Association of Holter-based measures including T-wave alternans with risk of sudden cardiac death in the community-dwelling elderly: the Cardiovascular Health Study☆
Introduction
Sudden cardiac death (SCD) is a common first manifestation of significant cardiovascular disease and has been reported to be responsible for 50% of cardiovascular mortality in the United States.1 Therefore, identification of those in the population at highest and lowest risk for SCD is of critical importance. Twenty-four-hour ambulatory electrocardiogram (ECG; ie, Holter) monitoring, which is noninvasive and easily performed in a naturalistic outpatient setting that more accurately reflects daily life, is an attractive source of information that might help identify higher and lower risk people. Among data potentially available for risk stratification and obtainable from Holter recordings are counts of ventricular premature beats, standard and novel heart rate variability (HRV) measures, heart rate turbulence (HRT), and measurement of T-wave alternans (TWA).
An increased frequency of ventricular premature beats has been associated with risk of SCD among the general population2 and in patients with known cardiovascular disease.3 Decreased HRV, reflecting abnormalities in cardiac autonomic modulation, is clearly associated with both all-cause and cardiac mortality in postinfarction patients, but the case for HRV as a predictor of SCD is far less clear.4 Decreased values for the short-term fractal scaling exponent, a “non-linear” HRV measure that captures the underlying pattern of the heart rate (HR) time series, have been linked to mortality post–myocardial infarction (MI)5 and also in the Cardiovascular Health Study (CHS),6 but not explicitly linked to risk of SCD. Abnormal HRT, which quantifies the HR responses to ventricular premature contractions (VPCs), seems to reflect baroreflex function, and predicts total and cardiovascular mortality in cardiac patients,7 and we have shown that it independently predicts cardiovascular mortality in the CHS.6 Abnormal HRT has also been linked to risk of SCD post-MI and in patients with heart failure.8, 9
“Electrical alternans,” the phenomenon of changing amplitude of the repolarization portion of the ECG that repeats on every other heart beat, has been shown to be a substrate for lethal ventricular arrhythmias. Microvolt TWA seen during treadmill or bicycle stress testing has identified patients at increased risk of SCD.10, 11, 12, 13 The modified moving average (MMA) method has been shown to be suitable for use during ambulatory ECG monitoring14, 15, 16 We have recently shown that TWA from Holter recordings was associated with risk of SCD in patients with a recent MI and severe left ventricular (LV) dysfunction.17
We therefore examined these potential Holter-based risk markers: ventricular premature beat counts, time domain, frequency domain and nonlinear HRV, HRT, and TWA in a nested case-control study of well-characterized population-dwelling older adults who died suddenly compared with 2:1 matched controls who were alive at the time of the death of the case who did not subsequently experience SCD. Participants were from the CHS, an ongoing epidemiologic study that seeks to identify risk factors for cardiovascular disease in older adults.
Section snippets
Participants
The CHS is an National Institutes of Health–sponsored population-based longitudinal study to identify risk factors that relate to the onset and course of coronary heart disease and stroke in 5,201 men and a women 65 years and older.18 Participants underwent extensive testing, at baseline (starting in 1989) and during a second examination cycle (starting in 1994), to identify the presence and severity of cardiovascular risk factors and the presence of overt disease. A less extensive follow-up
Results
Subjects were 73 ± 5 years, 99 males and 47 females, and were followed for up to 13 years. Time from Holter to SCD was 4.7 ± 3.0 (range, 0.2-10.4) years. Time from Holter to death for controls that died was 7.5 ± 2.6 years, (range, 2.3 -11.6 years, 33% mortality). One hundred seven were white and 39 were nonwhite. There was no ethnic difference in the prevalence of SCD. Based on qualitative echocardiography, 108 participants had normal LV function and 28 had borderline or abnormal LV function.27
Discussion
Our results suggest that information 24-hour Holter monitoring could identify people at increased and markedly decreased risk of SCD. Although HR and time domain HRV did not distinguish population-dwelling older adults at increased or decreased risk of SCD, Holter-based measures including increased frequency of ventricular premature beats, more abnormal HR TS, higher TWA, and lower values for the short-term fractal scaling exponent (DFA1) were seen among those who later died suddenly. Moreover,
Acknowledgments
The research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant number U01HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. In addition, this research was supported
References (35)
- et al.
Relation between ventricular premature complexes and sudden cardiac death in apparently healthy men
Am J Cardiol
(1987) - et al.
Noninvasive risk stratification in postinfarction patients with severe left ventricular dysfunction and methodology of the MADIT II noninvasive electrocardiology substudy
J Electrocardiol
(2003) - et al.
Fractal analysis of heart rate dynamics as a predictor of mortality in patients with depressed left ventricular function after acute myocardial infarction. TRACE Investigators. TRAndolapril Cardiac Evaluation
Am J Cardiol
(1999) - et al.
Heart rate turbulence predicts all-cause mortality and sudden death in congestive heart failure patients
Heart Rhythm
(2008) - et al.
Basis for sudden cardiac death prediction by T-wave alternans from an integrative physiology perspective
Heart Rhythm
(2009) - et al.
Time-domain T-wave alternans measured from Holter electrocardiograms predicts cardiac mortality in patients with left ventricular dysfunction: a prospective study
Heart Rhythm
(2009) - et al.
The Cardiovascular Health Study: design and rationale
Ann Epidemiol
(1991) - et al.
Efficient estimation of the heart period power spectrum suitable for physiologic or pharmacologic studies
Am J Cardiol
(1990) - et al.
Heart-rate turbulence after ventricular premature beats as a predictor of mortality after acute myocardial infarction
Lancet
(1999) - et al.
Fractal analysis and time- and frequency-domain measures of heart rate variability as predictors of mortality in patients with heart failure
Am J Cardiol
(2001)
Sudden cardiac death: exploring the limits or our knowledge
J Cardiovasc Electrophysiol
Ventricular ectopic beats and their relation to sudden and nonsudden cardiac death after myocardial infarction
Circulation
Heart rate turbulence: a new predictor for risk of sudden cardiac death
Ann Noninvasive Electrocardiol
Baroreflex sensitivity and heart rate variability in the identification of patients at risk for life-threatening arrhythmias. Implications for clinical trials
Circulation
Prevalence of t wave alternans in healthy subjects
PACE
T-wave alternans predicts mortality in a population undergoing a clinically indicated exercise test
Eur Heart J
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Disclosures: All authors declare no conflicts of interest and have nothing to declare financially.