specific data and write guidelines. The process includes additional representatives from other medical practitioner and specialty groups when appropriate. Writing committees are specifically charged to perform a formal literature review, weigh the strength of evidence for or against a particular treatment or procedure, and include estimates of expected health outcomes where data exist. Patient-specific modifiers and comorbidities and issues of patient preference that may influence the choice of particular tests or therapies are considered, as well as frequency of follow-up and cost-effectiveness. When available, information from studies on cost will be considered; however, review of data on efficacy and clinical outcomes will constitute the primary basis for preparing recommendations in these guidelines.

The ACC/AHA Task Force on Practice Guidelines makes every effort to avoid any actual, potential, or perceived conflicts of interest that may arise as a result of an industry relationship or personal interest of the writing committee. Specifically, all members of the writing committee, as well as peer reviewers of the document, were asked to provide disclosure statements of all such relationships that may be perceived as real or potential conflicts of interest. Writing committee members are also strongly encouraged to declare a previous relationship with industry that may be perceived as relevant to guideline development. If a writing committee member develops a new relationship with industry during his or her tenure, he or she is required to notify guideline staff in writing. The continued participation of the writing committee member will be reviewed. These statements are reviewed by the parent task force, reported orally to all members of the writing committee at each meeting, and updated and reviewed by the writing committee as changes occur. Please refer to the methodology manual for ACC/AHA guideline writing committees for further description of the relationships with industry policy.¹ See Appendix 1 for author relationships with industry and Appendix 2 for peer reviewer relationships with industry that are pertinent to this guideline.

These practice guidelines are intended to assist health care providers in clinical decision making by describing a range of generally acceptable approaches for the diagnosis, management, and prevention of specific diseases or conditions. Clinical decision making should consider the quality and availability of expertise in the area where care is provided. These guidelines attempt to define practices that meet the needs of most patients in most circumstances. These guideline recommendations reflect a consensus of expert opinion after a thorough review of the available current scientific evidence and are intended to improve patient care.

Patient adherence to prescribed and agreed upon medical regimens and lifestyles is an important aspect of treatment. Prescribed courses of treatment in accordance with these recommendations will only be effective if they are followed. Because lack of patient understanding and adherence may adversely affect treatment outcomes, physicians and other health care providers should make every effort to engage the patient in active participation with prescribed medical regimens and lifestyles.

If these guidelines are used as the basis for regulatory or payer decisions, the ultimate goal is quality of care and serving the patient’s best interests. The ultimate judgment regarding care of a particular patient must be made by the health care provider and the patient in light of all of the circumstances presented by that patient. There are circumstances in which deviations from these guidelines are appropriate.

The guidelines will be reviewed annually by the ACC/AHA Task Force on Practice Guidelines and will be considered current unless they are updated, revised, or sunsetted and withdrawn from distribution. The executive summary and recommendations are published in the May 27, 2008, issue of the Journal of the American College of Cardiology, May 27, 2008, issue of Circulation, and the June 2008 issue of Heart Rhythm. The full-text guidelines are e-published in the same issue of the journals noted above, as well as posted on the ACC (www.acc.org), AHA (http://my.americanheart.org), and Heart Rhythm Society (HRS) (www.hrsonline.org) Web sites. Copies of the full-text and the executive summary are available from each organization.

Sidney C. Smith, Jr, MD, FACC, FAHA Chair, ACC/AHA Task Force on Practice Guidelines

	1. Introduction

Top Introduction Preamble 1. Introduction 2. Indications for Pacing 3. Indications for Implantable... 4. Areas in Need... Staff References

 
1.1. Organization of Committee
This revision of the "ACC/AHA/NASPE Guidelines for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices" updates the previous versions published in 1984, 1991, 1998, and 2002. Revision of the statement was deemed necessary for multiple reasons: 1) Major studies have been reported that have advanced our knowledge of the natural history of bradyarrhythmias and tachyarrhythmias, which may be treated optimally with device therapy; 2) there have been tremendous changes in the management of heart failure that involve both drug and device therapy; and 3) major advances in the technology of devices to treat, delay, and even prevent morbidity and mortality from bradyarrhythmias, tachyarrhythmias, and heart failure have occurred.

The committee to revise the "ACC/AHA/NASPE Guidelines for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices" was composed of physicians who are experts in the areas of device therapy and follow-up and senior clinicians skilled in cardiovascular care, internal medicine, cardiovascular surgery, ethics, and socioeconomics. The committee included representatives of the American Association for Thoracic Surgery, Heart Failure Society of America, and Society of Thoracic Surgeons.

1.2. Document Review and Approval
The document was reviewed by 2 official reviewers nominated by each of the ACC, AHA, and HRS and by 11 additional peer reviewers. Of the total 17 peer reviewers, 10 had no significant relevant relationships with industry. In addition, this document has been reviewed and approved by the governing bodies of the ACC, AHA, and HRS, which include 19 ACC Board of Trustees members (none of whom had any significant relevant relationships with industry), 15 AHA Science Advisory Coordinating Committee members (none of whom had any significant relevant relationships with industry), and 14 HRS Board of Trustees members (6 of whom had no significant relevant relationships with industry). All guideline recommendations underwent a formal, blinded writing committee vote. Writing committee members were required to recuse themselves if they had a significant relevant relationship with industry. The guideline recommendations were unanimously approved by all members of the writing committee who were eligible to vote. The section "Pacing in Children and Adolescents" was reviewed by additional reviewers with special expertise in pediatric electrophysiology. The committee thanks all the reviewers for their comments. Many of their suggestions were incorporated into the final document.

1.3. Methodology and Evidence
The recommendations listed in this document are, whenever possible, evidence based. An extensive literature survey was conducted that led to the incorporation of 527 references. Searches were limited to studies, reviews, and other evidence conducted in human subjects and published in English. Key search words included but were not limited to antiarrhythmic, antibradycardia, atrial fibrillation, bradyarrhythmia, cardiac, CRT, defibrillator, device therapy, devices, dual chamber, heart, heart failure, ICD, implantable defibrillator, device implantation, long-QT syndrome, medical therapy, pacemaker, pacing, quality-of-life, resynchronization, rhythm, sinus node dysfunction, sleep apnea, sudden cardiac death, syncope, tachyarrhythmia, terminal care, and transplantation. Additionally, the committee reviewed documents related to the subject matter previously published by the ACC, AHA, and HRS. References selected and published in this document are representative and not all-inclusive.

