open access

Vol 79, No 10 (2021)
Review paper
Published online: 2021-10-14
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Syncope: new solutions for an old problem

Giulia Rivasi1, Andrea Ungar1, Angel Moya2, Michele Brignole3, Richard Sutton45, Artur Fedorowski56
DOI: 10.33963/KP.a2021.0138
·
Pubmed: 34668180
·
Kardiol Pol 2021;79(10):1068-1078.
Affiliations
  1. Division of Geriatric and Intensive Care Medicine, University of Florence and Azienda Ospedaliero Universitaria Careggi, Florence, Italy
  2. Cardiology and Arrhythmia Unit, University Hospital Dexeus, Barcelona, Spain
  3. IRCCS, Istituto Auxologico Italiano, Cardiology Unit and Department of Cardiovascular, Neural and Metabolic Sciences, S. Luca Hospital, Milan, Italy
  4. Department of Cardiology, National Heart & Lung Institute, Imperial College, Hammersmith Hospital Campus, London, UK
  5. Department of Clinical Sciences, Lund University, Malmö, Sweden
  6. Department of Cardiology, Karolinska University Hospital, and Department of Medicine, Karolinska Institute, Stockholm, Sweden

open access

Vol 79, No 10 (2021)
Review article
Published online: 2021-10-14

Abstract

Syncope is a frequent event in the general population. Approximately 1%–2% of all emergency department admissions are due to syncope and at least one-third of all people experience fainting in their life. Although consequences of cardiac syncope are generally feared, non-cardiac syncope is much more common and may be associated with severe injuries and quality-of-life impairment, particularly in older adults. Various diagnostic and therapeutic strategies have been created and implemented over decades, leading to significant improvements in diagnostic accuracy and treatment effectiveness. In recent years, diagnosis and treatment have further evolved according to an innovative approach focused on the hemodynamic mechanism underlying syncope, based upon the assumption that knowledge of the syncope mechanism is a prerequisite for effective syncope prevention and treatment. Therefore, a new classification of syncope has been proposed, which defines two main syncope phenotypes with different predominant mechanisms: the hypotensive phenotype, where hypotension or vasodepression prevails, and the bradycardic phenotype, where cardioinhibition prevails. Identification of syncope phenotype — bradycardic or hypotensive/vasodepressive — represents the first step towards personalized management of syncope, characterized by customized interventions for prevention. The present review aims to illustrate these new developments in the diagnosis and therapy of non-cardiac syncope within a mechanism-based perspective. Diagnosis and therapy of bradycardic and hypotensive phenotypes are discussed, with a focus on recent evidence.

Abstract

Syncope is a frequent event in the general population. Approximately 1%–2% of all emergency department admissions are due to syncope and at least one-third of all people experience fainting in their life. Although consequences of cardiac syncope are generally feared, non-cardiac syncope is much more common and may be associated with severe injuries and quality-of-life impairment, particularly in older adults. Various diagnostic and therapeutic strategies have been created and implemented over decades, leading to significant improvements in diagnostic accuracy and treatment effectiveness. In recent years, diagnosis and treatment have further evolved according to an innovative approach focused on the hemodynamic mechanism underlying syncope, based upon the assumption that knowledge of the syncope mechanism is a prerequisite for effective syncope prevention and treatment. Therefore, a new classification of syncope has been proposed, which defines two main syncope phenotypes with different predominant mechanisms: the hypotensive phenotype, where hypotension or vasodepression prevails, and the bradycardic phenotype, where cardioinhibition prevails. Identification of syncope phenotype — bradycardic or hypotensive/vasodepressive — represents the first step towards personalized management of syncope, characterized by customized interventions for prevention. The present review aims to illustrate these new developments in the diagnosis and therapy of non-cardiac syncope within a mechanism-based perspective. Diagnosis and therapy of bradycardic and hypotensive phenotypes are discussed, with a focus on recent evidence.

