Prognostic Role of Heart Rate Variability in Patients With a Recent Acute Myocardial Infarction Gaetano Antonio Lanza, MD, Vincenzo Guido, MD, M. Marco Galeazzi, MD, Marina Mustilli, MD, Rosaria Natali, MD, Carolina Ierardi, MD, Caterina Milici, MD, Francesco Burzotta, MD, Vincenzo Pasceri, MD, Francesco Tomassini, MD, Alessandro Lupi, MD, and Attilio Maseri, MD A low heart rate variability (HRV) has been shown to be a powerful predictor of cardiac events in patients sur- viving an acute myocardial infarction (MI), but it is not clear yet which among the HRV parameters has the best predictive value. Time domain and frequency domain HRV was assessed on 24-hour predischarge Holter re- cording of 239 patients with a recent MI. Patients were followed up for 6 to 54 months (median 28), during which 26 deaths (11%) occurred, 19 of which were cardiac in origin and 12 were sudden. Most HRVs did not show any difference between patients with or with- out mortality end points, but the average low-frequency and low-frequency/high-frequency ratio was lower in patients with events. However, when dichotomized ac- cording to cut points that maximized the risk of sudden death, several HRVs were significantly predictive of clin- ical end points. Overall, the mean of the standard devi- ations of all RR intervals for all 5-minute segments and the standard deviation of the mean RR intervals for all 5-minute segments were the time domain variables most significantly associated with mortality end points, whereas very low frequency was the most predictive frequency domain variable. Compared with the best time domain variables, very low frequency showed a better sensitivity (0.27 to 0.42 vs 0.19 to 0.33) for end points with only a small loss in specificity (0.92 vs 0.96). On multivariate Cox proportional analysis, a left ven- tricular ejection fraction <40% and a number of ventric- ular premature beats >10/hour were the most powerful independent predictors for all end points, whereas no HRV was independently associated with the events. A low frequency/high frequency ratio <1.05 only had a borderline association with sudden death (RR  2.86, p  0.076). Our data show a strong association be- tween HRV and mortality in patients surviving a recent MI, with a slight better sensitivity of frequency domain analysis. In our study, however, HRV did not add inde- pendent prognostic information to more classic prognos- tic variables (e.g., left ventricular function and ventricu- lar arrhythmias). 1998 by Excerpta Medica, Inc. (Am J Cardiol 1998;82:1323–1328) A reduced variability of RR intervals (heart rate variability [HRV]) has been shown to be a pow- erful predictor of subsequent mortality in patients surviving an acute myocardial infarction (MI). Whereas several studies have demonstrated a strong association of low HRV in the time domain with mortality, 1–5 there are few data regarding the prognos- tic value of frequency domain HRV analysis in this clinical setting. 6–8 Furthermore, it is not yet clear which among the most frequently used HRVs has the strongest usefulness in the risk assessment of patients with acute MI. Thus, in this study we investigated the value of the most widely used time- and frequency domain HRV variables in predicting total and cardiac mortality (both global and sudden) in a population of patients surviving an acute MI. METHODS Patients: Consecutive patients admitted to our cor- onary care unit because of acute MI and who under- went Holter monitoring before hospital discharge were eligible for the study. Acute MI was diagnosed according to typical prolonged chest pain (30 min- utes) with significant ST segment and/or T-wave changes, followed by typical elevation of total creat- ine kinase and its MB isoform, with (Q-wave MI) or without (non–Q-wave MI) the subsequent appearance of diagnostic Q waves on the standard electrocardio- gram. Of the 364 patients eligible for the study, 125 (34%) were excluded because of 1 of the following exclusion criteria: atrial fibrillation, frequent su- praventricular ectopic beats, pacemaker rhythm, asso- ciated significant valvular heart disease, Holter re- cordings lasting 20 hours or with technical defi- ciences resulting in unreliable analysis, inability of patients to be followed up. The final study population consisted of 239 pa- tients. The following variables were recorded for each patient: age, gender, MI location, history of previous MI, diabetes, hypertension, thrombolytic therapy, pre- discharge left ventricular ejection fraction as assessed by 2-dimensional echocardiography, and drug therapy at the time of Holter monitoring. Holter monitoring: All patients underwent 24-hour Holter recording 5 to 20 days after MI (median 7), From the Istituto di Cardiologia Universita’ Cattolica del S. Cuore, Rome, Italy. Manuscript received March 31, 1998; revised manu- script received and accepted July 13, 1998. Address for reprints: Gaetano A. Lanza, MD, Istituto di Cardiolo- gia, Universita’ Cattolica del S. Cuore, L.go A. Gemelli, 8, 00168 Roma, Italy. 1323 ©1998 by Excerpta Medica, Inc. 0002-9149/98/$19.00 All rights reserved. PII S0002-9149(98)00635-3