Abstract
Non-Gaussianity index (λ) is a new index of heart rate variability (HRV) that characterizes increased probability of the large heart rate deviations from its trend. A previous study has reported that increased λ is an independent mortality predictor among patients with chronic heart failure. The present study examined predictive value of λ in patients after acute myocardial infarction (AMI). Among 670 post-AMI patients, we performed 24-h Holter monitoring to assess λ and other HRV predictors, including SD of normal-to-normal interval, very-low frequency power, scaling exponent α1 of detrended fluctuation analysis, deceleration capacity, and heart rate turbulence (HRT). At baseline, λ was not correlated substantially with other HRV indices (|r| < 0.4 with either indices) and was decreased in patients taking β-blockers (P = 0.04). During a median follow-up period of 25 months, 45 (6.7%) patients died (32 cardiac and 13 non-cardiac) and 39 recurrent non-fatal AMI occurred among survivors. While all of these HRV indices but λ were significant predictors of both cardiac and non-cardiac deaths, increased λ predicted exclusively cardiac death (RR [95% CI], 1.6 [1.3–2.0] per 1 SD increment, P < 0.0001). The predictive power of increased λ was significant even after adjustments for clinical risk factors, such as age, diabetes, left ventricular function, renal function, prior AMI, heart failure, and stroke, Killip class, and treatment ([95% CI], 1.4 [1.1–2.0] per 1 SD increment, P = 0.01). The prognostic power of increased λfor cardiac death was also independent of all other HRV indices and the combination of increased λ and abnormal HRT provided the best predictive model for cardiac death. Neither λ nor other HRV indices was an independent predictor of AMI recurrence. Among post-AMI patients, increased λ is associated exclusively with increased cardiac mortality risk and its predictive power is independent of clinical risk factors and of other HRV predictors.
Highlights
Experimental models for sudden cardiac death after myocardial infarction (AMI) indicate that sympathetic stimulation under impaired reflex vagal antagonism provokes ventricular vulnerability to fibrillation during transient myocardial ischemia (Schwartz et al, 1984; Vanoli et al, 1991)
heart rate variability (HRV) AND NON-GAUSSIANITY INDICES The HRV indices that are considered as relating to cardiac vagal function were highly correlated with each other, while the nonGaussianity index of λ25 s showed no substantial correlations with these indices (Table 2)
Λ25 s correlated with neither the number of ventricular ectopies per 24 h (r = − 0.01) nor its products with turbulence onset (TO) or turbulence slope (TS) (r = 0.01, − 0.07), indicating that λ25 s is unrelated to heart rate fluctuations accompanying ventricular arrhythmias (“heart rate turbulence (HRT)”)
Summary
Experimental models for sudden cardiac death after myocardial infarction (AMI) indicate that sympathetic stimulation under impaired reflex vagal antagonism provokes ventricular vulnerability to fibrillation during transient myocardial ischemia (Schwartz et al, 1984; Vanoli et al, 1991). Autonomic dysfunction by heart rate variability (HRV) has been proposed for post-AMI risk stratification (Kleiger et al, 1987; La Rovere et al, 1998; Schmidt et al, 1999; Bauer et al, 2006). Most of HRV indices proposed, primarily reflect reduced or impaired vagal function (Camm et al, 1996; Marine et al, 2002; Bauer et al, 2006). As a marker potentially related to sympathetic cardiac overdrive, we have recently proposed increased non-Gaussianity of HRV (Kiyono et al, 2008). Non-Gaussianity has been used in fluid dynamics for characterizing intermittency of turbulence
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