Advertisement

2018 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay

A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society
Published:November 06, 2018DOI:https://doi.org/10.1016/j.hrthm.2018.10.037
      Glenn N. Levine, MD, FACC, FAHA, Chair

      KeyWords

      To read this article in full you will need to make a payment
      Subscribe to Heart Rhythm
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. Introduction

        • Slotwiner D.J.
        • Raitt M.H.
        • Del-Carpio Munoz F.
        • et al.
        Impact of physiologic versus right ventricular pacing among patients with left ventricular ejection fraction greater than 35%: a systematic review for the 2018 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidleines and the Heart Rhythm Society.
        Heart Rhythm. 2019; (In press)
        • Epstein A.E.
        • DiMarco J.P.
        • Ellenbogen K.A.
        • et al.
        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.
        J Am Coll Cardiol. 2008; 51: e1-e62
        • Epstein A.E.
        • DiMarco J.P.
        • Ellenbogen K.A.
        • et al.
        2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
        J Am Coll Cardiol. 2013; 61: e6-e75
        • Al-Khatib S.M.
        • Stevenson W.G.
        • Ackerman M.J.
        • et al.
        2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.
        J Am Coll Cardiol. 2018; 72: e91-e220
        • Shen W.K.
        • Sheldon R.S.
        • Benditt D.G.
        • et al.
        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.
        J Am Coll Cardiol. 2017; 70: e39-e110
        • Fihn S.D.
        • Blankenship J.C.
        • Alexander K.P.
        • et al.
        2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
        J Am Coll Cardiol. 2014; 64: 1929-1949
        • Fihn S.D.
        • Gardin J.M.
        • Abrams J.
        • et al.
        2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
        J Am Coll Cardiol. 2012; 60: e44-e164
        • January CT
        • Wann L.S.
        • Alpert J.S.
        • et al.
        2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
        J Am Coll Cardiol. 2014; 64: e1-e76
        • Fleisher LA
        • Fleischmann K.E.
        • Auerbach A.D.
        • et al.
        2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines.
        J Am Coll Cardiol. 2014; 64: e77-e137
        • Amsterdam EA
        • Wenger N.K.
        • Brindis R.G.
        • et al.
        2014 AHA/ACC guideline for the management of patients with non—ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
        J Am Coll Cardiol. 2014; 64: e139-e228
        • Yancy C.W.
        • Jessup M.
        • Bozkurt B.
        • et al.
        2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
        J Am Coll Cardiol. 2013; 62: e147-e239
        • O’Gara P.T.
        • Kushner F.G.
        • Ascheim D.D.
        • et al.
        2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
        J Am Coll Cardiol. 2013; 61: e78-e140
        • Hillis L.D.
        • Smith P.K.
        • Anderson J.L.
        • et al.
        2011 ACCF/AHA guideline for coronary artery bypass graft surgery. a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons.
        J Am Coll Cardiol. 2011; 58: e123-e210
        • Gersh B.J.
        • Maron B.J.
        • Bonow R.O.
        • et al.
        2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
        J Am Coll Cardiol. 2011; 58: e212-e260
        • Levine GN
        • Bates E.R.
        • Blankenship J.C.
        • et al.
        2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions.
        J Am Coll Cardiol. 2011; 58: e44-e122
        • Peberdy M.A.
        • Callaway C.W.
        • Neumar R.W.
        • et al.
        Part 9: post-cardiac arrest care: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care.
        Circulation. 2010; 122: S768-S786
        • Kusumoto FM
        • Schoenfeld M.H.
        • Wilkoff B.L.
        • et al.
        2017 HRS expert consensus statement on cardiovascular implantable electronic device lead management and extraction.
        Heart Rhythm. 2017; 14: e503-e551
        • Feingold B.
        • Mahle W.T.
        • Auerbach S.
        • et al.
        Management of cardiac involvement associated with neuromuscular diseases: a scientific statement from the American Heart Association.
        Circulation. 2017; 136: e200-e231
        • Indik J.H.
        • Gimbel J.R.
        • Abe H.
        • et al.
        2017 HRS expert consensus statement on magnetic resonance imaging and radiation exposure in patients with cardiovascular implantable electronic devices.
        Heart Rhythm. 2017; 14: e97-e153
        • Zipes D.P.
        • Link M.S.
        • Ackerman M.J.
        • et al.
        Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task Force 9: arrhythmias and conduction defects: a scientific statement from the American Heart Association and American College of Cardiology.
        J Am Coll Cardiol. 2015; 66: 2412-2423
        • Sheldon R.S.
        • Grubb 2nd, B.P.
        • Olshansky B.
        • et al.
        2015 Heart Rhythm Society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope.
        Heart Rhythm. 2015; 12: e41-e63
        • Khairy P
        • Van Hare G.F.
        • Balaji S.
        • et al.
        PACES/HRS expert consensus statement on the recognition and management of arrhythmias in adult congenital heart disease. Developed in partnership between the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS).
        Heart Rhythm. 2014; 11: e102-e165
        • Kusumoto F.M.
        • Calkins H.
        • Boehmer J.
        • et al.
        HRS/ACC/AHA expert consensus statement on the use of implantable cardioverter-defibrillator therapy in patients who are not included or not well represented in clinical trials.
        J Am Coll Cardiol. 2014; 64: 1143-1177
        • Birnie D.H.
        • Sauer W.H.
        • Bogun F.
        • et al.
        HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis.
        Heart Rhythm. 2014; 11: 1305-1323
        • Brignole M.
        • Auricchio A.
        • Baron-Esquivias G.
        • et al.
        2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on Cardiac Pacing and Resynchronization Therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA).
        Eur Heart J. 2013; 34: 2281-2329
        • Gillis A.M.
        • Russo A.M.
        • Ellenbogen K.A.
        • et al.
        HRS/ACCF expert consensus statement on pacemaker device and mode selection.
        J Am Coll Cardiol. 2012; 60: 682-703
        • Ackerman M.J.
        • Priori S.G.
        • Willems S.
        • et al.
        HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA).
        Heart Rhythm. 2011; 8: 1308-1339
        • Lampert R
        • Hayes D.L.
        • Annas G.J.
        • et al.
        HRS expert consensus statement on the management of cardiovascular implantable electronic devices (CIEDs) in patients nearing end of life or requesting withdrawal of therapy.
        Heart Rhythm. 2010; 7: 1008-1026
        • Surawicz B.
        • Childers R.
        • Deal B.J.
        • et al.
        AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part III: intraventricular conduction disturbances: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society.
        Circulation. 2009; 119: e235-e240
        • Hancock E.W.
        • Deal B.J.
        • Mirvis D.M.
        • et al.
        AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part V: electrocardiogram changes associated with cardiac chamber hypertrophy: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society.
