ARTICLE
Depressed heart rate variability identifies postinfarction patients who might benefit from prophylactic treatment with amiodarone
A substudy of EMIAT (the European Myocardial Infarct Amiodarone Trial)
Marek Malik, PhD, MD, FACC*,
A. John Camm, MD, FACC*,
Michiel J. Janse, MD ,
Desmond G. Julian, MD, FACC ,
Gerald A. Frangin, MD ,
Peter J. Schwartz, MD, FACC|| on behalf of the EMIAT Investigators
* Department of Cardiological Sciences, St. George’s Hospital Medical School, London, United Kingdom
Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Netherhall Gardens, London, United Kingdom
Sanofi Recherche, Montpellier, France
|| Department of Cardiology, University of Pavia and Policlinico S. Matteo IRCCS, Pavia, Italy
Manuscript received June 16, 1998;
revised manuscript received October 15, 1999,
accepted December 29, 1999.
Reprint requests and correspondence: Dr. Marek Malik, Department of Cardiological Sciences, St. George’s Hospital Medical School, London SW17 0RE, United Kingdom
m.malik{at}sghms.ac.uk
OBJECTIVES
This substudy tested a prospective hypothesis that European Myocardial Infarct Amiodarone Trial (EMIAT) patients with depressed heart rate variability (HRV) benefit from amiodarone treatment.
BACKGROUND
The EMIAT randomized 1,486 survivors of acute myocardial infarction (MI) aged  75 years with left ventricular ejection fraction (LVEF) 40% to amiodarone or placebo. Despite a reduction of arrhythmic mortality on amiodarone, all-cause mortality was not changed.
METHODS
Heart rate variability was assessed from prerandomization 24-h Holter tapes in 1,216 patients (606 on amiodarone). Two definitions of depressed HRV were used: standard deviation of normal to normal intervals (SDNN) 50 ms and HRV index 20 units. The survival of patients with depressed HRV was compared in the placebo and amiodarone arms. A retrospective analysis investigated the prospective dichotomy limits. All tests were repeated in five subpopulations: patients with first MI, patients on beta-adrenergic blocking agents, patients with LVEF 30%, patients with Holter arrhythmia and patients with baseline heart rate  75 beats/min.
RESULTS
Centralized Holter processing produced artificially high SDNN but accurate HRV index values. Heart rate variability index was 20 U in 363 (29.9%) patients (183 on amiodarone) with all-cause mortality 22.8% on placebo and 17.5% on amiodarone (23.2% reduction, p = 0.24) and cardiac arrhythmic mortality 12.8% on placebo and 4.4% on amiodarone (66% reduction, p = 0.0054). Among patients with prospectively defined depressed HRV, the largest reduction of all-cause mortality was in patients with first MI (placebo 17.9%, amiodarone 10.3%, 42.5% reduction, p = 0.079) and in patients with heart rate 75 beats/min (placebo 29.0%, amiodarone 19.3%, 33.7% reduction, p = 0.075). Among patients with first MI and depressed HRV, amiodarone treatment was an independent predictor of survival in a multivariate Cox analysis. The retrospective analysis found a larger reduction of mortality on amiodarone in 313 (25.7%) patients with HRV index 19 U: 23.9% on placebo and 17.1% on amiodarone (28.4% reduction, p = 0.15). This was more expressed in patients with first MI: 49.4% mortality reduction on amiodarone (p = 0.046), on beta-blockers: 69.0% reduction (p = 0.047) and with heart rate 75 beats/min: 37.9% reduction (p = 0.054).
