REVIEW ARTICLES Received: June 21, 2018 Accepted: June 29, 2018 Corresponding Authors: * The first two authors contributed equally to this work. Two authors contributed equally to this work as corresponding author Copyright 2018 The Official Journal of Korean Heart Rhythm Society Editorial Board ABSTRACT The general concept and initial approach to syncope patients have been mentioned in the general sections. This special section describes the clinical characteristics, diagnosis, patient education and treatment for the each syncope. The contents are in order of reflex syncope, orthostatic hypotension, postural orthostatic tachycardia syndrome (POTS), cardiac syncope, and unexplained syncope. Several clinical issues will have been dealt with in special issues. Neurological assessment is added when the patients were diagnosed with psychogenic pseudosyncope (PPS). Although most of syncope in children and adolescents is reflex syncope, they may be caused by cardiovascular events in patients with congenital heart disease. In the elderly patients, syncope occurs not only by a single cause but a combination of various conditions. When they visit the emergency department, a standardized systematic approach is required to determine whether hospitalize them according to the risk and the needs for the specialized syncope management. We also described the limitations put on driving, exercising and social life style that are relevant to syncope. In this guideline, we also reviewed the Korean published literatures and European/American guidelines on syncope. American College of Cardiology ACC American Heart Association AHA Arrhythmogenic right ventricular cardiomyopathy/dysplasia ARVC/D Atrioventicular block Atrioventricular nodal disease Autonomic nervous system Bifascicular block Benefit/risk ratio Brugada syndrome 145
Bundle branch block Cardiac syncope Cardiac output Cardioinhibitory Cerebral hypoperfusion Cascade Class of recommendation COR Cognitive behavioral therapy Compression garments Conduction system delay Conversion disorder Convulsive syncope Counter-pressure maneuver Cyanotic breath holding spell Early repolarization Ejection fraction Electrophysiological study EPS Emergency department observation units EDOU Epilepsy European Heart Rhythm Association EHRA European Society of Cardiology ESC Fludrocortisone Hazard ratio Head-up tilt test HUT Heart Rhythm Society HRS Hypertrophic cardiomyopathy Implantable cardioverter defibrillator ICD Implantable loop recorder ILR Ischemic cardiomyopathy Isometric contraction Korean Heart Rhythm Society KHRS Korean Society for Holter and Noninvasive Electrocardiology KSHNE Left cardiac sympathetic denervation 146
2018 KHRS guideline for the evaluation and management of syncope Leg crossing Level of evidence LOE Long QT syndrome Loss of consciousness LOC Mineralocorticoid Multiple systemic atrophy Neurally mediated syncope NMS Neurodegenerative disorder Neurogenic orthostatic hypotension Orthostatic hypotension OH Postural orthostatic tachycardia syndrome POTS Pre-excited QRS complexes Primary electrical disease Psychogenic pseudoseizure Psychogenic pseudosyncope PPS Psychogenic transient loss of consciousness Psychogenic non-epileptic seizure PNES Reflex syncope RS Sinus node disease Sinus node recovery time SNRT Situational syncope Squatting Subarachnoid hemorrhage Sudden cardiac death Syncope Syncope management unit Syncope unit Tonic clonic seizure Transient ischemic attack TIA Transient loss of consciousness TLOC Tunnel vision Unexplained syncope Vasodepressor 147
Vasovagal syncope VVS Venous return Vertebrobasilar insufficiency Video-EEG monitoring 1. Class of Recommendation (COR) Class of recommendation ClassI Class II Class IIa Class IIb Class III Definition Evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective. Conflicting evidence and/or divergence of opinion about usefulness/efficacy of the given treatment or procedure. Weight of evidence/opinion is in favor of usefulness/efficacy. Usefulness/efficacy is less well established by evidence/opinion. Evidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases may be harmful. 2. Level of Evidence (LOE) Class of recommendation Level of Evidence A Level of Evidence B Level of Evidence C Definition Data derived from multiple randomized clinical trials or meta-analyses. Data derived from a single randomized clinical trial or large nonrandomized studies. Consensus of opinion of the experts and/or small studies, retrospective studies, registries. 148
2018 KHRS guideline for the evaluation and management of syncope 149
150
2018 KHRS guideline for the evaluation and management of syncope 151
152
2018 KHRS guideline for the evaluation and management of syncope 153
154
2018 KHRS guideline for the evaluation and management of syncope 155
156
2018 KHRS guideline for the evaluation and management of syncope 157
158
2018 KHRS guideline for the evaluation and management of syncope 159
160
2018 KHRS guideline for the evaluation and management of syncope 161
162
2018 KHRS guideline for the evaluation and management of syncope 163
164
2018 KHRS guideline for the evaluation and management of syncope 165
166
2018 KHRS guideline for the evaluation and management of syncope LOC, loss of consciousness; OH: orthostatic hypotension, VVS: vasovagal syncope 167
168
2018 KHRS guideline for the evaluation and management of syncope 169
170
2018 KHRS guideline for the evaluation and management of syncope 171
172
2018 KHRS guideline for the evaluation and management of syncope 173
References 1) Writing Committee M, Shen WK, Sheldon RS, 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. Heart Rhythm 2017;14:e155-e217. 2) Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. European heart journal 2018. 3) Wieling W TR, van Dijk N, Wilde AA, Benditt DG, van Dijk JG. Symptoms and signs of syncope: a review of the link between physiology and clinical clues. Brain 2009;132:2630 42. 4) van Dijk JG TR, van Zwet E, Tannemaat MR, van Niekerk J, Benditt DG, Wieling W. The semiology of tilt-induced reflex syncope in relation to electroencephalographic changes. Brain 2014;137:576-85. 5) J. S. Fits and faints.: Oxford: Blackwell Scientific Publications; 1990. 6) van Dijk JG SR. Is there any point to vasovagal syncope? Clin Auton Res 2008;2008:167-9. 7) Alboni P AM, Bertorelle G. The origin of vasovagal syncope: to protect the heart or to escape predation? Clin Auton Res 2008;18:170-8. 8) Ganzeboom KS CN, Reitsma JB, Shen WK, Wieling W. Prevalence and triggers of syncope in medical students. Am J Cardiol 2003;91:1006-8. 174
