Background-The predictive value of heart rate variability (HRV) in chronic heart failure (CHF) has never been tested in a comprehensive multivariate model using short-term laboratory recordings designed to avoid the confounding effects of respiration and behavioral factors. Methods and Results-A multivariate survival model for the identification of sudden (presumably arrhythmic) death was developed with data from 202 consecutive patients referred between 1991 and 1995 with moderate to severe CHF (age 52Ϯ9 years, left ventricular ejection fraction 24Ϯ7%, New York Heart Association class 2.3Ϯ0.7; the derivation sample). Time-and frequency-domain HRV parameters obtained from an 8Ј recording of ECG at baseline and during controlled breathing (12 to 15 breaths/min) were challenged against clinical and functional parameters. This model was then validated in 242 consecutive patients referred between 1996 and 2001 (validation sample). In the derivation sample, sudden death was independently predicted by a model that included low-frequency power (LFP) of HRV during controlled breathing Յ13 ms 2 and left ventricular end-diastolic diameter Ն77 mm (relative risk [RR] 3.7, 95% CI 1.5 to 9.3, and RR 2.6, 95% CI 1.0 to 6.3, respectively). The derivation model was also a significant predictor in the validation sample (Pϭ0.04). In the validation sample, LFP Յ11 ms 2 during controlled breathing and Ն83 ventricular premature contractions per hour on Holter monitoring were both independent predictors of sudden death (RR 3.0, 95% CI 1.2 to 7.6, and RR 3.7, 95% CI 1.5 to 9.0, respectively). Conclusions-Reduced short-term LFP during controlled breathing is a powerful predictor of sudden death in patients withCHF that is independent of many other variables. These results refine the identification of patients who may benefit from prophylactic implantation of a cardiac defibrillator. (Circulation. 2003;107:565-570.)
Alterations of the baroreceptor-heart rate reflex (baroreflex sensitivity, BRS) contribute to the reciprocal reduction of parasympathetic activity and increase of sympathetic activity that accompany the development and progression of cardiovascular diseases. Therefore, the measurement of the baroreflex is a source of valuable information in the clinical management of cardiac disease patients, particularly in risk stratification. This article briefly recalls the pathophysiological background of baroreflex control, and reviews the most relevant methods that have been developed so far for the measurement of BRS. They include three "classic" methods: (i) the use of vasoactive drugs, particularly the α-adrenoreceptor agonist phenylephrine, (ii) the Valsalva maneuver, which produces a natural challenge for the baroreceptors by voluntarily increasing intrathoracic and abdominal pressure through straining, and (iii) the neck chamber technique, which allows a selective activation/deactivation of carotid baroreceptors by application of a negative/positive pressure to the neck region. Two more recent methods based on the analysis of spontaneous oscillations of systolic arterial pressure and RR interval are also reviewed: (i) the sequence method, which analyzes the relationship between increasing/decreasing ramps of blood pressure and related increasing/decreasing changes in RR interval through linear regression, and (ii) spectral methods, which assess the relationship (in terms of gain) between specific oscillatory components of the two signals. The limitations of the coherence criterion for the computation of spectral BRS are discussed, and recent proposals for overcoming them are presented. Most relevant clinical applications of BRS measurement are finally reviewed with particular reference to patients with myocardial infarction and heart failure. Ann Noninvasive Electrocardiol 2008;13(2):191-207baroreceptors; baroreflex sensitivity; autonomic nervous systemThe evaluation of baroreflex sensitivity (BRS) is an established tool for the assessment of autonomic control of the cardiovascular system. Besides the well-acknowledged physiological role in the maintenance of circulatory homeostasis, evidence has been accumulated that changes in the characteristics of baroreflex function reflect alterations in autonomic control of the cardiovascular system. 1 Thus, measuring the baroreflex has been shown to be a source of valuable information in the clinical management, particularly in prognostic evaluation and assessment of treatment effect, in a variety of cardiac diseases. Although several methods have been developed to study baroreflex function in humans, most of these techniques are of limited value for a daily practice in the clinical setting. This article will briefly address the pathophysiological background of baroreflex control, will focus on the advantages and limitations of the different methodologies in the quantification of baroreflex activity, and will discuss the main clinical findings and the most relevant implicati...
on behalf of the Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI) InvestigatorsBackground-The need for accurate risk stratification is heightened by the expanding indications for the implantable cardioverter defibrillator. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) focused interest on patients with both depressed left ventricular ejection fraction (LVEF) and the presence of nonsustained ventricular tachycardia (NSVT). Meanwhile, the prospective study Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI) demonstrated that markers of reduced vagal activity, such as depressed baroreflex sensitivity (BRS) and heart rate variability (HRV), are strong predictors of cardiac mortality after myocardial infarction. Methods and Results-We analyzed 1071 ATRAMI patients after myocardial infarction who had data on LVEF, 24-hour ECG recording, and BRS. During follow-up (21Ϯ8 months), 43 patients experienced cardiac death, 5 patients had episodes of sustained VT, and 30 patients experienced sudden death and/or sustained VT. NSVT, depressed BRS, or HRV were all significantly and independently associated with increased mortality. The combination of all 3 risk factors increased the risk of death by 22ϫ. Among patients with LVEFϽ35%, despite the absence of NSVT, depressed BRS predicted higher mortality (18% versus 4.6%, Pϭ0.01). This is a clinically important finding because this group constitutes 25% of all patients with depressed LVEF. For both cardiac and arrhythmic mortality, the sensitivity of low BRS was higher than that of NSVT and HRV. Conclusions-BRS and HRV contribute importantly and additionally to risk stratification. Particularly when LVEF is depressed, the analysis of BRS identifies a large number of patients at high risk for cardiac and arrhythmic mortality who might benefit from implantable cardioverter defibrillator therapy without disproportionately increasing the number of false-positives.
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