        Circulation. 2009; 119: e251-e261
        • Halperin J.L.
        • Levine G.N.
        • Al-Khatib S.M.
        • et al.
        Further evolution of the ACC/AHA clinical practice guideline recommendation classification system: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
        J Am Coll Cardiol. 2016; 67: 1572-1574

      2. Epidemiology and Definitions

        • Lev M.
        Aging changes in the human sinoatrial node.
        J Gerontol. 1954; 9: 1-9
        • Evans R.
        • Shaw D.B.
        Pathological studies in sinoatrial disorder (sick sinus syndrome).
        Br Heart J. 1977; 39: 778-786
        • Ferrer M.I.
        The sick sinus syndrome in atrial disease.
        JAMA. 1968; 206: 645-646
        • Rosenqvist M.
        • Obel I.W.
        Atrial pacing and the risk for AV block: is there a time for change in attitude?.
        Pacing Clin Electrophysiol. 1989; 12: 97-101
        • Baine WB
        • Yu W.
        • Weis K.A.
        Trends and outcomes in the hospitalization of older Americans for cardiac conduction disorders or arrhythmias, 1991-1998.
        J Am Geriatr Soc. 2001; 49: 763-770
        • Jensen P.N.
        • Gronroos N.N.
        • Chen L.Y.
        • et al.
        Incidence of and risk factors for sick sinus syndrome in the general population.
        J Am Coll Cardiol. 2014; 64: 531-538
        • Daley WR
        • Kaczmarek R.G.
        The epidemiology of cardiac pacemakers in the older US population.
        J Am Geriatr Soc. 1998; 46: 1016-1019
        • Demoulin JC
        • Kulbertus H.E.
        Histopathological correlates of sinoatrial disease.
        Br Heart J. 1978; 40: 1384-1389
        • Rasmussen K.
        Chronic sinus node disease: natural course and indications for pacing.
        Eur Heart J. 1981; 2: 455-459
        • Shaw D.B.
        • Linker N.J.
        • Heaver P.A.
        • et al.
        Chronic sinoatrial disorder (sick sinus syndrome): a possible result of cardiac ischaemia.
        Br Heart J. 1987; 58: 598-607
      1. National Institutes of Health. Pulse.
        (Available at:)
        https://medlineplus.gov/ency/article/003399.htm
        Date accessed: December 18, 2017
        • Jensen P.N.
        • Gronroos N.N.
        • Chen L.Y.
        • et al.
        Incidence of and risk factors for sick sinus syndrome in the general population.
        J Am Coll Cardiol. 2014; 64: 531-538
        • Rijnbeek P.R.
        • van Herpen G.
        • Bots M.L.
        • et al.
        Normal values of the electrocardiogram for ages 16-90 years.
        J Electrocardiol. 2014; 47: 914-921
        • Fleg J.L.
        • Kennedy H.L.
        Cardiac arrhythmias in a healthy elderly population: detection by 24-hour ambulatory electrocardiography.
        Chest. 1982; 81: 302-307
        • Talan DA
        • Bauernfeind R.A.
        • Ashley W.W.
        • et al.
        Twenty-four hour continuous ECG recordings in long-distance runners.
        Chest. 1982; 82: 19-24
        • Page R.L.
        • Joglar J.A.
        • Caldwell M.A.
        • et al.
        2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.
        Circulation. 2016; 133: e506-e574
        • Surawicz B.
        • Childers R.
        • Deal B.J.
        • et al.
        AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part III: intraventricular conduction disturbances: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society.
        Circulation. 2009; 119: e235-e240
        • Tanaka H.
        • Monahan K.D.
        • Seals D.R.
        Age-predicted maximal heart rate revisited.
        J Am Coll Cardiol. 2001; 37: 153-156
        • Ahmed H.M.
        • Al-Mallah M.H.
        • Keteyian S.J.
        • et al.
        Sex-specific maximum predicted heart rate and its prognosis for mortality and myocardial infarction.
        Med Sci Sports Exerc. 2017; 49: 1704-1710
        • Jin L.
        • Min G.
        • Wei C.
        • et al.
        Exercise training on chronotropic response and exercise capacity in patients with type 2 diabetes mellitus.
        Exp Ther Med. 2017; 13: 899-904
        • Kusumoto F.M.
        • Goldschlager N.
        Cardiac pacing.
        N Engl J Med. 1996; 334: 89-97
        • Hancock E.W.
        • Deal B.J.
        • Mirvis D.M.
        • et al.
        AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part V: electrocardiogram changes associated with cardiac chamber hypertrophy: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society.
        Circulation. 2009; 119: e251-e261
        • Galeotti L.
        • van Dam P.M.
        • Loring Z.
        • et al.
        Evaluating strict and conventional left bundle branch block criteria using electrocardiographic simulations.
        Europace. 2013; 15: 1816-1821

      3. Clinical Manifestation of Bradycardia and Conduction Disorders

        • Brubaker P.H.
        • Kitzman D.W.
        Chronotropic incompetence: causes, consequences, and management.
        Circulation. 2011; 123: 1010-1020
        • Barold S.S.
        • Hayes D.L.
        Second-degree atrioventricular block: a reappraisal.
        Mayo Clin Proc. 2001; 76: 44-57
        • Epstein A.E.
        • DiMarco J.P.
        • Ellenbogen K.A.
        • et al.
        2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
        J Am Coll Cardiol. 2013; 61: e6-e75
        • Goldschlager N
        Underlying assumptions in evaluating "symptomatic bradycardia" (or, are we asking the right questions?).
        Pacing Clin Electrophysiol. 1988; 11: 1105-1107
        • Surawicz B.
        • Childers R.
        • Deal B.J.
        • et al.
        AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part III: intraventricular conduction disturbances: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society.
        Circulation. 2009; 119: e235-e240
        • Galeotti L.
        • van Dam P.M.
        • Loring Z.
        • et al.
        Evaluating strict and conventional left bundle branch block criteria using electrocardiographic simulations.
        Europace. 2013; 15: 1816-1821

      4. General Evaluation of Patients With Documented or Suspected Bradycardia or Conduction Disorders

        • Al-Khatib S.M.
        • Stevenson W.G.
        • Ackerman M.J.
        • et al.
        2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.
        J Am Coll Cardiol. 2018; 72: e91-e220
        • Shen W.K.
        • Sheldon R.S.
        • Benditt D.G.
        • et al.
        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.
        J Am Coll Cardiol. 2017; 70: e39-e110
        • Mangrum J.M.
        • DiMarco J.P.
        The evaluation and management of bradycardia.
        N Engl J Med. 2000; 342: 703-709
        • Vogler J
        • Breithardt G.
        • Eckardt L.
        Bradyarrhythmias and conduction blocks.