2018 KHRS guideline for the evaluation and management of syncope 9) Middlekauff HR SW, Stevenson LW, Saxon LA. Syncope in advanced heart failure: high risk of sudden death regardless of origin of syncope. J Am Coll Cardiol 1993;21:110-6. 10) Serletis A RS, Sheldon AG, Sheldon RS. Vasovagal syncope in medical students and their first-degree relatives. European heart journal 2006;27:1965 70. 11) Colivicchi F AF, Melina D, Guido V, Imperoli G, Santini M, OESIL (Osservatorio Epidemiologico sulla Sincope nel Lazio) Study Investigators. Development and prospective validation of a risk stratification system for patients with syncope in the emergency department: the OESIL risk score. European heart journal 2003;24:811-9. 12) 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;94:1620-6. 13) Brignole M OD, Cogorno S, Menozzi C, Gianfranchi L, Bertulla A. Longterm outcome in symptomatic carotid sinus hypersensitivity. Am Heart J 1992;123:687 92. 14) Calkins H SY, Frumin H, Schork A, Morady F. The value of the clinical history in the differentiation of syncope due to ventricular tachycardia, atrioventricular block, and neurocardiogenic syncope. Am J Med 1995;98:365-73. 15) Deharo JC JC, Lanteaume A, Djiane P. An implantable loop recorder study of highly symptomatic vasovagal patients: the heart rhythm observed during a spontaneous syncope is identical to the recurrent syncope but not correlated with the head-up tilt test or adenosine triphosphate test. J Am Coll Cardiol 2006;47:587-93. 16) Huff JS DW, Q uinn JV, Perron AD, Napoli AM, Peeters S, Jagoda AS, American College of Emergency Physicians. Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with syncope. Annals of emergency medicine 2007;49:431 44. 17) Jamjoom AA N-EA, Fitzgerald JE. Operating theatre related syncope in medical students: a cross sectional study. BMC Med Educ 2009;9:14. 18) Sheldon R RS, Connolly S, Ritchie D, Koshman ML, Frenneaux M. Diagnostic criteria for vasovagal syncope based on a quantitative history. European heart journal 2006;27:344-50. 19) Brignole M SR, Menozzi C, Garcia-Civera R, Moya A, Wieling W, Andresen D, Benditt DG, Grovale N, De Santo T, Vardas P. International Study on Syncope of Uncertain Etiology 2 (ISSUE 2) Group. Lack of correlation between the responses to tilt testing and adenosine triphosphate test and the mechanism of spontaneous neurally mediated syncope. European heart journal 2006;27:2232 9. 20) Flevari P LD, Komborozos C, Fountoulaki K, Dagres N, Theodorakis G, Kremastinos D. Recurrent vasovagal syncope: comparison between clomipramine and nitroglycerin as drug challenges during head-up tilt testing. European heart journal 2009;30:2249-53. 21) Leitch JW KG, Yee R, Leather RA, Kim YH. Syncope associated with supraventricular tachycardia. An expression of tachycardia rate or vasomotor response?. Circulation 1992;85:1064-71. 22) Petersen ME WT, Gordon C, Chamberlain-Webber R, Sutton R. The normal response to prolonged passive head up tilt testing. Heart 2000;84:509 14 23) Furukawa T MR, Solano A, Croci F, Brignole M. Effect of clinical triggers on positive responses to tilt-table testing potentiated with nitroglycerin or clomipramine Am J Cardiol 2011;107. 24) Petix NR DRA, Furlan R, Guarnaccia V, Zipoli A. Nitratepotentiated head-up tilt testing (HUT) has a low diagnostic yield in patients with likely vasovagal syncope. Pacing Clin Electrophysiol 2014;37:164-72. 25) Raviele A MC, Brignole M, Gasparini G, Alboni P, Musso G, Lolli G, Oddone D, Dinelli M, Mureddu R. Value of head-up tilt testing potentiated with sublingual nitroglycerin to assess the origin of unexplained syncope. Am J Cardiol 1995;76:267-72. 26) Sutton R BM. Twenty-eight years of research permit reinterpretation of tilt-testing: hypotensive susceptibility rather than diagnosis. European heart journal 2017;35:2211 2. 27) Brignole M GL, Menozzi C, Raviele A, Oddone D, Lolli G, Bottoni N. Role of autonomic reflexes in syncope associated with paroxysmal atrial fibrillation. J Am Coll Cardiol 1993;22:1123-9. 28) Taneja I MA, Robertson D. Aortic stenosis and autonomic dysfunction:co-conspirators in syncope. Am J Med Sci 2004;327:281 3. 29) Thomson HL M-TJ, Atherton J, Frenneaux M. Reduced cardiopulmonary baroreflex sensitivity in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1998;31:1377 82. 30) Brignole M, Menozzi C, Gianfranchi L, Oddone D, Lolli G, Bertulla A. Neurally mediated syncope detected by carotid sinus massage and head-up tilt test in sick sinus syndrome. Am J Cardiol 1991;68:1032-6. 175
31) Alboni P, Menozzi C, Brignole M, et al. An abnormal neural reflex plays a role in causing syncope in sinus bradycardia. J Am Coll Cardiol 1993;22:1130-4. 32) Brignole M AF, Arabia F, Quartieri F, Tomaino M, Ungar A, Lunati M, Russo V, Del Rosso A, Gaggioli G. Syncope Unit Project (SUP) Two Investigators. Assessment of a standardized algorithm for cardiac pacing in older patients affected by severe unpredictable reflex syncopes. European heart journal 2015;36:1529 35 33) Solari D TF, Unterhuber M, Gaggioli G, Ungar A, Tomaino M, Brignole M. Stop vasodepressor drugs in reflex syncope: a randomised controlled trial. Heart 2017;103:449 55. 34) SPRINT Research Group WJJ, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, Reboussin DM, Rahman M, Oparil S, Lewis CE, Kimmel PL, Johnson KC, Goff DC Jr, Fine LJ, Cutler JA, Cushman WC, Cheung AK, Ambrosius WT. A Randomized Trial of Intensive versus Standard Blood- Pressure Control. The New England journal of medicine 2015;373:2103 16. 