The committee reviewed and ranked evidence supporting current recommendations, with the weight of evidence ranked as Level A if the data were derived from multiple randomized clinical trials that involved a large number of individuals. The committee ranked available evidence as Level B when data were derived either from a limited number of trials that involved a comparatively small number of patients or from well-designed data analyses of nonrandomized studies or observational data registries. Evidence was ranked as Level C when the consensus of experts was the primary source of the recommendation. In the narrative portions of these guidelines, evidence is generally presented in chronological order of development. Studies are identified as observational, randomized, prospective, or retrospective. The committee emphasizes that for certain conditions for which no other therapy is available, the indications for device therapy are based on expert consensus and years of clinical experience and are thus well supported, even though the evidence was ranked as Level C. An analogous example is the use of penicillin in pneumococcal pneumonia, for which there are no randomized trials and only clinical experience. When indications at Level C are supported by historical clinical data, appropriate references (e.g., case reports and clinical reviews) are cited if available. When Level C indications are based strictly on committee consensus, no references are cited. In areas where sparse data were available (e.g., pacing in children and adolescents), a survey of current practices of major centers in North America was conducted to determine whether there was a consensus regarding specific pacing indications. The schema for classification of recommendations and level of evidence is summarized in Table 1, which also illustrates how the grading system provides an estimate of the size of the treatment effect and an estimate of the certainty of the treatment effect.

View larger version (81K): [in this window] [in a new window]   Table 1. Applying Classification of Recommendations and Level of Evidence *Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as gender, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Even though randomized trials are not available, there may be a very clear clinical consensus that a particular test or therapy is useful or effective. In 2003, the ACC/AHA Task Force on Practice Guidelines developed a list of suggested phrases to use when writing recommendations. All guideline recommendations have been written in full sentences that express a complete thought, such that a recommendation, even if separated and presented apart from the rest of the document (including headings above sets of recommendations), would still convey the full intent of the recommendation. It is hoped that this will increase readers’ comprehension of the guidelines and will allow queries at the individual recommendation level.

The focus of these guidelines is the appropriate use of heart pacing devices (e.g., pacemakers for bradyarrhythmias and heart failure management, cardiac resynchronization, and implantable cardioverter-defibrillators [ICDs]), not the treatment of cardiac arrhythmias. The fact that the use of a device for treatment of a particular condition is listed as a Class I indication (beneficial, useful, and effective) does not preclude the use of other therapeutic modalities that may be equally effective. As with all clinical practice guidelines, the recommendations in this document focus on treatment of an average patient with a specific disorder and may be modified by patient comorbidities, limitation of life expectancy because of coexisting diseases, and other situations that only the primary treating physician may evaluate appropriately.

These guidelines include sections on selection of pacemakers and ICDs, optimization of technology, cost, and follow-up of implanted devices. Although the section on follow-up is relatively brief, its importance cannot be overemphasized: First, optimal results from an implanted device can be obtained only if the device is adjusted to changing clinical conditions; second, recent advisories and recalls serve as warnings that devices are not infallible, and failure of electronics, batteries, and leads can occur.^2,3

The committee considered including a section on extraction of failed/unused leads, a topic of current interest, but elected not to do so in the absence of convincing evidence to support specific criteria for timing and methods of lead extraction. A policy statement on lead extraction from the North American Society of Pacing and Electrophysiology (now the HRS) provides information on this topic.⁴ Similarly, the issue of when to discontinue long-term cardiac pacing or defibrillator therapy has not been studied sufficiently to allow formulation of appropriate guidelines⁵; however, the question is of such importance that this topic is addressed to emphasize the importance of patient-family-physician discussion and ethical principles.

The text that accompanies the listed indications should be read carefully, because it includes the rationale and supporting evidence for many of the indications, and in several instances, it includes a discussion of alternative acceptable therapies. Many of the indications are modified by the term "potentially reversible." This term is used to indicate abnormal pathophysiology (e.g., complete heart block) that may be the result of reversible factors. Examples include complete heart block due to drug toxicity (digitalis), electrolyte abnormalities, diseases with periatrioventricular node inflammation (Lyme disease), and transient injury to the conduction system at the time of open heart surgery. When faced with a potentially reversible situation, the treating physician must decide how long of a waiting period is justified before device therapy is begun. The committee recognizes that this statement does not address the issue of length of hospital stay vis-à-vis managed-care regulations. It is emphasized that these guidelines are not intended to address this issue, which falls strictly within the purview of the treating physician.

The term "symptomatic bradycardia" is used in this document. Symptomatic bradycardia is defined as a documented bradyarrhythmia that is directly responsible for development of the clinical manifestations of syncope or near syncope, transient dizziness or lightheadedness, or confusional states resulting from cerebral hypoperfusion attributable to slow heart rate. Fatigue, exercise intolerance, and congestive heart failure may also result from bradycardia. These symptoms may occur at rest or with exertion. Definite correlation of symptoms with a bradyarrhythmia is required to fulfill the criteria that define symptomatic bradycardia. Caution should be exercised not to confuse physiological sinus bradycardia (as occurs in highly trained athletes) with pathological bradyarrhythmias. Occasionally, symptoms may become apparent only in retrospect after antibradycardia pacing. Nevertheless, the universal application of pacing therapy to treat a specific heart rate cannot be recommended except in specific circumstances, as detailed subsequently.