        Rev Esp Cardiol (Engl Ed). 2012; 65: 656-667
        • Munro N.C.
        • McIntosh S.
        • Lawson J.
        • et al.
        Incidence of complications after carotid sinus massage in older patients with syncope.
        J Am Geriatr Soc. 1994; 42: 1248-1251
        • Del Rosso A.
        • Ungar A.
        • Maggi R.
        • et al.
        Clinical predictors of cardiac syncope at initial evaluation in patients referred urgently to a general hospital: the EGSYS score.
        Heart. 2008; 94: 1620-1626
        • Linzer M.
        • Yang E.H.
        • Estes 3rd, N.A.
        • et al.
        Diagnosing syncope. Part 1: Value of history, physical examination, and electrocardiography. Clinical Efficacy Assessment Project of the American College of Physicians.
        Ann Intern Med. 1997; 126: 989-996
        • Perez-Rodon J.
        • Martinez-Alday J.
        • Baron-Esquivias G.
        • et al.
        Prognostic value of the electrocardiogram in patients with syncope: data from the group for syncope study in the emergency room (GESINUR).
        Heart Rhythm. 2014; 11: 2035-2044
        • Thiruganasambandamoorthy V.
        • Hess E.P.
        • Turko E.
        • et al.
        Defining abnormal electrocardiography in adult emergency department syncope patients: the Ottawa Electrocardiographic Criteria.
        CJEM. 2012; 14: 248-258
        • Shen W.K.
        • Sheldon R.S.
        • Benditt D.G.
        • et al.
        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.
        J Am Coll Cardiol. 2017; 70: e39-e110
        • Lauer M.S.
        • Francis G.S.
        • Okin P.M.
        • et al.
        Impaired chronotropic response to exercise stress testing as a predictor of mortality.
        JAMA. 1999; 281: 524-529
        • Savonen KP
        • Kiviniemi V.
        • Laukkanen J.A.
        • et al.
        Chronotropic incompetence and mortality in middle-aged men with known or suspected coronary heart disease.
        Eur Heart J. 2008; 29: 1896-1902
        • Doi A.
        • Tsuchihashi K.
        • Kyuma M.
        • et al.
        Diagnostic implications of modified treadmill and head-up tilt tests in exercise-related syncope: comparative studies with situational and/or vasovagal syncope.
        Can J Cardiol. 2002; 18: 960-966
        • Woelfel AK
        • Simpson Jr., R.J.
        • Gettes L.S.
        • et al.
        Exercise-induced distal atrioventricular block.
        J Am Coll Cardiol. 1983; 2: 578-581
        • Issa ZF
        Atrioventricular conduction abnormalities.
        in: Miller J.M. Zipes D.P. Clinical Arrhythmology and Electrophysiology: A Companion to Braunwald’s Heart Disease. 2nd ed. Elsevier/Saunders, Philadelphia, PA2012: 175-193
        • Brubaker P.H.
        • Kitzman D.W.
        Chronotropic incompetence: causes, consequences, and management.
        Circulation. 2011; 123: 1010-1020
        • Dresing TJ
        • Blackstone E.H.
        • Pashkow F.J.
        • et al.
        Usefulness of impaired chronotropic response to exercise as a predictor of mortality, independent of the severity of coronary artery disease.
        Am J Cardiol. 2000; 86: 602-609
        • Bakst A
        • Goldberg B.
        • Schamroth L.
        Significance of exercise-induced second degree atrioventricular block.
        Br Heart J. 1975; 37: 984-986
        • Bharati S
        • Dhingra R.C.
        • Lev M.
        • et al.
        Conduction system in a patient with Prinzmetal’s angina and transient atrioventricular block.
        Am J Cardiol. 1977; 39: 120-125
        • Bobba P.
        • Salerno J.A.
        • Casari A.
        Transient left posterior hemiblock. Report of four cases induced by exercise test.
        Circulation. 1972; 46: 931-938
        • Boran K.J.
        • Oliveros R.A.
        • Boucher C.A.
        • et al.
        Ischemia-associated intraventricular conduction disturbances during exercise testing as a predictor of proximal left anterior descending coronary artery disease.
        Am J Cardiol. 1983; 51: 1098-1102
        • Coplan N.L.
        • Morales M.C.
        • Romanello P.
        • et al.
        Exercise-related atrioventricular block. Influence of myocardial ischemia.
        Chest. 1991; 100: 1728-1730
        • Oliveros R.A.
        • Seaworth J.
        • Weiland F.L.
        • et al.
        Intermittent left anterior hemiblock during treadmill exercise test. Correlation with coronary arteriogram.
        Chest. 1977; 72: 492-494
        • AlJaroudi WA
        • Alraies M.C.
        • Wazni O.
        • et al.
        Yield and diagnostic value of stress myocardial perfusion imaging in patients without known coronary artery disease presenting with syncope.
        Circ Cardiovasc Imaging. 2013; 6: 384-391
        • Barrett P.M.
        • Komatireddy R.
        • Haaser S.
        • et al.
        Comparison of 24-hour Holter monitoring with 14-day novel adhesive patch electrocardiographic monitoring.
        Am J Med. 2014; 127: 95.e11-95.e17
        • Brown A.P.
        • Dawkins K.D.
        • Davies J.G.
        Detection of arrhythmias: use of a patient-activated ambulatory electrocardiogram device with a solid-state memory loop.
        Br Heart J. 1987; 58: 251-253
        • Cumbee S.R.
        • Pryor R.E.
        • Linzer M.
        Cardiac loop ECG recording: a new noninvasive diagnostic test in recurrent syncope.
        South Med J. 1990; 83: 39-43
        • Gibson T.C.
        • Heitzman M.R.
        Diagnostic efficacy of 24-hour electrocardiographic monitoring for syncope.
        Am J Cardiol. 1984; 53: 1013-1017
        • Joshi A.K.
        • Kowey P.R.
        • Prystowsky E.N.
        • et al.
        First experience with a Mobile Cardiac Outpatient Telemetry (MCOT) system for the diagnosis and management of cardiac arrhythmia.
        Am J Cardiol. 2005; 95: 878-881
        • Linzer M.
        • Yang E.H.
        • Estes 3rd, N.A.
        • et al.
        Diagnosing syncope. Part 2: unexplained syncope. Clinical Efficacy Assessment Project of the American College of Physicians.
        Ann Intern Med. 1997; 127: 76-86
        • Locati ET
        • Moya A.
        • Oliveira M.
        • et al.
        External prolonged electrocardiogram monitoring in unexplained syncope and palpitations: results of the SYNARR-Flash study.
        Europace. 2016; 18: 1265-1272
        • Reiffel JA
        • Schwarzberg R.
        • Murry M.
        Comparison of autotriggered memory loop recorders versus standard loop recorders versus 24-hour Holter monitors for arrhythmia detection.