Get Citation

Keywords

reflex syncope, bradycardia, hypotension, cardioinhibition, vasodepression, low blood pressure

About this article
Title

Syncope: new solutions for an old problem

Journal

Kardiologia Polska (Polish Heart Journal)

Issue

Vol 79, No 10 (2021)

Article type

Review paper

Pages

1068-1078

Published online

2021-10-14

DOI

10.33963/KP.a2021.0138

Pubmed

34668180

Bibliographic record

Kardiol Pol 2021;79(10):1068-1078.

Keywords

reflex syncope
bradycardia
hypotension
cardioinhibition
vasodepression
low blood pressure

Authors

Giulia Rivasi
Andrea Ungar
Angel Moya
Michele Brignole
Richard Sutton
Artur Fedorowski

References (94)
  1. Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J. 2018; 39(21): 1883–1948.
  2. Brignole M, Rivasi G. New insights in diagnostics and therapies in syncope: a novel approach to non-cardiac syncope. Heart. 2021; 107(11): 864–873.
  3. Linzer M, Pontinen M, Gold D, et al. Impairment of physical and psychosocial function in recurrent syncope. Journal of Clinical Epidemiology. 1991; 44(10): 1037–1043.
  4. van Dijk N, Sprangers MA, Colman N, et al. Clinical factors associated with quality of life in patients with transient loss of consciousness. J Cardiovasc Electrophysiol. 2006; 17(9): 998–1003.
  5. Gill TM, Murphy TE, Gahbauer EA, et al. Association of injurious falls with disability outcomes and nursing home admissions in community-living older persons. Am J Epidemiol. 2013; 178(3): 418–425.
  6. Vellas BJ, Wayne SJ, Romero LJ, et al. Fear of falling and restriction of mobility in elderly fallers. Age Ageing. 1997; 26(3): 189–193.
  7. Gill TM, Murphy TE, Gahbauer EA, et al. The course of disability before and after a serious fall injury. JAMA Intern Med. 2013; 173(19): 1780–1786.
  8. Yasa E, Ricci F, Magnusson M, et al. Cardiovascular risk after hospitalisation for unexplained syncope and orthostatic hypotension. Heart. 2018; 104(6): 487–493.
  9. Rivasi G, Rafanelli M, Ungar A. Usefulness of tilt testing and carotid sinus massage for evaluating reflex syncope. Am J Cardiol. 2018; 122(3): 517–520.
  10. Ungar A, Tesi F, Chisciotti VM, et al. Assessment of a structured management pathway for patients referred to the Emergency Department for syncope: results in a tertiary hospital. Europace. 2016; 18(3): 457–462.
  11. Brignole M, Ungar A, Casagranda I, et al. Prospective multicentre systematic guideline-based management of patients referred to the Syncope Units of general hospitals. Europace. 2010; 12(1): 109–118.
  12. Brignole M, Rivasi G, Sutton R, et al. Low-blood pressure phenotype underpins the tendency to reflex syncope. J Hypertens. 2021; 39(7): 1319–1325.
  13. Stewart JM, Medow MS, Sutton R, et al. Mechanisms of vasovagal syncope in the young: reduced systemic vascular resistance versus reduced cardiac output. J Am Heart Assoc. 2017; 6(1).
  14. Nilsson D, Sutton R, Tas W, et al. Orthostatic changes in hemodynamics and cardiovascular biomarkers in dysautonomic patients. PLoS One. 2015; 10(6): e0128962.
  15. Kohno R, Detloff BLS, Chen LY, et al. Greater early epinephrine rise with head-up posture: A marker of increased syncope susceptibility in vasovagal fainters. J Cardiovasc Electrophysiol. 2019; 30(3): 289–296.
  16. Torabi P, Ricci F, Hamrefors V, et al. Impact of cardiovascular neurohormones on onset of vasovagal syncope induced by head-up tilt. J Am Heart Assoc. 2019; 8(12): e012559.
  17. Lindenberger M, Fedorowski A, Melander O, et al. Cardiovascular biomarkers and echocardiographic findings at rest and during graded hypovolemic stress in women with recurrent vasovagal syncope. J Cardiovasc Electrophysiol. 2019; 30(12): 2936–2943.