CONCLUSION
Measurement of HRV in a large set of centrally processed Holter recordings is feasible with robust methods of assessment. Patients with LVEF 40% and depressed HRV benefit from prophylactic antiarrhythmic treatment with amiodarone. However, this finding needs confirmation in an independent data set before clinical practice is changed.
|
Abbreviations and Acronyms
| | EMIAT | = European Myocardial Infarct Amiodarone Trial | | HRV | = heart rate variability | | LVEF | = left ventricular ejection fraction | | MI | = myocardial infarction | | SDNN | = standard deviation of normal to normal intervals |
|
This article has been cited by other articles:
|
|
|
|
 
L. Ding, W. Hua, H. Niu, K. Chen, and S. Zhang
Primary prevention of sudden cardiac death using implantable cardioverter defibrillators
Europace,
September 1, 2008;
10(9):
1034 - 1041.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ikeda, H. Yoshino, K. Sugi, K. Tanno, H. Shimizu, J. Watanabe, Y. Kasamaki, A. Yoshida, and T. Kato
Predictive Value of Microvolt T-Wave Alternans for Sudden Cardiac Death in Patients With Preserved Cardiac Function After Acute Myocardial Infarction: Results of a Collaborative Cohort Study
J. Am. Coll. Cardiol.,
December 5, 2006;
48(11):
2268 - 2274.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Developed in Collaboration With the European Heart, D. P. Zipes, A. J. Camm, M. Borggrefe, A. E. Buxton, B. Chaitman, M. Fromer, G. Gregoratos, G. Klein, A. J. Moss, et al.
ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death)
J. Am. Coll. Cardiol.,
September 5, 2006;
48(5):
e247 - e346.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Writing Committee Members, D. P. Zipes, A. J. Camm, M. Borggrefe, A. E. Buxton, B. Chaitman, M. Fromer, G. Gregoratos, G. Klein, A. J. Moss, et al.
ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society
Europace,
September 1, 2006;
8(9):
746 - 837.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M P Frenneaux
Autonomic changes in patients with heart failure and in post-myocardial infarction patients
Heart,
November 1, 2004;
90(11):
1248 - 1255.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Camm, C. M. Pratt, P. J. Schwartz, H. R. Al-Khalidi, M. J. Spyt, M. J. Holroyde, R. Karam, E. H. Sonnenblick, J. M.G. Brum, and on Behalf of the AzimiLide post Infarct surVival E
Mortality in Patients After a Recent Myocardial Infarction: A Randomized, Placebo-Controlled Trial of Azimilide Using Heart Rate Variability for Risk Stratification
Circulation,
March 2, 2004;
109(8):
990 - 996.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Miyauchi, S. Zhou, Y. Okuyama, M. Miyauchi, H. Hayashi, A. Hamabe, M. C. Fishbein, W. J. Mandel, L. S. Chen, P.-S. Chen, et al.
Altered Atrial Electrical Restitution and Heterogeneous Sympathetic Hyperinnervation in Hearts With Chronic Left Ventricular Myocardial Infarction: Implications for Atrial Fibrillation
Circulation,
July 22, 2003;
108(3):
360 - 366.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Halamek, T. Kara, P. Jurak, M. Soucek, D. P. Francis, L. C. Davies, W. K. Shen, A. J.S. Coats, M. Novak, Z. Novakova, et al.
Variability of Phase Shift Between Blood Pressure and Heart Rate Fluctuations: A Marker of Short-Term Circulation Control
Circulation,
July 22, 2003;
108(3):
292 - 297.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.K.L. Reyners, B.P.C. Hazenberg, W.D. Reitsma, and A.J. Smit
Heart rate variability as a predictor of mortality in patients with AA and AL amyloidosis
Eur. Heart J.,
January 2, 2002;
23(2):
157 - 161.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Bailey, A. S. Berson, H. Handelsman, and M. Hodges
Utility of current risk stratification tests for predicting major arrhythmic events after myocardial infarction
J. Am. Coll. Cardiol.,
December 1, 2001;
38(7):
1902 - 1911.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.G. Priori, E. Aliot, C. Blomstrom-Lundqvist, L. Bossaert, G. Breithardt, P. Brugada, A.J. Camm, R. Cappato, S.M. Cobbe, C. Di Mario, et al.
Task Force on Sudden Cardiac Death of the European Society of Cardiology
Eur. Heart J.,
August 2, 2001;
22(16):
1374 - 1450.
[PDF]
|
|
|
|
|
|
|
M. Kornitzer
Predictive value of electrocardiographic markers for autonomic nervous system dysfunction in healthy populations: more studies needed
Eur. Heart J.,
January 2, 2001;
22(2):
109 - 112.
[PDF]
|
|
|
|