        Am J Cardiol. 2005; 95: 1055-1059
        • Rosenberg M.A.
        • Samuel M.
        • Thosani A.
        • et al.
        Use of a noninvasive continuous monitoring device in the management of atrial fibrillation: a pilot study.
        Pacing Clin Electrophysiol. 2013; 36: 328-333
        • Rothman S.A.
        • Laughlin J.C.
        • Seltzer J.
        • et al.
        The diagnosis of cardiac arrhythmias: a prospective multi-center randomized study comparing mobile cardiac outpatient telemetry versus standard loop event monitoring.
        J Cardiovasc Electrophysiol. 2007; 18: 241-247
        • Sivakumaran S
        • Krahn A.D.
        • Klein G.J.
        • et al.
        A prospective randomized comparison of loop recorders versus Holter monitors in patients with syncope or presyncope.
        Am J Med. 2003; 115: 1-5
        • Turakhia M.P.
        • Hoang D.D.
        • Zimetbaum P.
        • et al.
        Diagnostic utility of a novel leadless arrhythmia monitoring device.
        Am J Cardiol. 2013; 112: 520-524
        • Crawford M.H.
        • Bernstein S.J.
        • Deedwania P.C.
        • et al.
        ACC/AHA guidelines for ambulatory electrocardiography: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the Guidelines for Ambulatory Electrocardiography). Developed in collaboration with the North American Society for Pacing and Electrophysiology.
        J Am Coll Cardiol. 1999; 34: 912-948
        • Steinberg J.S.
        • Varma N.
        • Cygankiewicz I.
        • et al.
        2017 ISHNE-HRS expert consensus statement on ambulatory ECG and external cardiac monitoring/telemetry.
        Heart Rhythm. 2017; 14: e55-e96
        • Bass E.B.
        • Curtiss E.I.
        • Arena V.C.
        • et al.
        The duration of Holter monitoring in patients with syncope. Is 24 hours enough?.
        Arch Intern Med. 1990; 150: 1073-1078
        • Zeldis S.M.
        • Levine B.J.
        • Michelson E.L.
        • et al.
        Cardiovascular complaints. Correlation with cardiac arrhythmias on 24-hour electrocardiographic monitoring.
        Chest. 1980; 78: 456-461
        • Linzer M
        • Pritchett E.L.
        • Pontinen M.
        • et al.
        Incremental diagnostic yield of loop electrocardiographic recorders in unexplained syncope.
        Am J Cardiol. 1990; 66: 214-219
        • Subbiah R
        • Chia P.L.
        • Gula L.J.
        • et al.
        Cardiac monitoring in patients with syncope: making that elusive diagnosis.
        Curr Cardiol Rev. 2013; 9: 299-307
        • Shen W.K.
        • Sheldon R.S.
        • Benditt D.G.
        • et al.
        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.
        J Am Coll Cardiol. 2017; 70: e39-e110
        • Brignole M
        • Vardas P.
        • Hoffman E.
        • et al.
        Indications for the use of diagnostic implantable and external ECG loop recorders.
        Europace. 2009; 11: 671-687
        • Schneider J.F.
        • Thomas Jr., H.E.
        • Kreger B.E.
        • et al.
        Newly acquired left bundle-branch block: the Framingham study.
        Ann Intern Med. 1979; 90: 303-310
        • Schneider J.F.
        • Thomas Jr., H.E.
        • Sorlie P.
        • et al.
        Comparative features of newly acquired left and right bundle branch block in the general population: the Framingham study.
        Am J Cardiol. 1981; 47: 931-940
        • Talreja D
        • Gruver C.
        • Sklenar J.
        • et al.
        Efficient utilization of echocardiography for the assessment of left ventricular systolic function.
        Am Heart J. 2000; 139: 394-398
        • Dhingra R
        • Ho Nam B.
        • Benjamin E.J.
        • et al.
        Cross-sectional relations of electrocardiographic QRS duration to left ventricular dimensions: the Framingham Heart Study.
        J Am Coll Cardiol. 2005; 45: 685-689
        • Dhingra R
        • Pencina M.J.
        • Wang T.J.
        • et al.
        Electrocardiographic QRS duration and the risk of congestive heart failure: the Framingham Heart Study.
        Hypertension. 2006; 47: 861-867
        • Badheka AO
        • Singh V.
        • Patel N.J.
        • et al.
        QRS duration on electrocardiography and cardiovascular mortality (from the National Health and Nutrition Examination Survey-III).
        Am J Cardiol. 2013; 112: 671-677
        • Bogale N.
        • Orn S.
        • James M.
        • et al.
        Usefulness of either or both left and right bundle branch block at baseline or during follow-up for predicting death in patients following acute myocardial infarction.
        Am J Cardiol. 2007; 99: 647-650
        • Eriksson P
        • Hansson P.O.
        • Eriksson H.
        • et al.
        Bundle-branch block in a general male population: the study of men born 1913.
        Circulation. 1998; 98: 2494-2500
        • Fahy G.J.
        • Pinski S.L.
        • Miller D.P.
        • et al.
        Natural history of isolated bundle branch block.
        Am J Cardiol. 1996; 77: 1185-1190
        • Imanishi R
        • Seto S.
        • Ichimaru S.
        • et al.
        Prognostic significance of incident complete left bundle branch block observed over a 40-year period.
        Am J Cardiol. 2006; 98: 644-648
        • Chiu DT
        • Shapiro N.I.
        • Sun B.C.
        • et al.
        Are echocardiography, telemetry, ambulatory electrocardiography monitoring, and cardiac enzymes in emergency department patients presenting with syncope useful tests? A preliminary investigation.
        J Emerg Med. 2014; 47: 113-118
        • Douglas P.S.
        • Garcia M.J.
        • Haines D.E.
        • et al.
        ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 appropriate use criteria for echocardiography: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Society of Echocardiography, American Heart Association, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Critical Care Medicine, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance American College of Chest Physicians.
        J Am Soc Echocardiogr. 2011; 24: 229-267
        • Menozzi C.
        • Brignole M.
        • Alboni P.
        • et al.
        The natural course of untreated sick sinus syndrome and identification of the variables predictive of unfavorable outcome.
        Am J Cardiol. 1998; 82: 1205-1209
        • Bluemke DA
        • Achenbach S.
        • Budoff M.
        • et al.
        Noninvasive coronary artery imaging: magnetic resonance angiography and multidetector computed tomography angiography: a scientific statement from the American Heart Association Committee on Cardiovascular Imaging and Intervention of the Council on Cardiovascular Radiology and Intervention, and the Councils on Clinical Cardiology and Cardiovascular Disease in the Young.
        Circulation. 2008; 118: 586-606
        • Bokhari S
        • Castano A.
        • Pozniakoff T.