35) Brignole M MC, Gaggioli G, Musso G, Foglia-Manzillo G, Mascioli G, Fradella G, Bottoni N, Mureddu R. Effects of longterm vasodilator therapy in patients with carotid sinus hypersensitivity. Am Heart J 1998;136:264 8. 36) Brignole M CF, Menozzi C, Solano A, Donateo P, Oddone D, Puggioni E, Lolli G Isometric arm counter-pressure maneuvers to abort impending vasovagal syncope. J Am Coll Cardiol 2002;40:2053 9. 37) Krediet CT vdn, Linzer M, van Lieshout JJ, Wieling W. Management of vasovagal syncope: controlling or aborting faints by leg crossing and muscle tensing. Circulation 2002;106:1684 9. 38) Kim KH CJ, Lee KO, Seo TJ, Shon CY, Lim SY, Yun KH, Sohn IS, Hong YJ, Park HW, Kim JH, Kim W, Ahn YK, Jeong MH, Park JC, Kang JC. Usefulness of physical maneuvers for prevention of vasovagal syncope. Circ J 2005;69:1084 8. 39) van Dijk N QF, Blanc JJ, Garcia-Civera R, Brignole M, Moya A, Wieling W, PCTrial Investigators. Effectiveness of physical counter pressure maneuvers in preventing vasovagal syncope: the Physical Counter pressure Maneuvers Trial (PC-Trial). J Am Coll Cardiol 2006;18:1652 7. 40) Reybrouck T HH, Van De Werf F, Ector H. Long-term follow-up results of tilt training therapy in patients with recurrent neurocardiogenic syncope. Pacing Clin Electrophysiol 2002;25:1441 6. 41) Zeng H GK, Zhang W, Wang G, Guo L. The effect of orthostatic training in the prevention of vasovagal syncope and its influencing factors. Int Heart J 2008;49:707 12. 42) On YK PJ, Huh J, Kim JS. Is home orthostatic self-training effective in preventing neurally mediated syncope? Pacing Clin Electrophysiol 2007;30:638 43. 43) Burklow TR MJ, Bailey JJ, Makhlouf FT. Neurally mediated cardiac syncope: autonomic modulation after normal saline infusion. J Am Coll Cardiol 1999;33:2059 66. 44) Sheldon R RS, Rose MS, Morillo CA, Krahn AD, Medina E, Talajic M, Kus T, Seifer CM, Lelonek M, Klingenheben T, Parkash R, Ritchie D, McRae M,POST 2 Investigators. Fludrocortisone for the prevention of vasovagal syncope: a randomized, placebo-controlled trial. J Am Coll Cardiol 2016;68:1 9 45) Salim MA DST. Effectiveness of fludrocortisone and salt in preventing syncope recurrence in children: a double-blind, placebo-controlled, randomized trial. J Am Coll Cardiol 2005;45:484 8. 46) Raviele A BM, Sutton R, Alboni P, Giani P, Menozzi C, Moya A. Effect of etilefrine in preventing syncopal recurrence in patients with vasovagal syncope: a double-blind, randomized, placebocontrolled trial. The Vasovagal Syncope International Study Circulation 1999;99:1452 7. 47) Izcovich A GMC, Manzotti M, Catalano HN, Guyatt G Midodrine for orthostatic hypotension and recurrent reflex syncope: a systematic review. Neurology 2014;83:1170 7. 48) Madrid AH OJ, Rebollo JG, Manzano JG, Segovia JG, Sanchez A, Pena G, Moro C. Lack of efficacy of atenolol for the prevention of neurally mediated syncope in a highly symptomatic population: a prospective, doubleblind, randomized and placebo-controlled study. J Am Coll Cardiol 2001;37:554 9. 49) Di Girolamo E DIC, Sabatini P, Leonzio L, Barbone C, Barsotti A. Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol 1999;33:1227 30. 50) Sheldon R, Rose S, Connolly S, Ritchie D, Koshman ML, Frenneaux M. Diagnostic criteria for vasovagal syncope based on a quantitative history. European heart journal 2006;27:344-50. 51) Theodorakis GN MM, Zarvalis E, Livanis EG, Flevari P, 176
2018 KHRS guideline for the evaluation and management of syncope Kremastinos DT. Provocation of neurocardiogenic syncope by clomipramine administration during the head-up tilt test in vasovagal syndrome J Am Coll Cardiol 2000;36:174 8. 52) Marquez MF U-MK, Gomez-Flores J, Sobrino A, Sotomayor- Gonzalez A, Gonzalez-Hermosillo A, Cardenas M. Comparison of metoprolol vs clonazepam as a first treatment choice among patients with neurocardiogenic syncope. Gac Med Mex 2008;144:503 7. 53) Kanjwal K SB, Karabin B, Kanjwal Y, Grubb BP. Use of octreotide in the treatment of refractory orthostatic intolerance. Am J Ther 2017;19:7-10. 54) Freeman R, Wieling W, Axelrod FB, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res 2011;21:69-72. 55) Zia A, Kamaruzzaman SB, Tan MP. Blood pressure lowering therapy in older people: Does it really cause postural hypotension or falls? Postgrad Med 2015;127:186-93. 56) McLachlan CY, Yi M, Ling A, Jardine DL. Adverse drug events are a major cause of acute medical admission. Intern Med J 2014;44:633-8. 57) Poon IO, Braun U. High prevalence of orthostatic hypotension and its correlation with potentially causative medications among elderly veterans. J Clin Pharm Ther 2005;30:173-8. 58) Huang JJ, Desai C, Singh N, et al. Summer syncope syndrome redux. Am J Med 2015;128:1140-3. 59) Schroeder C, Bush VE, Norcliffe LJ, et al. Water drinking acutely improves orthostatic tolerance in healthy subjects. Circulation 2002;106:2806-11. 60) Jordan J, Shannon JR, Grogan E, Biaggioni I, Robertson D. A potent pressor response elicited by drinking water. Lancet 1999;353:723. 61) Jordan J, Shannon JR, Black BK, et al. The pressor response to water drinking in humans : a sympathetic reflex? Circulation 2000;101:504-9. 62) Shannon JR, Diedrich A, Biaggioni I, et al. Water drinking as a treatment for orthostatic syndromes. Am J Med 2002;112:355-60. 63) Claydon VE, Hainsworth R. Salt supplementation improves orthostatic cerebral and peripheral vascular control in patients with syncope. Hypertension 2004;43:809-13. 64) El-Sayed H, Hainsworth R. Salt supplement increases plasma volume and orthostatic tolerance in patients with unexplained syncope. Heart 1996;75:134-40. 65) Canney M, O'Connell MD, Murphy CM, et al. Single Agent Antihypertensive Therapy and Orthostatic Blood Pressure Behaviour in Older Adults Using Beat-to-Beat Measurements: The Irish Longitudinal Study on Ageing. PLoS One 2016;11:e0146156. 66) Verwoert GC, Mattace-Raso FU, Hofman A, et al. Orthostatic hypotension and risk of cardiovascular disease in elderly people: the Rotterdam study. J Am Geriatr Soc 2008;56:1816-20. 67) Valbusa F, Labat C, Salvi P, et al. Orthostatic hypotension in very old individuals living in nursing homes: the PARTAGE study. J Hypertens 2012;30:53-60. 