Mirza W. Ahmed

Effects of autonomic stimulation and blockade on signal-averaged P wave duration.

OBJECTIVES This study sought to evaluate the effects of autonomic stimulation and blockade on the signal-averaged P wave duration. BACKGROUND Signal-averaged P wave duration has been shown to have prognostic implications for patients prone to develop atrial fibrillation, but autonomic influences on the signal-averaged P wave duration have not been studied. METHODS In 14 healthy volunteers (8 men, 6 women; mean [ +/- SD] age 28.5 +/- 4.8 years, range 22 to 38), signal-averaged P wave duration was measured on day 1 at baseline, during sympathetic stimulation with infusions of epinephrine (50 ng/kg body weight per min) and isoproterenol (50 ng/kg per min), beta-blockade with propranolol (0.2 mg/kg) and autonomic blockade with propranolol followed by atropine (0.04 mg/kg). On a second day, 10 of the 14 subjects returned for repeat baseline recordings and recordings during parasympathetic blockade with atropine (0.04 mg/kg). Signal averaging was performed using a P wave template. Both unfiltered and filtered (least-squares fit filter with 100-ms window) P wave durations were measured. Day to day and interobserver variability were assessed by calculation of intraclass correlation coefficients. RESULTS The mean ( +/- SD) baseline filtered P wave duration on day 1 was 141 +/- 10 ms. Isoproterenol infusion significantly shortened the P wave duration to 110 +/- 16 ms (p < 0.001), and epinephrine resulted in significant prolongation to 150 +/- 10 ms (p < 0.05). Beta-adrenergic blockade increased the P wave duration to 153 +/- 10 ms (p < 0.005). Autonomic blockade shortened the P wave duration to 143 +/- 16 ms (p < 0.05 vs. beta-blockade). On the second day, the mean baseline P wave duration was slightly longer (144 +/- 10 ms, p < 0.02). Parasympathetic blockade with atropine resulted in mild shortening of the P wave duration to 136 +/- 15 ms (p < 0.1). Interobserver reproducibility was excellent (intraclass correlation coefficient 0.99). Day to day reproducibility was good (intraclass correlation coefficient 0.56). CONCLUSIONS The signal-averaged P wave duration is not a fixed variable because it may change significantly under different autonomic conditions. This has important implications for the application of this test to the heterogeneous population susceptible to atrial fibrillation.

Effect of Graded Increases in Parasympathetic Tone on Heart Rate Variability

Parasympathetic Effects on Heart Rate Variability. Introduction: Time‐ and frequency‐domain measurements of heart rate variability have been used as indices of parasympathetic tone. However, studies of the effect of parasympathetic stimulation on these indices in humans have yielded conflicting results.

Uncertainty Principle of Signal-Averaged Electrocardiography

BACKGROUND Signal-averaged ECG (SAECG) reproducibility is reported to have a component that is independent of residual noise. Methods and Results-In group 1, multiple paired SAECGs were obtained to noise levels of 0.3+/-0.1 and 0.5+/-0.2 microV. For the 0.5- and 0. 3-microV noise recordings, QRS duration (QRSd) was 101.2+/-11.3 and 104.6+/-9.6 ms, respectively (P<0.0001), and the differences in paired QRSd (DeltaQRSd) were normally distributed, with variances of 11.4 and 26.2 ms(2) (P<0.0001). Paired SAECGs were obtained in group 2 patients without and with late potentials; DeltaQRSd variance was 3.3 and 217.9 ms(2) (P<0.0001). In group 3, >/=10 SAECGs were acquired at noise levels of 0.2 to 0.8 microV, in 0.1-microV increments. QRSd increased as noise level decreased. The variance was greater in low-noise (0.2 to 0.4 microV) versus higher-noise (0. 5 to 0.8 microV) recordings. In group 4, SAECGs were analyzed with bidirectional and Bispec filters, with no difference in QRSd between the 2 filters and a normally distributed DeltaQRSd. A computer simulation demonstrated that alterations in the phase relationship of noise to signal results in a normal distribution of signal end points. CONCLUSIONS Within the acceptable noise range for SAECG, lower noise results in longer QRSd and larger variance, suggesting that more accurate recordings may have less reproducibility. The random timing of noise relative to signal results in the distribution/variance of repeated measurements. Statistical strategies may be used to reduce some of this variance and may enhance the diagnostic utility of SAECG.

