Skip to main content
SpringerLink
Log in

Heart rate turbulence and deceleration capacity for risk prediction of serious arrhythmic events in Marfan syndrome

  • Original Paper
  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

Abstract

Objective

Marfan syndrome (MFS) is associated with a substantial risk for ventricular arrhythmia and sudden cardiac death (SCD). We used heart rate turbulence (HRT) and deceleration capacity (DC), to evaluate the risk stratification for these patients.

Methods

We enrolled 102 patients [45 male (44.1 %), age 40.5 ± 14.6 years] with MFS. Blood samples were obtained to determine N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Transthoracic echocardiography studies were conducted to evaluate heart function parameters and a 24-h holter ECG was performed. An analysis of two HRT parameters, turbulence onset (TO) and turbulence slope (TS), and DC was performed. Therefore, optimal cut-off values were calculated. Primary endpoint was the combination of SCD, ventricular arrhythmia and arrhythmogenic syncope. Secondary endpoint was total mortality.

Results

During a follow-up of 1145 ± 491 days, 12 (11.7 %) patients reached the primary and 8 (7.8 %) patients the secondary endpoint. Patients reaching the primary were significantly older, had a higher burden of premature ventricular complexes and NT-proBNP levels and lower values of LVEF, DC and HRT TS. Multivariate analysis identified NT-proBNP (HR 1.25, 95 % CI 1.01–1.56, p = .04) and the abnormal HRT (abnormal TS and/or TO (HR 7.04, 95 % CI 1.07–46.27, p = .04) as independent risk predictor of arrhythmogenic events.

Conclusion

Patients with Marfan syndrome are at risk for severe ventricular arrhythmias and SCD. Abnormal HRT parameters and NT-proBNP values are independent risk factors for arrhythmogenic events and SCD. The assessment of these tools may help predicting SCD patients with MFS.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. von Kodolitsch Y, Rybczynski M (2004) Cardiovascular aspects of the Marfan syndrome—A systematic review. In: Robinson PN, Godfrey M (eds) Marfan syndrome: a primer for clinicians and Scientists. Kluwer Academic Publishers, Dordrecht [ISBN 0-306-48238-X:45-69]

    Google Scholar 

  2. Devereux RB, Roman MJ (1999) Aortic disease in Marfan’s syndrome. N Engl J Med. 340:1358–1359

    Article  CAS  PubMed  Google Scholar 

  3. Savolainen A, Kupari M, Toivonen L, Kaitila I, Viitasalo M (1997) Abnormal ambulatory electrocardiographic findings in patients with the Marfan syndrome. J Intern Med 241(3):221–226

    Article  CAS  PubMed  Google Scholar 

  4. Yetman AT, Bornemeier RA, McCrindle BW (2003) Long-term outcome in patients with Marfan syndrome: is aortic dissection the only cause of sudden death? J Am Coll Cardiol 41(2):329–332

    Article  PubMed  Google Scholar 

  5. Hoffmann BA, Rybczynski M, Rostock T, Servatius H, Drewitz I, Steven D, Aydin A, Sheikhzadeh S, Darko V, von Kodolitsch Y, Willems S (2013) Prospective risk stratification of sudden cardiac death in Marfan’s syndrome. Int J Cardiol 167(6):2539–2545

    Article  PubMed  Google Scholar 

  6. Chen S, Fagan LF, Nouri S, Donahoe JL (1985) Ventricular dysrhythmias in children with Marfan’s syndrome. Am J Dis Child 139(3):273–276

    CAS  PubMed  Google Scholar 

  7. Aydin A, Adsay BA, Sheikhzadeh S, Keyser B, Rybczynski M, Sondermann C, Detter C, Steven D, Robinson PN, Berger J, Schmidtke J, Blankenberg S, Willems S, von Kodolitsch Y, Hoffmann BA (2013) Observational cohort study of ventricular arrhythmia in adults with Marfan syndrome caused by FBN1 mutations. PLoS One 8(12):e81281

    Article  PubMed Central  PubMed  Google Scholar 

  8. Schmidt G, Malik M, Barthel P, Schneider R, Ulm K, Rolnitzky L, Camm AJ, Bigger JT, Schömig A (1999) Heart-rate turbulence after ventricular premature beats as a predictor of mortality after acute myocardial infarction. Lancet 353(9162):1390–1396

    Article  CAS  PubMed  Google Scholar 

  9. Bauer A, Malik M, Schmidt G, Barthel P, Bonnemeier H, Cygankiewicz I, Guzik P, Lombardi F, Müller A, Oto A, Schneider R, Watanabe M, Wichterle D, Zareba W (2008) Heart rate turbulence: standards of measurement, physiological interpretation, and clinical use: International Society for Holter and Noninvasive Electrophysiology Consensus. J Am Coll Cardiol 52(17):1353–1365

