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Accelerated junctional rhythms during oral verapamil therapy
Accelerated junctional verapamil therapy
rhythms
during oral
This study examined the frequency of atrioventricular (AV) dissociation and accelerated junctional rhythms in 59 patients receiving oral verapamii. Accelerated junctional rhythms and AV dissociation were frequent in patients with supraventricuiaf tachyarrhythmias, particularly AV nodal reentry. Verapamii administration to these patients led to an asymptomatic increase in activity of these junctional pacemakers. In patients with various chest pain syndromes, verapamii neither increased the frequency of junctional rhythms nor suppressed their role as escape rhythms under physiologically appropriate circumstances. (AM HEART J 107:440, 1984.)
Janice B. Schwartz, M.D., Ming Jeang, M.D., Albert E. Raizner, M.D., Jerry C. Griffin, M.D., and Christopher R. Wyndham, M.D., Houston, Tex.
Verapamil is a calcium channel blocker efficacious in the management of patients with myocardial cardiac arrhythmias,6-10 ischemic syndromes,1-5 hypertension,l’ and hypertrophic cardiomyopathy.12, l3 During our early experience with verapamil in patients with supraventricular tachyarrhythmias (SVT), we observed unexpectedly frequent episodes of atrioventricular (AV) dissociation and accelerated junctional rhythms. The purpose of this study was to document the incidence of accelerated junctional rhythms in a wider spectrum of patients during oral verapamil therapy. Our findings document the suspected increased frequency of accelerated junctional rhythms during oral verapamil therapy in patients with SVT. In contrast, however, no increase in frequency of junctional rhythms was observed in patients who received verapamil for anginal syndromes or hypertrophic cardiomyopathy. METHODS Patients
with chest pain syndromes (Table I). Fortysix patients who entered into clinical trials of verapamil for the management of coronary artery spasm,unstable angina pectoris, or hypertrophic cardiomyopathy between January, 1979, and January, 1982, comprised the study population. Twenty were men and 26 were womenwith a mean age of 57.1 f 12.1 (ic + SD) years. Dosageof vera-
From the Department College of Medicine. Supported tion, Inc., Schwartz). Received Reprint College
440
by the Faculty
of Internal Pharmaceutical Development
for publication
July
Medicine,
Section
Manufacturer’s Award in Clinical 20, 1983;
accepted
of Cardiology,
Baylor
Association, FoundaPharmacology. (Dr. Aug.
15, 1983.
requests: Janice B. Schwartz, M.D., Section of Cardiology, of Medicine, 6565 Fannin, MS F 905, Houston, TX 77030.
Baylor
pamil for the group was 271 +- 109 (X * SD) mg/day. Sixteen also received digoxin (0.20 + 0.07 mglday, x + SD) and eight patients received concomitant beta-adrenergic antagonist therapy. Further description of this subgroup is presented in Table I. Patients with SVT (Table II). Thirteen patients with SVT, which terminated or substantially slowedfollowing intravenous verapamil administration, entered into a clinical investigation of the efficacy of oral verapamil for arrhythmia suppression between August, 1981, and March, 1983. Six were men and sevenwere women with a mean age of 52.5 * 14.5 years. The mean verapamil dosagewas 295 5 48 mglday. Eight patients were receiving digoxin (0.27 + 0.04 mglday) prior to verapamil therapy. Digoxin was continued during verapamil therapy in four patients with atria1 fibrillation, but none of the patients with AV nodal reentry arrhythmias received verapamil in combination with digoxin. Beta-adrenergicblocking drugs were being administered to five patients prior to the initiation of verapamil and were continued in three (two atrial fibrillation and one AV nodal reentry) during verapamil administration. Table II contains additional data regarding this subgroup. Patients in both groups gave informed consent prior to entry into the clinical