Autonomic nervous system activity and the spontaneous initiation of ventricular tachycardia. ESVEM Investigators. Electrophysiologic Study Versus Electrocardiographic Monitoring Trial.

OBJECTIVES: We hypothesized that neurohormonal activity contributes to the initiation of sustained ventricular tachycardia (VT) as reflected in indices of heart rate variability (HRV). BACKGROUND: Autonomic nervous system activity participates in experimental arrhythmias but clinical studies have been inconsistent. METHODS: Holter electrocardiograms from 53 patients with VT were analyzed. Heart rate variability indices were determined over 5 and 15 min and 24 h and examined for changes before the onset of VT. Heart rate variability indices in the frequency domain included ultra low frequency power (FP) (ULFP): 0-0.0033 Hz; very low FP (VLFP): 0.0033-0.04 Hz; low FP (LFP): 0.04-0.15 Hz; high FP (HFP): 0.15-0.4 Hz; total power (TP); normalized LFP (LFPn); normalized HFP (HFPn), and the ratio: LFP/HFP. RESULTS: Heart rate variability indices were severely diminished: TP: 12,009+/-11,076 ms2; ULFP: 10,087+/-9,565 ms2; VLFP: 1,416+/-1,571 ms2; LFP: 544+/-620 ms2; HFP: 161+/-176 ms2, and LFP/HFP: 3.68+/-2.83. Heart rate increased before VT (80.4+/-17.3 to 85.3+/-17.4 bpm, p < 0.001). Several HRV variables declined 30 min before VT compared to 24-h values (VLFP: -5.89+/-17.81%, p = 0.031; LFP: -5.23+/-14.3%, p = 0.003; HFP: -4.35+/-13.7%, p = 0.04). LFPn and the LFP/HFP ratio decreased significantly before the onset of VT (-17.7+/-46.9%, p = 0.035 and -8.24+/-38.8%, p = 0.037, respectively), whereas HFPn increased slightly (4.29+/-29.9%, p = 0.097). CONCLUSIONS: Heart rate rose, whereas LFP, LFPn and LFP/HFP fell before the onset of VT. This pattern of changes could be explained by a rise in sympathetic activity and saturation of the HRV signal resulting in dissociation of the average and rhythmical effects of sympathetic activity. These findings suggest that alterations in autonomic activity contributed to arrhythmogenesis in this group of patients.

Distinctive RR dynamics preceding two modes of onset of spontaneous sustained ventricular tachycardia. (ESVEM) Investigators. Electrophysiologic Study Versus Electrocardiographic Monitoring.

