Advertisement

Restitution metrics in Brugada syndrome: a systematic review and meta-analysis

Abstract

Background

Brugada syndrome (BrS) is an ion channelopathy that predisposes affected subjects to ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death. Restitution analysis has been examined in BrS patients but not all studies have reported significant differences between BrS patients and controls. Therefore, we conducted a systematic review and meta-analysis to investigate the different restitution indices used in BrS.

Methods

PubMed and Embase were searched until April 7, 2019, identifying 20 and 27 studies.

Results

A total of ten studies involving 178 BrS (mean age 38 years old, 63% male) and 102 controls (mean age 31 years old, 42% male) were included in this systematic review. Pacing was carried out at the right ventricular outflow tract (RVOT)/right ventricular apex (RPA) (n = 4), RPA (n = 4), or right atrium (RA) (n = 1). Basic cycle lengths of 400 (n = 4), 500 (n = 2), 600 (n = 6) and 750 ms (n = 1) were used. Recording methods include electrograms (n = 4), monophasic action potentials (n = 5), and electrocardiograms (n = 1). Signals were obtained from the RVOT (n = 8), RVA (n = 3), RA (n = 1), or the body surface (n = 1). The maximum restitution slope for endocardial repolarization at the RVOT was 0.87 for BrS patients (n = 5; 95% confidence interval [CI] 0.68–1.07) compared with 0.74 in control subjects (n = 4; 95% CI 0.42–1.06), with a significant mean difference of 0.40 (n = 4; 95% CI 0.11–0.69; P = 0.007).

Conclusions

Steeper endocardial repolarization restitution slopes are found in BrS patients compared with controls at baseline. Restitution analysis can provide important information for risk stratification in BrS.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 99

This is the net price. Taxes to be calculated in checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Change history

  • 15 January 2020

    The original version of this article unfortunately has a typo error. The name of the author “<Emphasis Type="Bold">Kamalan Jeeveratnam</Emphasis>” should be presented as “<Emphasis Type="Bold">Kamalan Jeevaratnam</Emphasis>” as shown above.

References

  1. 1.

    Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol. 1992;20(6):1391–6.

  2. 2.

    Sakamoto S, Takagi M, Tatsumi H, Doi A, Sugioka K, Hanatani A, et al. Utility of T-wave alternans during night time as a predictor for ventricular fibrillation in patients with Brugada syndrome. Heart Vessel. 2016;31(6):947–56.

  3. 3.

    Kawazoe H, Nakano Y, Ochi H, Takagi M, Hayashi Y, Uchimura Y, et al. Risk stratification of ventricular fibrillation in Brugada syndrome using noninvasive scoring methods. Heart Rhythm. 2016;13(10):1947–54.

  4. 4.

    Uchimura-Makita Y, Nakano Y, Tokuyama T, Fujiwara M, Watanabe Y, Sairaku A, et al. Time-domain T-wave alternans is strongly associated with a history of ventricular fibrillation in patients with Brugada syndrome. J Cardiovasc Electrophysiol. 2014;25(9):1021–7.

  5. 5.

    Tse G, Wong ST, Tse V, Yeo JM. Determination of action potential wavelength restitution in Scn5a(+/−) mouse hearts modelling human Brugada syndrome. J Geriatr Cardiol. 2017;14(9):595–6.

  6. 6.

    Tse G, Wong ST, Tse V, Yeo JM. Variability in local action potential durations, dispersion of repolarization and wavelength restitution in aged wild-type and Scn5a+/− mouse hearts modeling human Brugada syndrome. J Geriatr Cardiol. 2016;13(11):930–1.

  7. 7.

    Franz MR, Schaefer J, Schöttler M, Seed WA, Noble MI. Electrical and mechanical restitution of the human heart at different rates of stimulation. Circ Res. 1983;53(6):815–22.

  8. 8.

    Zaniboni M. Short-term action potential memory and electrical restitution: a cellular computational study on the stability of cardiac repolarization under dynamic pacing. PLoS One. 2018;13(3):e0193416.

  9. 9.

    Osadchii OE. Role of abnormal repolarization in the mechanism of cardiac arrhythmia. Acta Physiol (Oxford). 2017;220(Suppl 712):1–71.

  10. 10.

    Osadchii OE. Effects of ventricular pacing protocol on electrical restitution assessments in guinea-pig heart. Exp Physiol. 2012;97(7):807–21.

  11. 11.

    Tse G, Liu T, Li G, Keung W, Yeo JM, Fiona Chan YW, et al. Effects of pharmacological gap junction and sodium channel blockade on S1S2 restitution properties in Langendorff-perfused mouse hearts. Oncotarget. 2017;8(49):85341–52.