        • et al.
        (99m) Tc-pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses.
        Circ Cardiovasc Imaging. 2013; 6: 195-201
        • Cheong B.
        • Huber S.
        • Muthupillai R.
        • et al.
        Evaluation of myocardial iron overload by T(2)* cardiovascular magnetic resonance imaging.
        Tex Heart Inst J. 2005; 32: 448-449
        • Fontana M.
        • Pica S.
        • Reant P.
        • et al.
        Prognostic value of late gadolinium enhancement cardiovascular magnetic resonance in cardiac amyloidosis.
        Circulation. 2015; 132: 1570-1579
        • Franco A
        • Javidi S.
        • Ruehm S.G.
        Delayed myocardial enhancement in cardiac magnetic resonance imaging.
        J Radiol Case Rep. 2015; 9: 6-18
        • Greulich S
        • Deluigi C.C.
        • Gloekler S.
        • et al.
        CMR imaging predicts death and other adverse events in suspected cardiac sarcoidosis.
        JACC Cardiovasc Imaging. 2013; 6: 501-511
        • Haq M.
        • Pawar S.
        • Berk J.L.
        • et al.
        Can 99mTc-pyrophosphate aid in early detection of cardiac involvement in asymptomatic variant TTR amyloidosis?.
        JACC Cardiovasc Imaging. 2017; 10: 713-714
        • Taylor A.J.
        • Cerqueira M.
        • Hodgson J.M.
        • et al.
        ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac computed tomography: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance.
        J Am Coll Cardiol. 2010; 56: 1864-1894
        • Mendu M.L.
        • McAvay G.
        • Lampert R.
        • et al.
        Yield of diagnostic tests in evaluating syncopal episodes in older patients.
        Arch Intern Med. 2009; 169: 1299-1305
        • Recchia D
        • Barzilai B.
        Echocardiography in the evaluation of patients with syncope.
        J Gen Intern Med. 1995; 10: 649-655
        • Sarasin FP
        • Junod A.F.
        • Carballo D.
        • et al.
        Role of echocardiography in the evaluation of syncope: a prospective study.
        Heart. 2002; 88: 363-367
        • Dagres N.
        • Bongiorni M.G.
        • Dobreanu D.
        • et al.
        Current investigation and management of patients with syncope: results of the European Heart Rhythm Association survey.
        Europace. 2013; 15: 1812-1815
        • Rabkin S.W.
        • Mathewson F.A.
        • Tate R.B.
        Natural history of left bundle-branch block.
        Br Heart J. 1980; 43: 164-169
        • Zhang Z.M.
        • Rautaharju P.M.
        • Soliman E.Z.
        • et al.
        Mortality risk associated with bundle branch blocks and related repolarization abnormalities (from the Women’s Health Initiative [WHI]).
        Am J Cardiol. 2012; 110: 1489-1495
        • Lamb LE
        • Kable K.D.
        • Averill K.H.
        Electrocardiographic findings in 67,375 asymptomatic subjects. V. Left bundle branch block.
        Am J Cardiol. 1960; 6: 130-142
        • Rotman M.
        • Triebwasser J.H.
        A clinical and follow-up study of right and left bundle branch block.
        Circulation. 1975; 51: 477-484
        • Al Rajoub B
        • Noureddine S.
        • El Chami S.
        • et al.
        The prognostic value of a new left bundle branch block in patients with acute myocardial infarction: a systematic review and meta-analysis.
        Heart Lung. 2017; 46: 85-91
        • Iuliano S
        • Fisher S.G.
        • Karasik P.E.
        • et al.
        QRS duration and mortality in patients with congestive heart failure.
        Am Heart J. 2002; 143: 1085-1091
        • Kumar V
        • Venkataraman R.
        • Aljaroudi W.
        • et al.
        Implications of left bundle branch block in patient treatment.
        Am J Cardiol. 2013; 111: 291-300
        • Shamim W.
        • Francis D.P.
        • Yousufuddin M.
        • et al.
        Intraventricular conduction delay: a prognostic marker in chronic heart failure.
        Int J Cardiol. 1999; 70: 171-178
        • Baldasseroni S
        • Opasich C.
        • Gorini M.
        • et al.
        Left bundle-branch block is associated with increased 1-year sudden and total mortality rate in 5517 outpatients with congestive heart failure: a report from the Italian network on congestive heart failure.
        Am Heart J. 2002; 143: 398-405
        • Erne P
        • Iglesias J.F.
        • Urban P.
        • et al.
        Left bundle-branch block in patients with acute myocardial infarction: Presentation, treatment, and trends in outcome from 1997 to 2016 in routine clinical practice.
        Am Heart J. 2017; 184: 106-113
        • Yeo KK
        • Li S.
        • Amsterdam E.A.
        • et al.
        Comparison of clinical characteristics, treatments and outcomes of patients with ST-elevation acute myocardial infarction with versus without new or presumed new left bundle branch block (from NCDR(R)).
        Am J Cardiol. 2012; 109: 497-501
        • Brignole M.
        • Auricchio A.
        • Baron-Esquivias G.
        • et al.
        2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on Cardiac Pacing and Resynchronization Therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA).
        Eur Heart J. 2013; 34: 2281-2329
        • Epstein A.E.
        • DiMarco J.P.
        • Ellenbogen K.A.
        • et al.
        2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
        J Am Coll Cardiol. 2013; 61: e6-e75
        • Linzer M.
        • Yang E.H.
        • Estes 3rd, N.A.
        • et al.
        Diagnosing syncope. Part 1: Value of history, physical examination, and electrocardiography. Clinical Efficacy Assessment Project of the American College of Physicians.
        Ann Intern Med. 1997; 126: 989-996
        • Akbar JJ
        • Meyer C.A.
        • Shipley R.T.
        • et al.
        Cardiopulmonary imaging in sarcoidosis.
        Clin Chest Med. 2008; 29 (viii): 429-443
        • Blankenberg F.
        • Eisenberg S.
        • Scheinman M.N.
        • et al.
        Use of cine gradient echo (GRE) MR in the imaging of cardiac hemochromatosis.
        J Comput Assist Tomogr. 1994; 18: 136-138
        • Friedrich M.G.
        • Sechtem U.
        • Schulz-Menger J.
        • et al.
        Cardiovascular Magnetic Resonance in Myocarditis: A JACC White Paper.
        J Am Coll Cardiol. 2009; 53: 1475-1487
        • Kanao S
        • Tadamura E.
        • Yamamuro M.
        • et al.
        Demonstration of cardiac involvement of sarcoidosis by contrast-enhanced multislice computed tomography and delayed-enhanced magnetic resonance imaging.
        J Comput Assist Tomogr. 2005; 29: 745-748
        • Kondur AK
        • Li T.
        • Vaitkevicius P.