  18. Fedorowski A, Burri P, Struck J, et al. Novel cardiovascular biomarkers in unexplained syncopal attacks: the SYSTEMA cohort. J Intern Med. 2013; 273(4): 359–367.
  19. Fedorowski A, Rivasi G, Torabi P, et al. Underlying hemodynamic differences are associated with responses to tilt testing. Sci Rep. 2021; 11(1): 17894.
  20. Wieling W, Jardine DL, de Lange FJ, et al. Cardiac output and vasodilation in the vasovagal response: An analysis of the classic papers. Heart Rhythm. 2016; 13(3): 798–805.
  21. van Dijk JG, Ghariq M, Kerkhof FI, et al. Novel methods for quantification of vasodepression and cardioinhibition during tilt-induced vasovagal syncope. Circ Res. 2020; 127(5): e126–e138.
  22. Rivasi G, Torabi P, Secco G, et al. Age-related tilt test responses in patients with suspected reflex syncope. Europace. 2021; 23(7): 1100–1105.
  23. Monahan KD. Effect of aging on baroreflex function in humans. Am J Physiol Regul Integr Comp Physiol. 2007; 293(1): R3–RR12.
  24. Pfeifer M, Weinberg C, Cook D, et al. Differential changes of autonomic nervous system function with age in man. The American Journal of Medicine. 1983; 75(2): 249–258.
  25. Sutton R, Brignole M. Twenty-eight years of research permit reinterpretation of tilt-testing: hypotensive susceptibility rather than diagnosis. Eur Heart J. 2014; 35(33): 2211–2212.
  26. Brignole M, Moya A, Menozzi C, et al. Proposed electrocardiographic classification of spontaneous syncope documented by an implantable loop recorder. Europace. 2005; 7(1): 14–18.
  27. Freeman R, Abuzinadah AR, Gibbons C, et al. Orthostatic hypotension: JACC state-of-the-art review. J Am Coll Cardiol. 2018; 72(11): 1294–1309.
  28. Fedorowski A, van Wijnen VK, Wieling W. Delayed orthostatic hypotension and vasovagal syncope: a diagnostic dilemma. Clin Auton Res. 2017; 27(4): 289–291.
  29. WHO Expert Committee on Arterial Hypertension & World Health Organization. Arterial hypertension: report of a WHO expert committee [‎meeting held in Geneva from 13 to 21 March 1978]; 1978‎: 7–56.
  30. Owens PE, Lyons SP, O'Brien ET. Arterial hypotension: prevalence of low blood pressure in the general population using ambulatory blood pressure monitoring. J Hum Hypertens. 2000; 14(4): 243–247.
  31. Pemberton J. Does constitutional hypotension exist? BMJ. 1989; 298(6674): 660–662.
  32. Jacob G, Barbic F, Glago M, et al. Cardiovascular autonomic profile in women with constitutional hypotension. J Hypertens. 2018; 36(10): 2068–2076.
  33. De Buyzere M, Clement DL, Duprez D. Chronic low blood pressure: a review . Cardiovasc Drugs Ther. 1998; 12(1): 29–35.
  34. Sim JJ, Zhou H, Bhandari S, et al. Low systolic blood pressure from treatment and association with serious falls/syncope. Am J Prev Med. 2018; 55(4): 488–496.
  35. Sink KM, Evans GW, Shorr RI, et al. Syncope, hypotension, and falls in the treatment of hypertension: results from the randomized clinical systolic blood pressure intervention trial. J Am Geriatr Soc. 2018; 66(4): 679–686.
  36. Rivasi G, Rafanelli M, Mossello E, et al. Drug-Related orthostatic hypotension: beyond anti-hypertensive medications. Drugs Aging. 2020; 37(10): 725–738.
  37. Rivasi G, Brignole M, Rafanelli M, et al. Blood pressure management in hypertensive patients with syncope: how to balance hypotensive and cardiovascular risk. J Hypertens. 2020; 38(12): 2356–2362.
  38. Scuteri A, Modestino A, Frattari A, et al. Occurrence of hypotension in older participants. Which 24-hour ABPM parameter better correlate with? J Gerontol A Biol Sci Med Sci. 2012; 67(7): 804–810.