Characterization of the Factors that Determine the Effect of Sympathetic Stimulation on Heart Rate Variability

Heart rate variability analysis has been used to derive indices of sympathetic tone. As different sympathetic stimuli may give rise to divergent changes in heart rate variability, this study was designed to characterize the factors responsible for these divergent responses. Twelve healthy subjects (7 males, age 24.8 ±3.1 years) were evaluated. Five‐minute electrocardiographic recordings were obtained at baseline, following upright tilt, and during isoproterenol infusion (25 ng/kg per min) under control conditions and following parasympathetic blockade. Data were acquired during spontaneous respiration and when breathing was timed with a metronome (15 breaths/min). Under control conditions, both upright tilt and isoproterenol infusion resulted in significant decreases in the SD and MSSD from baseline values of 69 ± 3 ms and 64 ± 5 ms to 48 ± 4 ms and 21 ± 5 ms during tilt and 44 ± 4 ms and 20 ± 5 ms during isoproterenol infusion, respectively. LF power also significantly increased from 0.47 ±0.17 In (beats/min)2 at baseline to 1.90 ± 0.20. In (beats/min)2 and 1.34 ± 0.18. In (beats/min)2 during tilt and isoproterenoi infusion, respectively. No change in HF power was noted. Following parasympathetic blockade, all heart rate variability parameters were significantly decreased. No significant change from baseline in the SD, MSSD, or HF power was noted with either tilt or isoproterenol infusion. The LF power increased only with tilt from a baseline value of ‐3.17 ± 0.17 in (beats/min)2 to ‐0.41 ± 0.19 in (beats/min)2. Similar changes were noted during spontaneous respiration and metronome breathing. These findings demonstrate that the response of the sinus node to β–adrenergic stimulation depends on the mode of stimulation. In addition, the associated level of parasympathetic tone affects the observed changes in heart rate variability that are associated with sympathetic stimulation.

Autonomic Effects on Noise Recorded During Signal‐Averaged Electrocardiography

The purpose of this study was to assess the effects of autonomic stimulation and blockade on noise levels and to compare the noise measurements in the ST and TP segments of the signal‐averaged ECG. Five‐minute electrocardiographic data were recorded in 14 normal volunteers (8 males and 6 females; mean age 28.5 ± 5.0 years) on two separate days (day 1—baseline, epinephrine infusion, isoproterenol infusion, β‐blockade, and combined adrenergic and parasympathetic blockade; day 2—baseline, phenylephrine infusion, parasympathetic blockade, and during phenylephrine infusion following atropine). Signal averaging was done off‐line on 100 beats and noise was measured in both the ST and TP segments as the standard deviation of voltage in the segment of interest. For all conditions tested, the mean noise level measured in the ST segment (0.46 ± 0.16 μV) was significantly less than that measured in the TP segment (0.52 ± 0.24 μV; P = 0.0003). but there was good correlation between the noise measured in the STand the TP segment (R2= 0.62, P < 0.0001). Noise increased with isoproterenol infusion and decreased following adrenergic blockade. In addition, day 2 baseline noise was less than baseline noise on day 1. Finally, neither parasympathetic stimulation or blockade nor α‐adrenergic stimulation significantly affected signal‐averaged electrocardiography (SAECG) noise levels. Thus, the data support the notion that enhanced sympathetic tone increases noise levels and β‐adrenergic blockade may decrease noise levels, likely due to effects from muscle sympathetic nerve activity. These findings are important since the target population for the SAECG are patients with myocardial infarction and congestive heart failure, conditions associated with increased sympathetic tone, which may in turn impact on the reproducibility or technical aspects of the SAECG. In addition, because noise in the ST and TP segments are highly correlated and the noise measured in the ST segment is less than that in the TP segment, uniform adoption of noise measurement in the ST segment seems most appropriate.