Transcutaneous pacing: Patient tolerance, strength-interval relations and feasibility for programmed electrical stimulation

BRIEF

REPORTS

Transcutaneous Pacing: Relations and Feasibility Lawrence S. Klein,

MD,

William

Patient Tolerance, for Programmed

M. Miles,

MD,

James J. Heger,

oninvasive transcutaneous pacing has been used N successfully in situations requiring emergent ventricular pacing, l-* and has also been used to terminate ventricular (VT) or supraventricular tachycardia in some patients.g-13 Thus, transcutaneous pacing might logically be considered a suitable noninvasive substitute for endocardial pacing during programmed electrical stimulation studies. We therefore determined the following features of transcutaneous pacing using the Zoll noninvasive temporary pacemaker (Zoll NTP, ZMI Corp.): patient tolerance, which cardiac chambers were paced, the ventricular effective refractory period (ERP) compared with that determined by endocardial pacing and feasibility for programmed electrical stimulation in patients with ventricular tachyarrhythmias. Sixteen male patients underwent endocardial and then transcutaneous pacing during electrophsiologk study. The ventricular ERP was determined using the premature extrastimulus technique (5 ms decrements) after 8 ventricular paced complexes at either a 500 or 400 ms cycle length.!” Endocardial pacing was performed in all patients using a rectangular bipolar stimulus of 2 ms duration delivered at an intensity of twice late diastolic threshold. Programmed ventricular stimulation for VT induction was performed as previously described.t4 Before transcutaneous pacing, 15 of the 16 patients received intravenous midazolam (Versed) for conscious sedation. One patient refused sedation. Transcutaneous pacing threshold was determined (constant current, rectilinear pulse: anteroposterior patch configuration, 40 ms pulse width) to the nearest 5 mA. The ventricular ERP was then determined using transcutaneous pacing with the Zoll NTP (modified to allow it to trigger from a custom-built programmable stimulator) at threshold and at 5 or IO mA increments above threshold, up to patient tolerance. The same pacing cycle length was used for both transcutaneous and endocardial refractory period determinations. Atria1 endocardial recordings or P waves on the surface electrocardiogram were used to monitor atria1 activity during transcutaneous pacing. The ventricular ERP determined by transcutaneous pacing was defined as that obtained at the highest tolerated output during conscious sedation. Patients were defined as intolerant if they refused to allow From the Krannert Institute of Cardiology, the Department of Medicine, Indiana University School of Medicine, and the Roudebush Veterans Administration Medical Center, Indianapolis, Indiana 46202. This study was supported in part by the Herman C. Krannert Fund, Indianapolis, by grants HL-06308 and HL-07182 from the National Heart, Lung, and Blood Institute of the National Institutes of Health, US Public Health Service, Bethesda, Maryland, by the American Heart Association, Indiana Affiliate, Inc., by the Attorney General of Indiana Public Health Trust and by the Roudebush Veterans Administration Medical Center, Indianapolis. Manuscript received May 10, 1988; re vised manuscript received July 1, 1988, and accepted July 3.

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Strength-Interval Electrical Stimulation MD,

and Douglas P. Zipes,

MD

threshold or ERP determination by transcutaneous pacing. Single and double premature extrastimuli were introduced at 10 mA above threshold to initiate and terminate VT in patients with VT inducible by endocardial pacing. Patient characteristics are listed in Table I. Fifteen had sustained (n = 13) or nonsustained (n = 2) VT clinically, and 1 patient had syncope of undetermined etiology. Fourteen patients had coronary artery disease. One patient had a dilated cardiomyopathy, and 1 had no identifiable structural heart disease. The mean age was 61 years (range 48 to 83). Ten patients were receiving antiarrhythmic medications. Statistical analysis of results was performed using the Student’s t test on paired and grouped values. A p value of X0.05 was considered significant. Ventricular pacing threshold using transcutaneous pacing was determined in 11 of 16 patients; threshold could not be determined in 5 patients due to intolerable chest wall discomfort. In addition, 3 of the 11 patients in whom threshold was obtained could not tolerate thepacing for the duration required to complete the study. Therefore, only 8 of the ldpatients tolerated transcutaneous programmed pacing. Among these 8 (patients 1 through 8), the mean threshold was 61 mA (range 45 to 80). For 3 of the patients who could not tolerate transcutaneous pacing but in whom threshold could be determined (patients 13,14 and 16), the mean threshold was 88 mA (range 80 to IOO), and in the remaining Spatients in whom transcutaneous pacing threshold could not be determined (patients 9, 10, 11, 12 and 15), the mean threshold was >62 mA (range >40 to >90). Of the 11 patients in whom transcutaneous pacing threshold could be determined (patients 1 through 8,13,14 and 16), the threshold was 75 f 7 mA (mean f standard error of the mean) in patients receiving antiarrhythmic drugs (n = 6). The threshold was 60 f 6 mA in patients not receiving such drugs (n = 5) (difference not significant). The age of patients who tolerated transcutaneous pacing was 61 f 8 years (mean f standard error of the mean) versus 62 f 12 years for those who did not tolerate transcutaneous pacing (difference not signijkant). In no patient was the atrium paced transcutaneously. The ventricular ERP obtained by endocardial pacing was comparable with that determined using transcutaneous pacing (Figure 1). To establish the transcutaneous pacing output required to replicate the ERP achieved during endocardial stimulation at twice late diastolic threshold, the relation between the transcutaneous pacing ventricular ERP and the endocardial pacing ventricular ERP at increasing transcutaneous pacing outputs was examined in the 8 patients (Figure 2). Transcutaneous pacing output was increased by 5 or 10 mA increments (up to patient tolerance) to generate a series of