In these guidelines, the terms "persistent," "transient," and "not expected to resolve" are used but not specifically defined because the time element varies in different clinical conditions. The treating physician must use appropriate clinical judgment and available data in deciding when a condition is persistent or when it can be expected to be transient. Section 2.1.4, "Pacing for Atrioventricular Block Associated With Acute Myocardial Infarction," overlaps with the "ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction"⁶ and includes expanded indications and stylistic changes. The statement "incidental finding at electrophysiological study" is used several times in this document and does not mean that such a study is indicated. Appropriate indications for electrophysiological studies have been published.⁷

The section on indications for ICDs has been updated to reflect the numerous new developments in this field and the voluminous literature related to the efficacy of these devices in the treatment and prophylaxis of sudden cardiac death (SCD) and malignant ventricular arrhythmias. As previously noted, indications for ICDs, cardiac resynchronization therapy (CRT) devices, and combined ICDs and CRT devices (hereafter called CRT-Ds) are continuously changing and can be expected to change further as new trials are reported. Indeed, it is inevitable that the indications for device therapy will be refined with respect to both expanded use and the identification of patients expected to benefit the most from these therapies. Furthermore, it is emphasized that when a patient has an indication for both a pacemaker (whether it be single-chamber, dual-chamber, or biventricular) and an ICD, a combined device with appropriate programming is indicated.

In this document, the term "mortality" is used to indicate all-cause mortality unless otherwise specified. The committee elected to use all-cause mortality because of the variable definition of sudden death and the developing consensus to use all-cause mortality as the most appropriate end point of clinical trials.^8,9

These guidelines are not designed to specify training or credentials required for physicians to use device therapy. Nevertheless, in view of the complexity of both the cognitive and technical aspects of device therapy, only appropriately trained physicians should use device therapy. Appropriate training guidelines for physicians have been published previously.^10–13

The 2008 revision reflects what the committee believes are the most relevant and significant advances in pacemaker/ICD therapy since the publication of these guidelines in the Journal of the American College of Cardiology and Circulation in 2002.^14,15

All recommendations assume that patients are treated with optimal medical therapy according to published guidelines, as had been required in all the randomized controlled clinical trials on which these guidelines are based, and that human issues related to individual patients are addressed. The committee believes that comorbidities, life expectancy, and quality-of-life (QOL) issues must be addressed forthrightly with patients and their families. We have repeatedly used the phrase "reasonable expectation of survival with a good functional status for more than 1 year" to emphasize this integration of factors in decision-making. Even when physicians believe that the anticipated benefits warrant device implantation, patients have the option to decline intervention after having been provided with a full explanation of the potential risks and benefits of device therapy. Finally, the committee is aware that other guideline/expert groups have interpreted the same data differently.^16–19

In preparing this revision, the committee was guided by the following principles:

1. Changes in recommendations and levels of evidence were made either because of new randomized trials or because of the accumulation of new clinical evidence and the development of clinical consensus.
   
2. The committee was cognizant of the health care, logistic, and financial implications of recent trials and factored in these considerations to arrive at the classification of certain recommendations.
   
3. For recommendations taken from other guidelines, wording changes were made to render some of the original recommendations more precise.
   
4. The committee would like to reemphasize that the recommendations in this guideline apply to most patients but may require modification because of existing situations that only the primary treating physician can evaluate properly.
   
5. All of the listed recommendations for implantation of a device presume the absence of inciting causes that may be eliminated without detriment to the patient (e.g., nonessential drug therapy).
   
6. The committee endeavored to maintain consistency of recommendations in this and other previously published guidelines. In the section on atrioventricular (AV) block associated with acute myocardial infarction (AMI), the recommendations follow closely those in the "ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction."⁶ However, because of the rapid evolution of pacemaker/ICD science, it has not always been possible to maintain consistency with other published guidelines.
   

	2. Indications for Pacing

Top Introduction Preamble 1. Introduction 2. Indications for Pacing 3. Indications for Implantable... 4. Areas in Need... Staff References

 
2.1. Pacing for Bradycardia Due to Sinus and Atrioventricular Node Dysfunction
In some patients, bradycardia is the consequence of essential long-term drug therapy of a type and dose for which there is no acceptable alternative. In these patients, pacing therapy is necessary to allow maintenance of ongoing medical treatment.

2.1.1. Sinus Node Dysfunction
Sinus node dysfunction (SND) was first described as a clinical entity in 1968,²⁰ although Wenckebach reported the electrocardiographic (ECG) manifestation of SND in 1923. SND refers to a broad array of abnormalities in sinus node and atrial impulse formation and propagation. These include persistent sinus bradycardia and chronotropic incompetence without identifiable causes, paroxysmal or persistent sinus arrest with replacement by subsidiary escape rhythms in the atrium, AV junction, or ventricular myocardium. The frequent association of paroxysmal atrial fibrillation (AF) and sinus bradycardia or sinus bradyarrhythmias, which may oscillate suddenly from one to the other, usually accompanied by symptoms, is termed "tachy-brady syndrome."

SND is primarily a disease of the elderly and is presumed to be due to senescence of the sinus node and atrial muscle. Collected data from 28 different studies on atrial pacing for SND showed a median annual incidence of complete AV block of 0.6% (range 0% to 4.5%) with a total prevalence of 2.1% (range 0% to 11.9%).²¹ This suggests that the degenerative process also affects the specialized conduction system, although the rate of progression is slow and does not dominate the clinical course of disease.²¹ SND is typically diagnosed in the seventh and eighth decades of life, which is also the average age at enrollment in clinical trials of pacemaker therapy for SND.^22,23 Identical clinical manifestations may occur at any age as a secondary phenomenon of any condition that results in destruction of sinus node cells, such as ischemia or infarction, infiltrative disease, collagen vascular disease, surgical trauma, endocrinologic abnormalities, autonomic insufficiency, and others.²⁴

The clinical manifestations of SND are diverse, reflecting the range of typical sinoatrial rhythm disturbances. The most dramatic presentation is syncope. The mechanism of syncope is a sudden pause in sinus impulse formation or sinus exit block, either spontaneously or after the termination of an atrial tachyarrhythmia, that causes cerebral hypoperfusion. The pause in sinus node activity is frequently accompanied by an inadequate, delayed, or absent response of subsidiary escape pacemakers in the AV junction or ventricular myocardium, which aggravates the hemodynamic consequences.

