Risk stratification of sudden cardiac death in young patients without structural heart disease

Aim. To stratify the risk of recurrent syncope and the risk of sudden cardiac death (SCD) / sudden cardiac arrest in young patients with cardiogenic syncope without structural heart disease using the Evaluation of Guidelines in Syncope Study (EGSYS score). To conduct the first retrospective analysis of the personalized risk of sudden cardiac death, as well as the sensitivity of the EGSYS scale for patients with different nosological entities.

Methods. The study included 63 patients with syncope aged 18 to 44 years, the average age of the patients was 25,98±6,69 years. The patients were divided into 5 groups: the first group (12 patients, average age: 21,84±4,37 years) consisted of patients with cardiac channelopathies, the second group (16 patients, average age 25,84±6,56 years) consisted of patients with sinus node dysfunction in the form of arrest of the Kiss-Fleck node, the third group consisted of patients with atrioventricular block (15 patients, the average age 26,71±7,13 years), the fourth group consisted of patients with paroxysmal monomorphic and polymorphic ventricular tachycardia (15 patients, the average age of the group was 25,74±7,79 years), the fifth group consisted of patients with syncope in the Wolff-Parkinson-White (WPW) syndrome (5 patients, average age - 25,64±3,05 years). The frequency of recurrence of syncope and SCD episodes was assessed over a 2-year period from the time of the first syncope. The EGSYS score was used to stratify the risk of recurrence of syncope and SCD.

Results: A total of 23 patients, or 36.5% of the study population, had an EGSYS score more than 5 points (very high), with a 2-year risk of SCD of 21% and a risk of recurrent syncope of 77%. In addition, the highest score on the EGSYS scale was associated with a higher frequency of cardiogenic syncope and SCD episodes. Patients with cardiac channelopathies had the highest EGSYS score (mean score 5.84), which was associated with the highest incidence of syncope and episodes of SCD with cardiopulmonary resuscitation over a 2-year period (r=0,58, p=0,01). The risk of developing SCD over a 2-year period in the group of patients with sinus node dysfunction (sinus node arrest) does not exceed the average population (less than 2%), which was associated with the absence of episodes of sudden cardiac death (sudden cardiac arrest) for a period of 2 years in the patients in this group. The highest validation of the EGSYS score and the frequency of syncope over a 2-year period were in patients with ventricular tachycardia ((r=0,73, р=0,002).

Conclusion: Thus, already at the debut syncopal state there is a possibility of determining the personalized risk of recurrent syncope and sudden cardiac death using the EGSYS scale. According to the study, the area of the highest sensitivity of the scale was patients with ventricular tachycardia (the main cause of SCD), which allows us to consider this scale as a basis for constructing a prognostic model for stratifying the risk of sudden cardiac death in young patients with cardiogenic syncope without structural heart disease.

1. Brignole M, Moya A, de Lange FJ, et al. ESC scientific document group. 2018 ESC guidelines for the diagnosis and management of syncope. Eur. Heart J. 2018;39(21): 1883-1948. https://doi.org/10.1093/eurheartj/ehy037.

2. Priori SG, Blomström-Lundqvist C, Mazzanti A. еt al. ESC Scientific Document Group. 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). Eur. Heart J. 2015;36(41): 2793-2867. https://doi.org/10.1093/eurheartj/ehv316.

3. Shen WK, Sheldon RS, Benditt DG, 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(8):e155-217. https://doi.org/10.1016/j.hrthm.2017.03.004.

4. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Circulation. 2018;138(13):e272- 391. https://doi.org/10.1161/CIR.0000000000000549.

5. Wang W, Orgeron G, Tichnell C, еt al. Impact of exercise restriction on arrhythmic risk among patients with arrhythmogenic right ventricular cardiomyopathy. J. Am. Heart Assoc. 2018;7(12): e008843. https://doi.org/10.1161/JAHA.118.008843.

6. Shilova MA, Mamedov MN. Sudden cardiac death in young people: risk factors, causes, and morphological equivalents. Cardiology. 2015;7(55): 78- 53. (In Russ.)

7. Maron BJ, Doerer JJ, Haas TS, et al. Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, 1980-2006. Circulation. 2009;119(8):1085-1092. https://doi.org/10.1161/CIRCULATIONAHA.108.804617.