TABLE

I Characteristics

of the

16 Men

Heart Disease

Clinical Arrhythmia

Induced Arrhythmia*

Antiarrhythmic Medications

CAD CAD CAD CAD CAD CAD CAD CAD

VT-NS W-S W-S VT-S VT-S v-r-s VT-S VT-NS

None VT-S VT-S V-FNS VT-S VT-S VT-S None

0 Q. Dig Dig, M, P 0 0 0 A, M 0

VT-S Syncope VT-S V-K VT-S VT-S VT-S VT-S

VT-S None VT-S VT-S VT-S VT-S VT-S VT-S

A, P. pf 0 A pf P M A M F D

Pt

Age b-s)

Transcutaneous 1 2 3+ 4 5 6 7+ 8

Pacing 67 53 73 52 65 62 53 64

Tolerated

Transcutaneous 9 10 11 12 13 14 15 16+

Pacing 63 48 63 62 42 65 66 83

Not Tolerated CAD 0 CAD DC CAD CAD CAD CAD

Transcutaneous Pacing Threshold (mA)

50 50 65 45 60 65 70 80

>80 >90 A.0 >40 80 100 .60 85

A = amiodarone; CAD = coronary artery disease; D = disopyramlde; DC = dilated cardiomyopathy: Dig = digoxin; F = fkcainide; M = metiletine; propafenone; Q = quinidine; VT-NS = nonsustained ventricular tachycardia; VT-S = sustained ventricular tachycardia. *Arrhythmia induced by endocardial paang: + patients in whom ventricular tachycardia was initiated and terminated with transcutanequs pacing.

P = prqc&amide;

pf 77 -

ERP determinations in each patient. The ventricular above threshold. Only I patient tolerated transcutaneous ERP determined by transcutaneouspacing was signtft- pacing at >20 mA above threshold. cantly longer than that determined by endocardial pacIn 3 of the 5 patients who had sustained monomoring when transcutaneous pacing was performed at phic ventricular tachycardia induced by endocardial threshold and at 5, 10 and 1.5 mA increments above pacing (only 2 of whom allowed completion of theprototranscutaneouspacing threshold (Figure 2). A statistically signiJicant difference did not persist at 20 mA r *** T

32060 -0 .-0 t 0. 2 0 w :

300280-

k=^ a,5

;;

P=NS

4

I

260-

‘c z;m

0

=“; w-

240-

ii 5 0 .-L

220-

Transcutaneous Endocardial

-

,

0

I

*** ** *

< < <

vs. ERP 0.001 0.01 0.05 1

I

5

IO

Transcutaneous Above

: > Endocardial Pacing

Transcutaneous Pacing tolerated

(highest output)

FIGURE 1. Ventricular effectiie refractory period obtained by endocardial pacing versus transcutaneous pacing. There was no statistical difference between the ventricular effective refractory period when determined by these 2 pacing methods.

Pacing Threshold

I

I

15

20

Output (ma)

FIGURE 2. Diirence between transcutansous pacing effective refractory period (ERP) and endocardial pacing ERP at increasing transcutaneous pacing outputs. The difference between ventriilar ERP determined by the 2 pacing methods was significant at transcutaneous pacing threshold and at 5, 10 and 15 mA above transcutansous pacing threshold. At 20 mA above threshold, the ventricular ERP by tra-s pacing was no longer different than that determined by endo-’ cardial pacing. Numbers in parenfheseses represent the numkr of patients available for analysis at each transcutaneous pacing output. Data are expreso4 as mean f standard error of the mean.

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BRIEF

REPORTS

colfor transcutaneouspacing), terminated by transcutaneous

VT could be initiated and pacing (Figure 3).