INTRODUCTION: We hypothesized that autonomic activity preceding spontaneous sustained monomorphic ventricular tachycardia (VTsm) as assessed by heart rate (HR) and RR interval variability (RRV) differs between type 1 VTsm which is initiated by morphologically distinct, early cycle, possibly triggering premature ventricular complexes (PVCs) and type 2 VTsm in which the initial complex has a QRS waveform identical to subsequent complexes. METHODS AND RESULTS: Baseline Holter tapes (1,646) from a clinical trial were scanned for VTsm. QRS complexes of VTsm were compared by two-lead cross-correlation to distinguish type 1 and type 2 VTsm. Frequency domain RRV index were estimated over 5 minutes, 15 minutes, and 24 hours. Type 1 and type 2 VTsm were present in 15 (group 1) and 33 (group 2) of 48 patients, respectively. HR did not change in group 1 (88.4+/-15.2 to 89.7+/-13.0 beats/min, P = 0.89), but increased before the onset of VTsm in group 2 (74.3+/-16.3 to 81.2+/-18.0 beats/min, P < 0.001). RRV index were severely depressed in both groups. No RRV index changed significantly before the onset of type 1 VTsm, whereas significant changes occurred before type 2 VTsm from 24-hour average to 30 minutes before VTsm in very low (very low-frequency power [VLFP]: 6.62+/-1.53 to 6.20+/-2.07 ln msec2, P = 0.036), low (low-frequency power [LFP]: 5.61+/-1.43 to 5.28+/-1.59 ln msec2, P = 0.004), normalized low (normalized low-frequency power [LFPn]: -0.48+/-0.58 to -0.55+/-0.64 normalized units [nu], P = 0.05) and the ratio of LFP to high-frequency power (HFP) (LFP/HFP: 4.20+/-3.47 to 3.45+/-2.53, P = 0.017). Declines in RRV index between 2 hours to the 30-minute period before VTsm occurred in group 2 but not group 1 in LFP (5.85 +/- 1.42 to 5.28 +/- 1.59 In msec, P = 0.043) and HFP (4.94 +/- 5.14 to 3.46 +/- 2.52 In msec2, P = 0.008), with a downward trend in LFP/HFP (4.94+/-5.14 to 3.45+/-2.53, P = 0.127) and LFPn (-0.38+/-0.36 to -0.55+/-0.64, P = 0.15), while HFPn tended to rise (-1.47+/-0.65 to -1.27+/-0.64, P = 0.15). CONCLUSIONS: HR and RRV did not change before type 1 VTsm, suggesting that short-term changes in autonomic activity were not essential to initiation of apparent PVC-triggered VTsm. In contrast, RR interval dynamics before type 2 VTsm suggested that short-term changes in neurohormonal activity contributed to arrhythmia initiation. Heterogeneities in arrhythmia onset may reflect distinct triggers and substrate properties that could provide a basis for effective therapeutic targets.

Single catheter determination of local electrogram prematurity using simultaneous unipolar and bipolar recordings to replace the surface ECG as a timing reference.

Bipolar recordings eliminate much of the far-field signal, while minimally filtered unipolar recordings contain substantial far-field signal components. These properties may allow the onset of the unipolar recording to serve as a timing reference for the bipolar recording obtained from the same electrode catheter during mapping of focal atrial or ventricular tachycardias. Mapping and RF ablation were performed in 26 patients with focal ventricular tachycardia and 14 patients with focal atrial tachycardia. At 205 mapping sites, simultaneous recordings of (1) minimally filtered unipolar electrograms (0.5-500 Hz), (2) high pass filtered unipolar electrograms (100 Hz), and (3) filtered bipolar recordings (30-500 Hz) were analyzed. The interval between the onset of the minimally filtered unipolar electrogram and the first peak of the bipolar electrogram (UniOn-BiP) correlated closely with the timing of the local electrogram referenced to the surface ECG (r = 0.85, P < 0.001). Of 53 sites where RF ablation was performed, UniOn-BiP was shorter at successful compared to unsuccessful sites (3.8 +/- 3.5 vs 9.2 +/- 5.2 ms, P < 0.001) and was < 15 ms at all successful sites. In conclusion, the comparison of simultaneous unipolar and bipolar electrograms from a single catheter allows assessment of the prematurity of local electrograms from a focal source without the use of the P wave or QRS onset as a timing reference.

Dynamics of low-frequency R-R interval oscillations preceding spontaneous ventricular tachycardia.

