J. ELECTROCARDIOLOGY, 8 (3) 209-216

Overdrive Suppression in Diagnosis of Sick Sinus Syndrome BY JUNJI TOYAMA, M.D.,* ATSUSHI ITO, M.D.,** KEN SAWADA, M.D.,** TERUO ITO, M.D.,** YOSHIFUMI TANAHASHI, M.D.,** JITSUKI TSUZUKI, M.D.,** TOSHIYA WATANABE, M.D.** AND SHOJI YASUI, M.D.**

among the pauses obtained was used as a parameter indicating depression of cardiac a u t o m a t i c i t y . The m a x i m u m pause in the SSS group ranged from 5.6 to 9.0 sec (mean -+ SD = 7.0 -+ 1.2), while those in the NSR group ranged from 0.7 to 1.5 sec (mean -+ SD = 1.2 - 0.14). Therefore, the m a x i m u m pause was considered not only to reflect the severity of the symptoms necessitating pacem a k e r implantation in the 9 patients of the SSS group but to have warned us of sudden death in another patient. We concluded that overdrive suppression is useful as a supplementary challenge to determine indications for pacemaker implantation for the sick sinus syndrome, and that prolongation of the m a x i m u m pause beyond 5.0 sec is the critical level for pacemaker implantation.

SUMMARY A criterion to determine the indication for p a c e m a k e r implantation in the sick sinus syndrome by overdrive suppression is proposed. Overdrive suppression was performed in 10 patients with the sick sinus syndrome (SSS) and another 10 patients with normal sinus r h y t h m (NSR) who served as controls. In the SSS group, 9 patients had complained of such severe symptoms as Adams-Stokes att a c k and/or congestive failure and were referred to our laboratory for pacemaker implantation. One other patient, an apparently robust young man (20 years old) referred for detailed cardiac e x a m i n a t i o n , had no remarkable symptoms except for arrhythmias, but was found dead two months later. Atrial pacing for overdrive suppression was carried out at first at various rates ranging from 60 to 180 beats/rain for 15 sec, and then at a rate of 100 beats/min for various durations ranging from 5 to 180 sec. After cessation of the atrial pacing, asystolic pauses were measured and the m a x i m u m (maximum pause)

The sick sinus syndrome includes not only a s y m p t o m a t i c patients with otherwise explainable sinus bradycardia b u t those with Adams-Stokes attacks and/or congestive failure. 1-9 Therefore, t r e a t m e n t of these patients varies according to their symptoms. Recently, advanced sinus arrest or sinoatrial block leading to disturbances of consciousness has been successfully treated by pacemaker implantation, l~ However, indications for p a c e m a k e r i m p l a n t a t i o n s e e m to be determined solely by clinical symptoms rather t h a n by a n y l a b o r a t o r y examination. The main purpose of this paper is to propose a crit e r i o n to help d e t e r m i n e i n d i c a t i o n s for p a c e m a k e r implantation in the sick sinus syndrome utilizing overdrive suppression. ~s

From the Division of Respiration and Circulation, Research Institute of Environmental Medicine, Nagoya University* and the Department of the 1st Internal Medicine, Nagoya University School of Medicine,** Nagoya, Japan. Reprint requests to: Junji Toyama, M.D., Division of Respiration and Circulation, Research Institute of Environmental Meaicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan. 209

210

TOYAMA

We a c c o r d i n g l y p e r f o r m e d o v e r d r i v e s u p p r e s sion in 10 p a t i e n t s w i t h t h e sick s i n u s synd r o m e . N i n e o u t of t h e 10 p a t i e n t s h a d comp l a i n e d of s y m p t o m s , s u c h as A d a m s - S t o k e s attacks and/or congestive failure, severe e n o u g h to r e c e i v e p a c e m a k e r i m p l a n t a t i o n a n d w e r e r e f e r r e d to o u r cardiology division for p a c e m a k e r i m p l a n t a t i o n . T h i s p a p e r also will r e p o r t one case of s u d d e n d e a t h f r o m t h e sick s i n u s s y n d r o m e .