        • et al.
        Quantification of myocardial iron overload by cardiovascular magnetic resonance imaging T2* and review of the literature.
        Clin Cardiol. 2009; 32: E55-E59
        • Kouranos V.
        • Hansell D.M.
        • Sharma R.
        • et al.
        Advances in imaging of cardiopulmonary involvement in sarcoidosis.
        Curr Opin Pulm Med. 2015; 21: 538-545
        • Maceira A.M.
        • Joshi J.
        • Prasad S.K.
        • et al.
        Cardiovascular magnetic resonance in cardiac amyloidosis.
        Circulation. 2005; 111: 186-193
        • Mavrogeni SI
        • Markussis V.
        • Kaklamanis L.
        • et al.
        A comparison of magnetic resonance imaging and cardiac biopsy in the evaluation of heart iron overload in patients with beta-thalassemia major.
        Eur J Haematol. 2005; 75: 241-247
        • Patel M.R.
        • Cawley P.J.
        • Heitner J.F.
        • et al.
        Detection of myocardial damage in patients with sarcoidosis.
        Circulation. 2009; 120: 1969-1977
        • Raney A.R.
        • Bello D.
        Cardiovascular magnetic resonance assessment of ischemic and nonischemic cardiomyopathies.
        Heart Fail Clin. 2006; 2: 145-161
        • Ruberg F.L.
        • Appelbaum E.
        • Davidoff R.
        • et al.
        Diagnostic and prognostic utility of cardiovascular magnetic resonance imaging in light-chain cardiac amyloidosis.
        Am J Cardiol. 2009; 103: 544-549
        • Shimada T
        • Shimada K.
        • Sakane T.
        • et al.
        Diagnosis of cardiac sarcoidosis and evaluation of the effects of steroid therapy by gadolinium-DTPA-enhanced magnetic resonance imaging.
        Am J Med. 2001; 110: 520-527
        • Smedema J.P.
        • Snoep G.
        • van Kroonenburgh M.P.
        • et al.
        Evaluation of the accuracy of gadolinium-enhanced cardiovascular magnetic resonance in the diagnosis of cardiac sarcoidosis.
        J Am Coll Cardiol. 2005; 45: 1683-1690
        • Sparrow P.J.
        • Merchant N.
        • Provost Y.L.
        • et al.
        CT and MR imaging findings in patients with acquired heart disease at risk for sudden cardiac death.
        Radiographics. 2009; 29: 805-823
        • Stauder NI
        • Bader B.
        • Fenchel M.
        • et al.
        Images in cardiovascular medicine. Follow-up of cardiac sarcoidosis by magnetic resonance imaging.
        Circulation. 2005; 111: e158-e160
        • Vignaux O.
        Cardiac sarcoidosis: spectrum of MRI features.
        AJR Am J Roentgenol. 2005; 184: 249-254
        • Vogelsberg H
        • Mahrholdt H.
        • Deluigi C.C.
        • et al.
        Cardiovascular magnetic resonance in clinically suspected cardiac amyloidosis: noninvasive imaging compared to endomyocardial biopsy.
        J Am Coll Cardiol. 2008; 51: 1022-1030
        • Hendel R.C.
        • Patel M.R.
        • Kramer C.M.
        • et al.
        ACCF/ACR/SCCT/SCMR/ASNC/NASCI/SCAI/SIR 2006 appropriateness criteria for cardiac computed tomography and cardiac magnetic resonance imaging: a report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group, American College of Radiology, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, American Society of Nuclear Cardiology, North American Society for Cardiac Imaging, Society for Cardiovascular Angiography and Interventions, and Society of Interventional Radiology.
        J Am Coll Cardiol. 2006; 48: 1475-1497
        • Anguera I
        • Miro J.M.
        • Evangelista A.
        • et al.
        Periannular complications in infective endocarditis involving native aortic valves.
        Am J Cardiol. 2006; 98: 1254-1260
        • Arnett EN
        • Roberts W.C.
        Valve ring abscess in active infective endocarditis. Frequency, location, and clues to clinical diagnosis from the study of 95 necropsy patients.
        Circulation. 1976; 54: 140-145
        • Birmingham G.D.
        • Rahko P.S.
        • Ballantyne 3rd., F.
        Improved detection of infective endocarditis with transesophageal echocardiography.
        Am Heart J. 1992; 123: 774-781
        • Choudhary SK
        • Bhan A.
        • Reddy S.C.
        • et al.
        Aneurysm of sinus of Valsalva dissecting into interventricular septum.
        Ann Thorac Surg. 1998; 65: 735-740
        • Erbel R
        • Rohmann S.
        • Drexler M.
        • et al.
        Improved diagnostic value of echocardiography in patients with infective endocarditis by transoesophageal approach. A prospective study.
        Eur Heart J. 1988; 9: 43-53
        • Shiga T
        • Wajima Z.
        • Apfel C.C.
        • et al.
        Diagnostic accuracy of transesophageal echocardiography, helical computed tomography, and magnetic resonance imaging for suspected thoracic aortic dissection: systematic review and meta-analysis.
        Arch Intern Med. 2006; 166: 1350-1356
        • Walters M.I.
        • Ettles D.
        • Guvendik L.
        • et al.
        Interventricular septal expansion of a sinus of Valsalva aneurysm: a rare cause of complete heart block.
        Heart. 1998; 80: 202-203
        • Shen WK
        • Sheldon R.S.
        • Benditt D.G.
        • et al.
        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.
        J Am Coll Cardiol. 2017; 70: e39-e110
        • Chon SB
        • Kwak Y.H.
        • Hwang S.S.
        • et al.
        Severe hyperkalemia can be detected immediately by quantitative electrocardiography and clinical history in patients with symptomatic or extreme bradycardia: a retrospective cross-sectional study.
        J Crit Care. 2013; 28: 1112.e7-1112.e13
        • Mandell BF
        Cardiovascular involvement in systemic lupus erythematosus.
        Semin Arthritis Rheum. 1987; 17: 126-141
        • Nakayama Y.
        • Ohno M.
        • Yonemura S.
        • et al.
        A case of transient 2:1 atrioventricular block, resolved by thyroxine supplementation for subclinical hypothyroidism.
        Pacing Clin Electrophysiol. 2006; 29: 106-108
        • Noble K.
        • Isles C.
        Hyperkalaemia causing profound bradycardia.
        Heart. 2006; 92: 1063
        • Wan D.
        • Blakely C.
        • Branscombe P.
        • et al.
        Lyme carditis and high-degree atrioventricular block.
        Am J Cardiol. 2018; 121: 1102-1104
        • Ishikawa T.
        • Tsuji Y.
        • Makita N.
        Inherited bradyarrhythmia: a diverse genetic background.