In this study we have demonstrated that transcutaneous pacing may be used for noninvasive programmed stimulation of the heart in selected patients. Of the 16 patients in the present study, 8 tolerated transcutaneous pacing, but only 1 of these 8 tolerated pacing at >20 mA above threshold. Neither patient age nor presence of antiarrhythmic medications appeared to greatly influence pacing threshold or patient tolerance to transcutaneous pacing, and the atrium was never captured in any patient. The ventricular ERP with transcutaneous pacing was similar to that achieved with endocardial pacing, provided that a pacing output of > 15 mA above threshold could be tolerated. VT could be initiated and terminated in 3 of the 5 patients with sustained VT inducible by endocardial pacing. Transcutaneous pacing was not as well tolerated in the present study as has been reported previously,2-5 despite our use of multiple patch positions. The reasons for this difference are not entirely clear. Fifteen of our 16 patients received conscious sedation. The skin was prepared in all patients with either alcohol or acetone to facilitate patch adhesion to the skin. One difference between this and previous studies is that our patients were 1870

undergoing transcutaneous pacing at the end of an electrophysiology study, and tolerance may have been influenced by fatigue and the elective nature of the procedure. The ventricular ERP when determined by endocardial pacing was lower than that determined by transcutaneous pacing at threshold and up to 15 mA above transcutaneous pacing threshold. Only at 20 mA above threshold (tolerated in only 5 of 16 patients) was there no longer a difference in ventricular ERP between the 2 pacing methods. Because the ventricular ERP may be an important determinant of inducibility of VT,15 this difference between the 2 pacing methods may influence the clinical utility of transcutaneous pacing for programmed ventricular stimulation. Also, in this study and another7 transcutaneous pacing failed to capture the atrium directly. This has important implications for the use of transcutaneous programmed stimulation for some supraventricular tachycardias,‘O especially for those in which the arrhythmia circuit involves the atrium, but not the atrioventricular node or ventricle. The effect of antiarrhythmic medications on transcutaneous pacing threshold cannot be adequately determined by this study, because patients were not studied before and then during antiarrhythmic drug therapy. Separate analysis for each drug could not be performed ,,

,, A

I~~1

HRA

A 4 ,h-J-i--

RVA

Lead II

A 1870

RVA ---li

I *I

!

Lead II

FIGURE 3. Initiation and termination of ventricular tachycardia using transcutaneouo pacing (patient 7). Recordings are from the high right atrium (HRA), right ventriwlar apex (RVA) and lead II of the surface electrocardiogram. Stimuli of 40 me duration are introduced using the Zoll NTP. A, a drive train of 8 paced complexes (Sl) at a cycle length of 400 ms induces sustained VT having a cycle length of 500 ms; an extrastimulus (Ss) fails to capture the ventricle. At&ventricular dissociation &ring transcutaneous pacing and during ventricular tachycardia can be seen. B, termination of sustained ventricular tachycardia is accomplished using 3 extrastimuli (Ss, Ss, Sd) delivered via the transcutaneous pacemaker, after which sinus rkythm resumes. i

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due to the variety of agents used singly or in combination. Thus, the effect of antiarrhythmic drug therapy on transcutaneous pacing threshold requires further investigation. Pacing increments were performed in an escalating fashion (threshold to highest tolerated output) using transcutaneous pacing. Thus, the possible role of an increase of circulating catecholamines (due to chest wall pain) on the measured ventricular ERP is unknown. Transcutaneous pacing has been shown to be lifesaving for bradyarrhythmic arrest, cardiac standstill’-* and termination of ventricular9J l-l3 and supraventricularl” arrhythmias in some patients. Its feasibility for programmed electrical stimulation of the heart appears to be limited to a subset of patients with low transcutaneous ventricular pacing thresholds who tolerate transcutaneous pacing at >15 mA above threshold. 1. Zoll PM. Resuscitation of the heart in ventricular standstill by external electric stimulation. N Engl J Med 1952;247:768-771. 2. Falk RH, Zoll PM, Zoll RH. Safety and efficacy of non-invasive cardiac pacing: a preliminary report. N Engl J Med 1983:309:1166-1168. 3. Zoll PM, Zoll RH, Falk RH, Clinton JE, Eitel DR, Antman EM. External non-invasive temporary cardiac pacing: clinical trials. Circulation 1985;71:937-