ET AL

cardiographic findings of the 10 patients are listed in Table 2. Their arrhythmias included sinus arrest or sinoatrial block with A-V junctional escape in 4, bradycardia-tachycardia syndrome in 5 and atrial standstill in 1 patient. A control series of 10 patients with normal sinus rhythm was studied. These patients included 4 with congenital heart disease, 2 with valvular disease, 2 with coronary heart disease, and 2 with cardiomyopathy. Age distribution ranged from 16 to 55 years and the heart rate ranged from 62 to 83 beats/min. Studies were all undertaken at the time of diagnostic right heart catheterization.

MATERIALS AND METHODS Subjects:

Overdrive Suppression:

Ten patients were selected among 44 with the sick sinus syndrome (24 females and 20 males) a d m i t t e d to the First D e p a r t m e n t of I n t e r n a l Medicine, Nagoya University School of Medicine from March, 1972 to February, 1973. Their clinical and electrocardiographic features are summarized in Tables I and 2. All patients showed arrhythmias which meet the criteria of the sick sinus syndrome proposed by Ferrer. = Ages ranged from 20 to 70 years. The slowest heart rate for each patient was judged by comparing five or more electrocardiographic records. Slowest rates ranged from 25 to 43 b e a t s / m i n w i t h a m e a n v a l u e of 34.3 -+ 5.3 beats/min. Clinical manifestations in all patients except one (case 7) included one or more of various symptoms related to diminished cerebral or the other systematic arterial blood flow, e.g., syncope, dizziness, chest oppression or discomfort, and edema. They were treated by pacemaker implantation and have remained almost asymptomatic during the follow-up period. Another patient, who will be p r e s e n t e d as a case r e p o r t in brief, was asymptomatic except for arrhythmias. The electro-

All subjects were studied in the postabsorbtive state without receiving premedication. Under local anesthesia, the right great saphenous vein was isolated. Two bipolar catheters (USCI, No. 5F) were introduced; one catheter was positioned at the junction of superior vena cava and right atrium for overdrive pacing, the other positioned across the tricuspid valve for recording the His bundle electrogram. Stimuli for overdrive pacing were discharged from an A-C powered pulse generator for cardiac pacing (Fukuda Denshi, FPC-200). Overdrive pacing was performed at first at rates varying from 60 to 180 beats/min for a period of 15 sec and then at 100 beats/min for periods varying from 5 to 180 sec. In the former, the initial pacing rate was usually 60 beats/min; however, if the patient's control rate was above 60 beats/min, the rate was increased to 80 beats/min. It was then increased by increments of 20 beats/min to 180 beats/min. In the latter, pacing was usually carried out at 100 beats/min for periods of 5, 15, 30, 60, 120 and 180 see.

TABLE 1 Clinical Features of 10 Patients with the Sick Sinus Syndrome Symptoms Case No.

Pt

Age

Heart rate Sex Min. Max.

Syn- Tachycope cardia

1

N.S.

39

F

34

66

+

2

T.S.

47

M

38

110

3

T.S.

58

F

32

116

4

N.0.

20

M

25

5

E.K.

45

F

6

K.K.

56

F

7

M.F.

20

Others

Overdrive Suppression (Max pause) (sec) 5.8

Pacemaker implantation

Progress

-

Chest oppression, Dizziness, Edema

Myocardial

Well

-

+

Chest oppression, Dizziness, Palpitation

+

+

Chest oppression, Dizziness, Edema

5.6

Myocardial

Well

6.2

Transvenous Well

40

+

-

Dizziness

7.7

Myocardial

Well

43

140

+

+

General fatigue, Palpitation

7.2

Myocardial

Well

34

42

-

-

Dizziness

9.0

Myocardial

Well

M

36

48

-

+

Arrhythmia

7.1

-

Sudden death

8

H.O. i

25

F

32

55

-

-

Dizziness,General fatigue

9.0

Myocardial

Well

9

K.S.

51

F

30

110

+

-

Dizziness,Chest discomfort

6.4

Myocardial

Well

10

F.J.

63

F

43

75

-

-

Dizziness

6.4

Myocardial

Well

J. E L E C T R O C A R D I O L O G Y , VOL. 8, NO. 3, 1975

OVERDRIVE SUPPRESSION

IN D I A G N O S I S O F SSS

211

TABLE 2 Electrocardiographic Findings in 10 Patients with the Sick Sinus Syndrome Case No.

Pt

Age

Electrocardiographic Findings Arrhythmias

Sex

Others

1

N,S.

39

F

SA arrest, JEB, Tr atr standstill

Coronary T (V 4 - V 6)

2

T.S.