        J Arrhythm. 2016; 32: 352-358
        • Joshi AK
        • Kowey P.R.
        • Prystowsky E.N.
        • et al.
        First experience with a Mobile Cardiac Outpatient Telemetry (MCOT) system for the diagnosis and management of cardiac arrhythmia.
        Am J Cardiol. 2005; 95: 878-881
        • Smits J.P.P.
        • Veldkamp M.W.
        • Wilde A.A.M.
        Mechanisms of inherited cardiac conduction disease.
        EP Europace. 2005; 7: 122-137
        • Wolf C.M.
        • Berul C.I.
        Inherited conduction system abnormalities--one group of diseases, many genes.
        J Cardiovasc Electrophysiol. 2006; 17: 446-455
        • Ackerman M.J.
        • Priori S.G.
        • Willems S.
        • et al.
        HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA).
        Heart Rhythm. 2011; 8: 1308-1339
        • Milanesi R
        • Baruscotti M.
        • Gnecchi-Ruscone T.
        • et al.
        Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel.
        N Engl J Med. 2006; 354: 151-157
        • Schulze-Bahr E.
        • Neu A.
        • Friederich P.
        • et al.
        Pacemaker channel dysfunction in a patient with sinus node disease.
        J Clin Invest. 2003; 111: 1537-1545
        • Tilkian A.G.
        • Guilleminault C.
        • Schroeder J.S.
        • et al.
        Sleep-induced apnea syndrome. Prevalence of cardiac arrhythmias and their reversal after tracheostomy.
        Am J Med. 1977; 63: 348-358
        • Guilleminault C
        • Connolly S.J.
        • Winkle R.A.
        Cardiac arrhythmia and conduction disturbances during sleep in 400 patients with sleep apnea syndrome.
        Am J Cardiol. 1983; 52: 490-494
        • Shepard Jr., JW
        • Garrison M.W.
        • Grither D.A.
        • et al.
        Relationship of ventricular ectopy to oxyhemoglobin desaturation in patients with obstructive sleep apnea.
        Chest. 1985; 88: 335-340
        • Shepard Jr., J.W.
        Gas exchange and hemodynamics during sleep.
        Med Clin North Am. 1985; 69: 1243-1264
        • Hoffstein V.
        • Mateika S.
        Cardiac arrhythmias, snoring, and sleep apnea.
        Chest. 1994; 106: 466-471
        • Boudoulas H.
        • Schmidt H.S.
        • Clark R.W.
        • et al.
        Anthropometric characteristics, cardiac abnormalities and adrenergic activity in patients with primary disorders of sleep.
        J Med. 1983; 14: 223-238
        • Mehra R.
        • Benjamin E.J.
        • Shahar E.
        • et al.
        Association of nocturnal arrhythmias with sleep-disordered breathing: The Sleep Heart Health Study.
        Am J Respir Crit Care Med. 2006; 173: 910-916
        • Miller W.P.
        Cardiac arrhythmias and conduction disturbances in the sleep apnea syndrome. Prevalence and significance.
        Am J Med. 1982; 73: 317-321
        • Flemons WW
        • Remmers J.E.
        • Gillis A.M.
        Sleep apnea and cardiac arrhythmias. Is there a relationship?.
        Am Rev Respir Dis. 1993; 148: 618-621
        • Stegman S.S.
        • Burroughs J.M.
        • Henthorn R.W.
        Asymptomatic bradyarrhythmias as a marker for sleep apnea: appropriate recognition and treatment may reduce the need for pacemaker therapy.
        Pacing Clin Electrophysiol. 1996; 19: 899-904
        • Garrigue S.
        • Pepin J.L.
        • Defaye P.
        • et al.
        High prevalence of sleep apnea syndrome in patients with long-term pacing: the European Multicenter Polysomnographic Study.
        Circulation. 2007; 115: 1703-1709
        • Becker H.
        • Brandenburg U.
        • Peter J.H.
        • et al.
        Reversal of sinus arrest and atrioventricular conduction block in patients with sleep apnea during nasal continuous positive airway pressure.
        Am J Respir Crit Care Med. 1995; 151: 215-218
        • Koehler U
        • Fus E.
        • Grimm W.
        • et al.
        Heart block in patients with obstructive sleep apnoea: pathogenetic factors and effects of treatment.
        Eur Respir J. 1998; 11: 434-439
        • Grimm W.
        • Koehler U.
        • Fus E.
        • et al.
        Outcome of patients with sleep apnea-associated severe bradyarrhythmias after continuous positive airway pressure therapy.
        Am J Cardiol. 2000; 86 (a9): 688-692
        • Harbison J.
        • O’Reilly P.
        • McNicholas W.T.
        Cardiac rhythm disturbances in the obstructive sleep apnea syndrome: effects of nasal continuous positive airway pressure therapy.
        Chest. 2000; 118: 591-595
        • Daccarett M.
        • Segerson N.M.
        • Hamdan A.L.
        • et al.
        Relation of daytime bradyarrhythmias with high risk features of sleep apnea.
        Am J Cardiol. 2008; 101: 1147-1150
        • Bjerregaard P.
        Premature beats in healthy subjects 40-79 years of age.
        Eur Heart J. 1982; 3: 493-503
        • Clarke J.M.
        • Hamer J.
        • Shelton J.R.
        • et al.
        The rhythm of the normal human heart.
        Lancet. 1976; 1: 508-512
        • Fleg JL
        • Kennedy H.L.
        Cardiac arrhythmias in a healthy elderly population: detection by 24-hour ambulatory electrocardiography.
        Chest. 1982; 81: 302-307
        • Brodsky M.
        • Wu D.
        • Denes P.
        • et al.
        Arrhythmias documented by 24 hour continuous electrocardiographic monitoring in 50 male medical students without apparent heart disease.
        Am J Cardiol. 1977; 39: 390-395
        • Meytes I.
        • Kaplinsky E.
        • Yahini J.H.
        • et al.
        Wenckebach A-V block: a frequent feature following heavy physical training.
        Am Heart J. 1975; 90: 426-430
        • Northcote R.J.
        • Canning G.P.
        • Ballantyne D.
        Electrocardiographic findings in male veteran endurance athletes.
        Br Heart J. 1989; 61: 155-160
        • Viitasalo M.T.
        • Kala R.
        • Eisalo A.
        Ambulatory electrocardiographic recording in endurance athletes.
        Br Heart J. 1982; 47: 213-220
        • Young T
        • Palta M.
        • Dempsey J.
        • et al.
        The occurrence of sleep-disordered breathing among middle-aged adults.
        N Engl J Med. 1993; 328: 1230-1235
        • Kasai T.
        • Floras J.S.
        • Bradley T.D.
        Sleep apnea and cardiovascular disease: a bidirectional relationship.
        Circulation. 2012; 126: 1495-1510
        • Guilleminault C
        • Connolly S.
