Effect of atropine on heart rate turbulence.

Heart rate turbulence (HRT) is a recently described measurement of the short-term oscillation in sinus cycle length following a ventricular premature complex (VPC). It has been shown to be a powerful predictor of mortality in patients with acute myocardial infarction and congestive heart failure. As shown in Figure 1, after a VPC occurs in the normal state, heart rate accelerates immediately (2 to 3 beats) and then decelerates (maximum RR interval at about the 8th to 10th beat) before returning to baseline (before the 20th beat). The mechanism underlying normal HRT has not been established, although autonomic influences have been hypothesized. In this study, we sought to determine the response of induced HRT, as measured in the electrophysiology laboratory, to parasympathetic blockade with atropine. We also sought to determine whether the oscillation in RR intervals after VPCs that defines HRT results from variation in sinus rate, atrioventricular conduction, or both. • • • After providing written informed consent, 12 consecutive patients underwent electrophysiologic study, during which atropine was given for diagnostic purposes. Some patients received small doses of intravenous midazolam to relieve anxiety, but all patients remained awake and alert throughout the study protocol. Quadripolar catheters were placed in the high right atrium, His bundle region, and right ventricular apex. During sinus rhythm, a paced VPC from the right ventricular apex was induced at twice diastolic threshold and at 60% of sinus cycle length after every 25 sinus beats. At least 5 sequences were recorded in the baseline state and 5 more after intravenous administration of 1 mg atropine. Electrograms were recorded on a standard digital system and AA, AH, HV, and VV intervals were measured using on-line calipers at a speed of 200 mm/s. VV intervals from the right ventricular apex electrogram were used to calculate turbulence onset (TO) and turbulence slope (TS) for each VPC as previously described (see Figure 1). 1 In brief, TO was defined as the difference between the mean of the first 2 sinus VV intervals following the compensatory pause after a VPC and the mean last 2 sinus VV intervals preceding the VPC, expressed as a percentage. TS was defined as the maximum positive slope of a regression line calculated over any sequence of 5 consecutive VV intervals after a VPC. For each patient and in each condition, TS and TO obtained from each sequence were averaged, discarding the highest and lowest values to minimize the From the Section of Cardiology, Boston Medical Center and Department of Medicine, Boston University Medical School; and Center for Interdisciplinary Research on Complex Systems, Northeastern University, Boston, Massachusetts. Dr. Marine was supported by National Research Service Award 5 T32 HL07224-24, Bethesda, Maryland. Dr. Monahan’s address is: Section of Cardiology, Boston Medical Center, 88 East Newton Street, Boston, Massachusetts 02118. Email: kevin. monahan@bmc.org. Manuscript received July 2, 2001; revised manuscript received and accepted November 21, 2001. FIGURE 2. Raw data obtained from a representative patient demonstrating loss of HRT after administration of atropine. (A) Baseline condition. (B) After intravenous administration of atropine 1 mg. FIGURE 1. A, normal HRT response to a VPC. B, definitions of TS and TO. HR heart rate.