Preserved heart rate variability identifies low-risk patients with nonischemic dilated cardiomyopathy: Results from the DEFINITE trial

University of Rochester, Rochester, New York, United States
Heart Rhythm (Impact Factor: 5.08). 04/2006; 3(3):281-6. DOI: 10.1016/j.hrthm.2005.11.028
Source: PubMed


The recent expansion of indications for prophylactic implantable cardioverter-defibrillator (ICD) placement in subjects with nonischemic dilated cardiomyopathy has raised concerns about the cost-effectiveness of this therapy.
The purpose of this study was to identify low-risk patients with nonischemic dilated cardiomyopathy who may not require prophylactic ICD placement.
This was a prospective study of 274 participants in the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, a randomized controlled trial that evaluated the role of prophylactic ICD placement in patients with nonischemic dilated cardiomyopathy. The patients underwent 24-hour Holter recording for analysis of heart rate variability (HRV). The primary HRV variable was the standard deviation of normal R-R intervals (SDNN). Patients with atrial fibrillation and frequent ventricular ectopy (>25% of beats) were excluded from HRV analysis (23% of patients). SDNN was categorized in tertiles, and Kaplan-Meier analysis was performed to compare survival in the three tertiles and excluded patients.
The study population was 73% male, with a mean age of 59 +/- 12 years and mean left ventricular ejection fraction of 21% +/- 6%. After 3-year follow-up, significant differences in mortality rates were observed: SDNN >113 ms: 0 (0%), SDNN 81-113 ms: 5 (7%), SDNN <81 ms: 7 (10%), excluded patients: 11 (17%) (P = .03). There were no deaths in the tertile with SDNN >113 ms regardless of treatment assignment (ICD vs control).
Patients with nonischemic dilated cardiomyopathy and preserved HRV have an excellent prognosis and may not benefit from prophylactic ICD placement. Patients with severely depressed HRV and patients who are excluded from HRV analysis because of atrial fibrillation and frequent ventricular ectopy have the highest mortality.

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    • "These autonomic alterations are made worse by low day-time activity levels. Thus, both a diminished vagal and an increased sympathetic modulation of the sinus node may be reflected by a reduction in HRV (Kleiger et al., 1987; Malik and Camm, 1995; Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, 1996; Fauchier et al., 1997; Nolan et al., 1999; Rashba et al., 2006). This interpretation is in agreement with experimental evidence indicating a pro-arrhythmic effect of sympatho-excitation (Lown and Verrier, 1976) and also with the findings that a reduction of these parameters is associated with an increased cardiac mortality in almost all clinical conditions characterized by an autonomic imbalance, e.g., after myocardial infarction, in patients with heart failure, hypertension, or diabetes (Kleiger et al., 1987; Malik and Camm, 1995; Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology , 1996; Fauchier et al., 1997; Nolan et al., 1999; Rashba et al., 2006). "
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    ABSTRACT: Assessment of autonomic modulation of sinus node by non-invasive techniques has provided relevant clinical information in patients with several cardiac and non-cardiac diseases and has facilitated the appraisal of neural regulatory mechanisms in normal and diseased subjects. The finding that even during resting conditions the heart period changes on a beat to beat basis and that after a premature ventricular beat there are small variations in RR interval whose measurements may be utilised to evaluate the autonomic modulation of sinus node, has provided unprecedented clinical and pathophysiological information. Heart rate variability (HRV) and Heart Rate Turbulence (HRT) have been extensively utilised in the clinical setting. To explain the negative predictive value of a reduced HRV it was determined that overall HRV was largely dependent on vagal mechanisms and that a reduction in HRV could reflect an increased sympathetic and a reduced vagal modulation of sinus node; i.e. an autonomic alteration favouring cardiac electrical instability. This initial interpretation was challenged by several findings indicating a greater complexity of the relationship between neural input and sinus node responsiveness as well as the possible interference with non-neural mechanisms. Under controlled conditions, however, the computation of low and high frequency components and of their ratio seems capable of providing adequate information on sympatho-vagal balance in normal subjects as well as in most patients with a preserved left ventricular function, thus providing a unique tool to investigate neural control mechanisms. Analysis on non-linear dynamics of HRV has also been utilised to describe the fractal like characteristic of the variability signal and proven effective to identify patients at risk for sudden cardiac death. A reduction on HRT parameters reflecting reduced baroreflex sensitivity as a likely result of a reduced vagal and of an increased sympathetic modulation of sinus
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    • "Variables from non-invasive 24-hour ECG recordings (heart rate variability, T wave alternans, etc) have also been evaluated as predictors of SCD. Rashba et al. found that patients with severely depressed heart rate variability had the highest mortality [27]. "
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