8. Gregoratos G, Abrams J, Epstein AE, et al. ACC/AHA/ NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices: Summary Article: A Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines). Circulation. 2002; 106:2145-61. https://doi.org/10.1016/S0735-1097(02)02528-7.

9. Brugada J, Vardas P, Wolpert C. The EHRA White Book 2009. The Current Status of Cardiac Electrophysiology in ESC Member Countries. France: ESC; 2009.

10. Brignole M, Alboni P, Bendittetal DG. Guidelines on management (diagnosis and treatment) of syncope - update 2004. The task force on syncope, European Society of Cardiology. European Heart Journal. 2004;25(22): 2054- 2072. https://doi.org/10.1016/j.eupc.2004.08.008.

11. Soteriades ES, Evans JC, Larsonetal MG. Incidenceand prognosis of syncope. The New England Journal of Medicine. 2002;347(12): 878-885. https://doi.org/10.1056/NEJMoa012407.

12. Ackerman MJ, Priori SG, Dubin AM, еt al. Beta-blocker therapy for long QT syndrome and catecholaminergic polymorphic ventricular tachycardia: are all beta-blockers equivalent? Heart Rhythm. 2017;14(1): e41-44. https://doi.org/10.1016/j.hrthm.2016.09.012.

13. Moss AJ, Schwartz PJ, Crampton RS, et al. The long QT syndrome. Prospective longitudinal study of 328 families. Circulation. 1991;84(3): 1136-1144. https://doi.org/10.1161/01.CIR.84.3.1136.

14. Brignole M, Disertori M, Menozzi C, et al. Management of syncope referred urgently to general hospitals with and without syncope units. Europace. 2003;5(3): 293-298. https://doi.org/10.1016/S1099-5129(03)00047-3.

15. Kenny RA, O’Shea D, Walker HF. Impact of a dedicated syncope and falls facility for older adults on emergency beds. Age and Ageing. 2002;31(4):272-275. https://doi.org/10.1093/ageing/31.4.272.

16. Shen WK, Decker WW, Smarsetal PA,Syncope Evaluation in the Emergency Department Study (SEEDS): a multidisciplinary approach to syncope management. Circulation. 2005;110(24): 3636-3645. https://doi.org/10.1161/01.CIR.0000149236.92822.07.

17. Von Scheidt W, Bosch R, Klingenheben T, еt al. Commentary on the 2018 ESC Guidelines for the diagnosis and management of syncope. Kardiologe. 2019;13(3): 131- 137. https://doi.org/10.1007/s12181-019-0317-2.

18. Colivicchi F, Ammirati F, Melina D, et al. Development and prospective validation of a risk stratification system for patients with syncope in the emergency department: TheOESIL risk score. European Heart Journal. 2003;24(9): 811-819.https://doi.org/10.1016/S0195-668X(02)00827-8.

19. 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(12): 1620-1626. https://doi.org/10.1136/hrt.2008.143123.

20. João de Sousa B, Azevedo P, Mota T. EGSYS score for the prediction of cardiac etiology in syncope: Is it useful in an outpatient setting? Rev Port Cardiol. 2020;39(5): 255- 261. https://doi.org/10.1016/j.repc.2019.09.009.

21. Li Y, Liu J, Wang M. Predictive value of EGSYS score in the differential diagnosis of cardiac syncope and neurally mediated syncope in children. Front Cardiovascular Medicine. 2023;17(10): 1091778. https://doi.org/10.3389/fcvm.2023.1091778.

22. Moya A, Sutton R, Ammirati F, et al. Guidelines for the diagnosis and management of syncope (version 2009). European Heart Journal. 2009;30(21): 2631-2671. https://doi.org/10.1093/eurheartj/ehp298

23. Zamani M, Esmailian M, Yoosefian Z. QT interval in pregnant and non-pregnant women. Emergency. 2014;2(1): 22-25.

24. Linzer M, Yang EN, Estes III NA, et al. Clinical guideline: diagnosing syncope: part 1: value of history, physical examination, and electrocardiography. Annals of Internal Medicine. 1997;126(12): 989-996. https://doi.org/10.7326/0003-4819-126-12-199706150-00012.