944. 4. Zoll PM. Non-invasive

temporary cardiac pacing. J Electrophysiol 1987;l: 156-161. 5. Beland MJ, Hesslein PS, Finlay CD, Angel JEF, Williams WG, Rowe RD. Noninvasive transcutaneous cardiac pacing in children. PACE 1987;10:1262. 6. Hedges JR, Syverud SA, Dalsey WC, Ferro S, Easter R, Shultz B. Prehospital trial of emergency transcutaneous cardiac pacing. Circulation 1987,6;1337-1343. 7. Falk RH, Ngai STA, Kumaki DJ, Rubinstein JA. Cardiac activation during external cardiac pacing. PACE 1987:10:503-506. 8. Sharkey SW, Chaffee V, Kapsner S. Prophylactic external pacing during cardioversion of atria1 tachyarrhythmias. Am J Cardiol 1985;55:1632-1634. 9. Rosenthal ME, Stamato NJ, Marchlinski FE, Josephson ME. Non-invasive cardiac pacing for termination of sustained, uniform ventricular tachycardia. Am J Cardiol 1986;58:561-562. 10. Estes NAM, Deering TF, Han EH, Salem D, Mack K, van Opijnen K, Zoll PM. Non-invasive termination of sustained supraventricular and ventricular tachycardia with external cardiac programmed stimulation (abstr). JACC J987,9:2OOA. 11. Barold SS, Falkoff MD, Ong LS, Heinle RA. Termination of ventricular tachycardia by transcutaneous cardiac pacing. Am Heart J 1987;114;180-182. 12. Luck JC, Davis D. Termination of sustained tachycardia by external noninvasive pacing. PACE J987;JO:J 125. 13. Luck JC, Grubb BP, Artman SE, Steckbeck RT, Market ML. Termination of sustained ventricular tachycardia by external noninvasive pacing. Am J Cardiol J988;61:574-577. 14. Prystowsky EN, Miles WM, Evans JJ, Hubbard JE, Skale BT, Windle JR, Heger JJ, Zipes DP. Induction of ventricular tachycardia during programmed electrical stimulation: analysis of pacing methods. Circulation 1986;73;II-32-38. 15. Estes NAM III, Garan H, McGovern B, Ruskin JN. Influence of drive cycle length during programmed stimulation on induction of ventricular arrhythmias: analysis of 403 patients. Am J Cardiol 1986:57:108-112.

Adenylate Cyclase Activity Coupled to the Stimulatory Guanine Nucleotide Binding Protein in Patients Having Electrophysiologic Studies and Either Structurally Normal Hearts or Idiopathic Myocardial Disease Joel S. Karliner, MD, and Melvin Scheinman,

MD

here has been much recent interest in transmembrane T signaling involving adrenergic and other receptors both in animals and humans with congestive heart failure (CHF). In patients with idiopathic dilated cardiomyopathy and severe CHF, fl-adrenoceptor density and maximal adenylate cyclase activity stimulated by (-)-isoproterenol in the presence of guanosine triphosphate (GTP) are reduced.’ Other studies in animal models of CHF preceded by myocardial hypertrophy have revealed an increase in P-adrenoceptor density accompanied by reduced receptor affinity for agonist and a decrease in the stimulatory guanine nucleotide binding protein (Gs).*p3 To date, there are no data reporting functional alterations in Gs in humans. We obtained biopsiesfrom the right ventricular aspect of the ventricular septum using a Cordis bioptome from 5 men and 4 women aged 13 to 42 years. Informed written consentwas obtainedfrom each subject. All were undergoing elective electrophysiologic study for either spontaneousor exercise-induced ventricular tachycarFrom the Cardiology Sections of the Veterans Administration Medical Center and the Moftitt-Long Hospital, and the Department of Medicine and the Cardiovascular Research Institute, University of California, San Francisco, California 94121. This study was supported by program project grant HL 25847 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland, and the Veterans Administration Research Service, Washington, DC. Manuscript received April 25, 1988; revised manuscript received July 1, 1988, and accepted July 3.

dia. Of these patients 5 had no demonstrable cardiac abnormalities (group 1). Thesepatients all had normal heart size and left ventricular performance determined by echocardiography or contrast ventriculography. Their biopsieswere normal by light and electron microscopy. Three patients (group 2) had evidenceof cardiomyopathy as indicated by severe left ventricular dysfunction in 2 patients or biopsy evidence of myocardial diseasein one. One additional patient had evidence of recent myocarditis by clinical history and had postinflammatory changeson biopsy. Biopsieswere rapidly frozen in liquid NZ and thawed at the time of assay.Adenylate cyclase activity was determined as previously described.” Results are listed in Table I. The 3 patients in group 2 had a marked reduction in all measuresof adenylate cyclase activity that was significantly different from patients without evidence of structural heart diseaseor evidence of left or right ventricular myocardial dysfunction. The I patient with a history of myocarditis also had marked reductions in adenylate cyclase activity stimulated by guanylS-imidodiphosphate (GppNHp), a nonhydrolyzable analog of GTP, and by (-)-isoproterenol (472 and 110 pmol/mg protein/30 minutes, respectively).

Among the sites at which cyclic adenosine monophosphate accumulation may be regulated are the ,6-adrenoceptor, the guanine nucleotide regulatory proteins and

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