68) Romero-Ortuno R, O'Connell MD, Finucane C, Soraghan C, Fan CW, Kenny RA. Insights into the clinical management of the syndrome of supine hypertension--orthostatic hypotension (SH- OH): the Irish Longitudinal Study on Ageing (TILDA). BMC Geriatr 2013;13:73. 69) Fogari R, Zoppi A, Mugellini A, et al. Efficacy and safety of two treatment combinations of hypertension in very elderly patients. Arch Gerontol Geriatr 2009;48:401-5. 70) van Lieshout JJ, ten Harkel AD, Wieling W. Physical manoeuvres for combating orthostatic dizziness in autonomic failure. Lancet 1992;339:897-8. 71) Ten Harkel AD, van Lieshout JJ, Wieling W. Effects of leg muscle pumping and tensing on orthostatic arterial pressure: a study in normal subjects and patients with autonomic failure. Clin Sci (Lond) 1994;87:553-8. 72) Tutaj M, Marthol H, Berlin D, Brown CM, Axelrod FB, Hilz MJ. Effect of physical countermaneuvers on orthostatic hypotension in familial dysautonomia. J Neurol 2006;253:65-72. 73) Podoleanu C, Maggi R, Brignole M, et al. Lower limb and abdominal compression bandages prevent progressive orthostatic hypotension in elderly persons: a randomized single-blind controlled study. J Am Coll Cardiol 2006;48:1425-32. 74) Figueroa JJ, Singer W, Sandroni P, et al. Effects of patientcontrolled abdominal compression on standing systolic blood pressure in adults with orthostatic hypotension. Arch Phys Med Rehabil 2015;96:505-10. 75) Henry R, Rowe J, O'Mahony D. Haemodynamic analysis of efficacy of compression hosiery in elderly fallers with orthostatic hypotension. Lancet 1999;354:45-6. 177
76) Smit AA, Wieling W, Fujimura J, et al. Use of lower abdominal compression to combat orthostatic hypotension in patients with autonomic dysfunction. Clin Auton Res 2004;14:167-75. 77) Jankovic J, Gilden JL, Hiner BC, et al. Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine. Am J Med 1993;95:38-48. 78) Low PA, Gilden JL, Freeman R, Sheng KN, McElligott MA. Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group. JAMA 1997;277:1046-51. 79) Wright RA, Kaufmann HC, Perera R, et al. A double-blind, doseresponse study of midodrine in neurogenic orthostatic hypotension. Neurology 1998;51:120-4. 80) Rowe PC, Calkins H, DeBusk K, et al. Fludrocortisone acetate to treat neurally mediated hypotension in chronic fatigue syndrome: a randomized controlled trial. JAMA 2001;285:52-9. 81) van Lieshout JJ, ten Harkel AD, Wieling W. Fludrocortisone and sleeping in the head-up position limit the postural decrease in cardiac output in autonomic failure. Clin Auton Res 2000;10:35-42. 82) Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA 2002;287:236-40. 83) Kaufmann H, Freeman R, Biaggioni I, et al. Droxidopa for neurogenic orthostatic hypotension: a randomized, placebocontrolled, phase 3 trial. Neurology 2014;83:328-35. 84) Biaggioni I, Freeman R, Mathias CJ, et al. Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa. Hypertension 2015;65:101-7. 85) Hauser RA, Hewitt LA, Isaacson S. Droxidopa in patients with neurogenic orthostatic hypotension associated with Parkinson's disease (NOH306A). J Parkinsons Dis 2014;4:57-65. 86) Mathias CJ, Senard JM, Braune S, et al. L-threodihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multinational, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure. Clin Auton Res 2001;11:235-42. 87) Hauser RA, Isaacson S, Lisk JP, Hewitt LA, Rowse G. Droxidopa for the short-term treatment of symptomatic neurogenic orthostatic hypotension in Parkinson's disease (noh306b). Mov Disord 2015;30:646-54. 88) Omboni S, Smit AA, van Lieshout JJ, Settels JJ, Langewouters GJ, Wieling W. Mechanisms underlying the impairment in orthostatic tolerance after nocturnal recumbency in patients with autonomic failure. Clin Sci (Lond) 2001;101:609-18. 89) Ricci F, De Caterina R, Fedorowski A. Orthostatic Hypotension: Epidemiology, Prognosis, and Treatment. J Am Coll Cardiol 2015;66:848-60. 90) Ten Harkel AD, Van Lieshout JJ, Wieling W. Treatment of orthostatic hypotension with sleeping in the head-up tilt position, alone and in combination with fludrocortisone. J Intern Med 1992;232:139-45. 91) Hoeldtke RD, Dworkin GE, Gaspar SR, Israel BC, Boden G. Effect of the somatostatin analogue SMS-201-995 on the adrenergic response to glucose ingestion in patients with postprandial hypotension. Am J Med 1989;86:673-7. 92) Jarvis SS, Florian JP, Curren MJ, Pawelczyk JA. A somatostatin analog improves tilt table tolerance by decreasing splanchnic vascular conductance. J Appl Physiol (1985) 2012;112:1504-11. 93) Raimbach SJ, Cortelli P, Kooner JS, Bannister R, Bloom SR, Mathias CJ. Prevention of glucose-induced hypotension by the somatostatin analogue octreotide (SMS 201-995) in chronic autonomic failure: haemodynamic and hormonal changes. Clin Sci (Lond) 1989;77:623-8. 94) Gales BJ, Gales MA. Pyridostigmine in the treatment of orthostatic intolerance. Ann Pharmacother 2007;41:314-8. 95) Shibao C, Okamoto LE, Gamboa A, et al. Comparative efficacy of yohimbine against pyridostigmine for the treatment of orthostatic hypotension in autonomic failure. Hypertension 2010;56:847-51. 96) Benarroch EE. Postural tachycardia syndrome: a heterogeneous and multifactorial disorder. Mayo Clin Proc 2012;87:1214-25. 97) Alboni P, Menozzi C, Brignole M, et al. Effects of permanent pacemaker and oral theophylline in sick sinus syndrome the THEOPACE study: a randomized controlled trial. Circulation 1997;96:260-6. 98) Breivik K, Ohm OJ, Segadal L. Sick sinus syndrome treated with permanent pacemaker in 109 patients. A follow-up study. Acta Med Scand 1979;206:153-9. 99) Hartel G, Talvensaari T. Treatment of sinoatrial syndrome with permanent cardiac pacing in 90 patients. Acta Med Scand 1975;198:341-7. 100) Rasmussen K. Chronic sinus node disease: natural course and 178