25. Priori SG, Blomstrum-Lundqvist C, Mazzanti A, et al. ESC 2015 guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. European Heart Journal. 2015;36(41): 2793- 2867. https://doi.org/10.1016/j.rec.2016.01.001.

26. Vincent GM. The long QT and Brugada syndromes: causes of unexpected syncope and sudden cardiac death in children and young adults. Seminars in Pediatric Neurology. 2005;12: 15-24. https://doi.org/10.1016/j.spen.2004.11.008.

27. Patel Ch, Antzelevich Ch. Pharmacological approach to the treatment of long and short QT syndromes. Pharmacology and Therapeutices. 2008;118: 138-151. https://doi.org/10.1016/j.pharmthera.2008.02.001.

28. Obeyesekere MN, Antzelevitch C, Krahn AD. Management of ventricular arrhythmias in suspected channelopathies. Circulation: Arrhythmia and Electrophysiology. 2015;8: 221-231. https://doi.org/10.1161/CIRCEP.114.0023.

29. Ronald W, Verkerk A. Long QT Syndrome and Sinus Bradycardia-A Mini Review. Frontiers in Cardiovascular Medicine. 2018;5: 106. https://doi.org/10.3389/fcvm.2018.00106.

30. Chandler NJ, Greener ID, Tellez JO, et al. Molecular architecture of the human sinus node: insights into the function of the cardiac pacemaker. Circulation. 2009;119: 1562-75. https://doi.org/10.1161/CIRCULATIONAHA.108.804369.

31. Schwartz PJ. Idiopathic long QT syndrome: progress and questions. American Heart Journal. 1985;109: 399- 411. https://doi.org/10.1016/0002-8703(85)90626-X.

32. Num AK, Gislason G, Christianse CB, еt al. Syncope and motor vehicle crash risk: a Danish Nationwide study. JAMA Intern. Med. 2016;176(4): 503-510. https://doi:10.1001/jamainternmed.2015.8606.

33. Margulescu AD, Anderson MH. A review of driving restrictions in patients at risk of syncope and cardiac arrhythmias associated with sudden incapacity: differing global approaches to regulation and risk. Arrhythm Electrophysiol Rev. 2019;8(2): 90-98. https://doi:10.15420/aer.2019.13.2.

34. Quartieri F, Cauti F, Calo L, et al. Retrospective analysis of Confirm Rx SharpSense Technology using Real-World Data from the SMART Registry. Presented at Asia Pacific Heart Rhythm Society (APHRS); Bangkok, Thailand; Oct 27-29, 2019.

35. Piorkowski C, Shaik NA, Tilz RR, et al. Episode Rates with Confirm Rx SharpSense Technology using a Real-World Monitoring Database. Presented at Asia Pacific Heart Rhythm Society (APHRS); Bangkok, Thailand; Oct 27-29, 2019.

36. Piorkowski C, Manyam H, Lakkireddy D, et al. Effectiveness and performance of Confirm Rx SharpSense Technology: A Multi-center Retrospective Analysis. Presented at Asia Pacific Heart Rhythm Society (APHRS); Bangkok, Thailand; Oct 27-29, 2019.

37. Werf C, Hofman N, Tan H, et al. Diagnostic yield in sudden unexplained death and aborted cardiac arrest in the young: The experience of a tertiary referral center in The Netherlands. Heart Rhythm. 2010;7: 1383-1389. https://doi:10.1016/j.hrthm.2010.05.036.

38. Kariman H, Harati S, Safari S, et al. Validation of EGSYS Score in Prediction of Cardiogenic Syncope. Emergency Medicine International. 2015. https://doi.org/10.1155/2015/515370

39. Bispoa J, Azevedoa P, Mota T, et al. EGSYS score for the prediction in cardiac etiology in syncope: Is it useful in an out-patient setting? Revista Portuguesa de Cardiologia. 2020;39(5): 255-261. https://doi.org/10.1016/j.repce.2020.05.012.

40. Ungar A, Del Rosso A, Giada F, et al. Early and late outcome of treated patients referred for syncope to emergency department: the EGSYS 2 follow-up study. European Heart Journal. 2010 Aug;31(16): 2021-6. https://doi.org/10.1093/eurheartj/ehq115.