studieswhich had been reviewed and approved by the Institutional Review Boards of the Baylor Collegeof Medicine and The Methodist Hospital, Houston, Texas. Ambulatory ECG recordings. Each patient had at least 24 hours of ambulatory, two-channel ECG monitoring before and during verapamil therapy. Criteria for diagnosisof acceleratedjunctional rhythm in patients in normal sinusrhythm were the following? (1) AV dissociation, (2) normal QRS duration (unlessthere was preexisting bundle branch block), and/or (3) P waves of a configuration different from those of sinusorigin occurring 0.10 second before the QRS complex. The criteria usedfor the diagnosisof acceleratedjunctional rhythm in patients with atria1 fibrillation-flutter were: (1) a regular rhythm (less than
Volume Number
107 3
Table
Accelerated
1. Patients
rhythms
with
No. of patients artery
21
artery
19
Hypertrophic cardiomyopathy
6
Total
46
Age (yr)
Sex
days monitored ________ Before During verapamil verapamil
Verapamil (mglday)
54.1 6 M + 12.1 15 F 58 12 M k 12.6 7 F
AV block (on uerapamil)
441
1”
2”
3”
2
2
0
280 + 88 282 f 125
1.2 f 0.5 1.1 * 0.2
2.2 + 1.2 1.5 + 0.6
2 M 4 F
200 + 67
1.2 f 0.4
1.2 f 0.4
5
1
57.1 20 M + 12.1 26 F
271 + 104
1.13 f 0.4
1.8 -t 1.0
14
3
64.8 k 7.4
Junctional rhythm (No. of patients) Before verapamil
During verapamil
0
0
1
2*,t
0
0
11
2
1
3
702*
All values are mean + standard deviation. Abbreviations: AV = atrioventricular; 1’ = first degree; 2” = second degree; 3’ = third *Both patients were on digoxin and junctional rhythm occurred during periods of third-degree AV block. tNot same patient as before verapamil. fPatient on digoxin; junctional rhythm followed paroxysm of atrial fibrillation.
Table
verapamil
with chest pain No. of
Coronary spasm Coronary disease
junctional
Cycle length (msec)
600-750 before verapamil 705-800 during verapamil 600-925
degree.
II. Patients with SVT No. of
No. of patients AV nodal
reentry
Paroxysmal atria1 fibrillation Sustained atria1 fibrillation Accessory pathway Total
Age
days monitored ________ Before During verapamil verapamil
Verapamil (mglday)
(yr)
Sex
6
50.2 k 12.6
6 F
280 +- 44
1.7 k 1.6
3
57.7 f 10.2 63.0 f 1.0 20.0
3 M 2 M 1F M
333 + 23 267 + 46 360
52.5 f 14.5
6 M 7 F
295 * 48
3 1
13
A V block
Junctional rhythm (No. of patients)
(on verapamil)
Before verapamil
During verapamil
Cycle length (msec)
1”
2”
3”
1.5 f 0.5
0
0
0
3
5
5.0 * 3.5 1.7 k 0.6 4.0
1.6 f 0.6 2.7 +- 0.6 3.0
0
0
0
0
0
0
1
1200 800-880
2.6 + 2.3
1.8 + 0.8
-
-
-
0
0
0
0
1
0
0
0
3
7
750-1200 before verapamil 820-1000 during verapamil
All values are mean + standard deviation. Abbreviations: AV = atrioventricular; lo = first degree; 2O = second degree; 3’ = third degree.
15% variation in the R-R interval), and (2) narrow QRS complex. RESULTS Patients
with
chest
pain
syndromes
(Table
I).
Patients in this group were monitored for a mean of 1.13 f 0.4 days (X t SD) prior to verapamil therapy. Accelerated junctional rhythms with cycle lengths ranging from 600 to ‘750 msec were observed in only one patient, who was also receiving digoxin. Patients were monitored for a mean of 1.8 + 1.0 days during verapamil therapy. First-degree AV block was noted during verapamil therapy in 14 patients, second-degree AV block in three, and
third-degree AV block in two of the patients. Episodes of accelerated junctional rhythms with cycle lengths ranging between 600 and 925 msec were recorded in three patients. All three patients were receiving digoxin. The junctional rhythm occurred during episodes of third-degree AV block in two of these patients, one of whom had received epinephrine following cardiopulmonary arrest. In the third patient, the period of junctional rhythm occurred prior to the return of sinus rhythm following a paroxysm of atrial fibrillation. Patients with SVT (Table II). The mean number of days of monitoring prior to verapamil therapy in this group was 2.6 -t 2.3 (x + SD). Three patients with
442
Schwartz et al.