However, in many patients, the clinical manifestations of SND are more insidious and relate to an inadequate heart rate response to activities of daily living that can be difficult to diagnose.²⁵ The term "chronotropic incompetence" is used to denote an inadequate heart rate response to physical activity. Although many experienced clinicians claim to recognize chronotropic incompetence in individual patients, no single metric has been established as a diagnostic standard upon which therapeutic decisions can be based. The most obvious example of chronotropic incompetence is a monotonic daily heart rate profile in an ambulatory patient. Various protocols have been proposed to quantify subphysiological heart rate responses to exercise,^26,27 and many clinicians would consider failure to achieve 80% of the maximum predicted heart rate (220 minus age) at peak exercise as evidence of a blunted heart rate response.^28,29 However, none of these approaches have been validated clinically, and it is likely that the appropriate heart rate response to exercise in individual patients is too idiosyncratic for standardized testing.

The natural history of untreated SND may be highly variable. The majority of patients who have experienced syncope because of a sinus pause or marked sinus bradycardia will have recurrent syncope.³⁰ Not uncommonly, the natural history of SND is interrupted by other necessary medical therapies that aggravate the underlying tendency to bradycardia.²⁴ MOST (Mode Selection Trial) included symptomatic pauses greater than or equal to 3 seconds or sinus bradycardia with rates greater than 50 bpm, which restricted the use of indicated long-term medical therapy. Supraventricular tachycardia (SVT) including AF was present in 47% and 53% of patients, respectively, enrolled in a large randomized clinical trial of pacing mode selection in SND.^22,31 The incidence of sudden death is extremely low, and SND does not appear to affect survival whether untreated³⁰ or treated with pacemaker therapy.^32,33

The only effective treatment for symptomatic bradycardia is permanent cardiac pacing. The decision to implant a pacemaker for SND is often accompanied by uncertainty that arises from incomplete linkage between sporadic symptoms and ECG evidence of coexisting bradycardia. It is crucial to distinguish between physiological bradycardia due to autonomic conditions or training effects and circumstantially inappropriate bradycardia that requires permanent cardiac pacing. For example, sinus bradycardia is accepted as a physiological finding that does not require cardiac pacing in trained athletes. Such individuals may have heart rates of 40 to 50 bpm while at rest and awake and may have a sleeping rate as slow as 30 bpm, with sinus pauses or progressive sinus slowing accompanied by AV conduction delay (PR prolongation), sometimes culminating in type I second-degree AV block.^34,35 The basis of the distinction between physiological and pathological bradycardia, which may overlap in ECG presentation, therefore pivots on correlation of episodic bradycardia with symptoms compatible with cerebral hypoperfusion. Intermittent ECG monitoring with Holter monitors and event recorders may be helpful,^36,37 although the duration of monitoring required to capture such evidence may be very long.³⁸ The use of insertable loop recorders offers the advantages of compliance and convenience during very long-term monitoring efforts.³⁹

The optimal pacing system for prevention of symptomatic bradycardia in SND is unknown. Recent evidence suggests that ventricular desynchronization due to right ventricular apical (RVA) pacing may have adverse effects on left ventricular (LV) and left atrial structure and function.^40–47 These adverse effects likely explain the association of RVA pacing, independent of AV synchrony, with increased risks of AF and heart failure in randomized clinical trials of pacemaker therapy^45,48,49 and, additionally, ventricular arrhythmias and death during ICD therapy.^50,51 Likewise, although simulation of the normal sinus node response to exercise in bradycardia patients with pacemaker sensors seems logical, a clinical benefit on a population scale has not been demonstrated in large randomized controlled trials of pacemaker therapy.⁵² These rapidly evolving areas of clinical investigation should inform the choice of pacing system in SND (see Section 2.6, "Selection of Pacemaker Device").

Recommendations for Permanent Pacing in Sinus Node Dysfunction

Class I

1. Permanent pacemaker implantation is indicated for SND with documented symptomatic bradycardia, including frequent sinus pauses that produce symptoms. (Level of Evidence: C)^53–55
   
2. Permanent pacemaker implantation is indicated for symptomatic chronotropic incompetence. (Level of Evidence: C)^53–57
   
3. Permanent pacemaker implantation is indicated for symptomatic sinus bradycardia that results from required drug therapy for medical conditions. (Level of Evidence: C)
   

Class IIa

1. Permanent pacemaker implantation is reasonable for SND with heart rate less than 40 bpm when a clear association between significant symptoms consistent with bradycardia and the actual presence of bradycardia has not been documented. (Level of Evidence: C)^{53–55,58–60}
   
2. Permanent pacemaker implantation is reasonable for syncope of unexplained origin when clinically significant abnormalities of sinus node function are discovered or provoked in electrophysiological studies. (Level of Evidence: C)^61,62
   

Class IIb

1. Permanent pacemaker implantation may be considered in minimally symptomatic patients with chronic heart rate less than 40 bpm while awake. (Level of Evidence: C)^{53,55,56,58–60}
   

Class III

1. Permanent pacemaker implantation is not indicated for SND in asymptomatic patients. (Level of Evidence: C)
   
2. Permanent pacemaker implantation is not indicated for SND in patients for whom the symptoms suggestive of bradycardia have been clearly documented to occur in the absence of bradycardia. (Level of Evidence: C)
   
3. Permanent pacemaker implantation is not indicated for SND with symptomatic bradycardia due to nonessential drug therapy. (Level of Evidence: C)
   

2.1.2. Acquired Atrioventricular Block in Adults
AV block is classified as first-, second-, or third-degree (complete) block; anatomically, it is defined as supra-, intra-, or infra-His. First-degree AV block is defined as abnormal prolongation of the PR interval (greater than 0.20 seconds). Second-degree AV block is subclassified as type I and type II. Type I second-degree AV block is characterized by progressive prolongation of the interval between the onset of atrial (P wave) and ventricular (R wave) conduction (PR) before a nonconducted beat and is usually seen in conjunction with QRS. Type I second-degree AV block is characterized by progressive prolongation of the PR interval before a nonconducted beat and a shorter PR interval after the blocked beat. Type II second-degree AV block is characterized by fixed PR intervals before and after blocked beats and is usually associated with a wide QRS complex. When AV conduction occurs in a 2:1 pattern, block cannot be classified unequivocally as type I or type II, although the width of the QRS can be suggestive, as just described. Advanced second-degree AV block refers to the blocking of 2 or more consecutive P waves with some conducted beats, which indicates some preservation of AV conduction. In the setting of AF, a prolonged pause (e.g., greater than 5 seconds) should be considered to be due to advanced second-degree AV block. Third-degree AV block (complete heart block) is defined as absence of AV conduction.

