Atrioventricular nodal Wenckebach phenomenon

LETTERS TO THE, EDITOR

ATRIOVENTRICULAR NODAL WENCKEBACH PHENOMENON

There has been considerable speculation through the years that, during the successive beats in an atrioventricular (A-V) nodal Wenckebach cycle, thlere was a concomitant, progressive increase in refractoriness of the junctional conducting tissues. The well designed and extensive series of experiments by Simson et al.* recently published in this journal have provided the critical evidence for such contentions. Furthermore, these authors provided a comprehensive survey of the various hypotheses advanced to explain the Wenckebach phenomenon and analyzed their data in an effort to determine which hypothesis was correct. In 1974, my collaborators and I attempted to analyze the Wenckebach phenomenon on the basis of a positive feedback mechanism.2,3 We proposed that, given a virtually constant cardiac cycle length, a delay in A-V conduction (reflected by a prolonged P-R interval) might initiate a sequence of electrophysiologic changes so that the next atria1 activation wave would arrive at the A-V junction at an earlier phase of the relative refractory period (reflected by the shorter R-P interval). This in turn would cause an even greater lengthening of the P-R interval. This sequence of progressive lengthening of the P-R interval and shortening of the R-P interval would continue until the wave of atria1 activation arrived at the A-V junction during its effective refractory period, at which point it would be blocked. Schaffer and DePasquale4 proposed that the most likely electrophysiologic basis for this phenomenon involved electrotonic interactions among the conducting fibers in the A-V node. Our group2J and Sim son et a1.l agreed that such interactions probably accounted for the progressive retardation of A-V conduction within a Wenckebach cycle. However, we chose to interpret such phenomena in terms of control systems theory, whereas Simson et al. interpreted them in terms of a “cumulative effect.” Because the electrotonic interaction mechanism underlies the hypotheses of both groups, the differences appear to be largely semantic. Simson et a1.l did concede that their cumulative effect could be considered to be a “form of positive feedback.” However, their principal objection to our feedback formulation appeared to he the “instability” of one of the functions in our control systems block diagram. They are certainly correct about the ;stability of the function, but such information does not inval:idate the overall hypothesis. The contents of the involved block must simply be replaced by a more precise transfer function. A control systems model is one way to state formally a working hypothesis. As more information is gained, the model is altered accordingly. Although it appears that the differences between our hypothesis and that of Simson et al. are semantic rather than conceptual, we believe that the use of the term “cumulative” is especially misleading. In their paper, Simson et al. use that term as if it were equivalent to “fatigue.” In our animal experiments,2 whether or not we succeeded in establishing the existence of a positive feedback system, we did rule out unequivocally the involvement of fatigue as the definitive factor. We did acknowledge that cumulative effects are a prominent feature of A-V conduction2 and cited appropriate references. However, we showed experimentally that during an established Wenckebach rhythm, such cumulative effects must have been at a steady state. Hence, they played no more than

a negligible role in producing a progressive retardation of A-V conduction. When we programmed our computer to break abruptly the cycle of diminishing R-P intervals, the Wenckebach phenomenon was abrogated instantly (from one heartbeat to the next). We equated this with “opening” a feedback loop. Conversely, when we “closed” the loop again by allowing the R-P intervals to take on whatever values they would at the prevailing atria1 pacing frequency, the Wenckebach cycles resumed immediately. We aver that such behavior is incompatible with a fatigue mechanism. Matthew N. Levy, MD Investigative Medicine Mt. Sinai Hospital of Cleveland Cleveland, Ohio References 1. SlmsonMB, Spear JF, MooreEN: Electrophysiologic Wenckebach

cycles. Am J Cardiol41:244-258.

studies on atrioventricular

nodal

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2. LevyMN, MartinPJ, Zleske H, AdlerE: Roleof positivefeedbackinthe atdoventrlcUk% nodalWenckebachphenomenon. Circ Res 34:697-710, 1974 3. LevyMN, Marth PJ, EdelstehJ, GokR@ag LB:The AV nodalWenckebachphsnornemm as a positivefeedbackmechanism.ProgCardiovasc Dis i&601-613, 1974 4. Sch& A, DePasqualeNP:MechanismofWenckebachA-V blockandthe obliitcq ventricularecho. CardiovascRes 7:696-702, 1973

REPLY

Our findings do not invalidate the positive feedback hypothesis of Levy et al. In studies on Wenckebach cycles we were unable to define a single transfer function of the form A-H = f(H-A) that fit the experimental data obtained during testing with premature beats. Instead of one transfer function that described A-V nodal conduction properties during 4~3 Wenckebach cycles, we found a family of at least three transfer functions (see Fig. 6 of our paper). We were also unable to find a transfer function of two independent variables that fit the data. We concluded that, in a formal definition of A-V nodal conduction as a positive feedback control system, the transfer function is likely to be complex and to involve multiple variables, and it has yet to be precisely defined. We do not fully understand Levy’s comment in his letter that during an established Wenckebach arrhythmia “cumulative effects must have been at a steady state.” We believe our experiments demonstrated a cumulative effect on refractoriness after a blocked beat that increased as the limit of 1:l conduction was approached and that can be observed during Wenckbach cycles. An important point is that we defined refractoriness in terms of the atria1 test interval, as is traditionally done. Our understanding of Levy’s positive feedback model is that it also would cause progressive changes in refractoriness, a cumulative effect, after blocked beats and during Wenckebach cycles. In the experiments Levy describes in his letter, clamping the R-P interval at a fixed value has the incidental effect of increasing the P-P interval, consequently, it is not surprising that the A-V node conduct& in a 1:l fashion. Moreover, because the atrial test interval was not held constant, the experiment does not evaluate refractoriness in terms of the atria1 test interval. We interpret the clamped R-P experiment as a test for the stability of the transfer function P-R = f(R-P). The fact that P-R intervals remain constant with a clamped R-P interval suggests that the transfer function is stable over subsequent beats. Our data support such an interpretation. In Figure 6