AV nodal reentry experienced periods of asymptomatic accelerated junctional rhythms with cycle lengths ranging from 750 to 1200 msec. In one patient, these occurred during digoxin therapy; in the second, junctional rhythms occurred in the absence of digoxin; and in the third patient, junctional rhythms occurred both in the presence and absence of digoxin. During verapamil therapy, patients were monitored for 1.8 -t 0.8 (X f SD) days. No evidence of first-, second-, or third-degree AV block was recorded on ambulatory ECG monitoring during verapamil therapy. The absence of AV block in this group probably reflects the infrequent use of digoxin and beta blocker therapy in combination with verapamil as opposed to frequent combination therapy in the patients with chest pain. Episodes of accelerated junctional rhythms with cycle lengths ranging from 800 to 1000 msec were recorded in seven patients. The three patients with episodes of junctional rhythm prior to verapamil therapy had more frequent and, in one case, almost incessant junctional rhythm during verapamil therapy. In one patient, junctional rhythm occurred during sinus bradycardia after pauses of approximately 2200 msec. DISCUSSION
Early in our experience with verapamil in patients with paroxysmal AV nodal reentry arrhythmias, we noted an unusually high frequency of accelerated junctional rhythms following intravenous verapamil administration and during oral verapamil therapy. When verapamil was discontinued, junctional rhythms continued to be relatively frequent in these patients either off all drugs or when they received other antiarrhythmic drugs. This led us to quantitatively examine the incidence of junctional rhythms in this group and the incidence of junctional rhythms during verapamil therapy in patients with other disorders. Verapamil-induced accelerated junctional rhythms in SVT patients. Our current results in patients with
SVT are similar to those recently reported by Walker et a1.15 In both studies, accelerated junctional rhythms were seen in some patients with SVT during drug-free periods. Following the initiation of oral verapamil therapy, these rhythms markedly increased in frequency. In other patients with SVT, junctional rhythms only became manifest during oral verapamil therapy. Although subgroup analysis is not presented by Walker et a1.,15 we found that junctional rhythms were more frequent and prolonged in patients with documented AV nodal reentry
American
March. ,984 Heart Journal
arrhythmias (“dual pathways”) when compared to our patients with sustained or paroxysmal atria1 fibrillation or flutter. It is pertinent that early reports of verapamil administration to patients with chronic atrial fibrillation described a “regularization” (less than 15% variation in R-R interval) of the ventricular response rate in over one half of the digitalized patients.16.1g This regularization of the ventricular response rate in atria1 fibrillation has also been noted during the oral administration of verapamil to digitalized patients. 1g,20 Although the mechanism had previously been debated,17. la, 2o interpreting these regularized rhythms to be accelerated junctional rhythms would be compatible with current observations. Absence of verapamil-induced rhythms in chest pain syndromes.
