Sudden cardiac death usually is caused by malignant ventricular arrhythmias. Malignant ventricular arrhythmias, in coronary heart disease, are due to an interplay among substrate (scarred ventricles), triggering events (spontaneous ventricular arrhythmias), and the autonomic nervous system. Non-invasive methods are needed to evaluate these three components of risk in order to develop comprehensive detection and prevention programs. There are reasonable non-invasive screening test for the arrhythmogenic substrate (left ventricular ejection fraction and signal averaged electro-cardiograms), and for triggering events (24-hour continuous ECG recordings). We believe that measures of heart rate or heart period variability may provide the means for non-invasive assessment of autonomic nervous system activity. We have found that a broad band measure of heart period variability, the standard deviation of all normal R-R intervals in a continuous 24-hour ECG recording made 11 plus/minus 3 days after myocardial infarction, predicts mortality in the subsequent two to four years independently of left ventricular dysfunction and spontaneous ventricular arrhythmias. We propose to evaluate various measurements of heart rate or period variability in the time and frequency domains made early after myocardial infarction for their accuracy in predicting death (total, cardiac, sudden, and arrhythmic death). We will compare measurements of short and long- term heart rate and heart period variability. We will determine the day-to-day reproducibility and the time course of change of our measures of heart rate variability and heart rate variability measured late after myocardial infarction for subsequent mortality and development of malignant ventricular arrhythmias. We will contrast the heart rate and heart period variability findings after myocardial infarction with those in age and sex matched normal subjects and with those made in patients with malignant ventricular arrhythmias. We will conduct these analyses in several large samples of patients with previous myocardial infarction or malignant ventricular arrhythmias and in a sample of normal subjects. We hope to develop new, improved non-invasive methods for detecting those patients most likely to develop malignant ventricular arrhythmias and sudden cardiac death and point the way to improved detection and prevention of sudden cardiac death.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL041552-01
Application #
3359331
Study Section
Cardiovascular Study Section (CVA)
Project Start
1988-12-01
Project End
1992-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Bloomfield, D M; Zweibel, S; Bigger Jr, J T et al. (1998) R-R variability detects increases in vagal modulation with phenylephrine infusion. Am J Physiol 274:H1761-6
Roose, S P; Glassman, A H; Attia, E et al. (1998) Cardiovascular effects of fluoxetine in depressed patients with heart disease. Am J Psychiatry 155:660-5
La Rovere, M T; Bigger Jr, J T; Marcus, F I et al. (1998) Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet 351:478-84
Bloomfield, D M; Kaufman, E S; Bigger Jr, J T et al. (1997) Passive head-up tilt and actively standing up produce similar overall changes in autonomic balance. Am Heart J 134:316-20
Bigger Jr, J T; Steinman, R C; Rolnitzky, L M et al. (1996) Power law behavior of RR-interval variability in healthy middle-aged persons, patients with recent acute myocardial infarction, and patients with heart transplants. Circulation 93:2142-51
Anderson, K P; Bigger Jr, J T; Freedman, R A (1996) Electrocardiographic predictors in the ESVEM trial: unsustained ventricular tachycardia, heart period variability, and the signal-averaged electrocardiogram. Prog Cardiovasc Dis 38:463-88
Bloomfield, D M; Bigger Jr, J T; Pavri, B B et al. (1995) Vagal modulation of RR intervals during head-up tilt and the infusion of isoproterenol. Am J Cardiol 75:1145-50
Bigger Jr, J T; Fleiss, J L; Steinman, R C et al. (1995) RR variability in healthy, middle-aged persons compared with patients with chronic coronary heart disease or recent acute myocardial infarction. Circulation 91:1936-43
Bigger Jr, J T; Rolnitzky, L M; Steinman, R C et al. (1994) Predicting mortality after myocardial infarction from the response of RR variability to antiarrhythmic drug therapy. J Am Coll Cardiol 23:733-40
Bigger Jr, J T; Fleiss, J L; Rolnitzky, L M et al. (1993) Frequency domain measures of heart period variability to assess risk late after myocardial infarction. J Am Coll Cardiol 21:729-36

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