Skip to main content

Prognostic value of heart rate variability and ventricular arrhythmias during 13-year follow-up in patients with mild to moderate heart failure

Abstract

Background

In contrast to patients with moderate to severe chronic heart failure (CHF), data regarding long-term outcome in patients with mild CHF are scarce. We examined the place of Holter monitoring to study the prognostic value of ventricular arrhythmias and heart rate variability (HRV) in patients with mild to moderate CHF during long-term follow-up.

Methods

We studied 90 patients with mild to moderate CHF and NYHA class II who had been enrolled in the Dutch Ibopamine Multicenter Trial. At baseline their mean age was 60.5 ± 8.0 years, left ventricular ejection fraction (LVEF) was 0.29 ± 0.09, and 85% were males. At the start of the study, patients were only using diuretics, while digoxin, and particularly ACE inhibitors and β-blockers were initiated later. Univariate and multivariate proportional hazard analyses were performed.

Results

At baseline 80% of patients were in NYHA class II, and 20% were in class III; their mean age was 60 years, mean LVEF was 0.29, and 85% were men. During a follow-up of 13 years, 47 patients (53%) died. Cardiovascular (CV) death occurred in 39 patients, of which 28 were sudden cardiac death (SCD). For both CV death and SCD, LVEF <30% and ventricular premature beats/h (>20) were independent risk markers. Of the HRV parameters, total power (>2,500 ms2) was an important risk marker for CV death, but not for SCD.

Conclusion

The present 13-year follow-up study in 90 patients with mild to moderate CHF showed that ventricular premature beats and HRV may have important value in predicting outcome.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  1. Ahn SA, Jong P, Yusuf S, Bangdiwala SI, Pouleur HG, Rousseau MF (2006) Early versus delayed enalapril in patients with left ventricular systolic dysfunction: impact on morbidity and mortality 15 years after the SOLVD trial. J Am Coll Cardiol 47:1904–1905

    PubMed  Article  CAS  Google Scholar 

  2. Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson J, Johnson G, McNulty SE, Clapp-Channing N, Davidson-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH (2005) Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 352:225–237

    PubMed  Article  CAS  Google Scholar 

  3. Bohm M, Werner N, Kindermann M (2006) Drug treatment of chronic heart failure. Clin Res Cardiol 95(Suppl 4):36–54

    PubMed  Article  CAS  Google Scholar 

  4. Brouwer J, van Veldhuisen DJ, Man in “t Veld AJ, Dunselman PH, Boomsma F, Haaksma J, Lie KI (1995) Heart rate variability in patients with mild to moderate heart failure: effects of neurohormonal modulation by digoxin and ibopamine The Dutch Ibopamine Multicenter Trial (DIMT) Study Group. J Am Coll Cardiol 26:983–990

    PubMed  Article  CAS  Google Scholar 

  5. Brouwer J, van Veldhuisen DJ, Man in ‘t Veld AJ, Haaksma J, Dijk WA, Visser KR, Boomsma F, Dunselman PH (1996) Prognostic value of heart rate variability during long-term follow-up in patients with mild to moderate heart failure The Dutch Ibopamine Multicenter Trial Study Group. J Am Coll Cardiol 28:1183–1189

    PubMed  Article  CAS  Google Scholar 

  6. Buch P, Rasmussen S, Abildstrom SZ, Kober L, Carlsen J, Torp-Pedersen C (2005) The long-term impact of the angiotensin-converting enzyme inhibitor trandolapril on mortality and hospital admissions in patients with left ventricular dysfunction after a myocardial infarction: follow-up to 12 years. Eur Heart J 26:145–152

    PubMed  Article  CAS  Google Scholar 

  7. Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS, Simon AB, Rector T (1984) Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 311:819–823

    PubMed  CAS  Google Scholar 

  8. Cowburn PJ, Cleland JG, Coats AJ, Komajda M (1998) Risk stratification in chronic heart failure. Eur Heart J 19:696–710

    PubMed  Article  CAS  Google Scholar 

  9. De Maria R, Gavazzi A, Caroli A, Ometto R, Biagini A, Camerini F (1992) Ventricular arrhythmias in dilated cardiomyopathy as an independent prognostic hallmark Italian Multicenter Cardiomyopathy Study (SPIC) Group. Am J Cardiol 69:1451–1457

    PubMed  Article  Google Scholar 

  10. Floras JS (1993) Clinical aspects of sympathetic activation and parasympathetic withdrawal in heart failure. J Am Coll Cardiol 22:72A–84A

    PubMed  CAS  Google Scholar 

  11. Frankenstein L, Zugck C, Nelles M, Schellberg D, Remppis A, Katus H (2008) Primary ICD-therapy in patients with advanced heart failure: selection strategies and future trials. Clin Res Cardiol 97:594–600