accelerated
junctional
This effect of verapamil on the cardiac rhythm in patients with SVT was strikingly different from the effects observed in patients who received verapamil for the treatment of various chest pain disorders. In the latter patients, we found no increased incidence of accelerated junctional rhythms during digoxin therapy or during therapy with oral verapamil. Furthermore, in patients with chest pain syndromes in whom episodes of accelerated junctional rhythms were observed, high-degree AV block and sinus node depression preceded the junctional rhythms. Under such circumstances, a junctional rhythm would be a physiologically appropriate escape rhythm. It is of clinical importance to note that verapamil did not suppress these escape rhythms. In concordance with our findings, other studies utilizing 24-hour ambulatory ECG monitoring during placebo and verapamil administration to patients with angina1 syndromes21-24 or hypertension” make no mention of accelerated junctional rhythms. Isolated reports, however, have appeared. Winniford et a1.4 reported that 1 of 27 patients with Prinzmetal’s angina experienced accelerated junctional rhythms during oral verapamil therapy, while Packer et a1.25reported transient junctional rhythms in 1 of 15 patients who received 120 mg oral verapamil. Epstein and Rosingz6 reported an approximately 11% incidence of accelerated junctional rhythm in patients who received either intravenous or oral verapamil for treatment of idiopathic hypertrophic subaortic stenosis. The number of patients with preexisting arrhythmias was not noted, but sinus bradycardia + hypotension was said to have preceded accelerated junctional rhythms.*‘j Therefore, when accelerated junctional rhythms are
Volume Number
107 3
Accelerated
observed in patients with chest pain syndromes during verapamil therapy, either underlying or drug-induced abnormalities of sinus or AV nodal function or SVT should be suspected. Conclusions. It appears that accelerated junctional rhythms are more frequent in patients with SVT, particularly AV nodal reentry. By some as yet undefined mechanism, verapamil administration to these patients leads to a usually asymptomatic increase in activity of these junctional pacemakers. In the absence of SVT, verapamil neither stimulates junctional rhythms nor suppresses the normal physiologic functioning of junctional pacemakers. We thank Susan Akers, R.N., and Sharon Magro, assistance in the care of these patients, and Barbara preparation of the manuscript.
P.A., Bond
for for
REFERENCES 1. Sandler 2. 3.
4.
5.
6.
7.
8.
9.
10.
G, Clayton GA, Thornicroft SG: Clinical evaluation of verapamil in angina pectoris. Br Med J 3:224, 1968. Phear DN: Verapamil in angina: A double-blind trial. Br Med J 2:740, 1968. Livesley B, Catley PF, Campbell RC, Oram S: Double-blind evaluation of verapamil, propranolol and isosorbide dinitrate against a placebo in the treatment of angina pectoris. Br Med J 1:375, 1975. Winniford MD, Johnson SM, Mauritson DR, Rellas JS, Redish GA, Willerson JT, Hillis LD: Verapamil therapy for Prinzmetal’s variant angina: Comparison with placebo and nifediuine. Am J Cardiol 50:913, 1982. Johnson SM, Mauritaon DR, Willerson JT, Hillis LD: A controlled trial of verapamil for Prinzmetal’s variant angina. N Engl J Med 304:862, 1981. Waxman HL, Myerburg RJ, Appel R, Sung RI: Verapamil for control of ventricular rate in paroxysmal supraventricular tachycardia and atria1 fibrillation or flutter. Ann Intern Med 94:1, 1981. Sung RJ, Elser B, McAllister Jr RG: Intravenous verapamil for termination of re-entrant supraventricular tachycardias. Ann Intern Med 93:682, 1980. Heng MK, Singh BN, Roche AHG, Norris RM, Mercer CJ: Effects of intravenous verapamil on cardiac arrhythmias and on the electrocardiogram. AM HEART J 90:487, 1975. Klein HO, Pauzner H, Segni ED, David D, Kaplinsky E: The beneficial effects of verapamil in chronic atria1 fibrillation. Arch Int Med 139:747, 1979. Brichard G, Zimmerman PE: Verapamil in cardiac dysrhythmias during anaesthesia. Br J Anaesth 42:1005, 1970.