BACKGROUND: Increased sympathetic activity is believed to be an important trigger of sustained ventricular tachyarrhythmias (VT) and is believed to be responsible for the increased heart rate that we and others have reported before the onset of spontaneous VT. However, in the patients reported herein, heart rate variability (HRV) indexes that reflect sympathetic activity unexpectedly declined, whereas heart rate increased. To explain this apparent paradoxic behavior, we tested the hypothesis that baseline levels of HRV determine its reaction to short-term autonomic perturbations before the onset of VT. METHODS AND RESULTS: Holter electrocardiograms from 47 patients (ejection fraction 36% +/- 15%) with recorded VT were analyzed. Frequency domain HRV indexes (low-frequency power [LFP] 0. 04 to 0.15 Hz, high-frequency power [HFP] 0.15 to 0.4 Hz, and total power [TP] 0.01 to 0.4 Hz) were studied in 5-minute intervals and over a period of 24 hours. Patients were divided into those with a decrease in LFP in the 2-hour period before VT (group A, n = 32) and those with an increase or no change (group B, n = 15). The data were logarithmically transformed. Heart rate increased 15 minutes before the onset of VT compared with the 24-hour mean in both groups (group A: 80.3 +/- 15.4 to 86.1 +/- 20.0 beats/min, P =.005; group B: 80.6 +/- 13.5 to 86.7 +/- 14.0 beats/min, P =.017). Group A had higher TP, LFP, and LFP/HFP 2 hours before VT, and these variables decreased 15 minutes before the onset of VT (TP from 7.31 +/- 1.28 to 6.88 +/- 1.35, LFP from 6.09 +/- 1.28 to 5.38 +/- 1.33, LFP/HFP from 1.33 +/- 0.89 to 0.96 +/- 0.80, P <.001 for all 3 variables). HFP also decreased 15 minutes before VT compared with 2 hours (from 4.78 +/- 1.05 to 4.49 +/- 1.24, P =.028). In group B, which had lower baseline TP, LFP, and LFP/HFP at 2 hours before VT, these variables increased 15 minutes before the event (TP from 6.41 +/- 1.41 to 6.86 +/- 1.42, P =.004; LFP from 4.59 +/- 1.51 to 4.95 +/- 0.62, P <.001; LFP/HFP from 0.22 +/- 1.22 to 0.52 +/- 1.38, P =.10), whereas HFP did not change significantly (4.40 +/- 0.94 and 4.53 +/- 1.01, P =. 50). CONCLUSIONS: An increase in heart rate and a drop in the low-frequency oscillations of R-R intervals before the onset of VT occurred in patients with higher baseline level of oscillatory activity. These changes suggest a dissociation between the average and rhythmic modulation of R-R intervals. A decline of the low-frequency oscillations in the setting of increasing heart rate could reflect an abnormal response to increased sympathetic activity in most of the patients from the studied group. The different behaviors of the HRV indexes before the onset of VT in the 2 groups suggest that change in the dynamics of R-R intervals, rather than the direction of change, facilitates arrhythmogenesis.

Changes in autonomic activity and ventricular repolarization.

An increase in sympathetic activity, manifested by shortening of RR intervals (RRi) and changes in RRi variability, precedes and possibly triggers ventricular tachyarrhythmias (VTAs) by altering repolarization. We examined the effects of autonomic activity on the projection of repolarization as detected by body surface potential maps (BSPMs). We recorded 32 lead/192-point BSPMs during passive head-up tilt, tilt + infusion of isoproterenol, rapid atrial pacing, and atrial pacing + infusion of isoproterenol. Changes in QT; recovery time; activation-recovery interval (ARi); T-wave amplitude; and QT, QRST, and ST integrals and their dispersion were analyzed. Autonomic effects on sinus node were inferred from the Fourier transform-derived low and high frequency powers of RRi variability. Patients were divided into those with (SHD) and without structural heart disease (NSHD). Heart rate increased, whereas QT interval and ARi declined with tilt in both groups. RRi variability indices of sympathetic activity increased in NSHD but did not change in SHD. T-wave amplitudes declined in NSHD but did not change in SHD, suggesting altered responsiveness of ventricular repolarization to autonomic stimulation. Tilt and rapid atrial pacing during infusion of isoproterenol resulted in a paradoxical increase in T-wave amplitudes in some patients, similar to that observed before the onset of spontaneous arrhythmias. We conclude that altering autonomic activity by head-up tilt and/or infusion of sympathomimetic agents results in significant changes in the body surface projection of cardiac repolarization, which differ in patients with SHD from those without SHD. Similar paradoxical changes in the T-wave amplitude have been observed before the onset of spontaneous VTA, suggesting that abnormal response of repolarization to autonomic stimulation predisposes to arrhythmogenesis.