2018 KHRS guideline for the evaluation and management of syncope indications for pacing. European heart journal 1981;2:455-9. 101) Sasaki Y, Shimotori M, Akahane K, et al. Long-term follow-up of patients with sick sinus syndrome: a comparison of clinical aspects among unpaced, ventricular inhibited paced, and physiologically paced groups. Pacing Clin Electrophysiol 1988;11:1575-83. 102) Sgarbossa EB, Pinski SL, Jaeger FJ, Trohman RG, Maloney JD. Incidence and predictors of syncope in paced patients with sick sinus syndrome. Pacing Clin Electrophysiol 1992;15:2055-60. 103) Ng Kam Chuen MJ, Kirkfeldt RE, Andersen HR, Nielsen JC. Syncope in paced patients with sick sinus syndrome from the DANPACE trial: incidence, predictors and prognostic implication. Heart 2014;100:842-7. 104.) Langenfeld H, Grimm W, Maisch B, Kochsiek K. Course of symptoms and spontaneous ECG in pacemaker patients: a 5-year follow-up study. Pacing Clin Electrophysiol 1988;11:2198-206. 105.) Aste M, Oddone D, Donateo P, et al. Syncope in patients paced for atrioventricular block. Europace 2016;18:1735-9. 106) Donateo P, Brignole M, Alboni P, et al. A standardized conventional evaluation of the mechanism of syncope in patients with bundle branch block. Europace 2002;4:357-60. 107) Brignole M, Menozzi C, Moya A, et al. Mechanism of syncope in patients with bundle branch block and negative electrophysiological test. Circulation 2001;104:2045-50. 108) Moya A, Garcia-Civera R, Croci F, et al. Diagnosis, management, and outcomes of patients with syncope and bundle branch block. European heart journal 2011;32:1535-41. 109) Azocar D, Ruiz-Granell R, Ferrero A, et al. Syncope and bundle branch block. Diagnostic yield of a stepped use of electrophysiology study and implantable loop recorders. Rev Esp Cardiol 2011;64:213-9. 110) Kalscheur MM, Donateo P, Wenzke KE, et al. Long-Term Outcome of Patients with Bifascicular Block and Unexplained Syncope Following Cardiac Pacing. Pacing Clin Electrophysiol 2016;39:1126-31. 111) Santini M, Castro A, Giada F, et al. Prevention of syncope through permanent cardiac pacing in patients with bifascicular block and syncope of unexplained origin: the PRESS study. Circ Arrhythm Electrophysiol 2013;6:101-7. 112) Englund A, Bergfeldt L, Rehnqvist N, Astrom H, Rosenqvist M. Diagnostic value of programmed ventricular stimulation in patients with bifascicular block: a prospective study of patients with and without syncope. J Am Coll Cardiol 1995;26:1508-15. 113) Morady F, Higgins J, Peters RW, et al. Electrophysiologic testing in bundle branch block and unexplained syncope. Am J Cardiol 1984;54:587-91. 114) Tabrizi F, Rosenqvist M, Bergfeldt L, Englund A. Long-term prognosis in patients with bifascicular block--the predictive value of noninvasive and invasive assessment. J Intern Med 2006;260:31-8. 115) Olshansky B, Poole JE, Johnson G, et al. Syncope predicts the outcome of cardiomyopathy patients: analysis of the SCD-HeFT study. J Am Coll Cardiol 2008;51:1277-82. 116) Ruwald MH, Okumura K, Kimura T, et al. Syncope in high-risk cardiomyopathy patients with implantable defibrillators: frequency, risk factors, mechanisms, and association with mortality: results from the multicenter automatic defibrillator implantation trial-reduce inappropriate therapy (MADIT-RIT) study. Circulation 2014;129:545-52. 117) Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/ HRS Guideline for the Evaluation and Management of Patients With Syncope: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2017;136:e25-e59. 118) Task Force for the D, Management of S, European Society of C, et al. Guidelines for the diagnosis and management of syncope (version 2009). European heart journal 2009;30:2631-71. 119) Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. European heart journal 2018;39:1883-948. 120) Chapelon-Abric C, de Zuttere D, Duhaut P, et al. Cardiac sarcoidosis: a retrospective study of 41 cases. Medicine 2004;83:315-34. 121) Priori SG, Blomstrom-Lundqvist C, Mazzanti A, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). European heart journal 2015;36:2793-867. 179
122) Kusumoto FM, 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. Circulation 2014;130:94-125. 123) Epstein AE, DiMarco JP, Ellenbogen KA, 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. Circulation 2013;127:e283-352. 124) Spirito P, Autore C, Rapezzi C, et al. Syncope and risk of sudden death in hypertrophic cardiomyopathy. Circulation 2009;119:1703-10. 125) Authors/Task Force m, Elliott PM, Anastasakis A, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). European heart journal 2014;35:2733-79. 126) Schinkel AF. Implantable cardioverter defibrillators in arrhythmogenic right ventricular dysplasia/cardiomyopathy: patient outcomes, incidence of appropriate and inappropriate interventions, and complications. Circ Arrhythm Electrophysiol 2013;6:562-8. 127) Corrado D, Calkins H, Link MS, et al. Prophylactic implantable defibrillator in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior ventricular fibrillation or sustained ventricular tachycardia. Circulation 2010;122:1144-52. 128) Corrado D, Wichter T, Link MS, et al. Treatment of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia: An International Task Force Consensus Statement. Circulation 2015;132:441-53. 129) Link MS, Laidlaw D, Polonsky B, et al. Ventricular arrhythmias in the North American multidisciplinary study of ARVC: predictors, characteristics, and treatment. J Am Coll Cardiol 2014;64:119-25. 130) Goldenberg I, Moss AJ. Long QT syndrome. J Am Coll Cardiol 2008;51:2291-300. 131) Fauchier L, Isorni MA, Clementy N, Pierre B, Simeon E, Babuty D. Prognostic value of programmed ventricular stimulation in Brugada syndrome according to clinical presentation: an updated meta-analysis of worldwide published data. International journal of cardiology 2013;168:3027-9. 132) 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). European heart journal 2013;34:2281-329. 133) Zhao W, Meng R, Ma C, et al. Safety and Efficacy of Remote Ischemic Preconditioning in Patients With Severe Carotid Artery Stenosis Before Carotid Artery Stenting: A Proof-of- Concept, Randomized Controlled Trial. Circulation 2017;135:1325-35. 134) van der Lende M, Surges R, Sander JW, Thijs RD. Cardiac arrhythmias during or after epileptic seizures. J Neurol Neurosurg Psychiatry 2016;87:69-74. 