junctional
rhythms
with
verapamil
443
11. Gould BA, Mann S, Kieso H, Bala Subramanian V, Raftery EB: The 24-hour ambulatory blood pressure profile with verapamil. Circulation 66:22, 1982. 12. Rosing DR, Kent KM, Borer JS, Seides SF, Maron BJ, Epstein SE: Verapamil therapy: A new approach to the pharmacologic treatment of hypertrophic cardiomyopathy. I. Hemodynamic effects. Circulation 60:1201, 1979. 13. Rosing DR, Kent KM, Maron BJ, Epstein SE: Verapamil therapy: A new approach to the pharmacologic treatment of hypertrophic cardiomyopathy. II. Effects on exercise capacity and symptomatic status. Circulation 60:1208, 1979. 14. Chou TC: Electrocardiography in clinical practice. New York, 1979, Grune & Stratton, Inc, p 393. 15. Walker WS, Winniford MD, Mauritson DR, Johnson SM, Hillis LD: Atrioventricular junctional rhythm in patients receiving oral verapamil therapy. JAMA 249:389, 1983. E. Kauschke: Inter16. Bender F. Kelot HW. Most E, Schmidt vall-Histogramme der Kammerfrequenz bei Vorhofflimmer nach Verapamil (Isoptin). Med Welt 24:1004, 1973. 17. Shamroth L, Krikler DM, Garrett C: Immediate effects of intravenous verapamil in cardiac arrhythmias. Br Med J 1:660, 1972. 18. Shamroth L: The clinical use of intravenous verapamil. AM HEART J 100:1070, 1980. 19. Schwartz JB, Keefe D, Kates RE, Kirsten E, Harrison DC: Acute and chronic pharmacodynamic interaction of verapamil and digoxin in atria1 fibrillation. Circulation 65:1163, 1982. 20. Khalsa A, Olsson SB: Verapamil-induced ventricular regularity in atria1 fibrillation. Acta Med Stand 206:509, 1979. 21. Johnson SM. Mauritson DR. Corbett JR. Woodward W. Willerson JT; Hillis LD: Double-blind, randomized, placebo: controlled comparison of propranolol and verapamil in the treatment of patients with stable angina pectoris. Am J Med 71:443, 1981. 22. Johnson SM, Mauritson DR, Willerson JT, Hillis LD: Comparison of verapamil and nifedipine in the treatment of variant angina pectoris: Preliminary observations in 10 patients. Am J Cardiol 47:1295, 1981. 23. Bala Subramanian V, Bowles MJ, Khurmi NS, Davies AB, Raftery EB: Randomized double-blind comparison of verapamil and nifedipine in chronic stable angina. Am J Cardiol 50:696, 1982. 24. Bala Subramanian V, Bowles MJ, Davies AB, Raferty EB: Combined therapy with verapamil and propranolol in chronic stable angina. Am J Cardiol 49:125, 1982. 25. Packer M, Meller J, Medina N, Yushak M, Smith H, Holt J, Guererro J, Todd GD, McAllister RG, Gorlin R: Hemodynamic consequences of combined beta-adrenergic and slow calcium channel blockade in man. Circulation 65:660, 1982. 26. Epstein SE, Rosing DR: Verapamil: Its potential for causing serious complications in patients with hypertrophic cardiomyopathy. Circulation 64:437, 1981.
rhythms
during oral
This study examined the frequency of atrioventricular (AV) dissociation and accelerated junctional rhythms in 59 patients receiving oral verapamii. Accelerated junctional rhythms and AV dissociation were frequent in patients with supraventricuiaf tachyarrhythmias, particularly AV nodal reentry. Verapamii administration to these patients led to an asymptomatic increase in activity of these junctional pacemakers. In patients with various chest pain syndromes, verapamii neither increased the frequency of junctional rhythms nor suppressed their role as escape rhythms under physiologically appropriate circumstances. (AM HEART J 107:440, 1984.)
Janice B. Schwartz, M.D., Ming Jeang, M.D., Albert E. Raizner, M.D., Jerry C. Griffin, M.D., and Christopher R. Wyndham, M.D., Houston, Tex.
