Donald H. Singer

Power Spectral Analysis of Heart Rate Varability in Sudden Cardiac Death: Comparison to Other Methods

Power spectrum analysis of heart rate variability is described and compared to four other reported methods, with respect to their efficacy as predictors of risk of sudden cardiac death (SCD). Approximate frequency domain representations were obtained for each. The underlying physiologic processes which may give rise to spectral components are considered. These methods were employed to analyze 24-h ambulatory ECGs of patient populations at different degrees of risk of SCD. Heart rate variability was found to be reduced in cardiac patients known to be at increased risk of SCD, when compared to those not at increased risk. These differences were greatest in power spectral methods. Thus, power spectrum analysis appears to be more effective than the other methods in segregating these populations, suggesting that this method may be useful in categorizing cardiac patients according to risk of sudden cardiac death.

Heart Rate Variability: Frequency Domain Analysis

Experience with frequency domain analysis over the past two decades strongly suggests that it represents a unique, noninvasive tool for achieving a more precise assessment of autonomic function in both the experimental and clinical settings. Available studies indicate that the significance of the HF component is far better understood than that of the lower frequency components. In general, it is considered to reflect vagal activity, and because it is readily manipulated pharmacologically, is used as a an index of that activity. However, some caution is required because this parameter also is strongly influenced by the degree of coupling between respiration and heart rate, which, in turn, reflects the intensity of the respiratory effort as well as of parasympathetic activity. Respiratory pattern also can significantly influence HF power. The use of controlled breathing minimizes these problems, improves reproducibility of test findings, and also facilitates quantitative comparisons. The situation with respect to LF power is more complicated because it is modulated by both sympathetic and parasympathetic outflows (see previous discussion) as well as by other factors, including baroreceptor activity. Therefore, LF analysis per se cannot afford a precise delineation of the state of sympathetic activation. Determinations of the LF/HF ratio, an index of sympathovagal balance both under control conditions and in conjunction with interventions that maximize sympathetic and parasympathetic activity, provide additional insights, as do correlations between spectral activity and direct nerve recordings, plasma norepinephrine concentrations, and radionuclide imaging of adrenergic nerves. Renewed interest has recently been evinced in frequencies lower than 0.04 Hz in view of reports that the VLF portion of the spectrum (0.01-0.04 Hz) reflects a purer form of sympathetic activity than does the LF band. Despite the potential applicability to clinical problems, only very little is known about the physiologic basis of the VLF and ULF bands. Further study is required. However, it is important to note that meaningful determinations of VLF and ULF power may be difficult because decreases in frequency to such low levels are associated with an increasing propensity to violate the rules governing power spectral determinations (see previous discussion and appendix), violations that diminish reliability despite the most sophisticated preprocessing. It is also noteworthy that the reliability of spectral power determinations diminishes with decreases in the power of the signal and of the signal-to-noise ratio.(ABSTRACT TRUNCATED AT 400 WORDS)

Heart rate variability and sudden death secondary to coronary artery disease during ambulatory electrocardiographic monitoring

Data are analyzed from 5 patients who died suddenly during ambulatory electrocardiographic monitoring. Three of the patients were also assessed in terms of 2 recently developed indexes of heart rate (HR) variability. One of these, the standard deviation of RR intervals during successive 5-minute segments averaged over 24 hours, has been reported to be a putative index of vagal tone. Comparisons were made with HR variability findings in 20 normal volunteers. Sudden death was due to ventricular tachycardia degenerating into ventricular fibrillation in all cases. Both early (3 patients) and late cycle (2 patients) ventricular premature complexes initiated the terminal dysrhythmia. An increased density of ventricular ectopic activity was noted in the hour before onset of ventricular fibrillation. HR variability as measured by the standard deviation was significantly (p less than 0.01) lower in the patients who died suddenly (30 +/- 10 ms) than in the normal subjects (76 +/- 14 ms). These findings support suggestions that HR variability analysis may be useful in identifying patients at a higher risk of sudden death.

Reproducibility and Relation to Mean Heart Rate of Heart Rate Variability in Normal Subjects and in Patients with Congestive Heart Failure Secondary to Coronary Artery Disease