  39. Ceccofiglio A, Mussi C, Rafanelli M, et al. Increasing prevalence of orthostatic hypotension as a cause of syncope with advancing age and multimorbidity. J Am Med Dir Assoc. 2019; 20(5): 586–588.
  40. Ungar A, Mussi C, Ceccofiglio A, et al. Etiology of syncope and unexplained falls in elderly adults with dementia: Syncope and Dementia (SYD) study. J Am Geriatr Soc. 2016; 64(8): 1567–1573.
  41. Liang Y, Fratiglioni L, Wang R, et al. Effects of biological age on the associations of blood pressure with cardiovascular and non-cardiovascular mortality in old age: A population-based study. Int J Cardiol. 2016; 220: 508–513.
  42. Rivasi G, Tortù V, D'Andria MF, et al. Hypertension management in frail older adults: a gap in evidence. J Hypertens. 2021; 39(3): 400–407.
  43. Stergiou GS, Palatini P, Parati G, et al. 2021 European Society of Hypertension practice guidelines for office and out-of-office blood pressure measurement. J Hypertens. 2021; 39(7): 1293–1302.
  44. Ishikawa J, Ishikawa Y, Edmondson D, et al. Age and the difference between awake ambulatory blood pressure and office blood pressure: a meta-analysis. Blood Press Monit. 2011; 16(4): 159–167.
  45. Vallelonga F, Romagnolo A, Merola A, et al. Detection of orthostatic hypotension with ambulatory blood pressure monitoring in parkinson's disease. Hypertens Res. 2019; 42(10): 1552–1560.
  46. Stuebner E, Vichayanrat E, Low DA, et al. Twenty-four hour non-invasive ambulatory blood pressure and heart rate monitoring in Parkinson's disease. Front Neurol. 2013; 4: 49.
  47. Alquadan KF, Singhania G, Koratala A, et al. Office orthostatic blood pressure measurements and ambulatory blood pressure monitoring in the prediction of autonomic dysfunction. Clin Hypertens. 2017; 23: 3.
  48. Giulia Rivasi, Antonella Groppelli, Michele Brignole, Davide Soranna, Antonella Zambon, Grzegorz Bilo, Martino Pengo, Bashaaer Sharad, Viktor Hamrefors, Martina Rafanelli, Giuseppe Dario Testa, Richard Sutton, Andrea Ungar, Artur Fedorowski GP Ambulatory blood pressure monitoring: a new diagnostic approach for detection of hypotension in reflex syncope. 2021(SynABPM 1 study): Submitted.
  49. Conroy SP, Harrison JK, Van Der Wardt V, et al. Ambulatory blood pressure monitoring in older people with dementia: a systematic review of tolerability. Age Ageing. 2016; 45(4): 456–462.
  50. Sutton R, Fedorowski A, Olshansky B, et al. Tilt testing remains a valuable asset. Eur Heart J. 2021; 42(17): 1654–1660.
  51. Torabi P, Ricci F, Hamrefors V, et al. Classical and delayed orthostatic hypotension in patients with unexplained syncope and severe orthostatic intolerance. Front Cardiovasc Med. 2020; 7: 21.
  52. Brignole M, Kessisoglu F, Croci F, et al. Complementary effectiveness of carotid sinus massage and tilt testing for the diagnosis of reflex syncope in patients older than 40 years: a cohort study. Europace. 2020; 22(11): 1737–1741.
  53. Sutton R. Reflex Atrioventricular Block. Front Cardiovasc Med. 2020; 7: 48.
  54. Brignole M, Deharo JC, Menozzi C, et al. The benefit of pacemaker therapy in patients with neurally mediated syncope and documented asystole: a meta-analysis of implantable loop recorder studies. Europace. 2018; 20(8): 1362–1366.
  55. Moya A, Brignole M, Menozzi C, et al. Mechanism of syncope in patients with isolated syncope and in patients with tilt-positive syncope. Circulation. 2001; 104(11): 1261–1267.
  56. Deharo JC, Guieu R, Mechulan A, et al. Syncope without prodromes in patients with normal heart and normal electrocardiogram: a distinct entity. J Am Coll Cardiol. 2013; 62(12): 1075–1080.