    PubMed  Article  Google Scholar 

  12. Goldman S, Johnson G, Cohn JN, Cintron G, Smith R, Francis G (1993) Mechanism of death in heart failure. The vasodilator-heart failure trials. The V-HeFT VA Cooperative Studies Group. Circulation 87:24–31

    Google Scholar 

  13. Gottlieb SS, Kukin ML, Ahern D, Packer M (1989) Prognostic importance of atrial natriuretic peptide in patients with chronic heart failure. J Am Coll Cardiol 13:1534–1539

    PubMed  CAS  Google Scholar 

  14. Gradman A, Deedwania P, Cody R, Massie B, Packer M, Pitt B, Goldstein S (1989) Predictors of total mortality and sudden death in mild to moderate heart failure Captopril-Digoxin Study Group. J Am Coll Cardiol 14:564–570

    PubMed  CAS  Google Scholar 

  15. Hampton JR, van Veldhuisen DJ, Kleber FX, Cowley AJ, Ardia A, Block P, Cortina A, Cserhalmi L, Follath F, Jensen G, Kayanakis J, Lie KI, Mancia G, Skene AM (1997) Randomised study of effect of ibopamine on survival in patients with advanced severe heart failure. Second prospective randomised study of ibopamine on mortality and efficacy (PRIME II) investigators. Lancet 349:971–977

    PubMed  Article  CAS  Google Scholar 

  16. (1996) Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation 93:1043–1065

  17. Hillege HL, Nitsch D, Pfeffer MA, Swedberg K, McMurray JJ, Yusuf S, Granger CB, Michelson EL, Ostergren J, Cornel JH, de Zeeuw D, Pocock S, van Veldhuisen DJ (2006) Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation 113:671–678

    PubMed  Article  Google Scholar 

  18. Kearney MT, Nolan J, Lee AJ, Brooksby PW, Prescott R, Shah AM, Zaman AG, Eckberg DL, Lindsay HS, Batin PD, Andrews R, Fox KA (2003) A prognostic index to predict long-term mortality in patients with mild to moderate chronic heart failure stabilised on angiotensin converting enzyme inhibitors. Eur J Heart Fail 5:489–497

    PubMed  Article  CAS  Google Scholar 

  19. Kjekshus J, Apetrei E, Barrios V, Bohm M, Cleland JG, Cornel JH, Dunselman P, Fonseca C, Goudev A, Grande P, Gullestad L, Hjalmarson A, Hradec J, Janosi A, Kamensky G, Komajda M, Korewicki J, Kuusi T, Mach F, Mareev V, McMurray JJ, Ranjith N, Schaufelberger M, Vanhaecke J, van Veldhuisen DJ, Waagstein F, Wedel H, Wikstrand J (2007) Rosuvastatin in older patients with systolic heart failure. N Engl J Med 357:2248–2261

    PubMed  Article  CAS  Google Scholar 

  20. 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

    PubMed  Article  CAS  Google Scholar 

  21. Komajda M, Lapuerta P, Hermans N, Gonzalez-Juanatey JR, van Veldhuisen DJ, Erdmann E, Tavazzi L, Poole-Wilson P, Le PC (2005) Adherence to guidelines is a predictor of outcome in chronic heart failure: the MAHLER survey. Eur Heart J 26:1653–1659

    PubMed  Article  Google Scholar 

  22. McMurray JJ, Teerlink JR, Cotter G, Bourge RC, Cleland JG, Jondeau G, Krum H, Metra M, O’Connor CM, Parker JD, Torre-Amione G, van Veldhuisen DJ, Lewsey J, Frey A, Rainisio M, Kobrin I (2007) Effects of tezosentan on symptoms and clinical outcomes in patients with acute heart failure: the VERITAS randomized controlled trials. JAMA 298:2009–2019

    PubMed  Article  CAS  Google Scholar 

  23. Nolan J, Batin PD, Andrews R, Lindsay SJ, Brooksby P, Mullen M, Baig W, Flapan AD, Cowley A, Prescott RJ, Neilson JM, Fox KA (1998) Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart). Circulation 98:1510–1516

    PubMed  CAS  Google Scholar 

  24. Packer M (1992) Lack of relation between ventricular arrhythmias and sudden death in patients with chronic heart failure. Circulation 85:I50–I56

    PubMed  CAS  Google Scholar 

  25. Rapaport E (1988) Sudden cardiac death. Am J Cardiol 62:3I–6I

    PubMed  Article  CAS  Google Scholar 

  26. Smilde TD, Hillege HL, Voors AA, Dunselman PH, van Veldhuisen DJ (2004) Prognostic importance of renal function in patients with early heart failure and mild left ventricular dysfunction. Am J Cardiol 94:240–243