        • Winkle R.
        • et al.
        Cyclical variation of the heart rate in sleep apnoea syndrome. Mechanisms, and usefulness of 24 h electrocardiography as a screening technique.
        Lancet. 1984; 1: 126-131
        • Farwell DJ
        • Freemantle N.
        • Sulke A.N.
        Use of implantable loop recorders in the diagnosis and management of syncope.
        Eur Heart J. 2004; 25: 1257-1263
        • Krahn AD
        • Klein G.J.
        • Yee R.
        • et al.
        Randomized assessment of syncope trial: conventional diagnostic testing versus a prolonged monitoring strategy.
        Circulation. 2001; 104: 46-51
        • Podoleanu C
        • DaCosta A.
        • Defaye P.
        • et al.
        Early use of an implantable loop recorder in syncope evaluation: a randomized study in the context of the French healthcare system (FRESH study).
        Arch Cardiovasc Dis. 2014; 107: 546-552
        • Krahn A.D.
        • Klein G.J.
        • Yee R.
        • et al.
        Final results from a pilot study with an implantable loop recorder to determine the etiology of syncope in patients with negative noninvasive and invasive testing.
        Am J Cardiol. 1998; 82 (A8-A9): 117-119
        • Shen WK
        • Sheldon R.S.
        • Benditt D.G.
        • et al.
        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.
        J Am Coll Cardiol. 2017; 70: e39-e110
        • DiMarco JP
        • Garan H.
        • Ruskin J.N.
        Approach to the patient with recurrent syncope of unknown cause.
        Mod Concepts Cardiovasc Dis. 1983; 52: 11-16
        • Fisher J.D.
        Role of electrophysiologic testing in the diagnosis and treatment of patients with known and suspected bradycardias and tachycardias.
        Prog Cardiovasc Dis. 1981; 24: 25-90
        • Gulamhusein S
        • Naccarelli G.V.
        • Ko P.T.
        • et al.
        Value and limitations of clinical electrophysiologic study in assessment of patients with unexplained syncope.
        Am J Med. 1982; 73: A53
        • Krol RB
        • Morady F.
        • Flaker G.C.
        • et al.
        Electrophysiologic testing in patients with unexplained syncope: Clinical and noninvasive predictors of outcome.
        J Am Coll Cardiol. 1987; 10: 358-363
        • Denniss A.R.
        • Ross D.L.
        • Richards D.A.
        • et al.
        Electrophysiologic studies in patients with unexplained syncope.
        Int J Cardiol. 1992; 35: 211-217
        • Shen W.K.
        • Sheldon R.S.
        • Benditt D.G.
        • et al.
        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.
        J Am Coll Cardiol. 2017; 70: e39-e110
        • Altschuler H
        • Fisher J.D.
        • Furman S.
        Significance of isolated H-V interval prolongation in symptomatic patients without documented heart block.
        Am Heart J. 1979; 97: 19-26
        • Fujimura O
        • Yee R.
        • Klein G.J.
        • et al.
        The diagnostic sensitivity of electrophysiologic testing in patients with syncope caused by transient bradycardia.
        N Engl J Med. 1989; 321: 1703-1707

      5. Bradycardia Attributable to SND

        • Boyett M.R.
        • Honjo H.
        • Kodama I.
        The sinoatrial node, a heterogeneous pacemaker structure.
        Cardiovasc Res. 2000; 47: 658-687
        • den Hoed M.
        • Eijgelsheim M.
        • Esko T.
        • et al.
        Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.
        Nat Genet. 2013; 45: 621-631
        • Deo R
        • Nalls M.A.
        • Avery C.L.
        • et al.
        Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: a genome-wide association study of 13,372 participants.
        Heart Rhythm. 2013; 10: 401-408
        • Eijgelsheim M.
        • Newton-Cheh C.
        • Sotoodehnia N.
        • et al.
        Genome-wide association analysis identifies multiple loci related to resting heart rate.
        Hum Mol Genet. 2010; 19: 3885-3894
        • Holm H.
        • Gudbjartsson D.F.
        • Arnar D.O.
        • et al.
        Several common variants modulate heart rate, PR interval and QRS duration.
        Nat Genet. 2010; 42: 117-122
        • Holm H.
        • Gudbjartsson D.F.
        • Sulem P.
        • et al.
        A rare variant in MYH6 is associated with high risk of sick sinus syndrome.
        Nat Genet. 2011; 43: 316-320
        • Mezzano V.
        • Liang Y.
        • Wright A.T.
        • et al.
        Desmosomal junctions are necessary for adult sinus node function.
        Cardiovasc Res. 2016; 111: 274-286
        • Csepe TA
        • Kalyanasundaram A.
        • Hansen B.J.
        • et al.
        Fibrosis: a structural modulator of sinoatrial node physiology and dysfunction.
        Front Physiol. 2015; 6: 37
        • Thery C
        • Gosselin B.
        • Lekieffre J.
        • et al.
        Pathology of sinoatrial node. Correlations with electrocardiographic findings in 111 patients.
        Am Heart J. 1977; 93: 735-740
        • Lien W.P.
        • Lee Y.S.
        • Chang F.Z.
        • et al.
        The sick sinus syndrome: natural history of dysfunction of the sinoatrial node.
        Chest. 1977; 72: 628-634
        • Dharod A.
        • Soliman E.Z.
        • Dawood F.
        • et al.
        Association of asymptomatic bradycardia with incident cardiovascular disease and mortality: the multi-ethnic study of atherosclerosis (MESA).
        JAMA Intern Med. 2016; 176: 219-227
        • Gann D.
        • Tolentino A.
        • Samet P.
        Electrophysiologic evaluation of elderly patients with sinus bradycardia: a long-term follow-up study.
        Ann Intern Med. 1979; 90: 24-29
        • Menozzi C.
        • Brignole M.
        • Alboni P.
        • et al.
        The natural course of untreated sick sinus syndrome and identification of the variables predictive of unfavorable outcome.
        Am J Cardiol. 1998; 82: 1205-1209
        • Engeseth K
        • Hodnesdal C.
        • Grundvold I.
        • et al.
        Temporal reduction in chronotropic index predicts risk of cardiovascular death among healthy middle-aged men: a 28-year follow-up study.
        J Am Heart Assoc. 2016; 5e004555
        • Lauer M.S.
        • Francis G.S.
        • Okin P.M.
        • et al.
        Impaired chronotropic response to exercise stress testing as a predictor of mortality.
        JAMA. 1999; 281: 524-529
        • Byrne E.A.
        • Fleg J.L.
        • Vaitkevicius P.V.
        • et al.
        Role of aerobic capacity and body mass index in the age-associated decline in heart rate variability (1985).
        J Appl Physiol. 1996; 81: 743-750