  57. Brignole M, Guieu R, Tomaino M, et al. Mechanism of syncope without prodromes with normal heart and normal electrocardiogram. Heart Rhythm. 2017; 14(2): 234–239.
  58. Joulia F, Coulange M, Lemaitre F, et al. Plasma adenosine release is associated with bradycardia and transient loss of consciousness during experimental breath-hold diving. Int J Cardiol. 2013; 168(5): e138–e141.
  59. Solari D, Tesi F, Unterhuber M, et al. Stop vasodepressor drugs in reflex syncope: a randomised controlled trial. Heart. 2017; 103(6): 449–455.
  60. Bress AP, Kramer H, Khatib R, et al. Potential Deaths Averted and Serious Adverse Events Incurred From Adoption of the SPRINT (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen in the United States: Projections From NHANES (National Health and Nutrition Examination Survey). Circulation. 2017; 135(17): 1617–1628.
  61. van der Wardt V, Harrison JK, Welsh T, et al. Withdrawal of antihypertensive medication: a systematic review. J Hypertens. 2017; 35(9): 1742–1749.
  62. Verhaeverbeke I, Mets T. Drug-induced orthostatic hypotension in the elderly: avoiding its onset. Drug Saf. 1997; 17(2): 105–118.
  63. Duschek S, Heiss H, Buechner B, et al. Hemodynamic determinants of chronic hypotension and their modification through vasopressor application. J Physiol Sci. 2009; 59(2): 105–112.
  64. Izcovich A, González Malla C, Manzotti M, et al. Midodrine for orthostatic hypotension and recurrent reflex syncope: A systematic review. Neurology. 2014; 83(13): 1170–1177.
  65. Eschlböck S, Wenning G, Fanciulli A. Evidence-based treatment of neurogenic orthostatic hypotension and related symptoms. J Neural Transm (Vienna). 2017; 124(12): 1567–1605.
  66. Sheldon R, Faris P, Tang A, et al. Midodrine for the prevention of vasovagal syncope: a randomized clinical trial. Ann Intern Med. 2021 [Epub ahead of print].
  67. Sheldon R, Raj SR, Rose MS, et al. POST 2 Investigators. Fludrocortisone for the prevention of Vasovagal syncope: a randomized, placebo-controlled trial. J Am Coll Cardiol. 2016; 68(1): 1–9.
  68. Hakamäki T, Rajala T, Lehtonen A. Ambulatory 24-hour blood pressure recordings in patients with Parkinson's disease with or without fludrocortisone. Int J Clin Pharmacol Ther. 1998; 36(7): 367–369.
  69. 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(1): 35–42.
  70. Kaufmann H, Freeman R, Biaggioni I, et al. Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial. Neurology. 2014; 83(4): 328–335.
  71. Hauser RA, Isaacson S, Lisk JP, et al. Droxidopa for the short-term treatment of symptomatic neurogenic orthostatic hypotension in Parkinson's disease (nOH306B). Mov Disord. 2015; 30(5): 646–654.
  72. Keating GM. Droxidopa: a review of its use in symptomatic neurogenic orthostatic hypotension. Drugs. 2015; 75(2): 197–206.
  73. Sheldon RS, Lei L, Guzman JC, et al. A proof of principle study of atomoxetine for the prevention of vasovagal syncope: the Prevention of Syncope Trial VI. Europace. 2019; 21(11): 1733–1741.
  74. Sheldon RS, Ritchie D, McRae M, et al. Norepinephrine transport inhibition for treatment of vasovagal syncope. J Cardiovasc Electrophysiol. 2013; 24(7): 799–803.
  75. Tajdini M, Aminorroaya A, Tavolinejad H, et al. Atomoxetine as an adjunct to nonpharmacological treatments for preventing vasovagal attacks in patients with recurrent vasovagal syncope: A pilot randomized-controlled trial. Int J Cardiol Heart Vasc. 2021; 34: 100789.
  76. Baron-Esquivias G, Morillo CA, Moya-Mitjans A, et al. Dual-Chamber pacing with closed loop stimulation in recurrent reflex vasovagal syncope: the SPAIN study. J Am Coll Cardiol. 2017; 70(14): 1720–1728.
