Elsevier

Journal of Electrocardiology

Volume 43, Issue 3, May–June 2010, Pages 251-259
Journal of Electrocardiology

Association of Holter-based measures including T-wave alternans with risk of sudden cardiac death in the community-dwelling elderly: the Cardiovascular Health Study

https://doi.org/10.1016/j.jelectrocard.2009.12.009Get rights and content

Abstract

Background

Sudden cardiac death (SCD) can be the first manifestation of cardiovascular disease. Development of screening methods for higher/lower risk is critical.

Methods

The Cardiovascular Health Study is a population-based study of risk factors for coronary heart disease and stroke those 65 years or older. Forty-nine (of 1649) with usable Holters and in normal sinus rhythm had SCD during follow-up and were matched with 2 controls, alive at the time of death of the case and not experiencing SCD on follow-up. Univariate and multivariate conditional logistic regression determined the association of Holter-based information and SCD.

Results

In univariate models, the upper half of ventricular premature contraction (VPC) counts, abnormal heart rate turbulence, decreased normalized low-frequency power, increased T-wave alternans (TWA), and decreased the short-term fractal scaling exponent (DFA1) were associated with SCD, but time domain heart rate variability was not. In multivariate models, the upper half of VPC counts (odds ratio [OR], 6.6) and having TWA of 37 μV or greater on channel 2 (OR, 4.8) were independently associated with SCD. Also, the upper half of VPC counts (OR, 6.9) and having a DFA1 of less than 1.05 (OR, 5.0) were independently associated with SCD. When additive effects were explored, having both higher VPCs and higher TWA was associated with an OR of 8.2 for SCD compared with 2.6 for having either. Also, having both higher VPCs and lower DFA1 was associated with an OR of 9.6 for SCD compared with 3.1 for having either.

Conclusions

Results support a potential role for 24-hour Holter recordings to identify older adults at increased or lower risk of SCD.

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

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    Disclosures: All authors declare no conflicts of interest and have nothing to declare financially.

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