W.J. WAJSZCZUK,  J. PRZYBYLSKI, T. PAŁKO, M. WORPELL, TH. BAULD AND M.   RUBENFIRE. Electrocardiology '81, Budapest, Hungary.  Z. Antaloczy, and I. Preda (eds.)., pp. 89-94.

(From the Institute of Physiological Sciences of the Medical Academy, Institute of Precision and Biomedical Engineering, Technical University, Warsaw, Poland and Section of  Cardiovascular Diseases, Department  of Medicine, Sinai Hospital and Wayne State University, Detroit,   Michigan, USA.

* Supported by Sinai Hospital General Research Support Grant RR-05641, Car­diology Research  and Education Fund, Sinai Hospital Guild.)

Basic laboratory and clinical research during the past eight years, has demonstrated the feasibility of recording potentials generated in the car­diac conduction system from the surface of the chest. The technique in­volves high-gain signal amplification, filtering and averaging of one or more hundreds of consecutive cardiac cycles to free the signal of interest from the noise originating from the patient, instrumentation, and the environment. Initial studies allowed identification of the His bundle activity. (Wajszczuk et al 1978 a,b,c). More recently, we have also demonstrated the ability to record non-invasively the sinus node region potentials. (Pałko et al. 1980, Wajszczuk et al. 1981). In this report, we summarize briefly our experience with the clinical application of the method and present supplemental data which substantiate the origin of the individual waveforms.

INSTRUMENTATION  AND  METHODS

The four-channel system allows QRS pre-triggering, analog/digital con­version, variable filter selection, and signal averaging. In addition, it has the ability to plot vectorcardiograms of any portion of the signals and has provisions for instantaneous display and hard copy records. The system is self-contained and mobile. Digitizing can be performed either at 8 bit or 12 bit resolution.The main frame has a 4 K memory which then allows 1 K of memory per channel.     The sampling rate is 2 KHz. The input pre-amplifiers are set at a gain of 10⁴ with fixed bandwidth of 0.5-8,000 Hz. They are used to acquire simultaneously any three external signals plus a surface lead for triggering. The outputs of the pre-amplifiers are fed to a 4-channel amplifier/filter with a gain range of 0.2-80. Normally, the bandwidth for signal acquisition is set identically in three channels at 0.5-300 or 30-300 Hz and at 10-30 Hz for the trigger signal. Anti-­aliasing filters are set at 1 KHz. Triggering threshold can be adjusted so that triggering occurs when the slope of the QRS exceeds a certain value. The window can be preselected to include various time segments of the incoming signal before or after the trigger signal.

The most commonly used leads include the anterior chest ("Y") lead with a negative electrode in the third right intercostal space parasternally and a positive electrode in the fifth left intercostal space in the area of the apex, the antero-posterior (Z) lead with the positive electrode anteriorly and parasternally at the level of left fourth intercostal space and the X lead with the electrodes at the same level in the right and left (positive) mid-axillary line.  Additional information is occasionally ob­tained by using a bipolar precordial lead perpendicular to the Y lead (Y+90) or unipolar precordial leads at various left parasternal levels. (Wajszczuk et al. 1978 b,c)

RESULTS

Clinical Studies.

An example of a recording demonstrating pre-P (sinus node region) and His bundle activity is illustrated in Figure 1A. Multi­ple deflections, which occur asynchronously in the three perpendicular leads, represent the activation of various portions of the conduction sys­tem (His bundle and branches). Late deflections, best seen in leads Y and Z, which immediately precede the onset of ventricular activation, probably originate from the terminal branching portions of the His bundle or from the His-Purkinje system (see below). The onset of the P wave in the refer­ence lead is preceded by small deflections which represent the activation of the sinus node region. These potentials are best seen in the Z lead. Vectorial plotting of the potentials developing during the P-R interval is shown in Figure 1B and of the sinus node region activity in Figure 1C. Vectorial display aids in analysis of the directions, velocity, and dura­tion of the spread of activation. In patients, the display of the His bun­dle activity can best be obtained with 30-300 Hz filtering. In experimen­tal animals, narrowing the bandwidth to 100-300 Hz was sometimes advan­tageous because it allowed elimination of the slopes of atrial repolarization. (Wajszczuk et al.1978 b).

Figure 1B - magnification, in an attempt to improve visualization of the loops

Figure 2 illustrates examples of recordings of the sinus node region activity. The filter setting of 0.5-300 allows detection of early low frequency and low voltage components of spontaneous depolarization, while filter setting of 30-300 Hz accentuates the transition points between the components of the slopes and is more advantageous for time interval measurements, although early diastolic potentials are eliminated.