  77. Brignole M, Russo V, Arabia F, et al. Cardiac pacing in severe recurrent reflex syncope and tilt-induced asystole. Eur Heart J. 2021; 42(5): 508–516.
  78. Glikson M, Nielsen JC, Kronborg MB, et al. 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. Eur Heart J. 2021; 42(35): 3427–3520.
  79. Rivasi G, Solari D, Rafanelli M, et al. Incidence and predictors of syncope recurrence after cardiac pacing in patients with carotid sinus syndrome. Int J Cardiol. 2018; 266: 119–123.
  80. Yasa E, Ricci F, Holm H, et al. Pacing therapy in the management of unexplained syncope: a tertiary care centre prospective study. Open Heart. 2019; 6(1): e001015.
  81. Brignole M, Tomaino M, Gargaro A. Vasovagal syncope with asystole: the role of cardiac pacing. Clin Auton Res. 2017; 27(4): 245–251.
  82. Brignole M, Donateo P, Tomaino M, et al. Benefit of pacemaker therapy in patients with presumed neurally mediated syncope and documented asystole is greater when tilt test is negative. Circ Arrhythmia Electrophysiol. 2014; 7(1): 10–16.
  83. Solari D, Maggi R, Oddone D, et al. Clinical context and outcome of carotid sinus syndrome diagnosed by means of the 'method of symptoms'. Europace. 2014; 16(6): 928–934.
  84. Saal DP, Thijs RD, van Zwet EW, et al. Temporal relationship of asystole to onset of transient loss of consciousness in tilt-induced reflex syncope. JACC Clin Electrophysiol. 2017; 3(13): 1592–1598.
  85. Brignole M, Iori M, Solari D, et al. Efficacy of theophylline in patients with syncope without prodromes with normal heart and normal ECG. Int J Cardiol. 2019; 289: 70–73.
  86. Hu F, Zheng L, Liang E, et al. Right anterior ganglionated plexus: The primary target of cardioneuroablation? Heart Rhythm. 2019; 16(10): 1545–1551.
  87. Sun W, Zheng L, Qiao Yu, et al. Catheter ablation as a treatment for vasovagal syncope: long-term outcome of endocardial autonomic modification of the left atrium. J Am Heart Assoc. 2016; 5(7).
  88. Pachon JC, Pachon EI, Cunha Pachon MZ, et al. Catheter ablation of severe neurally meditated reflex (neurocardiogenic or vasovagal) syncope: cardioneuroablation long-term results. Europace. 2011; 13(9): 1231–1242.
  89. Debruyne P, Rossenbacker T, Janssens L, et al. Durable physiological changes and decreased syncope burden 12 months after unifocal right-sided ablation under computed tomographic guidance in patients with neurally mediated syncope or functional sinus node dysfunction. Circ Arrhythm Electrophysiol. 2021; 14(6): e009747.
  90. Calo L, Rebecchi M, Sette A, et al. Catheter ablation of right atrial ganglionated plexi to treat cardioinhibitory neurocardiogenic syncope: a long-term follow-up prospective study. J Interv Card Electrophysiol. 2021; 61(3): 499–510.
  91. Aksu T, Güler TE, Bozyel S, et al. Cardioneuroablation in the treatment of neurally mediated reflex syncope: a review of the current literature. Turk Kardiyol Dern Ars. 2017; 45(1): 33–41.
  92. Wieling W, Jardine DL. Cardioneuroablation for recurrent vasovagal syncope: Important questions need to be answered. Heart Rhythm. 2021 [Epub ahead of print].
  93. O'Brien E, Murphy J, Tyndall A, et al. Twenty-four-hour ambulatory blood pressure in men and women aged 17 to 80 years: the Allied Irish Bank Study. J Hypertens. 1991; 9(4): 355–360.
  94. Ejaz AA, Sekhon IS, Munjal S. Characteristic findings on 24-h ambulatory blood pressure monitoring in a series of patients with Parkinson's disease. Eur J Intern Med. 2006; 17(6): 417–420.

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