135) Rugg-Gunn FJ, Simister RJ, Squirrell M, Holdright DR, Duncan JS. Cardiac arrhythmias in focal epilepsy: a prospective long-term study. Lancet 2004;364:2212-9. 136) Benditt DG, van Dijk G, Thijs RD. Ictal asystole: life-threatening vagal storm or a benign seizure self-termination mechanism? Circ Arrhythm Electrophysiol 2015;8:11-4. 137) Kang DY, Oh IY, Lee SR, et al. Recurrent syncope triggered by temporal lobe epilepsy: ictal bradycardia syndrome. Korean Circ J 2012;42:349-51. 138) Rocamora R, Kurthen M, Lickfett L, Von Oertzen J, Elger CE. Cardiac asystole in epilepsy: clinical and neurophysiologic features. Epilepsia 2003;44:179-85. 139) Schuele SU, Bermeo AC, Alexopoulos AV, et al. Videoelectrographic and clinical features in patients with ictal asystole. Neurology 2007;69:434-41. 140) Bestawros M, Darbar D, Arain A, et al. Ictal asystole and ictal syncope: insights into clinical management. Circ Arrhythm Electrophysiol 2015;8:159-64. 141) Lamberts RJ, Thijs RD, Laffan A, Langan Y, Sander JW. Sudden unexpected death in epilepsy: people with nocturnal seizures may be at highest risk. Epilepsia 2012;53:253-7. 142) Lamberts RJ, Blom MT, Wassenaar M, et al. Sudden cardiac arrest in people with epilepsy in the community: Circumstances and risk factors. Neurology 2015;85:212-8. 180
2018 KHRS guideline for the evaluation and management of syncope 143) Horrocks IA, Nechay A, Stephenson JB, Zuberi SM. Anoxicepileptic seizures: observational study of epileptic seizures induced by syncopes. Arch Dis Child 2005;90:1283-7. 144) Stephenson J, Breningstall G, Steer C, et al. Anoxic-epileptic seizures: home video recordings of epileptic seizures induced by syncopes. Epileptic Disord 2004;6:15-9. 145) Song PS, Kim JS, Park J, et al. Seizure-like activities during headup tilt test-induced syncope. Yonsei Med J 2010;51:77-81. 146) van Dijk JG, Thijs RD, van Zwet E, et al. The semiology of tiltinduced reflex syncope in relation to electroencephalographic changes. Brain 2014;137:576-85. 147) Tannemaat MR, van Niekerk J, Reijntjes RH, Thijs RD, Sutton R, van Dijk JG. The semiology of tilt-induced psychogenic pseudosyncope. Neurology 2013;81:752-8. 148) Hoefnagels WA, Padberg GW, Overweg J, van der Velde EA, Roos RA. Transient loss of consciousness: the value of the history for distinguishing seizure from syncope. J Neurol 1991;238:39-43. 149) Abubakr A, Wambacq I. Seizures in the elderly: Video/EEG monitoring analysis. Epilepsy Behav 2005;7:447-50. 150) Kang GH, Oh JH, Kim JS, et al. Diagnostic patterns in the evaluation of patients presenting with syncope at the emergency or outpatient department. Yonsei Med J 2012;53:517-23. 151) Pires LA, Ganji JR, Jarandila R, Steele R. Diagnostic patterns and temporal trends in the evaluation of adult patients hospitalized with syncope. Arch Intern Med 2001;161:1889-95. 152) Sclafani JJ, My J, Zacher LL, Eckart RE. Intensive education on evidence-based evaluation of syncope increases sudden death risk stratification but fails to reduce use of neuroimaging. Arch Intern Med 2010;170:1150-4. 153) Mendu ML, McAvay G, Lampert R, Stoehr J, Tinetti ME. Yield of diagnostic tests in evaluating syncopal episodes in older patients. Arch Intern Med 2009;169:1299-305. 154) Johnson PC, Ammar H, Zohdy W, Fouda R, Govindu R. Yield of diagnostic tests and its impact on cost in adult patients with syncope presenting to a community hospital. South Med J 2014;107:707-14. 155) Hoefnagels WA, Padberg GW, Overweg J, Roos RA. Syncope or seizure? A matter of opinion. Clin Neurol Neurosurg 1992;94:153-6. 156) Benbadis SR, Wolgamuth BR, Goren H, Brener S, Fouad-Tarazi F. Value of tongue biting in the diagnosis of seizures. Arch Intern Med 1995;155:2346-9. 157) Tannemaat MR, Thijs RD, van Dijk JG. Managing psychogenic pseudosyncope: Facts and experiences. Cardiol J 2014;21:658-64. 158) Raj V, Rowe AA, Fleisch SB, Paranjape SY, Arain AM, Nicolson SE. Psychogenic pseudosyncope: diagnosis and management. Auton Neurosci 2014;184:66-72. 159) The European Society of Cardiology Guidelines for the diagnosis and management of syncope reviewed by Angel Moya, MD, FESC, Chair of the Guideline Taskforce with J. Taylor, MPhil. European heart journal 2009;30:2539-40. 160) Benbadis SR, Chichkova R. Psychogenic pseudosyncope: an underestimated and provable diagnosis. Epilepsy Behav 2006;9:106-10. 161) LaFrance WC, Jr., Baker GA, Duncan R, Goldstein LH, Reuber M. Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: a staged approach: a report from the International League Against Epilepsy Nonepileptic Seizures Task Force. Epilepsia 2013;54:2005-18. 162) LaFrance WC, Jr., Reuber M, Goldstein LH. Management of psychogenic nonepileptic seizures. Epilepsia 2013;54 Suppl 1:53-67. 163) Saal DP, Overdijk MJ, Thijs RD, van Vliet IM, van Dijk JG. Long-term follow-up of psychogenic pseudosyncope. Neurology 2016;87:2214-9. 164) LaFrance WC, Jr., Keitner GI, Papandonatos GD, et al. Pilot pharmacologic randomized controlled trial for psychogenic nonepileptic seizures. Neurology 2010;75:1166-73. 165) LaFrance WC, Jr., Baird GL, Barry JJ, et al. Multicenter pilot treatment trial for psychogenic nonepileptic seizures: a randomized clinical trial. JAMA Psychiatry 2014;71:997-1005. 166) Kanjwal K, Calkins H. Syncope in Children and Adolescents. Cardiol Clin 2015;33:397-409. 167) Massin MM, Bourguignont A, Coremans C, Comte L, Lepage P, Gerard P. Syncope in pediatric patients presenting to an emergency department. J Pediatr-Us 2004;145:223-8. 168) DiMario FJ, Jr. Prospective study of children with cyanotic and pallid breath-holding spells. Pediatrics 2001;107:265-9. 169) Kelly AM, Porter CJ, McGoon MD, Espinosa RE, Osborn MJ, Hayes DL. Breath-holding spells associated with significant 181