  12. 12.

    Tse G, Wong ST, Tse V, Yeo JM. Restitution analysis of alternans using dynamic pacing and its comparison with S1S2 restitution in heptanol-treated, hypokalaemic Langendorff-perfused mouse hearts. Biomed Rep. 2016;4(6):673–80.

  13. 13.

    Srinivasan NT, Orini M, Providencia R, Dhinoja MB, Lowe MD, Ahsan SY, et al. Prolonged action potential duration and dynamic transmural action potential duration heterogeneity underlie vulnerability to ventricular tachycardia in patients undergoing ventricular tachycardia ablation. Europace. 2019;21(4):616–25.

  14. 14.

    Orini M, Taggart P, Srinivasan N, Hayward M, Lambiase PD. Interactions between activation and repolarization restitution properties in the intact human heart: in-vivo whole-heart data and mathematical description. PLoS One. 2016;11(9):e0161765.

  15. 15.

    Orini M, et al. Analytical description of the slope of the APD-restitution curve to assess the interacting contribution of conduction and repolarization dynamics. Conf Proc IEEE Eng Med Biol Soc. 2015;2015:5672–5.

  16. 16.

    Gomes J, Finlay M, Ahmed AK, Ciaccio EJ, Asimaki A, Saffitz JE, et al. Electrophysiological abnormalities precede overt structural changes in arrhythmogenic right ventricular cardiomyopathy due to mutations in desmoplakin-a combined murine and human study. Eur Heart J. 2012;33(15):1942–53.

  17. 17.

    Nolasco JB, Dahlen RW. A graphic method for the study of alternation in cardiac action potentials. J Appl Physiol. 1968;25(2):191–6.

  18. 18.

    Banville I, Gray RA. Effect of action potential duration and conduction velocity restitution and their spatial dispersion on alternans and the stability of arrhythmias. J Cardiovasc Electrophysiol. 2002;13(11):1141–9.

  19. 19.

    Weiss JN, et al. Electrical restitution and cardiac fibrillation. J Cardiovasc Electrophysiol. 2002;13(3):292–5.

  20. 20.

    Postema PG, van Dessel P, de Bakker JM, Dekker LR, Linnenbank AC, Hoogendijk MG, et al. Slow and discontinuous conduction conspire in Brugada syndrome: a right ventricular mapping and stimulation study. Circ Arrhythm Electrophysiol. 2008;1(5):379–86.

  21. 21.

    Bhar-Amato J, Finlay M, Santos D, Orini M, Chaubey S, Vyas V, et al. Pharmacological modulation of right ventricular endocardial-epicardial gradients in Brugada syndrome. Circ Arrhythm Electrophysiol. 2018;11(9):e006330.

  22. 22.

    S S, et al. Risk stratification of sudden cardiac death: positive evaluation of novel surface electrocardiogram biomarkers in a Brugada syndrome cohort. EP Europace. 2016;17(suppl_5):v10–3.

  23. 23.

    Marshall SC, et al. Predictors of driving ability following stroke: a systematic review. Top Stroke Rehabil. 2007;14(1):98–114.

  24. 24.

    Ashino S, et al. Effects of quinidine on the action potential duration restitution property in the right ventricular outflow tract in patients with brugada syndrome. Circ J. 2011;75(9):2080–6.

  25. 25.

    Kofune M, Watanabe I, Ohkubo K, Ashino S, Okumura Y, Nagashima K, et al. Abnormal atrial repolarization and depolarization contribute to the inducibility of atrial fibrillation in Brugada syndrome. Int Heart J. 2010;51(3):159–65.

  26. 26.

    Hayashi M, Takatsuki S, Maison-Blanche P, Messali A, Haggui A, Milliez P, et al. Ventricular repolarization restitution properties in patients exhibiting type 1 Brugada electrocardiogram with and without inducible ventricular fibrillation. J Am Coll Cardiol. 2008;51(12):1162–8.

  27. 27.

    Lambiase PD, et al. High-density substrate mapping in Brugada syndrome: combined role of conduction and repolarization heterogeneities in arrhythmogenesis. Circulation. 2009;120(2):106–17 1-4.

  28. 28.

    Nishii N, Nagase S, Morita H, Kusano KF, Namba T, Miura D, et al. Abnormal restitution property of action potential duration and conduction delay in Brugada syndrome: both repolarization and depolarization abnormalities. Europace. 2010;12(4):544–52.

  29. 29.

    Sang Weon P, et al. Relation between action potential duration restitution kinetics and inducibility of ventricular fibrillation in brugada syndrome. J Am Coll Cardiol. 2003;41(6, Supplement 1):105.

  30. 30.