Verapamil is a calcium channel blocker efficacious in the management of patients with myocardial cardiac arrhythmias,6-10 ischemic syndromes,1-5 hypertension,l’ and hypertrophic cardiomyopathy.12, l3 During our early experience with verapamil in patients with supraventricular tachyarrhythmias (SVT), we observed unexpectedly frequent episodes of atrioventricular (AV) dissociation and accelerated junctional rhythms. The purpose of this study was to document the incidence of accelerated junctional rhythms in a wider spectrum of patients during oral verapamil therapy. Our findings document the suspected increased frequency of accelerated junctional rhythms during oral verapamil therapy in patients with SVT. In contrast, however, no increase in frequency of junctional rhythms was observed in patients who received verapamil for anginal syndromes or hypertrophic cardiomyopathy. METHODS Patients
with chest pain syndromes (Table I). Fortysix patients who entered into clinical trials of verapamil for the management of coronary artery spasm,unstable angina pectoris, or hypertrophic cardiomyopathy between January, 1979, and January, 1982, comprised the study population. Twenty were men and 26 were womenwith a mean age of 57.1 f 12.1 (ic + SD) years. Dosageof vera-
From the Department College of Medicine. Supported tion, Inc., Schwartz). Received Reprint College
440
by the Faculty
of Internal Pharmaceutical Development
for publication
July
Medicine,
Section
Manufacturer’s Award in Clinical 20, 1983;
accepted
of Cardiology,
Baylor
Association, FoundaPharmacology. (Dr. Aug.
15, 1983.
requests: Janice B. Schwartz, M.D., Section of Cardiology, of Medicine, 6565 Fannin, MS F 905, Houston, TX 77030.
Baylor
pamil for the group was 271 +- 109 (X * SD) mg/day. Sixteen also received digoxin (0.20 + 0.07 mglday, x + SD) and eight patients received concomitant beta-adrenergic antagonist therapy. Further description of this subgroup is presented in Table I. Patients with SVT (Table II). Thirteen patients with SVT, which terminated or substantially slowedfollowing intravenous verapamil administration, entered into a clinical investigation of the efficacy of oral verapamil for arrhythmia suppression between August, 1981, and March, 1983. Six were men and sevenwere women with a mean age of 52.5 * 14.5 years. The mean verapamil dosagewas 295 5 48 mglday. Eight patients were receiving digoxin (0.27 + 0.04 mglday) prior to verapamil therapy. Digoxin was continued during verapamil therapy in four patients with atria1 fibrillation, but none of the patients with AV nodal reentry arrhythmias received verapamil in combination with digoxin. Beta-adrenergicblocking drugs were being administered to five patients prior to the initiation of verapamil and were continued in three (two atrial fibrillation and one AV nodal reentry) during verapamil administration. Table II contains additional data regarding this subgroup. Patients in both groups gave informed consent prior to entry into the clinical studieswhich had been reviewed and approved by the Institutional Review Boards of the Baylor Collegeof Medicine and The Methodist Hospital, Houston, Texas. Ambulatory ECG recordings. Each patient had at least 24 hours of ambulatory, two-channel ECG monitoring before and during verapamil therapy. Criteria for diagnosisof acceleratedjunctional rhythm in patients in normal sinusrhythm were the following? (1) AV dissociation, (2) normal QRS duration (unlessthere was preexisting bundle branch block), and/or (3) P waves of a configuration different from those of sinusorigin occurring 0.10 second before the QRS complex. The criteria usedfor the diagnosisof acceleratedjunctional rhythm in patients with atria1 fibrillation-flutter were: (1) a regular rhythm (less than
Volume Number
107 3
Table
Accelerated
1. Patients
rhythms
with
No. of patients artery
21
artery
19
Hypertrophic cardiomyopathy
6
Total
46
Age (yr)
Sex
days monitored ________ Before During verapamil verapamil
Verapamil (mglday)
54.1 6 M + 12.1 15 F 58 12 M k 12.6 7 F
AV block (on uerapamil)
441
1”
2”
3”
2
2
0
280 + 88 282 f 125
1.2 f 0.5 1.1 * 0.2
2.2 + 1.2 1.5 + 0.6
2 M 4 F
200 + 67
1.2 f 0.4
1.2 f 0.4
5
1
57.1 20 M + 12.1 26 F
271 + 104
1.13 f 0.4
1.8 -t 1.0
14
3
64.8 k 7.4
Junctional rhythm (No. of patients) Before verapamil
During verapamil
0
0
1
2*,t
0
0
11
2
1
3
702*
All values are mean + standard deviation. Abbreviations: AV = atrioventricular; 1’ = first degree; 2” = second degree; 3’ = third *Both patients were on digoxin and junctional rhythm occurred during periods of third-degree AV block. tNot same patient as before verapamil. fPatient on digoxin; junctional rhythm followed paroxysm of atrial fibrillation.
