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(Circulation. 2001;103:2072.)
© 2001 American Heart Association, Inc.


Clinical Investigation and Reports

Baroreflex Sensitivity and Heart Rate Variability in the Identification of Patients at Risk for Life-Threatening Arrhythmias

Implications for Clinical Trials

Maria Teresa La Rovere, MD; Gian Domenico Pinna, MS; Stefan H. Hohnloser, MD; Frank I. Marcus, MD; Andrea Mortara, MD; Ryuji Nohara, MD; J. Thomas Bigger, Jr, MD; A. John Camm, MD; Peter J. Schwartz, MD; on behalf of the Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI) Investigators

From the Centro Medico di Montescano, Fondazione "Salvatore Maugeri" IRCCS, Montescano, Pavia, Italy (M.T.L.R., G.D.P., A.M.); the Klinikum der Johann Wolfgang Goethe-Universitat, Medizinische Klinik IV, Kardiologie und Nephrologie, Frankfurt, Germany (S.H.H.); the Department of Internal Medicine, Section of Cardiology, University of Arizona Health Sciences Center, Tucson, Ariz (F.I.M.); the Division of Cardiology, Policlinico di Monza, Monza, Italy (A.M.); the Third Division of Internal Medicine, Kyoto University Hospital, Kyoto, Japan (R.N.); the Department of Medicine, Cardiology Division, Columbia University, College of Physicians and Surgeons, New York, NY (J.T.B.); the Department of Cardiological Sciences, St George’s Hospital Medical School, London, UK (A.J.C.); and the Department of Cardiology, University of Pavia and Policlinico S. Matteo Istituto di Ricovero e Cura a Carattere Scientifico, Pavia, Italy (P.J.S.).

Background—The need for accurate risk stratification is heightened by the expanding indications for the implantable cardioverter defibrillator. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) focused interest on patients with both depressed left ventricular ejection fraction (LVEF) and the presence of nonsustained ventricular tachycardia (NSVT). Meanwhile, the prospective study Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI) demonstrated that markers of reduced vagal activity, such as depressed baroreflex sensitivity (BRS) and heart rate variability (HRV), are strong predictors of cardiac mortality after myocardial infarction.

Methods and Results—We analyzed 1071 ATRAMI patients after myocardial infarction who had data on LVEF, 24-hour ECG recording, and BRS. During follow-up (21±8 months), 43 patients experienced cardiac death, 5 patients had episodes of sustained VT, and 30 patients experienced sudden death and/or sustained VT. NSVT, depressed BRS, or HRV were all significantly and independently associated with increased mortality. The combination of all 3 risk factors increased the risk of death by 22x. Among patients with LVEF<35%, despite the absence of NSVT, depressed BRS predicted higher mortality (18% versus 4.6%, P=0.01). This is a clinically important finding because this group constitutes 25% of all patients with depressed LVEF. For both cardiac and arrhythmic mortality, the sensitivity of low BRS was higher than that of NSVT and HRV.

Conclusions—BRS and HRV contribute importantly and additionally to risk stratification. Particularly when LVEF is depressed, the analysis of BRS identifies a large number of patients at high risk for cardiac and arrhythmic mortality who might benefit from implantable cardioverter defibrillator therapy without disproportionately increasing the number of false-positives.


Key Words: nervous system, autonomic • baroreceptors • heart rate • myocardial infarction • arrhythmia




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CirculationHome page
S. H. Hohnloser and B. J. Gersh
Changing Late Prognosis of Acute Myocardial Infarction: Impact on Management of Ventricular Arrhythmias in the Era of Reperfusion and the Implantable Cardioverter-Defibrillator
Circulation, February 25, 2003; 107(7): 941 - 946.
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Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
P. A. Lanfranchi and V. K Somers
Arterial baroreflex function and cardiovascular variability: interactions and implications
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2002; 283(4): R815 - R826.
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CirculationHome page
M. T. La Rovere, C. Bersano, M. Gnemmi, G. Specchia, and P. J. Schwartz
Exercise-Induced Increase in Baroreflex Sensitivity Predicts Improved Prognosis After Myocardial Infarction
Circulation, August 20, 2002; 106(8): 945 - 949.
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J. Physiol.Home page
D. P Francis, K. Willson, P. Georgiadou, R. Wensel, L C. Davies, A. Coats, and M. Piepoli
Physiological basis of fractal complexity properties of heart rate variability in man
J. Physiol., July 15, 2002; 542(2): 619 - 629.
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JNMHome page
M. Pietila, K. Malminiemi, R. Vesalainen, T. Jartti, M. Teras, K. Nagren, P. Lehikoinen, and L.-M. Voipio-Pulkki
Exercise Training in Chronic Heart Failure: Beneficial Effects on Cardiac 11C-Hydroxyephedrine PET, Autonomic Nervous Control, and Ventricular Repolarization
J. Nucl. Med., June 1, 2002; 43(6): 773 - 779.
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J Am Coll CardiolHome page
P. Kaushal and J. A. Taylor
Inter-relations among declines in arterial distensibility, baroreflex function and respiratory sinus arrhythmia
J. Am. Coll. Cardiol., May 1, 2002; 39(9): 1524 - 1530.
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CirculationHome page
T. H. Makikallio, H. V. Huikuri, M. T. La Rovere, G. D. Pinna, S. H. Hohnloser, F. I. Marcus, A. Mortara, R. Nohara, J. T. Bigger Jr, A. J. Camm, et al.
Risks in Risk Stratification: What Is Relevant in Practice? * Response
Circulation, March 26, 2002; 105 (12): e69 - e70.
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J. Am. Soc. Nephrol.Home page
C. Zoccali, F. Mallamaci, and G. Tripepi
Nocturnal Hypoxemia Predicts Incident Cardiovascular Complications in Dialysis Patients
J. Am. Soc. Nephrol., March 1, 2002; 13(3): 729 - 733.
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Mayo Clin Proc.Home page
B. M. Curtis and J. H. O'Keefe Jr
Autonomic Tone as a Cardiovascular Risk Factor: The Dangers of Chronic Fight or Flight
Mayo Clin. Proc., January 1, 2002; 77(1): 45 - 54.
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J Am Coll CardiolHome page
M. J. Eisenberg
Risk stratification for arrhythmic events: are the bangs worth the bucks?
J. Am. Coll. Cardiol., December 1, 2001; 38(7): 1912 - 1915.
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