Patients with abnormalities of AV conduction may be asymptomatic or may experience serious symptoms related to bradycardia, ventricular arrhythmias, or both. Decisions regarding the need for a pacemaker are importantly influenced by the presence or absence of symptoms directly attributable to bradycardia. Furthermore, many of the indications for pacing have evolved over the past 40 years on the basis of experience without the benefit of comparative randomized clinical trials, in part because no acceptable alternative options exist to treat most bradycardias.

Nonrandomized studies strongly suggest that permanent pacing does improve survival in patients with third-degree AV block, especially if syncope has occurred.^63–68 Although there is little evidence to suggest that pacemakers improve survival in patients with isolated first-degree AV block,⁶⁹ it is now recognized that marked (PR more than 300 milliseconds) first-degree AV block can lead to symptoms even in the absence of higher degrees of AV block.⁷⁰ When marked first-degree AV block for any reason causes atrial systole in close proximity to the preceding ventricular systole and produces hemodynamic consequences usually associated with retrograde (ventriculoatrial) conduction, signs and symptoms similar to the pacemaker syndrome may occur.⁷¹ With marked first-degree AV block, atrial contraction occurs before complete atrial filling, ventricular filling is compromised, and an increase in pulmonary capillary wedge pressure and a decrease in cardiac output follow. Small uncontrolled trials have suggested some symptomatic and functional improvement by pacing of patients with PR intervals more than 0.30 seconds by decreasing the time for AV conduction.⁷⁰ Finally, a long PR interval may identify a subgroup of patients with LV dysfunction, some of whom may benefit from dual-chamber pacing with a short(er) AV delay.⁷² These same principles also may be applied to patients with type I second-degree AV block who experience hemodynamic compromise due to loss of AV synchrony, even without bradycardia. Although echocardiographic or invasive techniques may be used to assess hemodynamic improvement before permanent pacemaker implantation, such studies are not required.

Type I second-degree AV block is usually due to delay in the AV node irrespective of QRS width. Because progression to advanced AV block in this situation is uncommon,^73–75 pacing is usually not indicated unless the patient is symptomatic. Although controversy exists, pacemaker implantation is supported for this finding.^76–78 Type II second-degree AV block is usually infranodal (either intra- or infra-His), especially when the QRS is wide. In these patients, symptoms are frequent, prognosis is compromised, and progression to third-degree AV block is common and sudden.^73,75,79 Thus, type II second-degree AV block with a wide QRS typically indicates diffuse conduction system disease and constitutes an indication for pacing even in the absence of symptoms. However, it is not always possible to determine the site of AV block without electrophysiological evaluation, because type I second-degree AV block can be infranodal even when the QRS is narrow.⁸⁰ If type I second-degree AV block with a narrow or wide QRS is found to be intra- or infra-Hisian at electrophysiological study, pacing should be considered.

Because it may be difficult for both patients and their physicians to attribute ambiguous symptoms such as fatigue to bradycardia, special vigilance must be exercised to acknowledge the patient’s concerns about symptoms that may be caused by a slow heart rate. In a patient with third-degree AV block, permanent pacing should be strongly considered even when the ventricular rate is more than 40 bpm, because the choice of a 40 bpm cutoff in these guidelines was not determined from clinical trial data. Indeed, it is not the escape rate that is necessarily critical for safety but rather the site of origin of the escape rhythm (i.e., in the AV node, the His bundle, or infra-His).

AV block can sometimes be provoked by exercise. If not secondary to myocardial ischemia, AV block in this circumstance usually is due to disease in the His-Purkinje system and is associated with a poor prognosis; thus, pacing is indicated.^81,82 Long sinus pauses and AV block can also occur during sleep apnea. In the absence of symptoms, these abnormalities are reversible and do not require pacing.⁸³ If symptoms are present, pacing is indicated as in other conditions.

Recommendations for permanent pacemaker implantation in patients with AV block in AMI, congenital AV block, and AV block associated with enhanced vagal tone are discussed in separate sections. Neurocardiogenic causes in young patients with AV block should be assessed before proceeding with permanent pacing. Physiological AV block in the presence of supraventricular tachyarrhythmias does not constitute an indication for pacemaker implantation except as specifically defined in the recommendations that follow.

In general, the decision regarding implantation of a pacemaker must be considered with respect to whether AV block will be permanent. Reversible causes of AV block, such as electrolyte abnormalities, should be corrected first. Some diseases may follow a natural history to resolution (e.g., Lyme disease), and some AV block can be expected to reverse (e.g., hypervagotonia due to recognizable and avoidable physiological factors, perioperative AV block due to hypothermia, or inflammation near the AV conduction system after surgery in this region). Conversely, some conditions may warrant pacemaker implantation because of the possibility of disease progression even if the AV block reverses transiently (e.g., sarcoidosis, amyloidosis, and neuromuscular diseases). Finally, permanent pacing for AV block after valve surgery follows a variable natural history; therefore, the decision for permanent pacing is at the physician’s discretion.⁸⁴

Recommendations for Acquired Atrioventricular Block in Adults

Class I

1. Permanent pacemaker implantation is indicated for third-degree and advanced second-degree AV block at any anatomic level associated with bradycardia with symptoms (including heart failure) or ventricular arrhythmias presumed to be due to AV block. (Level of Evidence: C)^59,63,76,85
   
2. Permanent pacemaker implantation is indicated for third-degree and advanced second-degree AV block at any anatomic level associated with arrhythmias and other medical conditions that require drug therapy that results in symptomatic bradycardia. (Level of Evidence: C)^59,63,76,85
   
3. Permanent pacemaker implantation is indicated for third-degree and advanced second-degree AV block at any anatomic level in awake, symptom-free patients in sinus rhythm, with documented periods of asystole greater than or equal to 3.0 seconds⁸⁶ or any escape rate less than 40 bpm, or with an escape rhythm that is below the AV node. (Level of Evidence: C)^53,58
   