    Nerbonne JM, Kass RS. Molecular physiology of cardiac repolarization. Physiol Rev. 2005;85(4):1205–53.

  31. 31.

    Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, et al. Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature. 1998;392(6673):293–6.

  32. 32.

    Tse G, et al. Electrophysiological mechanisms of Brugada syndrome: insights from pre-clinical and clinical studies. Front Physiol. 2016;7:467.

  33. 33.

    Shimizu W, Aiba T, Kamakura S. Mechanisms of disease: current understanding and future challenges in Brugada syndrome. Nat Clin Pract Cardiovasc Med. 2005;2(8):408–14.

  34. 34.

    Rodriguez-Manero M, et al. Monomorphic ventricular tachycardia in patients with Brugada syndrome: a multicenter retrospective study. Heart Rhythm. 2016;13(3):669–82.

  35. 35.

    Robyns T, et al. Evaluation of index of cardio-electrophysiological balance (iCEB) as a new biomarker for the identification of patients at increased arrhythmic risk. Ann Noninvasive Electrocardiol. 2016;21(3):294–304.

  36. 36.

    Tse G. Both transmural dispersion of repolarization and of refractoriness are poor predictors of arrhythmogenicity: a role for iCEB (QT/QRS)? J Geriatr Cardiol. 2016;13(9):813–4.

  37. 37.

    Trethewey SP, Nicolson WB, Ng GA. Investigation of the relationship between two novel electrocardiogram-based sudden cardiac death risk markers and autonomic function. J Electrocardiol. 2018;51(5):889–94.

  38. 38.

    Nicolson WB, McCann G, Smith MI, Sandilands AJ, Stafford PJ, Schlindwein FS, et al. Prospective evaluation of two novel ECG-based restitution biomarkers for prediction of sudden cardiac death risk in ischaemic cardiomyopathy. Heart. 2014;100(23):1878–85.

  39. 39.

    Nicolson WB, et al. A novel surface electrocardiogram-based marker of ventricular arrhythmia risk in patients with ischemic cardiomyopathy. J Am Heart Assoc. 2012;1(4):e001552.

  40. 40.

    Mironov S, Jalife J, Tolkacheva EG. Role of conduction velocity restitution and short-term memory in the development of action potential duration alternans in isolated rabbit hearts. Circulation. 2008;118(1):17–25.

  41. 41.

    Sabir IN, Li LM, Jones VJ, Goddard CA, Grace AA, Huang CL. Criteria for arrhythmogenicity in genetically-modified Langendorff-perfused murine hearts modelling the congenital long QT syndrome type 3 and the Brugada syndrome. Pflugers Arch. 2008;455(4):637–51.

  42. 42.

    Aiba T, Shimizu W, Hidaka I, Uemura K, Noda T, Zheng C, et al. Cellular basis for trigger and maintenance of ventricular fibrillation in the Brugada syndrome model: high-resolution optical mapping study. J Am Coll Cardiol. 2006;47(10):2074–85.

  43. 43.

    Clayton RH, Taggart P. Regional differences in APD restitution can initiate wavebreak and re-entry in cardiac tissue: a computational study. Biomed Eng Online. 2005;4(1):54.

  44. 44.

    Tse G, Wong ST, Tse V, Lee YT, Lin HY, Yeo JM. Cardiac dynamics: Alternans and arrhythmogenesis. J Arrhythm. 2016;32(5):411–7.

  45. 45.

    Glynn P, Onal B, Hund TJ. Cycle length restitution in Sinoatrial node cells: a theory for understanding spontaneous action potential dynamics. PLoS One. 2014;9(2):e89049.

  46. 46.

    Haanschoten DM, et al. Catheter ablation in highly symptomatic Brugada patients: a Dutch case series. Clin Res Cardiol. 2019.

  47. 47.

    Aanhaanen WTJ, et al. Epicardial and subsequent endocardial ablation in a patient with Brugada syndrome. JACC Clin Electrophysiol. 2018;4(9):1268–70.

  48. 48.

    Leong KM, et al. Repolarization abnormalities unmasked with exercise in sudden cardiac death survivors with structurally normal hearts. J Cardiovasc Electrophysiol. 2017.

Download references

Author information

Correspondence to Gary Tse or Konstantinos P. Letsas.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The original version of this article was revised: The name of the author should be written as Kamalan Jeevaratnam.

Electronic supplementary material

ESM 1

(DOCX 18 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Tse, G., Lee, S., Gong, M. et al. Restitution metrics in Brugada syndrome: a systematic review and meta-analysis. J Interv Card Electrophysiol (2019) doi:10.1007/s10840-019-00675-z

Download citation

Keywords

  • Restitution
  • Repolarization
  • Conduction
  • Brugada syndrome