Before heart rate (HR) variability can be used for predictive purposes in the clinical setting, day-to-day variation and reproducibility need to be defined as do relations to mean HR. HR variability and mean HR were therefore determined in 2 successive 24-hour ambulatory electrocardiograms obtained from 33 normal subjects (age 34 +/- 7 years, group I), and 22 patients with coronary disease and stable congestive heart failure (CHF) (age 59 +/- 7 years, group II). Three measures were used: (1) SDANN (standard deviation of all mean 5-minute normal sinus RR intervals in successive 5-minute recording periods over 24 hours); (2) SD (the mean of the standard deviation of all normal sinus RR intervals in successive 5-minute recording periods over 24 hours); and (3) CV (coefficient of variation of the SD measure), a new measure that compensates for HR effects. Group mean HR was higher and HR variability lower in group II than in group I (80 +/- 10 vs 74 +/- 9 beats/min, p less than 0.04). Mean group values for HR and HR variability showed good correlations between days 1 and 2 (mean RR, r = 0.89, 0.97; SDANN, r = 0.87, 0.87; SD, r = 0.93, 0.97; CV, r = 0.95, 0.97 in groups I and II, respectively). In contrast, considerable individual day-to-day variation occurred (group I, 0 to 46%; group II, 0 to 51%). Low HR variability values were more consistent than high values. SDANN and SD correlated moderately with HR in both groups (r = 0.50 to 0.64). The CV measure minimizes HR effects on HR variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiological properties of diseased human atrium. I. Low diastolic potential and altered cellular response to potassium.

Isolated specimens of right atrial appendage from 138 subjects with atrial disease or dysfunction and from seven subjects with clinically normal atria were examined electrophysiologically by conventional microelectrode techniques. The endocardial surfaces of diseased atrial appendage were found to be characterized primarily by cells with diastolic transmembrane potentials of − 56 ± 0.7 (SEM) mV, whereas potentials of normal atria were −74.4 ± 1.0 mV. The response of the hypopolarized cells of diseased atria to K* was radically different from that defined for normally polarized cells of normal atria. The diastolic potential of hypopolarized cells was insensitive to changes in K+ concentration in the Tyrodes perfusion solution of between 2 and approximately 12 mM. Between 20 and 50 miu, the cells depolarized 34 mV per 10-fold increase in K+ concentration. The K+ electrode properties of hypopolarized cells were unaffected by reducing Na+ concentration by as much as 50-fold or by varying Ca1+ concentration from 1 to 5 mM. Acetylcholine hyperpolarized cells of diseased atria to within 5 mV of the mean resting potential for cells of normal atria. Voltage and current clamp studies on a trabecula of diseased atrium indicated that the steady state current-voltage relationship may be different from that described for nonhuman mammalian atria. These data suggest that the K+ conductance is not the principal determinant of the diastolic potential of cells in diseased atria, that the K* conductance relative to other significant membrane conductances may be substantially reduced, and that the absolute level of the K+ conductance may be reduced in cells of diseased atrium. The functional importance of the hypopolarization to the electrical and mechanical activity of the diseased atrial appendage is explored. Circ Res 44: S4S-5S7, 1979

Aberrancy: Electrophysiologic aspects

Abstract Possible electrophysiologic causes of aberrancy are discussed on the basis of data derived from studies on transmembrane potentials of single cardiac cells. Aberrancy is considered to result from impulse spread in fibers of the His-Purkinje system (1) in which membrane potential at excitation is reduced (that is, it is less negative than the normal resting potential) due to incomplete repolarization, enhanced automaticity (phase 4 depolarization) of latent pacemakers and low resting potential; (2) in which responsiveness is depressed; or (3) in which some combination of these conditions prevails. For purposes of this discussion aberrancy is classified into 3 general groups: (1) aberrancy occurring in conjunction with shortening of the cycle; (2) aberrancy occurring in conjunction with prolongation of the cycle; and (3) aberrancy occurring in the absence of changes in cycle length. Comparisons are made between data derived from studies on animals and from studies on human cardiac tissues in order to assess the extent to which hypotheses and predictions based on the former are applicable to considerations of aberrancy in man. Such comparisons also provide clues as to the greater incidence of aberrancy in the diseased as compared to the normal heart.

Effects of Atrial Premature Systoles on Sinus Rhythm in the Rabbit

Although it is well known that atrial premature depolarizations (APDs) frequently lead to lengthening of the next cycle (returning cycle), it is usually not appreciated that shortening of the returning cycle (RC) can also occur. Moreover, the mechanism for these alterations is not clearly understood. APDs were therefore electrically induced in rabbit sinoatrial (SA) preparations, and four basic patterns of alteration in the SA nodal rhythm were observed. The type of change depended very much on the timing of the APD in the cycle. The atrial events, more often than not, failed to reflect the underlying SA nodal events. Thus, lengthened atrial RCs occurred in spite of shortened SA nodal RCs. This and other discrepancies indicate that the extracellular records of atrial activity do not faithfully reflect the events within the SA node and that information gathered from them should be interpreted with caution. Timing of the APD in the cycle, antegrade and retrograde SA conduction time, SA nodal action potential characteristics, and shifts in pacemaker sites are important in the determination of the altered SA nodal and atrial responses to APDs.