4. Permanent pacemaker implantation is indicated for third-degree and advanced second-degree AV block at any anatomic level in awake, symptom-free patients with AF and bradycardia with 1 or more pauses of at least 5 seconds or longer. (Level of Evidence: C)
   
5. Permanent pacemaker implantation is indicated for third-degree and advanced second-degree AV block at any anatomic level after catheter ablation of the AV junction. (Level of Evidence: C)^87,88
   
6. Permanent pacemaker implantation is indicated for third-degree and advanced second-degree AV block at any anatomic level associated with postoperative AV block that is not expected to resolve after cardiac surgery. (Level of Evidence: C)^84,85,89,90
   
7. Permanent pacemaker implantation is indicated for third-degree and advanced second-degree AV block at any anatomic level associated with neuromuscular diseases with AV block, such as myotonic muscular dystrophy, Kearns-Sayre syndrome, Erb dystrophy (limb-girdle muscular dystrophy), and peroneal muscular atrophy, with or without symptoms. (Level of Evidence: B)^91–97
   
8. Permanent pacemaker implantation is indicated for second-degree AV block with associated symptomatic bradycardia regardless of type or site of block. (Level of Evidence: B)⁷⁴
   
9. Permanent pacemaker implantation is indicated for asymptomatic persistent third-degree AV block at any anatomic site with average awake ventricular rates of 40 bpm or faster if cardiomegaly or LV dysfunction is present or if the site of block is below the AV node. (Level of Evidence: B)^76,78
   
10. Permanent pacemaker implantation is indicated for second- or third-degree AV block during exercise in the absence of myocardial ischemia. (Level of Evidence: C)^81,82
    

Class IIa

1. Permanent pacemaker implantation is reasonable for persistent third-degree AV block with an escape rate greater than 40 bpm in asymptomatic adult patients without cardiomegaly. (Level of Evidence: C)^{59,63,64,76,82,85}
   
2. Permanent pacemaker implantation is reasonable for asymptomatic second-degree AV block at intra- or infra-His levels found at electrophysiological study. (Level of Evidence: B)^74,76,78
   
3. Permanent pacemaker implantation is reasonable for first- or second-degree AV block with symptoms similar to those of pacemaker syndrome or hemodynamic compromise. (Level of Evidence: B)^70,71
   
4. Permanent pacemaker implantation is reasonable for asymptomatic type II second-degree AV block with a narrow QRS. When type II second-degree AV block occurs with a wide QRS, including isolated right bundle-branch block, pacing becomes a Class I recommendation. (See Section 2.1.3, "Chronic Bifascicular Block.") (Level of Evidence: B)^70,76,80,85
   

Class IIb

1. Permanent pacemaker implantation may be considered for neuromuscular diseases such as myotonic muscular dystrophy, Erb dystrophy (limb-girdle muscular dystrophy), and peroneal muscular atrophy with any degree of AV block (including first-degree AV block), with or without symptoms, because there may be unpredictable progression of AV conduction disease. (Level of Evidence: B)^91–97
   
2. Permanent pacemaker implantation may be considered for AV block in the setting of drug use and/or drug toxicity when the block is expected to recur even after the drug is withdrawn. (Level of Evidence: B)^98,99
   

Class III

1. Permanent pacemaker implantation is not indicated for asymptomatic first-degree AV block. (Level of Evidence: B)⁶⁹ (See Section 2.1.3, "Chronic Bifascicular Block.")
   
2. Permanent pacemaker implantation is not indicated for asymptomatic type I second-degree AV block at the supra-His (AV node) level or that which is not known to be intra- or infra-Hisian. (Level of Evidence: C)⁷⁴
   
3. Permanent pacemaker implantation is not indicated for AV block that is expected to resolve and is unlikely to recur¹⁰⁰ (e.g., drug toxicity, Lyme disease, or transient increases in vagal tone or during hypoxia in sleep apnea syndrome in the absence of symptoms). (Level of Evidence: B)^99,100
   

2.1.3. Chronic Bifascicular Block
Bifascicular block refers to ECG evidence of impaired conduction below the AV node in the right and left bundles. Alternating bundle-branch block (also known as bilateral bundle-branch block) refers to situations in which clear ECG evidence for block in all 3 fascicles is manifested on successive ECGs. Examples are right bundle-branch block and left bundle-branch block on successive ECGs or right bundle-branch block with associated left anterior fascicular block on 1 ECG and associated left posterior fascicular block on another ECG. Patients with first-degree AV block in association with bifascicular block and symptomatic, advanced AV block have a high mortality rate and a substantial incidence of sudden death.^64,101 Although third-degree AV block is most often preceded by bifascicular block, there is evidence that the rate of progression of bifascicular block to third-degree AV block is slow.¹⁰² Furthermore, no single clinical or laboratory variable, including bifascicular block, identifies patients at high risk of death due to a future bradyarrhythmia caused by bundle-branch block.¹⁰³

Syncope is common in patients with bifascicular block. Although syncope may be recurrent, it is not associated with an increased incidence of sudden death.^73,102–112 Even though pacing relieves the neurological symptoms, it does not reduce the occurrence of sudden death.¹⁰⁸ An electrophysiological study may be helpful to evaluate and direct the treatment of inducible ventricular arrhythmias^113,114 that are common in patients with bifascicular block. There is convincing evidence that in the presence of permanent or transient third-degree AV block, syncope is associated with an increased incidence of sudden death regardless of the results of the electrophysiological study.^64,114,115 Finally, if the cause of syncope in the presence of bifascicular block cannot be determined with certainty, or if treatments used (such as drugs) may exacerbate AV block, prophylactic permanent pacing is indicated, especially if syncope may have been due to transient third-degree AV block.^{102–112,116}