bradycardia: successful treatment with permanent pacemaker implantation. Pediatrics 2001;108:698-702. 170) Writing Committee M, Shen WK, Sheldon RS, et al. 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm 2017;14:e218-e54. 171) Tretter JT, Kavey RE. Distinguishing cardiac syncope from vasovagal syncope in a referral population. J Pediatr-Us 2013;163:1618-23 e1. 172) Zhang Q, Du J, Wang C, Du Z, Wang L, Tang C. The diagnostic protocol in children and adolescents with syncope: a multi-centre prospective study. Acta Paediatr 2009;98:879-84. 173) Avari Silva JN, Bromberg BI, Emge FK, Bowman TM, Van Hare GF. Implantable Loop Recorder Monitoring for Refining Management of Children With Inherited Arrhythmia Syndromes. J Am Heart Assoc 2016;5. 174) Joseph Rossano BB, Narayanswami Sreeram,Seshadri Balaji, and Maully J. Shah. Efficacy of Implantable Loop Recorders in Establishing Symptom-Rhythm Correlation in Young Patients With Syncope and Palpitations. Pediatrics 2003;112:e228-e33. 175) Al Dhahri KN, Potts JE, Chiu CC, Hamilton RM, Sanatani S. Are implantable loop recorders useful in detecting arrhythmias in children with unexplained syncope? Pacing Clin Electrophysiol 2009;32:1422-7. 176) Strieper MJ, Campbell RM. Efficacy of alpha-adrenergic agonist therapy for prevention of pediatric neurocardiogenic syncope. J Am Coll Cardiol 1993;22:594-7. 177) McLeod KA, Wilson N, Hewitt J, Norrie J, Stephenson JB. Cardiac pacing for severe childhood neurally mediated syncope with reflex anoxic seizures. Heart 1999;82:721-5. 178) Zhang Q, Jin H, Wang L, Chen J, Tang C, Du J. Randomized comparison of metoprolol versus conventional treatment in preventing recurrence of vasovagal syncope in children and adolescents. Med Sci Monitor 2008;14:CR199-203. 179) Maron MS, Olivotto I, Zenovich AG, et al. Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction. Circulation 2006;114:2232-9. 180) Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/ HRS Guideline for the Evaluation and Management of Patients With Syncope: Executive Summary: 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;70:620-63. 181) Khairy P, Aboulhosn J, Gurvitz MZ, et al. Arrhythmia burden in adults with surgically repaired tetralogy of Fallot: a multiinstitutional study. Circulation 2010;122:868-75. 182) Khairy P, Harris L, Landzberg MJ, et al. Sudden death and defibrillators in transposition of the great arteries with intra-atrial baffles: a multicenter study. Circ Arrhythm Electrophysiol 2008;1:250-7. 183) Berul CI, Van Hare GF, Kertesz NJ, et al. Results of a multicenter retrospective implantable cardioverter-defibrillator registry of pediatric and congenital heart disease patients. J Am Coll Cardiol 2008;51:1685-91. 184) Khairy P, Landzberg MJ, Gatzoulis MA, et al. Value of programmed ventricular stimulation after tetralogy of fallot repair: a multicenter study. Circulation 2004;109:1994-2000. 185) Ungar A, Mussi C, Del Rosso A, et al. Diagnosis and characteristics of syncope in older patients referred to geriatric departments. J Am Geriatr Soc 2006;54:1531-6. 186) Goyal P, Maurer MS. Syncope in older adults. Journal of geriatric cardiology : JGC 2016;13:380-6. 187) Ruwald MH, Hansen ML, Lamberts M, et al. Comparison of incidence, predictors, and the impact of co-morbidity and polypharmacy on the risk of recurrent syncope in patients <85 versus >/=85 years of age. Am J Cardiol 2013;112:1610-5. 188) Romme JJ, van Dijk N, Boer KR, et al. Influence of age and gender on the occurrence and presentation of reflex syncope. Clin Auton Res 2008;18:127-33. 189) Bhangu JS, King-Kallimanis B, Cunningham C, Kenny RA. The relationship between syncope, depression and anti-depressant use in older adults. Age and ageing 2014;43:502-9. 190) Jansen S, Kenny RA, de Rooij SE, van der Velde N. Self-reported cardiovascular conditions are associated with falls and syncope in community-dwelling older adults. Age and ageing 2015;44:525-9. 191) Mossello E, Pieraccioli M, Nesti N, et al. Effects of low blood pressure in cognitively impaired elderly patients treated with antihypertensive drugs. JAMA internal medicine 2015;175:578-85. 192) Ryan DJ, Harbison JA, Meaney JF, Rice CP, King-Kallimanis B, Kenny RA. Syncope causes transient focal neurological 182
2018 KHRS guideline for the evaluation and management of syncope symptoms. QJM : monthly journal of the Association of Physicians 2015;108:711-8. 193) Parry SW, Kenny RA. Drop attacks in older adults: systematic assessment has a high diagnostic yield. J Am Geriatr Soc 2005;53:74-8. 194) Davies AJ, Kenny RA. Falls presenting to the accident and emergency department: types of presentation and risk factor profile. Age and ageing 1996;25:362-6. 195) Jansen S, Bhangu J, de Rooij S, Daams J, Kenny RA, van der Velde N. The Association of Cardiovascular Disorders and Falls: A Systematic Review. Journal of the American Medical Directors Association 2016;17:193-9. 196) Rafanelli M, Ruffolo E, Chisciotti VM, et al. Clinical aspects and diagnostic relevance of neuroautonomic evaluation in patients with unexplained falls. Aging clinical and experimental research 2014;26:33-7. 197) Kenny RA, Richardson DA, Steen N, Bexton RS, Shaw FE, Bond J. Carotid sinus syndrome: a modifiable risk factor for nonaccidental falls in older adults (SAFE PACE). J Am Coll Cardiol 2001;38:1491-6. 198) O'Dwyer C, Bennett K, Langan Y, Fan CW, Kenny RA. Amnesia for loss of consciousness is common in vasovagal syncope. Europace 2011;13:1040-5. 199) Shaw FE, Bond J, Richardson DA, et al. Multifactorial intervention after a fall in older people with cognitive impairment and dementia presenting to the accident and emergency department: randomised controlled trial. BMJ (Clinical research ed) 2003;326:73. 200) Frewen J, Finucane C, Savva GM, Boyle G, Kenny RA. Orthostatic hypotension is associated with lower cognitive performance in adults aged 50 plus with supine hypertension. The journals of gerontology Series A, Biological sciences and medical sciences 2014;69:878-85. 201) Robertson DA, Savva GM, Coen RF, Kenny RA. Cognitive function in the prefrailty and frailty syndrome. J Am Geriatr Soc 2014;62:2118-24. 202) Robertson DA, Savva GM, Kenny RA. Frailty and cognitive impairment--a review of the evidence and causal mechanisms. Ageing research reviews 2013;12:840-51. 203) Racco F, Sconocchini C, Alesi C, Zappelli L, Pratillo G. Longterm follow-up after syncope. A group of 183 patients observed for 5 years. Minerva cardioangiologica 2000;48:69-78. 