The success rate in obtaining adequate recordings for time interval measurements was 85% with the older, single channel instrumentation, which required a relatively noise-free environment. (Wajszczuk et al. 1978 a,b,c) The currently used instrumentation (described above), which has better re­solution and memory capacity, provided excellent and reproducible recor­dings in over 90% of the patients studied. A 3-dimensional system of transthoracic bipolar leads was necessary to assure the completeness of representation of the activity originating in the conduction system.

Comparisons with Experimental Mapping.

Various techniques of direct mapping of the sequence of activation have been used in order to identify the origin of individual deflections occurring before the P wave and dur­ing the P-R interval. (Stopczyk et al.1979; Wajszczuk et al.1979) They included direct recordings with intra-cardiac catheter electrode localized in the sinus node region, the
A-V node region and along the course of the His bundle, a multi-electrode patch on the epicardium over the sinus node re­gion or sutured over the right aspect of the interventricular septum and needle electrodes introduced into the A-V node region and along the course of the His bundle including the terminal His-Purkinje-myocardial junctions.

An example of simultaneous recordings of a reference lead, external X and Z lead, unipolar intra-atrial catheter recording from the region of the A-V node and a bipolar intracavitary right ventricular recording from the common His bundle region is illustrated in Figure 3. 

Fig.3(left) Simultaneous recording of external X and Z leads, direct recor­ding with right atrial catheter electrode in the A-V node region and direct His bundle recording with the catheter electrode in the right ventricle.

Fig.4 (right) Simultaneous external X,Y,Z recordings with the reference lead and direct recording with a plunge electrode in the lower R-V septum.

Multiple deflec­tions of activity in the external recordings continue beyond the onset and termination of the His bundle spike in the direct recording. The large negative deflection in the intra-atrial recording immediately follows the atrial activity potentials and precedes the His bundle potentials. It is assumed that this deflection represents the activity of the A-V node re­gion.

Corresponding deflections can be seen in the external averaged leads. In this animal, the H-V interval was 35 msec and the interval between the onset of the A-V node region activity deflection and the onset of ventric­ular activity was approximately 50 msec.

Figure 4 demonstrates direct recording obtained with a needle electrode inserted in the peri-apical location on the right septal surface.  Its de­flection coincides with the terminal portions of the His bundle activity deflections, which immediately precede the onset of ventricular activation.

It is felt that this activity represents the potentials from the ter­minal His-Purkinje system. The interval between this deflection and the subsequent myocardial activity deflection signifies that the conduction did not spread from these fibers directly to the myocardium but arrived there with a delay via a circular route.

Experimental Blocks.

In the experiment illustrated in Figure 5, after ablation of the sinus node and trans-section of the right bundle branch, the recording shows change in the morphology of the His bundle and QRS deflec­tion. There is greater separation between the His spikes and prolongation of the H-V interval. The heart rate was 40/minute and it appeared that the rhythm initiated in the His bundle below the point of trans-section.

Fig. 5 External recordings obtained before and after sinus node ablation and trans-section of the right bundle. The rhythm appears to initiate in the His bundle below trans-section and QRS demonstrates altered morphology.

Pharmacologic Interventions.

Besides the potential diagnostic applica­tions in blocks, and for serial studies of cardiac conduction, the non-in­vasive recordings could be used for evaluation of the effect of medica­tions. An example of lack of significant changes in conduction after intravenous  administration  of  Xylocaine  is  shown  in Figure  6.    

Fig. 6 (left) External recordings taken before and after I.V. administration of Xylocaine in a dog. No change in the P-R interval or His bundle activity deflections was demonstrated.

Fig. 7 (right) External recordings obtained before and after intravenous adminis­tration of Propranolol in a dog. Note prolongation of the P-R interval, increased separation of the His bundle activity deflections and better visualization of early (A-V nodal?) potentials (in the Y lead).

Figure 7 shows; on the other hand, a prolongation of the P-R interval and increased separa­tion of   individual  deflections of the His bundle activity after administration of  Propranolol. Also, in the  Y lead, the early negative deflection (A-V node region activation?), which follows atrial depolarization is better seen (see also Figure 3). We have previously demonstrated, with the non-invasive recordings, the Propranolol-induced prolongation of  the sino-atrial conduc­tion time.    (Wajszczuk et al. 1981).