    Article  PubMed  Google Scholar 

  10. Bauer A, Kantelhardt JW, Barthel P, Schneider R, Mäkikallio T, Ulm K, Hnatkova K, Schömig A, Huikuri H, Bunde A, Malik M, Schmidt G (2006) Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: cohort study. Lancet 367(9523):1674–1681

    Article  PubMed  Google Scholar 

  11. Bauer A, Barthel P, Müller A, Ulm K, Huikuri H, Malik M, Schmidt G (2009) Risk prediction by heart rate turbulence and deceleration capacity in postinfarction patients with preserved left ventricular function retrospective analysis of 4 independent trials. J Electrocardiol 42(6):597–601

    Article  PubMed  Google Scholar 

  12. Sade E, Aytemir K, Oto A, Nazli N, Ozmen F, Ozkutlu H, Tokgözoglu L, Aksöyek S, Ovünç K, Kabakçi G, Ozer N, Kes S (2003) Assessment of heart rate turbulence in the acute phase of myocardial infarction for long-term prognosis. Pacing Clin Electrophysiol 26(2 Pt 1):544–550

    Article  PubMed  Google Scholar 

  13. Grimm W, Schmidt G, Maisch B, Sharkova J, Müller HH, Christ M (2003) Prognostic significance of heart rate turbulence following ventricular premature beats in patients with idiopathic dilated cardiomyopathy. J Cardiovasc Electrophysiol 14(8):819–824

    Article  PubMed  Google Scholar 

  14. Koyama J, Watanabe J, Yamada A, Koseki Y, Konno Y, Toda S, Shinozaki T, Miura M, Fukuchi M, Ninomiya M, Kagaya Y, Shirato K (2002) Evaluation of heart-rate turbulence as a new prognostic marker in patients with chronic heart failure. Circ J 66(10):902–907

    Article  PubMed  Google Scholar 

  15. Balcioğlu S, Arslan U, Türkoğlu S, Ozdemir M, Cengel A (2007) Heart rate variability and heart rate turbulence in patients with type 2 diabetes mellitus with versus without cardiac autonomic neuropathy. Am J Cardiol 100(5):890–893

    Article  PubMed  Google Scholar 

  16. Zuern CS, Eick C, Rizas KD, Stoleriu C, Barthel P, Scherer C, Müller KA, Gawaz M, Bauer A (2012) Severe autonomic failure in moderate to severe aortic stenosis: prevalence and association with hemodynamics and biomarkers. Clin Res Cardiol 101(7):565–572

    Article  CAS  PubMed  Google Scholar 

  17. Ribeiro AL, Schmidt G, Sousa MR, Lombardi F, Gomes ME, Perez AA, Barros MV, Machado FS, Rocha MO (2003) Heart rate turbulence in Chagas disease. Pacing Clin Electrophysiol 26(1 Pt 2):406–410

    PubMed  Google Scholar 

  18. Rybczynski M, Bernhardt AM, Rehder U, Fuisting B, Meiss L, Voss U, Habermann C, Detter C, Robinson PN, Arslan-Kirchner M, Schmidtke J, Mir TS, Berger J, Meinertz T, von Kodolitsch Y (2008) The spectrum of syndromes and manifestations in individuals screened for suspected Marfan syndrome. Am J Med Genet A 146A(24):3157–3166

    Article  PubMed  Google Scholar 

  19. De Paepe A, Devereux RB, Dietz HC, Hennekam RC, Pyeritz RE (1996) Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet 62(4):417–426

    Article  PubMed  Google Scholar 

  20. Sheldon R, Rose S, Connolly S, Ritchie D, Koshman ML, Frenneaux M (2006) Diagnostic criteria for vasovagal syncope based on a quantitative history. Eur Heart J 27(3):344–350

    Article  PubMed  Google Scholar 

  21. Rybczynski M, Koschyk DH, Aydin MA, Robinson PN, Brinken T, Franzen O, Berger J, Hofmann T, Meinertz T, von Kodolitsch Y (2007) Tissue Doppler imaging identifies myocardial dysfunction in adults with Marfan syndrome. Clin Cardiol 30(1):19–24

    Article  PubMed  Google Scholar 

  22. Kiotsekoglou A, Sutherland GR, Moggridge JC, Kapetanakis V, Bajpai A, Bunce N, Mullen MJ, Louridas G, Nassiri DK, Camm J, Child AH (2009) Impaired right ventricular systolic function demonstrated by reduced atrioventricular plane displacement in adults with Marfan syndrome. Eur J Echocardiogr 10(2):295–302