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LETTERS

of our paper the transfer functions for beats 3 and 4 were similar, whereas the transfer functions for beats 1 and 2 were displaced rightward. These data suggest that the transfer function may be stable several beats after a blocked beat, and that it may be a useful descriptor of A-V nodal conduction during sequences of beats that do not immediately follow a blocked beat. Levy et al. (his Ref. 2) have provided data during 1:l conduction at varying cycle lengths that are in agreement with this hypothesis. Michael B. Simson, MD Joseph F. Spear, PhD, FACC E. Neil Moore, DVM, PhD, FACC Department of Medicine Hospital of the University of Pennsylvania Philadelphia, Pennsylvania

voltage, in children the resultant P wave generally does not exceed normal limits.3 In our 12 year old patient, the P wave amplitude in leads II and aVF clearly exceeded age-dependent normal limits.4 Finally, treadmill exercise testing 14 months after recovery from Reye’s symdrome produced no P wave abnormalities in our patient, despite an exercise-induced tachycardia of 155 beats/min (Fig. 1). The abnormal P wave pattern observed in our patient during her acute illness was intimately related to a period of central nervous system decompensation with concomitant increased intracranial pressure. Although it was present when the P waves were abnormally high, tachycardia itself is unlikely to have been the major determinant of P wave size. Jeffrey M. Isner, MD National Heart, Lung, and Blood Institute National Institutes of Health Bethesda, Maryland Barbara Guller, MD, FACC Lewis P. Scott, MD, FACC Children’s Hospital National Medical Center Washington, DC

ABNORMAL P WAVE IN REYE’S SYNDROME-II

The report by Isner et al.’ regarding the abnormal P wave pattern in Reye’s syndrome requires comment. The prominent P waves with a T-, wave inscription noted in leads II and aVF in the initial tracing were certainly secondary to the tachycardia. The S-T segment sagging in leads V4 to Vs was most likely hyperventilation-rate related. To consider a primary control nervous system etiology is totally inappropriate. R. H. Wasserburger, MD

References Hersch C: Electrocardiographic changes in head injuries. Circulation 23:653-660, 1961 Eisalo A, Perasalo J, Halonen PI: Electrocardiographic abnormalities and some laboratory findings in patients with subarachnoid hem&age. Sr Heart J 34217-226. 1970 Green EW: Electrocardiographic pattern of atrial enlargement and abnormal impulse formation and conduction: In. Ele&bcardiography in Infants and Childen (Casseis DE, Baler RF. ad). New York and London. Grune 8 Stratton. 1966. D 116-130 Liebman J: Electrocardiography. In, Heart Disease in lnfa&, &hen. and Adolescents (Moss AJ. Adams FH, Emmanouilides GC. ed). Baltimore, Williams 8 Wilkins, 1977, p 16-61

University ECG-Computer Service University of Wisconsin Medical Center Madison, Wisconsin

A LESSON FROM CONTROLLED THERAPEUTIC

Reference 1. lsner J, Guller 8, Scott LP: Abnormal P wave in F&ye’s syndrome. Am J Cardiol 41: 350-351, 1978

REPLY

Wasserburger’s opinion notwithstanding, there is a dearth of investigative studies to suggest that P wave abnormalities frequently result from central nervous system disorders independent of changes in heart rate. Hersch,’ for example, found that of head injury victims with tall P waves, nearly 40 percent had a heart rate of 55 to 90 beats/min. In a similar study by Eisalo and associates,2 71 percent of patients with tall P waves in the setting of head injury had a heart rate of 60 to 100 beats/min. Both studies concluded that tachycardia alone was insufficient to explain the P wave abnormalities. Furthermore, although “sympathetic overactivity” (with associated tachycardia) may temporarily augment P wave

FIGURE 1. Exercise treadmill test: the lead II electrocardiogram shows no P wave abnormalities despite tachycardia (rate 155Imin). Paper speed is 22 mm/sac.

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TRIALS

Spectacular technical achievement in the surgical therapy for acquired heart disease has been widely acclaimed. However, broad application of new procedures should await the scientific scrutiny necessary to establish indications, risks and acceptable evidence of results in appropriate patients. Sound clinical trials provide this knowledge more efficiently than the usual more empiric and often assailable data base that has generally accompanied the initial application of new surgical interventions. Most physicians can recall operations that were abandoned after objective follow-up studies became available. In the interest of optimal patient care, research and development time should not be prolonged more than absolutely necessary. The misleading results of uncontrolled trials of medical and surgical therapy have wasted the public’s money and cost the medical community a measure of its credibility. It is the responsibility of the physician to improve upon the experience of his predecessors as well as his contemporaries. It should not be necessary to repeat the therapeutic errors of the past. If a new surgical procedure is devised, should not appropriate models or reliable clinical trials, or both; be made, analyzed and reviewed before the procedure is offered to all comers as if it had been so investigated? The unreliability of the initial individual clinical impressions of many physicians and surgeons has been amply demonstrated by the need to reevaluate thousands of drugs and the abandonment of what were considered efficacious surgical procedures. The freedom of physicians and surgeons to offer newly devised, inadequately studied and expensive surgical procedures to the trusting, optimistic public is a freedom whose time for regulation has come.

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