Baroreflex sensitivity and heart rate variability in the identification ofpatients at risk for life-threatening arrhythmias - Implications for clinical trials

Background-The need for accurate risk stratification is heightened by the e xpanding indications for the implantable cardioverter defibrillator, The Mu lticenter Automatic Defibrillator Implantation Trial (MADIT) focused intere st on patients with both depressed left ventricular ejection fraction (LVEF ) and the presence of nonsustained ventricular tachycardia (NSVT), Meanwhil e, the prospective study Autonomic Tone and Reflexes After Myocardial Infar ction (ATRAMI) demonstrated that markers of reduced vagal activity, such as depressed baroreflex sensitivity (BRS) and heart rate variability (HRV), a re strong predictors of cardiac mortality after myocardial infarction. Methods and Results We analyzed 1071 ATRAMI patients after myocardial infar ction who had data on LVEF, 24-hour ECG recording, and BRS, During follow-u p (21+/-8 months), 43 patients experienced cardiac death, 5 patients had ep isodes of sustained VT, and 30 patients experienced sudden death and/or sus tained VT. NSVT, depressed BRS, or HRV were all significantly and independe ntly associated with increased mortality. The combination of all 3 risk fac tors increased the risk of death by 22x, Among patients with LVEF<35%, desp ite the absence of NSVT, depressed BRS predicted higher mortality (18% vers us 4.6%, P=0.01). 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 NS VT and HRV. Conclusions-BRS and HRV contribute importantly and additionally to risk str atification. Particularly when LVEF is depressed, the analysis of BRS ident ifies a large number of patients at high risk for cardiac and arrhythmic mo rtality who might benefit from implantable cardioverter defibrillator thera py without disproportionately increasing the number of false-positives.