Abstract
Background: Acute myocardial infarction (MI) is associated with an increased risk of death, with a 1‐year mortality close to 10% in patients discharged from hospital alive. During the first year following MI, close to 50% of deaths are assumed to be due to arrhythmic events.
Hypothesis: The study was undertaken to determine the interaction between dofetilide treatment and pretreatment QTc interval and QT dispersion regarding mortality in patients with left ventricular (LV) dysfunction and a recent MI.
Methods: The study population consisted of 894 patients with a recent MI and LV systolic dysfunction, who were randomized to receive dofetilide or placebo. The study was a sub‐study of the Danish Investigations of Arrhythmia and Mortality on Dofetilide‐MI (DIAMOND‐MI).
Results: During a minimum of 1‐year follow‐up, 261 (29%) patients died. Baseline QTc interval did not hold any prognostic value on mortality for placebo‐treated patients. When pretreatment QTc interval was < 429 ms, dofetilide resulted in a 45% reduction of mortality (hazard ratio 0.55, 95% confidence limits 0.34–0.88, p < 0.02) compared with placebo. When QTc interval was > 429 ms, dofetilide did not influence mortality significantly. This study revealed no statistically significant relation between QT dispersion, dofetilide treatment, and mortality.
Conclusion: In patients with a recent MI, LV dysfunction, and a short baseline QTc interval, dofetilide is associated with significant survival benefit. This benefit is not seen with a longer QTc interval. QT dispersion is not a risk factor in this population.
Keywords: QT interval, QT dispersion, prognosis, antiar‐rhythmic agents, myocardial infarction
Full Text
The Full Text of this article is available as a PDF (60.9 KB).
References
- 1. Le Feuvre CA, Connolly SJ, Cairns JA, Gent M, Roberts RS: Comparison of mortality from acute myocardial infarction between 1979 and 1992 in a geographically defined stable population. Am J Cardiol 1996; 78 (12): 1345–1349 [DOI] [PubMed] [Google Scholar]
- 2. Alexander RW, Pratt CM, Roberts R: Diagnosis and management of patients with acute myocardial infarction In Hurst's the Heart (Eds. Alexander RW, Schlant RC, Fuster V.), p. 1345–1433. New York: McGraw‐Hill, 1998. [Google Scholar]
- 3. Perkiomaki JS, Koistinen MJ, Yli MS, Huikuri HV: Dispersion of QT interval in patients with and without susceptibility to ventricular tachyarrhythmias after previous myocardial infarction. J Am Coll Cardiol 1995; 26 (1): 174–179 [DOI] [PubMed] [Google Scholar]
- 4. Day CP, McComb JM, Campbell RW: QT dispersion: An indication of arrhythmia risk in patients with long QT intervals. Br Heart J 1990; 63 (6): 342–344 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Vaughan Williams EM: A classification of antiarrhythmic actions reassessed after a decade of new drugs. J Clin Pharmacol 1984; 24 (4): 129–147 [DOI] [PubMed] [Google Scholar]
- 6. Hohnloser SH, Singh BN: Proarrhythmia with class III antiarrhythmic drugs: Definition, electrophysiologic mechanisms, incidence, predisposing factors, and clinical implications. J Cardiovasc Electrophysiol 1995; 6 (10 Pt 2): 920–936 [DOI] [PubMed] [Google Scholar]
- 7. Brendorp B, Elming H, Jun L, Kober L, Malik M, Jensen GB, Torp‐Pedersen C: QTc interval as a guide to select those patients with congestive heart failure and reduced left ventricular systolic function who will benefit from antiarrhythmic treatment with dofetilide. Circulation 2001; 103 (10): 1422–1427 [DOI] [PubMed] [Google Scholar]
- 8. The DIAMOND Investigators : Dofetilide in patients with left ventricular dysfunction and either heart failure or acute myocardial infarction: Rationale, design, and patient characteristics of the DIAMOND studies. Danish Investigations of Arrhythmia and Mortality ON Dofetilide. Clin Cardiol 1997; 20 (8): 704–710 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Kober L, Bloch Thomsen PE, Moller M, Torp‐Pedersen C, Carlsen J, Sandoe E, Egstrup K, Agner E, Videbaek J, Marchant B, Camm AJ: Effect of dofetilide in patients with recent myocardial infarction and left‐ventricular dysfunction: A randomised trial. Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) Study Group. Lancet 2000; 356 (9247): 2052–2058 [DOI] [PubMed] [Google Scholar]
- 10. Greene HL, Richardson DW, Barker AH, Roden DM, Capone RJ, Echt DS, Friedman LM, Gillespie MJ, Hallstrom AP, Verter J: Classification of deaths after myocardial infarction as arrhythmic or nonarrhythmic (the Cardiac Arrhythmia Pilot Study). Am J Cardiol 1989; 63 (1): 1–6 [DOI] [PubMed] [Google Scholar]
- 11. Simon R, Altman DG: Statistical aspects of prognostic factor studies in oncology. Br J Cancer 1994; 69 (6): 979–985 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Concato J, Feinstein AR, Holford TR: The risk of determining risk with multivariable models. Ann Intern Med 1993; 118 (3): 201–210 [DOI] [PubMed] [Google Scholar]