    PubMed  Article  Google Scholar 

  27. Strauss M, Gitt AK, Becker T, Kleemann T, Schiele R, Darius H, Junger C, Senges J, Seidl K (2008) Prehospital cardiac arrest: a marker for higher mortality in patients with acute myocardial infarction and moderately reduced left ventricular function: results from the MITRA plus registry. Clin Res Cardiol 97:748–752

    PubMed  Article  Google Scholar 

  28. Swedberg K, Kjekshus J, Snapinn S (1999) Long-term survival in severe heart failure in patients treated with enalapril. Ten year follow-up of CONSENSUS I. Eur Heart J 20:136–139

    PubMed  Article  CAS  Google Scholar 

  29. Tuininga YS, van Veldhuisen DJ, Brouwer J, Haaksma J, Crijns HJ, Man in ‘t Veld AJ, Lie KI (1994) Heart rate variability in left ventricular dysfunction and heart failure: effects and implications of drug treatment. Br Heart J 72:509–513

    PubMed  Article  CAS  Google Scholar 

  30. van den Broek SA, van Veldhuisen DJ, de Graeff PA, Landsman ML, Hillege H, Lie KI (1992) Comparison between New York Heart Association classification and peak oxygen consumption in the assessment of functional status and prognosis in patients with mild to moderate chronic congestive heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 70:359–363

    PubMed  Article  Google Scholar 

  31. van den Broek SA, van Veldhuisen DJ, de Graeff PA, Crijns HJ, van Gilst WH, Hillege H, Lie KI (1993) Mode of death in patients with congestive heart failure: comparison between possible candidates for heart transplantation and patients with less advanced disease. J Heart Lung Transplant 12:367–371

    PubMed  Google Scholar 

  32. van der Horst, I, Voors AA, van Veldhuisen DJ (2007) Treatment of heart failure with ACE inhibitors and beta-blockers: what is next? Aldosterone receptor antagonists? Clin Res Cardiol 96:193–195

    PubMed  Article  CAS  Google Scholar 

  33. van Veldhuisen DJ, Man in “t Veld AJ, Dunselman PH, Lok DJ, Dohmen HJ, Poortermans JC, Withagen AJ, Pasteuning WH, Brouwer J, Lie KI (1993) Double-blind placebo-controlled study of ibopamine and digoxin in patients with mild to moderate heart failure: results of the Dutch Ibopamine Multicenter Trial (DIMT). J Am Coll Cardiol 22:1564–1573

    PubMed  Article  Google Scholar 

  34. van Veldhuisen DJ, Voors AA (2005) Implantable cardioverter-defibrillators. N Engl J Med 352:2022–2025

    PubMed  Article  Google Scholar 

  35. van Veldhuisen DJ, Crijns HJ, Girbes AR, Tobe TJ, Wiesfeld AC, Lie KI (1991) Electrophysiologic profile of ibopamine in patients with congestive heart failure and ventricular tachycardia and relation to its effects on hemodynamics and plasma catecholamines. Am J Cardiol 68:1194–1202

    PubMed  Article  Google Scholar 

  36. van Veldhuisen DJ, Girbes AR, de Graeff PA, Lie KI (1992) Effects of dopaminergic agents on cardiac and renal function in normal man and in patients with congestive heart failure. Int J Cardiol 37:293–300

    PubMed  Article  Google Scholar 

  37. van Veldhuisen DJ, Charlesworth A, Crijns HJ, Lie KI, Hampton JR (1999) Differences in drug treatment of chronic heart failure between European countries. Eur Heart J 20:666–672

    PubMed  Article  Google Scholar 

  38. Weil J, Schunkert H (2006) Pathophysiology of chronic heart failure. Clin Res Cardiol 95 (Suppl 4):1–15

    PubMed  Article  CAS  Google Scholar 

  39. Werner C, Baumhakel M, Teo KK, Schmieder R, Mann J, Unger T, Yusuf S, Bohm M (2008) RAS blockade with ARB and ACE inhibitors: current perspective on rationale and patient selection. Clin Res Cardiol 97:418–431

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tom D. J. Smilde MD, PhD.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Smilde, T.D.J., van Veldhuisen, D.J. & van den Berg, M.P. Prognostic value of heart rate variability and ventricular arrhythmias during 13-year follow-up in patients with mild to moderate heart failure. Clin Res Cardiol 98, 233–239 (2009). https://doi.org/10.1007/s00392-009-0747-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-009-0747-0

Keywords

  • chronic heart failure
  • prognosis
  • heart rate variability
  • neurohormones