Of the many laboratory variables, the PR and HV intervals have been identified as possible predictors of third-degree AV block and sudden death. Although PR-interval prolongation is common in patients with bifascicular block, the delay is often at the level of the AV node. There is no correlation between the PR and HV intervals or between the length of the PR interval, progression to third-degree AV block, and sudden death.^107,109,116 Although most patients with chronic or intermittent third-degree AV block demonstrate prolongation of the HV interval during anterograde conduction, some investigators^110,111 have suggested that asymptomatic patients with bifascicular block and a prolonged HV interval should be considered for permanent pacing, especially if the HV interval is greater than or equal to 100 milliseconds.¹⁰⁹ Although the prevalence of HV-interval prolongation is high, the incidence of progression to third-degree AV block is low. Because HV prolongation accompanies advanced cardiac disease and is associated with increased mortality, death is often not sudden or due to AV block but rather is due to the underlying heart disease itself and nonarrhythmic cardiac causes.^{102,103,108,109,111,114–117}

Atrial pacing at electrophysiological study in asymptomatic patients as a means of identifying patients at increased risk of future high- or third-degree AV block is controversial. The probability of inducing block distal to the AV node (i.e., intra- or infra-His) with rapid atrial pacing is low.^{102,110,111,118–121} Failure to induce distal block cannot be taken as evidence that the patient will not develop third-degree AV block in the future. However, if atrial pacing induces nonphysiological infra-His block, some consider this an indication for pacing.¹¹⁸ Nevertheless, infra-His block that occurs during either rapid atrial pacing or programmed stimulation at short coupling intervals may be physiological and not pathological, simply reflecting disparity between refractoriness of the AV node and His-Purkinje systems.¹²²

Recommendations for Permanent Pacing in Chronic Bifascicular Block

Class I

1. Permanent pacemaker implantation is indicated for advanced second-degree AV block or intermittent third-degree AV block. (Level of Evidence: B)^63–68,101
   
2. Permanent pacemaker implantation is indicated for type II second-degree AV block. (Level of Evidence: B)^73,75,79,123
   
3. Permanent pacemaker implantation is indicated for alternating bundle-branch block. (Level of Evidence: C)¹²⁴
   

Class IIa

1. Permanent pacemaker implantation is reasonable for syncope not demonstrated to be due to AV block when other likely causes have been excluded, specifically ventricular tachycardia (VT). (Level of Evidence: B)^{102–111,113–119,123,125}
   
2. Permanent pacemaker implantation is reasonable for an incidental finding at electrophysiological study of a markedly prolonged HV interval (greater than or equal to 100 milliseconds) in asymptomatic patients. (Level of Evidence: B)¹⁰⁹
   
3. Permanent pacemaker implantation is reasonable for an incidental finding at electrophysiological study of pacing-induced infra-His block that is not physiological. (Level of Evidence: B)¹¹⁸
   

Class IIb

1. Permanent pacemaker implantation may be considered in the setting of neuromuscular diseases such as myotonic muscular dystrophy, Erb dystrophy (limb-girdle muscular dystrophy), and peroneal muscular atrophy with bifascicular block or any fascicular block, with or without symptoms. (Level of Evidence: C)^91–97
   

Class III

1. Permanent pacemaker implantation is not indicated for fascicular block without AV block or symptoms. (Level of Evidence: B)^{103,107,109,116}
   
2. Permanent pacemaker implantation is not indicated for fascicular block with first-degree AV block without symptoms. (Level of Evidence: B)^{103,107,109,116}
   

2.1.4. Pacing for Atrioventricular Block Associated With Acute Myocardial Infarction
Indications for permanent pacing after myocardial infarction (MI) in patients experiencing AV block are related in large measure to the presence of intraventricular conduction defects. The criteria for patients with MI and AV block do not necessarily depend on the presence of symptoms. Furthermore, the requirement for temporary pacing in AMI does not by itself constitute an indication for permanent pacing (see "ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction."⁶) The long-term prognosis for survivors of AMI who have had AV block is related primarily to the extent of myocardial injury and the character of intraventricular conduction disturbances rather than the AV block itself.^66,126–130 Patients with AMI who have intraventricular conduction defects, with the exception of isolated left anterior fascicular block, have an unfavorable short- and long-term prognosis and an increased risk of sudden death.^{66,79,126,128,130} This unfavorable prognosis is not necessarily due to development of high-grade AV block, although the incidence of such block is higher in postinfarction patients with abnormal intraventricular conduction.^126,131,132

When AV or intraventricular conduction block complicates AMI, the type of conduction disturbance, location of infarction, and relation of electrical disturbance to infarction must be considered if permanent pacing is contemplated. Even with data available, the decision is not always straightforward, because the reported incidence and significance of various conduction disturbances vary widely.¹³³ Despite the use of thrombolytic therapy and primary angioplasty, which have decreased the incidence of AV block in AMI, mortality remains high if AV block occurs.^{130,134–137}

Although more severe disturbances in conduction have generally been associated with greater arrhythmic and nonarrhythmic mortality,^{126–129,131,133} the impact of preexisting bundle-branch block on mortality after AMI is controversial.^112,133 A particularly ominous prognosis is associated with left bundle-branch block combined with advanced second- or third-degree AV block and with right bundle-branch block combined with left anterior or left posterior fascicular block.^{105,112,127,129} Regardless of whether the infarction is anterior or inferior, the development of an intraventricular conduction delay reflects extensive myocardial damage rather than an electrical problem in isolation.¹²⁹ Although AV block that occurs during inferior MI can be associated with a favorable long-term clinical outcome, in-hospital survival is impaired irrespective of temporary or permanent pacing in this situation.^{134,135,138,139} Pacemakers generally should not be implanted with inferior MI if the peri-infarctional AV block is expected to resolve or is not expected to negatively affect long-term prognosis.¹³⁶ When symptomatic high-degree or third-degree heart block complicates inferior MI, even when the QRS is narrow, permanent pacing may be considered if the block does not resolve. For the patient with recent MI with a left ventricular ejection fraction (LVEF) less than or equal to 35% and an indication for permanent pacing, consideration may be given to use of an ICD, a CRT device that provides pacing but not defibrillation capability (CRT-P), or a CRT device that incorporates both pacing and defibrillation capabilities (CRT-D) when improvement in LVEF is not anticipated.