Glass Microelectrode Studies on Intramural Papillary Muscle Cells Description of Preparation and Studies on Normal Dog Papillary Muscle

Although the electrophysiological properties of intramural ventricular myocardial cells are important to an understanding of cardiac excitation and conduction, they have not been well defined. The paucity of information stems from limitations on the depth of penetration by glass microelectrodes and from difficulties in perfusing the deep layers. Therefore, a tissue slicing technique that satisfactorily exposes all the layers of a papillary muscle specimen from the endocardium to the epicardium was developed for electrophysiological examination. Glass microelectrodes were then used to explore these slice preparations to define the electrophysiological characteristics of intramural cells in the normal dog. Transmem-brane potentials recorded from subendocardial and deep myocardial cells in the papillary muscle slices were comparable to those recorded from standard preparations. Similarities included action potential duration and configuration, relationships among resting potential, action potential configuration, and extracellular potassium concentration, and dependency of action potential duration on cycle length. However, the average magnitudes of measured electrophysiological characteristics were consistently greater in the subsurface cells tested in papillary muscle slices than they were in the surface cells tested in the standard preparations, i.e., resting potential was 2–4 my more negative, action potential amplitude was 7–9 my larger, and maximum rate of voltage change (maximum dV/dt) was 40–140 v/sec larger. Deep myocardial tissues also exhibited enhanced responsiveness (the curve relating activation potential to maximum dV/dt of the response shifted up and to the left), cell populations with large maximum dV/dt, and estimated conduction velocities in excess of three times those in the surface cell layers. These findings provide a reasonable explanation for (1) discrepancies between previously reported values for ventricular conduction velocity, (2) rapid impulse spread to the papillary muscle tip, and (3) bidirectional activation of the papillary muscle and large trabeculae. They also suggest the possibility of functional pathways that facilitate rapid activation of the deep myocardial lavers.

An analysis of lidocaine block of sodium current in isolated human atrial and ventricuiar myocytes

Lidocaine is a Na+ channel blocker that is highly effective for the treatment of ventricular tachyarrhythmias, but is largely ineffective against atrial arrhythmias. If is not known if this differential efficacy is the result of differences in lidocaine inhibition of atrial v ventricular Na+ channels. The purpose of the present study was to characterize lidocaine block of Na+ channels in human atrium and ventricle. We used the whole cell voltage clamp technique with low external and internal Na+ concentrations (5 mM) to study the Na+ current (INa) in single human atrial and ventricular cells isolated enzymatically from specimens obtained during surgery. We found that tonic block of peak INa by lidocaine (200 microM, holding potential = -140 mV, 0.1 Hz, at 17 degrees C) was not voltage dependent in either cell type. Reduction of maximal peak Na+ conductance in 41 atrial cells (19.8 +/- 2.7%) and nine ventricular cells (22.6 +/- 1.7%) was virtually identical. The rate of onset of block development was determined during depolarization to either -80 mV or -20 mV. The time course of onset of block was described by a single exponential at -80 mV and by a double exponential at -20 mV. When the rate of block onset during a single conditioning depolarization was compared to that which developed during conditioning by a train of brief pulses (3 ms, 30 Hz), onset was faster during the pulse train. The results were nearly identical for atrial and ventricular INa. The time constants of recovery from block following either single pulse or multiple-pulse conditioning did not differ. These data suggest that lidocaine binds to both the activated and inactivated states of the human cardiac Na+ channel. Using an analytical method based upon the Guarded Receptor Hypothesis, we calculated apparent rate constants describing lidocaines interaction with the three primary states of the human Na+ channel (resting, activated and inactivated). Rate constants were similar to those reported for other mammalian species. Our results demonstrate that lidocaine block of INa is virtually identical for human atrial and ventricular cells; thus additional mechanisms must be invoked to explain the differential efficacy of lidocaine against ventricular as compared to atrial dysrhythmias.

Ventricular parasystole and re-entry: Clinical-electrophysiological correlations

Abstract A 23-year-old patient with ventricular parasystole is described. Detailed analysis of ECGs obtained during 260 hours of Holter monitoring revealed a complex arrhythmia best explained in terms of the occurrence of manifest and concealed re-entry within the parasystolic focus. Re-entry, when manifest, resulted in premature beats coupled to the parasystolic beats, and brief runs of ventricular tachycardia. When concealed, re-entry produced an irregularity in the timing of the parasystolic beats. Re-entry within the parasystolic focus was also induced by sinus beats, giving rise to a pattern of bigeminy. Correlation with data obtained from glass microelectrode studies on canine Purkinje fibers and human cardiac tissue permits speculation regarding the electrophysiologic basis of “protection,” and the possible interrelationships between parasystole and other types of ectopic ventricular rhythm.