    Article  PubMed  Google Scholar 

  23. Ramirez F, Dietz HC (2007) Marfan syndrome: from molecular pathogenesis to clinical treatment [Curr Opin Genet Dev 17 (2007) 252–258]. Curr Opin Genet Dev 17(4):367

    Article  CAS  Google Scholar 

  24. Leistner DM, Klotsche J, Pieper L, Palm S, Stalla GK, Lehnert H, Silber S, März W, Wittchen HU, Zeiher AM (2013) Prognostic value of NT-pro-BNP and hs-CRP for risk stratification in primary care: results from the population-based DETECT study. Clin Res Cardiol 102(4):259–268

    Article  PubMed  Google Scholar 

  25. Franke J, Lindmark A, Hochadel M, Zugck C, Koerner E, Keppler J, Ehlermann P, Winkler R, Zahn R, Katus HA, Senges J, Frankenstein L (2014) Gender aspects in clinical presentation and prognostication of chronic heart failure according to NT-proBNP and the Heart Failure Survival Score. Clin Res Cardiol 104(4):334–341

    Article  PubMed  Google Scholar 

  26. Cygankiewicz I, Zareba W, Vazquez R, Vallverdu M, Gonzalez-Juanatey JR, Valdes M, Almendral J, Cinca J, Caminal P, de Luna AB, Muerte Subita en Insuficiencia Cardiaca Investigators (2008) Heart rate turbulence predicts all-cause mortality and sudden death in congestive heart failure patients. Heart Rhythm 5(8):1095–1102

    Article  PubMed  Google Scholar 

  27. Moore RK, Groves DG, Barlow PE, Fox KA, Shah A, Nolan J, Kearney MT (2006) Heart rate turbulence and death due to cardiac decompensation in patients with chronic heart failure. Eur J Heart Fail 8(6):585–590

    Article  PubMed  Google Scholar 

  28. Alpendurada F, Wong J, Kiotsekoglou A, Banya W, Child A, Prasad SK, Pennell DJ, Mohiaddin RH (2010) Evidence for Marfan cardiomyopathy. Eur J Heart Fail 12(10):1085–1091

    Article  PubMed  Google Scholar 

  29. Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ (1987) Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 59:256–262

    Article  CAS  PubMed  Google Scholar 

  30. Kleiger RE, Miller JP, Krone RJ, Bigger JT Jr (1990) The independence of cycle length variability and exercise testing on predicting mortality of patients surviving acute myocardial infarction. The Multicenter Postinfarction Research Group. Am J Cardiol 65:408–411

    Article  CAS  PubMed  Google Scholar 

  31. Lin LY, Hwang JJ, Lai LP, Chan HL, Du CC, Tseng YZ, Lin JL (2004) Restoration of heart rate turbulence by titrated beta-blocker therapy in patients with advanced congestive heart failure: positive correlation with enhanced vagal modulation of heart rate. J Cardiovasc Electrophysiol 15(7):752–756

    Article  PubMed  Google Scholar 

  32. Gunduz H, Arinc H, Kayardi M, Akdemir R, Ozyildirim S, Uyan C (2006) Heart rate turbulence and heart rate variability in patients with mitral valve prolapse. Europace 8(7):515–520

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Special thanks to Prof. Dr. Georg Schmidt, Alexander Müller and Raphael Schneider, Department of Cardiology, Technical University, Munich, Germany for providing the custom-made software.

Conflict of interest

All Authors declare that there is no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Cardiology - Electrophysiology, University Heart Center, University Hospital Hamburg, Martinistr. 52, 20246, Hamburg, Germany

    Benjamin N. Schaeffer, Julia Moser, Mario Jularic, Doreen Schreiber, Stephan Willems & Boris A. Hoffmann

  2. Department of Cardiology, University Heart Center, University Hospital Hamburg, Hamburg, Germany

    Meike Rybczynski, Sara Sheikhzadeh, Ruken Ö. Akbulak & Yskert von Kodolitsch

  3. Department of Medical Biometry and Epidemiology, University Hospital Hamburg, Hamburg, Germany

    Anne Daubmann

Authors
  1. Benjamin N. Schaeffer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Meike Rybczynski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sara Sheikhzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ruken Ö. Akbulak
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Julia Moser
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mario Jularic
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Doreen Schreiber
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anne Daubmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Stephan Willems
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yskert von Kodolitsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Boris A. Hoffmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Benjamin N. Schaeffer.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schaeffer, B.N., Rybczynski, M., Sheikhzadeh, S. et al. Heart rate turbulence and deceleration capacity for risk prediction of serious arrhythmic events in Marfan syndrome. Clin Res Cardiol 104, 1054–1063 (2015). https://doi.org/10.1007/s00392-015-0873-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-015-0873-9

Keywords

Search

Navigation