Table
verapamil
with chest pain No. of
Coronary spasm Coronary disease
junctional
Cycle length (msec)
600-750 before verapamil 705-800 during verapamil 600-925
degree.
II. Patients with SVT No. of
No. of patients AV nodal
reentry
Paroxysmal atria1 fibrillation Sustained atria1 fibrillation Accessory pathway Total
Age
days monitored ________ Before During verapamil verapamil
Verapamil (mglday)
(yr)
Sex
6
50.2 k 12.6
6 F
280 +- 44
1.7 k 1.6
3
57.7 f 10.2 63.0 f 1.0 20.0
3 M 2 M 1F M
333 + 23 267 + 46 360
52.5 f 14.5
6 M 7 F
295 * 48
3 1
13
A V block
Junctional rhythm (No. of patients)
(on verapamil)
Before verapamil
During verapamil
Cycle length (msec)
1”
2”
3”
1.5 f 0.5
0
0
0
3
5
5.0 * 3.5 1.7 k 0.6 4.0
1.6 f 0.6 2.7 +- 0.6 3.0
0
0
0
0
0
0
1
1200 800-880
2.6 + 2.3
1.8 + 0.8
-
-
-
0
0
0
0
1
0
0
0
3
7
750-1200 before verapamil 820-1000 during verapamil
All values are mean + standard deviation. Abbreviations: AV = atrioventricular; lo = first degree; 2O = second degree; 3’ = third degree.
15% variation in the R-R interval), and (2) narrow QRS complex. RESULTS Patients
with
chest
pain
syndromes
(Table
I).
Patients in this group were monitored for a mean of 1.13 f 0.4 days (X t SD) prior to verapamil therapy. Accelerated junctional rhythms with cycle lengths ranging from 600 to ‘750 msec were observed in only one patient, who was also receiving digoxin. Patients were monitored for a mean of 1.8 + 1.0 days during verapamil therapy. First-degree AV block was noted during verapamil therapy in 14 patients, second-degree AV block in three, and
third-degree AV block in two of the patients. Episodes of accelerated junctional rhythms with cycle lengths ranging between 600 and 925 msec were recorded in three patients. All three patients were receiving digoxin. The junctional rhythm occurred during episodes of third-degree AV block in two of these patients, one of whom had received epinephrine following cardiopulmonary arrest. In the third patient, the period of junctional rhythm occurred prior to the return of sinus rhythm following a paroxysm of atrial fibrillation. Patients with SVT (Table II). The mean number of days of monitoring prior to verapamil therapy in this group was 2.6 -t 2.3 (x + SD). Three patients with
442
Schwartz et al.