SUMMARY AND CONCLUSIONS

Our investigative efforts over the past several years have been aimed at the development of instrumentation and refinement of a method to allow non-invasive recording of electrical activity originating in or around the sinus node, His bundle and its branches, and possibly the A-V node region or A-V node itself. The latter is difficult to identify non-invasively as well as invasively, perhaps because of its overlapping with the terminal forces of atrial depolarization and repolarization. Further study of the frequency spectra of atrial activation and of the A-V node depolarization po­tentials may allow selective filtering leading to visualization of the A-V node potentials.

A three-dimensional lead system appears to be necessary for complete evaluation of the three-dimensional cardiac conduction system. The origins of multiple deflections that can be recorded during the P-R interval have yet to be fully established. Although the H-V interval measured non-in­vasively appears to be similar to that measured invasively, on occasion difficulty occurs in proper selection of points or deflections for measurements. Despite pattern variability among normal individuals, the recor­dings are reproducible in the same individual, when similar frequency bands are utilized. No typical diagnostic patterns or norms have been yet es­tablished for abnormal conditions such as bundle branch blocks or fascicular blocks. To establish criteria for abnormality, a large collection of patients with clinical-pathologic correlations and further experimental simulations will be needed.

Since the non-invasive method of recording cardiac potentials yields reproducible results, it will be very useful for serial determination and long-term follow-up of cardiac conduction abnormalities.  Similarly, the effect of medications on conduction parameters may be measured.  While the technique of signal averaging can be applied only during stable conditions of cardiac rhythm and conduction, a recent technical advance has allowed the non-invasive analysis of a single heart beat.  We could thus extend the application of the non-invasive method to conditions of unstable cardiac rhythm, which may be invaluable for rhythm analysis. This new technique will be reported at this symposium in a separate communication from our labora­tories. (Palko et al.1981).

Acknowledgements: We wish to thank Mrs. Linda A. Gabel for her excellent secretarial assistance and Mrs. Janet Kopka and Miss Cathy Bartlett for preparation of graphic material.

REFERENCES

PAŁKO, T., WAJSZCZUK, W.J., PRZYBYLSKI, J., STOPCZYK, M.J., BAULD, T., RUBENFIRE, M. (1980): Noninvasive recording of the activity of the sino-atrial node. IRCS Medical Science 8: 337.

PAŁKO, T., WAJSZCZUK, W.J., KOHUTNICKI, M., PAWLICKI, G., BAULD, T., RUBENFIRE, M. (1981): Beat-to-beat high-resolution non-invasive recording from the cardiac conduction system. Proceedings of the 8th International Congress on Electrocardiology, Budapest, Hungary, September 1-4, 1981.

STOPCZYK, M.J., WAJSZCZUK, W.J., ŻOCHOWSKI, R.J., RUBENFIRE, M. (1979): Pre-P (sino-atrial node region) activity recording from the right atrial cavity by signal averaging.  PACE 2: 156-161.

WAJSZCZUK, W.J. , STOPCZYK, M.J., MOSKOWITZ, M.S., ŻOCHOWSKI, R.J., BAULD, T., DABOS, P.L., RUBENFIRE, M. (1978a): Noninvasive recording of His-Purkinje activity in man by QRS-triggered signal averaging. Circulation 58: 95-102.

WAJSZCZUK, W.J., PAŁKO, T., BAULD, T., PRZYBYLSKI, J., RUBENFIRE, M. (1978b):  Non-invasive real-time recording of cardiac conduction system activity.  IN: Noninvasive Cardiovascular Diagnosis. Current Concepts, edited by Edward B. Dietrich, University Park Press, Baltimore, Maryland, Chapter 35, pages 337-359.

WAJSZCZUK, W.J., MOSKOWITZ, M.S., BAULD, T., DABOS, P., WEISS, R., RUBEN­FIRE, M. (1978c): Noninvasive external recording of cardiac conduction system (His bundle) activity.  Medical Instrumentation 12: 282-287.

WAJSZCZUK, W.J., PAŁKO, T., PRZYBYLSKI, J., STOPCZYK, M.J., HAMADA, 0., BAULD, T., MOSKOWITZ, M.S., RUBENFIRE, M. (1979) : Feasibility of non-in­vasive recording of the cardiac conduction system activity: Experimental correlations.  IN: Progress in Electrocardiology, edited by Peter W. Macfarlane, Pitman Medical Publishing Co., Kent, England, pages 27-32.

WAJSZCZUK, W.J., PAŁKO, T., PRZYBYLSKI, J., STOPCZYK, M.J., BAULD, T.J., RUBENFIRE, M. (1981): External recording of sinus node region activity in animals and in man.  Proceedings of the International Symposium on the Signal Averaging Technique, in Clinical Cardiology, Cologne, May 7-9, 1981, Springer-Verlag. (IN PRESS)