- 13. Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias MD, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL, Hunter ML, Richardson DW: Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991; 324 (12): 781–788 [DOI] [PubMed] [Google Scholar]
- 14. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. The Cardiac Arrhythmia Suppression Trial II Investigators. N Engl J Med 1992; 327 (4): 227–233 [DOI] [PubMed] [Google Scholar]
- 15. BHAT (Beta‐blocker Heart Attack Trial) Writing Committee : A randomized trial of propranolol in patients with acute myocardial infarction. I. Mortality results. J Am Med Assoc 1982; 247 (12): 1707–1714 [DOI] [PubMed] [Google Scholar]
- 16. The CIBIS‐II Investigators : The Cardiac Insufficiency Bisoprolol Study II (CIBIS‐II): A randomised trial. Lancet 1999; 353 (9146): 9–13 [PubMed] [Google Scholar]
- 17. The MERIT‐HF Investigators : Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT‐HF). Lancet 1999; 353 (9169): 2001–2007 [PubMed] [Google Scholar]
- 18. Singh SN, Fletcher RD, Fisher SG, Singh BN, Lewis HD, Deedwania PC, Massie BM, Colling C, Lazzeri D: Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure. N Engl J Med 1995; 333 (2): 77–82 [DOI] [PubMed] [Google Scholar]
- 19. Cairns JA, Connolly SJ, Roberts R, Gent M: Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators. Lancet 1997; 349 (9053): 675–682 [DOI] [PubMed] [Google Scholar]
- 20. Julian DG, Camm AJ, Frangin G, Janse MJ, Munoz A, Schwartz PJ, Simon P: Randomised trial of effect of amiodarone on mortality in patients with left‐ventricular dysfunction after recent myocardial infarction: EMIAT. European Myocardial Infarct Amiodarone Trial Investigators. Lancet 1997; 349 (9053): 667–674 [DOI] [PubMed] [Google Scholar]
- 21. Waldo AL, Camm AJ, deRuyter H, Friedman PL, MacNeil DJ, Pauls JF, Pitt B, Pratt CM, Schwartz PJ, Veltri EP: Effect of d‐sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d‐Sotalol. Lancet 1996; 348 (9019): 7–12 [DOI] [PubMed] [Google Scholar]
- 22. Gwilt M, Arrowsmith JE, Blackburn KJ, Burges RA, Cross PE, Dalrymple HW, Higgins AJ: UK‐68,798: A novel, potent and highly selective class III antiarrhythmic agent which blocks potassium channels in cardiac cells. J Pharmacol Exp Ther 1991; 256 (1): 318–324 [PubMed] [Google Scholar]
- 23. Higham PD, Furniss SS, Campbell RW: QT dispersion and components of the QT interval in ischaemia and infarction. Br Heart J 1995; 73 (1): 32–36 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Sporton SC, Taggart P, Sutton PM, Walker JM, Hardman SM: Acute is‐chaemia: A dynamic influence on QT dispersion. Lancet 1997; 349 (9048): 306–309 [DOI] [PubMed] [Google Scholar]
- 25. Tobe TJ, de‐Langen CD, Crijns HJ, Wiesfeld AC, van‐Gilst WH, Faber KG, Lie KI, Wesseling H: Late potentials, QTc prolongation, and prediction of arrhythmic events after myocardial infarction. Int J Cardiol 1994; 46 (2): 121–128 [DOI] [PubMed] [Google Scholar]
- 26. Glancy JM, Weston PJ, Bhullar HK, Garratt CJ, Woods KL, de‐Bono DP: Reproducibility and automatic measurement of QT dispersion. Eur Heart J 1996; 17 (7): 1035–1039 [DOI] [PubMed] [Google Scholar]
- 27. Kautzner J, Malik M: QT interval dispersion and its clinical utility. Pacing Clin Electrophysiol 1997; 20 (10 Pt 2): 2625–2640 [DOI] [PubMed] [Google Scholar]
- 28. Spargias KS, Lindsay SJ, Kawar GI, Greenwood DC, Cowan JC, Ball SG, Hall AS: QT dispersion as a predictor of long‐term mortality in patients with acute myocardial infarction and clinical evidence of heart failure. Eur Heart J 1999; 20 (16): 1158–1165 [DOI] [PubMed] [Google Scholar]
- 29. Galinier M, Vialette JC, Fourcade J, Cabrol P, Dongay B, Massabuau P, Boveda S, Doazan JP, Fauvel JM, Bounhoure JP: QT interval dispersion as a predictor of arrhythmic events in congestive heart failure. Importance of aetiology. Eur Heart J 1998; 19 (7): 1054–1062 [DOI] [PubMed] [Google Scholar]
- 30. Zabel M, Klingenheben T, Franz MR, Hohnloser SH: Assessment of QT dispersion for prediction of mortality or arrhythmic events after myocardial infarction: Results of a prospective, long‐term follow‐up study. Circulation 1998; 97 (25): 2543–2550 [DOI] [PubMed] [Google Scholar]
- 31. Pedretti RF, Catalano O, Ballardini L, de Bono DP, Radice E, Tramarin R: Prognosis in myocardial infarction survivors with left ventricular dysfunction is predicted by electrocardiographic RR interval but not QT dispersion. Int J Cardiol 1999; 68 (1): 83–93 [DOI] [PubMed] [Google Scholar]
- 32. Kors JA, van Herpen G, van Bemmel JH: QT dispersion as an attribute of T‐loop morphology. Circulation 1999; 99 (11): 1458–1463 [DOI] [PubMed] [Google Scholar]