AV nodal reentry experienced periods of asymptomatic accelerated junctional rhythms with cycle lengths ranging from 750 to 1200 msec. In one patient, these occurred during digoxin therapy; in the second, junctional rhythms occurred in the absence of digoxin; and in the third patient, junctional rhythms occurred both in the presence and absence of digoxin. During verapamil therapy, patients were monitored for 1.8 -t 0.8 (X f SD) days. No evidence of first-, second-, or third-degree AV block was recorded on ambulatory ECG monitoring during verapamil therapy. The absence of AV block in this group probably reflects the infrequent use of digoxin and beta blocker therapy in combination with verapamil as opposed to frequent combination therapy in the patients with chest pain. Episodes of accelerated junctional rhythms with cycle lengths ranging from 800 to 1000 msec were recorded in seven patients. The three patients with episodes of junctional rhythm prior to verapamil therapy had more frequent and, in one case, almost incessant junctional rhythm during verapamil therapy. In one patient, junctional rhythm occurred during sinus bradycardia after pauses of approximately 2200 msec. DISCUSSION
Early in our experience with verapamil in patients with paroxysmal AV nodal reentry arrhythmias, we noted an unusually high frequency of accelerated junctional rhythms following intravenous verapamil administration and during oral verapamil therapy. When verapamil was discontinued, junctional rhythms continued to be relatively frequent in these patients either off all drugs or when they received other antiarrhythmic drugs. This led us to quantitatively examine the incidence of junctional rhythms in this group and the incidence of junctional rhythms during verapamil therapy in patients with other disorders. Verapamil-induced accelerated junctional rhythms in SVT patients. Our current results in patients with
SVT are similar to those recently reported by Walker et a1.15 In both studies, accelerated junctional rhythms were seen in some patients with SVT during drug-free periods. Following the initiation of oral verapamil therapy, these rhythms markedly increased in frequency. In other patients with SVT, junctional rhythms only became manifest during oral verapamil therapy. Although subgroup analysis is not presented by Walker et a1.,15 we found that junctional rhythms were more frequent and prolonged in patients with documented AV nodal reentry
American
March. ,984 Heart Journal
arrhythmias (“dual pathways”) when compared to our patients with sustained or paroxysmal atria1 fibrillation or flutter. It is pertinent that early reports of verapamil administration to patients with chronic atrial fibrillation described a “regularization” (less than 15% variation in R-R interval) of the ventricular response rate in over one half of the digitalized patients.16.1g This regularization of the ventricular response rate in atria1 fibrillation has also been noted during the oral administration of verapamil to digitalized patients. 1g,20 Although the mechanism had previously been debated,17. la, 2o interpreting these regularized rhythms to be accelerated junctional rhythms would be compatible with current observations. Absence of verapamil-induced rhythms in chest pain syndromes.
accelerated
junctional
This effect of verapamil on the cardiac rhythm in patients with SVT was strikingly different from the effects observed in patients who received verapamil for the treatment of various chest pain disorders. In the latter patients, we found no increased incidence of accelerated junctional rhythms during digoxin therapy or during therapy with oral verapamil. Furthermore, in patients with chest pain syndromes in whom episodes of accelerated junctional rhythms were observed, high-degree AV block and sinus node depression preceded the junctional rhythms. Under such circumstances, a junctional rhythm would be a physiologically appropriate escape rhythm. It is of clinical importance to note that verapamil did not suppress these escape rhythms. In concordance with our findings, other studies utilizing 24-hour ambulatory ECG monitoring during placebo and verapamil administration to patients with angina1 syndromes21-24 or hypertension” make no mention of accelerated junctional rhythms. Isolated reports, however, have appeared. Winniford et a1.4 reported that 1 of 27 patients with Prinzmetal’s angina experienced accelerated junctional rhythms during oral verapamil therapy, while Packer et a1.25reported transient junctional rhythms in 1 of 15 patients who received 120 mg oral verapamil. Epstein and Rosingz6 reported an approximately 11% incidence of accelerated junctional rhythm in patients who received either intravenous or oral verapamil for treatment of idiopathic hypertrophic subaortic stenosis. The number of patients with preexisting arrhythmias was not noted, but sinus bradycardia + hypotension was said to have preceded accelerated junctional rhythms.*‘j Therefore, when accelerated junctional rhythms are
Volume Number
107 3
Accelerated
observed in patients with chest pain syndromes during verapamil therapy, either underlying or drug-induced abnormalities of sinus or AV nodal function or SVT should be suspected. Conclusions. It appears that accelerated junctional rhythms are more frequent in patients with SVT, particularly AV nodal reentry. By some as yet undefined mechanism, verapamil administration to these patients leads to a usually asymptomatic increase in activity of these junctional pacemakers. In the absence of SVT, verapamil neither stimulates junctional rhythms nor suppresses the normal physiologic functioning of junctional pacemakers. We thank Susan Akers, R.N., and Sharon Magro, assistance in the care of these patients, and Barbara preparation of the manuscript.
P.A., Bond
for for
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