204) Matthews IG, Tresham IA, Parry SW. Syncope in the Older Person. Cardiol Clin 2015;33:411-21. 205) de Ruiter SC, Wold JFH, Germans T, Ruiter JH, Jansen R. Multiple causes of syncope in the elderly: diagnostic outcomes of a Dutch multidisciplinary syncope pathway. Europace 2018;20:867-72. 206) Colivicchi F, Ammirati F, Biffi A, Verdile L, Pelliccia A, Santini M. Exercise-related syncope in young competitive athletes without evidence of structural heart disease. Clinical presentation and long-term outcome. European heart journal 2002;23:1125-30. 207) Sneddon JF, Scalia G, Ward DE, McKenna WJ, Camm AJ, Frenneaux MP. Exercise induced vasodepressor syncope. British heart journal 1994;71:554-7. 208) Sakaguchi S, Shultz JJ, Remole SC, Adler SW, Lurie KG, Benditt DG. Syncope associated with exercise, a manifestation of neurally mediated syncope. Am J Cardiol 1995;75:476-81. 209) Pappas LK, Efremidis M, Sideris A, Letsas KP, Kounas SP, Kardaras F. Exercise-induced second-degree atrioventricular block. International journal of cardiology 2006;111:461-3. 210) Ho WJ, Chu PH, Cheng NJ, Hsu TS, Lee YS. Exercise-induced myocardial ischaemia complicated by paroxysmal complete atrioventricular block. International journal of clinical practice Supplement 2005:19-22. 211) Woelfel AK, Simpson RJ, Jr., Gettes LS, Foster JR. Exerciseinduced distal atrioventricular block. J Am Coll Cardiol 1983;2:578-81. 212) Shah JS, Esteban MT, Thaman R, et al. Prevalence of exerciseinduced left ventricular outflow tract obstruction in symptomatic patients with non-obstructive hypertrophic cardiomyopathy. Heart 2008;94:1288-94. 213) Colivicchi F, Ammirati F, Santini M. Epidemiology and prognostic implications of syncope in young competing athletes. European heart journal 2004;25:1749-53. 214) Hastings JL, Levine BD. Syncope in the athletic patient. Progress in cardiovascular diseases 2012;54:438-44. 215) Vettor G, Zorzi A, Basso C, Thiene G, Corrado D. Syncope as a Warning Symptom of Sudden Cardiac Death in Athletes. Cardiol Clin 2015;33:423-32. 216) Asplund CA, O'Connor FG, Noakes TD. Exercise-associated collapse: an evidence-based review and primer for clinicians. 183
British journal of sports medicine 2011;45:1157-62. 217) Pelliccia A, Zipes DP, Maron BJ. Bethesda Conference #36 and the European Society of Cardiology Consensus Recommendations revisited a comparison of U.S. and European criteria for eligibility and disqualification of competitive athletes with cardiovascular abnormalities. J Am Coll Cardiol 2008;52:1990-6. 218) Zipes DP, Link MS, Ackerman MJ, 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. Circulation 2015;132:e315-25. 219) O'Connor FG, Levine BD, Childress MA, Asplundh CA, Oriscello RG. Practical management: a systematic approach to the evaluation of exercise-related syncope in athletes. Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine 2009;19:429-34. 220) Albert RK, Schuller JL, Network CCR. Macrolide antibiotics and the risk of cardiac arrhythmias. American journal of respiratory and critical care medicine 2014;189:1173-80. 221) Simpson C, Dorian P, Gupta A, et al. Assessment of the cardiac patient for fitness to drive: drive subgroup executive summary. The Canadian journal of cardiology 2004;20:1314-20. 222) an VH, Ritchie D, Maxey C, Sheldon R, Investigators P. Prospective Assessment of the Risk of Vasovagal Syncope During Driving. JACC Clin Electrophysiol 2016;2:203-8. 223) Sorajja D, Shen WK. Driving guidelines and restrictions in patients with a history of cardiac arrhythmias, syncope,or implantable devices. Current treatment options in cardiovascular medicine 2010;12:443-56. 224) Lamb LE, Green HC, Combs JJ, Cheeseman SA, Hammond J. Incidence of loss of consciousness in 1,980 Air Force personnel. Aerospace medicine 1960;31:973-88. 225) Morichetti A, Astorino G. [Epidemiological and clinical findings in 697 syncope events]. Minerva medica 1998;89:211-20. 226) Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. The New England journal of medicine 2002;347:878-85. 227) Blanc JJ, L'Her C, Touiza A, Garo B, L'Her E, Mansourati J. Prospective evaluation and outcome of patients admitted for syncope over a 1 year period. European heart journal 2002;23:815-20. 228) Costantino G, Perego F, Dipaola F, et al. Short- and long-term prognosis of syncope, risk factors, and role of hospital admission: results from the STePS (Short-Term Prognosis of Syncope) study. J Am Coll Cardiol 2008;51:276-83. 229) Shen WK, Decker WW, Smars PA, et al. Syncope Evaluation in the Emergency Department Study (SEEDS): a multidisciplinary approach to syncope management. Circulation 2004;110:3636-45. 230) Brignole M, Shen WK. Syncope management from emergency department to hospital. J Am Coll Cardiol 2008;51:284-7. 231) 2011;22:662-668. 232) Grossman AM, Volz KA, Shapiro NI, et al. Comparison of 1-Day Emergency Department Observation and Inpatient Ward for 1-Day Admissions in Syncope Patients. The Journal of emergency medicine 2016;50:217-22. 233) Lin M, Wolfe RE, Shapiro NI, Novack V, Lior Y, Grossman SA. Observation vs admission in syncope: can we predict short length of stays? The American journal of emergency medicine 2015;33:1684-6. 234) Numeroso F, Mossini G, Lippi G, Cervellin G. Role of emergency department observation units in the management of patients with unexplained syncope: a critical review and metaanalysis. Clinical and experimental emergency medicine 2017;4:201-7. 235) Probst MA, Sun BC. How can we improve management of syncope in the Emergency Department? Cardiol J 2014;21:643-50. 236) Shin TG, Kim JS, Song HG, Jo IJ, Sim MS, Park SJ. Standardized approaches to syncope evaluation for reducing hospital admissions and costs in overcrowded emergency departments. Yonsei Med J 2013;54:1110-8. 237) Sun BC, McCreath H, Liang LJ, et al. Randomized clinical trial of an emergency department observation syncope protocol versus routine inpatient admission. Annals of emergency medicine 2014;64:167-75. 238) Sheldon R, Rose S, Ritchie D, et al. Historical criteria that distinguish syncope from seizures. J Am Coll Cardiol 2002;40:142-8. 184