Benhur Aysin

Autonomic nervous system activity and the spontaneous initiation of ventricular tachycardia

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). LFPnand 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 HFPnincreased slightly (4.29 ± 29.9%, p = 0.097). Conclusions. Heart rate rose, whereas LFP, LFPnand 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.

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.

Distinctive RR Dynamics Preceding Two Modes of Onset of Spontaneous Sustained Ventricular Tachycardia

RR Dynamics Before VT. 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.

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.

Orthonormal-basis partitioning and time-frequency representation of cardiac rhythm dynamics

Although a number of time-frequency representations have been proposed for the estimation of time-dependent spectra, the time-frequency analysis of multicomponent physiological signals, such as beat-to-beat variations of cardiac rhythm or heart rate variability (HRV), is difficult. We thus propose a simple method for 1) detecting both abrupt and slow changes in the structure of the HRV signal, 2) segmenting the nonstationary signal into the less nonstationary portions, and 3) exposing characteristic patterns of the changes in the time-frequency plane. The method, referred to as orthonormal-basis partitioning and time-frequency representation (OPTR), is validated using simulated signals and actual HRV data. Here we show that OPTR can be applied to long multicomponent ambulatory signals to obtain the signal representation along with its time-varying spectrum.

Autonomic nervous system effects on ventricular repolarization and RR interval variability during head-up tilt

Changes in ventricular repolarization (VR) were analyzed using 32-lead high spatial resolution ECGs (HSRE). FFT-derived low (0.04-0.15 Hz) and high (0.15-0.4 Hz) frequency powers (LF & HF, respectively) of RR interval variability (RRIV) and their ratio were used to assess changes in the autonomic activity elicited by 70/spl deg/ tilt in 9 patients with structural heart disease (SHD) and 19 control (CON) subjects. Heart rate (HR) increased with tilt in CON and SHD. HF and LF/HF increased with tilt in CON, but not in SHD. Peak and mean T-wave amplitudes declined with tilt in CON but not in SHD. In contrast to CON subjects, RRIV and VR failed to change in SHD patients despite increased HR. This suggests preserved tonic but reduced rhythmic autonomic nervous system activity (ANSA) related modulation of HR, and reduced ANSA effects on VR.

Detection of transients in heart rate variability signals using a time-varying varying Karhunen-Loeve expansion

We present a method to capture transient changes in heart-rate variability (HRV) signals. To deal with the nonstationarities in these signals we propose a time-dependent Karhunen-Loeve expansion. Using this expansion together with an entropy criterion we are able to partition the signal into quasi-stationary segments that can be further analyzed. Local eigenvalues and eigenvectors are then computed from a time-varying autocorrelation matrix in each segment. Application of our procedure resides in the dynamic assessment of the activity of the autonomic nervous system. An example is the capture of changes in HRV that might predict the initiation of cardiac arrhythmias. Previously, after performing and analyzing a stationary Karhunen-Loeve expansion of HRV signals, we showed that a significant increase in the dynamic range of the coefficients occurs shortly before the onset of life-threatening disturbances of cardiac rhythm. With the method proposed in this paper, we extend our previous results and we attempt a more precise determination of transients associated with changes in the autonomic nervous system.

Denoising of non-stationary signals using optimized Karhunen-Loeve expansion

We show that denoising a non-stationary signal is possible by means of a Karhunen-Loeve (KL) expansion optimized by an entropy criterion. This criterion is used to segment the noisy signal and to choose the most parsimonious KL representation possible for each segment. The entropy of the KL coefficients for different window lengths determines the appropriate number and the lengths of the windows. To find the KL coefficients in each segment, a time-varying autocorrelation matrix is estimated using the evolutionary periodogram. Eigenvalues and eigenvectors needed in the expansion are computed from this matrix. The local eigenvectors are the basis for each segment. An estimate of the evolutionary spectrum of the signal is obtained from the KL expansion. Choosing the KL coefficients corresponding to the most significant eigenvalues and time-windowing are shown to constitute masking in the time-frequency plane. This masking permits the denoising of non-stationary signals corrupted by white noise.

Time-frequency analysis of cardiac rhythm to reveal patterns of adaptation to orthostatic challenge

Beat-to-beat changes in cardiac rhythm or heart rate variability (HRV), evoked by changes in the autonomic nervous system activity (ANSA), are complex and often remain unexposed by the traditional HRV analysis. In particular, this analysis does not reveal individual ANSA adjustments to changes in the body position during head-up tilt. Although tilt-related changes in the traditional HRV indices have been reported, the differences between successful and unsuccessful ANSA adaptation remain uncertain. To investigate HRV patterns in tilt-symptomatic and tilt-asymptomatic subjects, we used a time-frequency representation of the HRV signals. This representation, recently developed by the authors, is based on an orthogonal linear decomposition.

Instantaneous changes in the heart rate variability during head-up tilt revealed by positive time-frequency distribution

Energy distribution of the heart rate variability signal is perturbed in patients with impaired cardiac function compared to normal subjects (Li et al., 1997). We hypothesized that the energy distribution reflects the changes in autonomic regulation that are not exposed by conventional methods estimating the power in the empirically defined frequency ranges. To test this hypothesis instantaneous power changes in the heart rate variability signal were computed between 0.0025 and 0.25 Hz in 20 patients undergoing head-up tilting. Positive time frequency distribution (TFD) was obtained by the method of minimum cross entropy (Loughlin et al., 1994) that satisfies the time and frequency marginals. The distribution of power was calculated by separating the total frequency range into seven scales. Significant changes in the mean spectral power and its distribution were observed in those patients who experienced symptoms compared to those who were asymptomatic. We conclude that the loss of spectral power and changes in the power distribution revealed by positive TFD can be useful for assessment of physiological adaptation and diagnosis of the disorders related to autonomic imbalance.