Predictive value for future arrhythmic events of fractal dimension, a measure of time clustering of ventricular premature complexes, after myocardial infarction. CAST Investigators. Cardia Arrhythmia Suppression Trial.

OBJECTIVES Our objective was to test fractal dimension (D), a measure of clustering of ventricular premature complexes (VPCs), on entry Holter recording as a predictor of future arrhythmic death and other-cause mortality in postinfarction patients in the Cardiac Arrhythmic Suppression Trial (CAST). BACKGROUND Nonlinear dynamic methods of signal processing are being applied in medicine to provide new insights into apparently "chaotic" biologic events, including cardiac arrhythmias. One such application is the derivation of a fractal D to describe the clustering of VPCs in time. METHODS Baseline Holter recordings were analyzed in blinded manner for 484 patients: 237 died or had a resuscitated cardiac arrest during follow-up, and 247 matched patients had no events. Fractal D, measured in four ways, was assessed as a predictor using Cox regression. RESULTS One measure of D (high resolution D) was a significant univariate (relative hazard ratio 0.79 per SD change, p = 0.011) and multivariate (hazard ratio 0.75, p = 0.046) predictor of arrhythmic death but not other death (univariate p = 0.95, relative hazard 0.95, p = 0.66). Fractal D was greater (VPCs less clustered) in those patients free of arrhythmic events. On subgroup analysis, the predictive value of D resided in the randomized patient group (i.e., those who showed VPC suppression during initial antiarrhythmic drug titration and were randomized to blinded therapy with active drug or placebo) (multivariate hazard ratio 0.57, p = 0.001). CONCLUSIONS A high resolution fractal D was predictive of arrhythmic (but not nonarrhythmic) death in a large postinfarction cohort. Further study of this new signal processing approach to ambulatory electrocardiographic recording will be of interest.

[1]  P Kligfield,et al.  Computer‐Assisted Analysis of Holter Recordings , 1990, Annals of the New York Academy of Sciences.

[2]  G. Diamond,et al.  Fascinating rhythm: a primer on chaos theory and its application to cardiology. , 1990, American heart journal.

[3]  J. Fleiss,et al.  The ability of several short-term measures of RR variability to predict mortality after myocardial infarction. , 1993, Circulation.

[4]  A. Winfree,et al.  Sudden Cardiac Death: A Problem in Topology , 1983 .

[5]  Leon Glass,et al.  Complex cardiac rhythms , 1987, Nature.

[6]  Jørgen K. Kanters,et al.  Lack of Evidence for Low‐Dimensional Chaos in Heart Rate Variability , 1994, Journal of cardiovascular electrophysiology.

[7]  A. Goldberger,et al.  Loss of 'complexity' and aging. Potential applications of fractals and chaos theory to senescence. , 1992, JAMA.

[8]  H. Greene,et al.  The healthy responder phenomenon in non-randomized clinical trials. CAST Investigators. , 1991, Statistics in medicine.

[9]  P Kligfield,et al.  Fractal clustering of ventricular ectopy in dilated cardiomyopathy. , 1990, The American journal of cardiology.

[10]  M. Weir,et al.  The Cardiac Arrhythmia Suppression Trial Investigators: Preliminary Report: Effect of Encainide and Flecainide on Mortality in a Randomized Trial of Arrhythmia Suppression After Myocardial Infarction. , 1990 .

[11]  S L Winters,et al.  The prognostic significance of quantitative signal-averaged variables relative to clinical variables, site of myocardial infarction, ejection fraction and ventricular premature beats: a prospective study. , 1989, Journal of the American College of Cardiology.

[12]  D. Wyse,et al.  Events in the Cardiac Arrhythmia Suppression Trial (CAST): mortality in patients surviving open label titration but not randomized to double-blind therapy. , 1991, Journal of the American College of Cardiology.

[13]  T. Bair,et al.  Fractal dimension predicts arrhythmia recurrence in patients being treated for life-threatening ventricular arrhythmias. ESVEM Investigators. , 1995, Journal of electrocardiology.

[14]  Robert Lemery,et al.  Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. , 1992, The New England journal of medicine.

[15]  P. Denes,et al.  Definition of the best prediction criteria of the time domain signal-averaged electrocardiogram for serious arryhthmic events in the postinfarction period , 1995 .

[16]  P. Grassberger,et al.  Measuring the Strangeness of Strange Attractors , 1983 .

[17]  P Kligfield,et al.  Application of fractal geometry to the analysis of ventricular premature contractions. , 1990, Journal of electrocardiology.

[18]  P. Kligfield,et al.  Fractal clustering of ventricular ectopy and sudden death in mitral regurgitation. , 1992, Journal of electrocardiology.

[19]  N Lippman,et al.  Fractal rhythms of the heart. , 1992, Journal of electrocardiology.

[20]  C. Furberg,et al.  Prognostic significance of ventricular ectopic activity in survivors of acute myocardial infarction. , 1987, Journal of the American College of Cardiology.

[21]  James Gleick Chaos: Making a New Science , 1987 .

[22]  J. Bigger,et al.  Events in the Cardiac Arrhythmia Suppression Trial (CAST): mortality in the entire population enrolled. , 1991, Journal of the American College of Cardiology.

[23]  D. T. Kaplan,et al.  Chaos in Cardiology , 1991 .

[24]  M Huther,et al.  Relations between heart failure, ejection fraction, arrhythmia suppression and mortality: analysis of the Cardiac Arrhythmia Suppression Trial. , 1995, Journal of the American College of Cardiology.

[25]  H L Greene,et al.  Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. , 1991, The New England journal of medicine.

[26]  R M Whitlock,et al.  Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. , 1987, Circulation.

[27]  W. Rogers,et al.  Mortality following ventricular arrhythmia suppression by encainide, flecainide, and moricizine after myocardial infarction. The original design concept of the Cardiac Arrhythmia Suppression Trial (CAST). , 1993, JAMA.

[28]  J P Miller,et al.  The relationships among ventricular arrhythmias, left ventricular dysfunction, and mortality in the 2 years after myocardial infarction. , 1984, Circulation.

[29]  D. Cox Regression Models and Life-Tables , 1972 .

[30]  Benoit B. Mandelbrot,et al.  Fractal Geometry of Nature , 1984 .

[31]  W. Rogers,et al.  Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. , 1989, The New England journal of medicine.