Recommendations for Permanent Pacing After the Acute Phase of Myocardial Infarction^*

Class I

1. Permanent ventricular pacing is indicated for persistent second-degree AV block in the His-Purkinje system with alternating bundle-branch block or third-degree AV block within or below the His-Purkinje system after ST-segment elevation MI. (Level of Evidence: B)^{79,126–129,131}
   
2. Permanent ventricular pacing is indicated for transient advanced second- or third-degree infranodal AV block and associated bundle-branch block. If the site of block is uncertain, an electrophysiological study may be necessary. (Level of Evidence: B)^126,127
   
3. Permanent ventricular pacing is indicated for persistent and symptomatic second- or third-degree AV block. (Level of Evidence: C)
   

Class IIb

1. Permanent ventricular pacing may be considered for persistent second- or third-degree AV block at the AV node level, even in the absence of symptoms. (Level of Evidence: B)⁵⁸
   

Class III

1. Permanent ventricular pacing is not indicated for transient AV block in the absence of intraventricular conduction defects. (Level of Evidence: B)¹²⁶
   
2. Permanent ventricular pacing is not indicated for transient AV block in the presence of isolated left anterior fascicular block. (Level of Evidence: B)¹²⁸
   
3. Permanent ventricular pacing is not indicated for new bundle-branch block or fascicular block in the absence of AV block. (Level of Evidence: B)^66,126
   
4. Permanent ventricular pacing is not indicated for persistent asymptomatic first-degree AV block in the presence of bundle-branch or fascicular block. (Level of Evidence: B)¹²⁶
   

2.1.5. Hypersensitive Carotid Sinus Syndrome and Neurocardiogenic Syncope
The hypersensitive carotid sinus syndrome is defined as syncope or presyncope resulting from an extreme reflex response to carotid sinus stimulation. There are 2 components of the reflex:

Cardioinhibitory, which results from increased parasympathetic tone and is manifested by slowing of the sinus rate or prolongation of the PR interval and advanced AV block, alone or in combination.

Vasodepressor, which is secondary to a reduction in sympathetic activity that results in loss of vascular tone and hypotension. This effect is independent of heart rate changes.

Before concluding that permanent pacing is clinically indicated, the physician should determine the relative contribution of the 2 components of carotid sinus stimulation to the individual patient’s symptom complex. Hyperactive response to carotid sinus stimulation is defined as asystole due to either sinus arrest or AV block of more than 3 seconds, a substantial symptomatic decrease in systolic blood pressure, or both.¹⁴⁰ Pauses up to 3 seconds during carotid sinus massage are considered to be within normal limits. Such heart rate and hemodynamic responses may occur in normal subjects and patients with coronary artery disease. The cause-and-effect relation between the hypersensitive carotid sinus and the patient’s symptoms must be drawn with great caution.¹⁴¹ Spontaneous syncope reproduced by carotid sinus stimulation should alert the physician to the presence of this syndrome. Minimal pressure on the carotid sinus in elderly patients may result in marked changes in heart rate and blood pressure yet may not be of clinical significance. Permanent pacing for patients with an excessive cardioinhibitory response to carotid stimulation is effective in relieving symptoms.^142,143 Because 10% to 20% of patients with this syndrome may have an important vasodepressive component of their reflex response, it is desirable that this component be defined before one concludes that all symptoms are related to asystole alone. Among patients whose reflex response includes both cardioinhibitory and vasodepressive components, attention to the latter is essential for effective therapy in patients undergoing pacing.

Carotid sinus hypersensitivity should be considered in elderly patients who have had otherwise unexplained falls. In 1 study, 175 elderly patients who had fallen without loss of consciousness and who had pauses of more than 3 seconds during carotid sinus massage (thus fulfilling the diagnosis of carotid sinus hypersensitivity) were randomized to pacing or nonpacing therapy. The paced group had a significantly lower likelihood of subsequent falling episodes during follow-up.¹⁴⁴

Neurocardiogenic syncope and neurocardiogenic syndromes refer to a variety of clinical scenarios in which triggering of a neural reflex results in a usually self-limited episode of systemic hypotension characterized by both bradycardia and peripheral vasodilation.^145,146 Neurocardiogenic syncope accounts for an estimated 10% to 40% of syncope episodes. Vasovagal syncope is a term used to denote one of the most common clinical scenarios within the category of neurocardiogenic syncopal syndromes. Patients classically have a prodrome of nausea and diaphoresis (often absent in the elderly), and there may be a positive family history of the condition. Spells may be considered situational (e.g., they may be triggered by pain, anxiety, stress, specific bodily functions, or crowded conditions). Typically, no evidence of structural heart disease is present. Other causes of syncope such as LV outflow obstruction, bradyarrhythmias, and tachyarrhythmias should be excluded. Head-up tilt-table testing may be diagnostic.

The role of permanent pacing in refractory neurocardiogenic syncope associated with significant bradycardia or asystole remains controversial. Approximately 25% of patients have a predominant vasodepressor reaction without significant bradycardia. Many patients will have a mixed vasodepressive/cardioinhibitory cause of their symptoms. It has been estimated that approximately one third of patients will have substantial bradycardia or asystole during head-up tilt testing or during observed and recorded spontaneous episodes of syncope. Outcomes from clinical trials have not been consistent. Results from a randomized controlled trial¹⁴⁷ in highly symptomatic patients with bradycardia demonstrated that permanent pacing increased the time to the first syncopal event. Another study demonstrated that DDD (a dual-chamber pacemaker that senses/paces in the atrium/ventricle and is inhibited/triggered by intrinsic rhythm) pacing with a sudden bradycardia response function was more effective than beta blockade in preventing recurrent syncope in highly symptomatic patients with vasovagal syncope and relative bradycardia during tilt-table testing.¹⁴⁸ In VPS (Vasovagal Pacemaker Study),¹⁴⁹ the actuarial rate of recurrent syncope at 1 year was 18.5% for pacemaker patients and 59.7% for control patients. However, in VPS-II (Vasovagal Pacemaker Study II),¹⁵⁰ a double-blind randomized trial, pacing therapy did not reduce the risk of recurrent syncopal events. In VPS-II, all patients received a permanent pacemaker and were randomized to therapy versus no therapy in contrast to VPS, in which patients were randomized to pacemaker implantation versus no pacemaker. On the basis of VPS-II and prevailing expert opinion,