Multidimensional Rhythm Disturbances as a Precursor of Sustained Ventricular Tachyarrhythmias

Abstract

Abstract-Cardiac cycle dynamics reflect underlying physiological changes that could predict imminent arrhythmias but are obscured by high complexity, nonstationarity, and large interindividual differences. To overcome these problems, we developed an adaptive technique, referred to as the modified Karhunen-Loeve transform (MKLT), that identifies an individual characteristic ("core") pattern of cardiac cycles and then tracks the changes in the pattern by projecting the signal onto characteristic eigenvectors. We hypothesized that disturbances in the core pattern, indicating progressive destabilization of cardiac rhythm, would predict the onset of spontaneous sustained ventricular tachyarrhythmias (VTAs) better than previously reported methods. We analyzed serial ambulatory ECGs recorded in 57 patients at the time of VTA and non-VTA 24-hour periods. The disturbances in the pattern were found in 82% of the recordings before the onset of impending VTA, and their dimensionality, defined as the number of unstable orthogonal projections, increased gradually several hours before the onset. MKLT provided greater sensitivity and specificity (70% and 93%) compared with the best traditional method (68% and 67%, respectively). We present a theoretical analysis of MKLT and describe the effects of ectopy and slow changes in cardiac cycles on the disturbances in the pattern. We conclude that MKLT provides greater predictive accuracy than previously reported methods. The improvement is due to the use of individual patterns as a reference for tracking the changes. Because this approach is independent of the group reference values or the underlying clinical context, it should have substantial potential for predicting other forms of arrhythmic events in other populations. Key Words: ventricular arrhythmias Ⅲ cardiac cycle dynamics Ⅲ orthogonal decomposition A lthough substantial progress has been made in the understanding of arrhythmia mechanisms and identification of individuals at risk, short-term prediction of the timing of onset of sustained ventricular tachyarrhythmias (VTAs) has lagged, delaying development of preventive treatments. 1 Because autonomic activity is thought to be an important trigger of VTA and because cardiac cycle lengths (CCLs) are modulated by autonomic tone, it has been assumed that the analysis of the changes in CCL could predict the timing as well as the triggers of VTA. 2 This has been confirmed by studies that demonstrated heart rate increase before the VTA onset in many patients. [2][3][4][5] However, the change in heart rate before the onset of VTA is usually small and indistinguishable from random daily variations. 2,6 Descriptors of heart rate variability proved useful in general risk assessment but failed to predict the timing of VTA. 5,7 Probable reasons for the failure include the high complexity of the interacting physiological influences and violation of the statistical assumptions that underlie traditional techniques. 8 In addition, the attempts to summarize highly nonstationary and indivi...

Upsurge in T-Wave Alternans and Nonalternating Repolarization Instability Precedes Spontaneous Initiation of Ventricular Tachyarrhythmias in Humans

“…26 Because changes in the pattern of cardiac rhythm spanned multiple frequency ranges, 26 they could have led to the development of multiform repolarization instabilities spanning different frequencies as well. Further support for this hypothesis comes from the experimental studies and computer simulations that demonstrated a delayed, exponentially decaying adaptation of repolarization to changes in cardiac cycle lengths.…”

“…Analysis of the predictive value would require a different analytical approach, which includes selection of a training and test groups, determining the cutoff values in the training group, and testing these cutoffs in the test group. 26 The present investigation has been designed as a feasibility study; the results reported here suggest that further research into the predictive value of repolarization instability is warranted.…”

V-Shaped Trough in Autonomic Activity Is a Possible Precursor of Life-Threatening Cardiac Events

“…Shusterman et al reported that disturbances in the characteristic pattern of cardiac cycles, which were detected using their proposed technique, precede the onset of spontaneous, sustained ventricular tachyarrhythmias with a sensitivity of 70% and a specificity of 93%. 20 One probable reason for the higher sensitivity of V-trough (91%) reported in the present study is that it is based on disturbances in the pattern of cardiac cycles for ln(LF/HF) and ln(HF). The specificity for the presence of a V-trough (84%), however, was somewhat lower, because the no event group had 30 false positives, including 12 subjects who had a V-trough for ln(LF/HF) and 18 for ln(HF).…”

“…20 We surmised that one of the reasons for this low sensitivity and specificity for LF, HF, and LF/HF was that there were considerable differences in the variables in each subject. Based on other studies 9 we calculated the moving average of 5 successive values for LF, HF, and LF/HF and used the natural logarithms of the moving average to make these distributions approximate a normal distribution.…”

“…between occurrence of an sV-trough, pV-trough, or neither between the event group and the no event group was examined on chi-square test for a 3×2-contingency table of { [22,9,3]× [10,20,161]}, and the difference proved to be significant (P<0.001). The ratio of slp(-)V-trough to slp(+)V-trough (17/14=1.21) in the event group was compared with that (6/24=0.25) in the no event group on Fisher's exact probability test, and the former was significantly larger than the latter (P<0.01).…”