47

M

SA arrest, SA block, Atr fib

ST depression (V5, V 6)

3

T.S.

58

F

SA arrest, JEB, Tr atr standstill, Atr fib

ST depression (V5, V 6)

4

N.O.

20

IVl

Persistent atr standstill

LVH

5

E.K.

45

F

SA block JEB, ECB, Atr fl and fib

ST depression (V 4 - V 6)

6

K.K.

56

F

SA block JEB, ECB, AV dissociation

ST depression (V4 - V 6)

7

M.F.

20

M

SA block JEB, PAT

LVH

8

H.O.

25

F

SA arrest SA block, JEB, Atr fib

9

K.S.

51

F

SA arrest SA block, JEB

10

F.J.

63

F

SA arrest SA block, JEB

ST depression

Atr = atrial; AV = atrioventricular; ECB = escapecapture bigeminy; Fib = fibrillation; FI = flutter; JEB = junctional escape beat; LVH = left ventricular hypertrophy; SA = sinoatrial; Tr = transient

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Fig. 1: Electrocardiograms in a case of sudden death (case 7). A to C: 12 lead tracing taken during bradycardia (39 beats/min). QRS patterns of the left ventricular hypertrophy nnd junctional type ST depression are noted in A and B. C shows sinoatrial block. D: lead III and V1, taken during tachycardia (68 beat/min). Auricular flutter with 2:1 to 4:1 A-V conduction is noted. J. ELECTROCARDIOLOGY, VOL.8, NO. 3, 1975

212

TOYAMA ET AL

:-st;

_

T

_

_

t

-

v

Fig. 2: Asystolic pause after cessation of atrial pacing (case 7). Top and bottom panels are continuous. Asystolic pause for 7.1 sec, as shown by shaded strip at the lower part of each panel, was observed after cessation of atrial pacing at a rate of 100 beats/min for 15 sec. Black arrow (St) at the left upper part of the top panel indicates the last stimulus of the atrial pacing. The QRS complex of the first spontaneous beat after the long asystolic pause, which is shown in the right corner of the bottom panel, follows after neither P wave nor the atrial activity in His bundle electrogram (HBE), but it follows only H wave in HBE. Thus it indicates that the first spontaneous beat is considered to rise from the A-V junction.

Lead II or III electrocardiogram (ECG) and His bundle electrogram were recorded at a paper speed of 100 mm/sec simultaneously on a multichannel oscillographic photographic recorder (Yokogawa Electric, EMO-62). Cardiac automaticity was estimated by measuring asystolic pauses after cessation of overdrive pacing. The pause was defined as the interval from the last paced P wave to the first spontaneously occurring P wave or the spike of His bundle electrogram if the first beat was an A-V junctional escape beat. Brief description of a case of sudden death: Patient M. F. (case 7), a 20-year-old man, was a worker in a paper factory. He was quite well except for occasional transient palpitations. He was admitted to a local community hospital located near his plant in December, 1970, because of a femoral fracture at work. Electrocardiograms taken during this hospitalization revealed sinoatrial block with A-V junctional escape beat (Fig. 1, A to C) and arial flutter with block (Fig. 1 D). He was advised to undergo thorough cardiac examination when he was out of the hospital. Two years later he was

referred to our laboratory and admitted to Nagoya University Hospital in March, 1972. He denied syncope, dizziness, dyspnea, chest oppression or edema. There was nothing in the family history to suggest any cardiac disease. Past history of diphtheria was also denied. P h y s i c a l e x a m i n a t i o n revealed a welldeveloped, robust young man. His blood pressure was 134/50 mm Hg. The pulse was slow and quite irregular, varying between 37 and 43 beats/min, averaging 40 beats/min. Neck veins were not distended. Lungs were clear. There was a grade II to III/VI mid-systolic m u r m u r in the 3rd and 4th interspace at the left sternal border. The liver was not palpable, and there was no pretibial edema. Laboratory studies: Chest X-ray film revealed slight cardiomegaly with no specific chamber enlargement. Complete bloOd count, liver function tests, serum sodium, potassium, chloride, blood urea nitrogen and urinalysis were all within normal. The ECG taken at the time of admission showed almost the same pattern as illustrated in Fig. 1, A to C. In addition to the rhythm disorder there was some prolongation of the P-R interval

J. ELECTROCARDIOLOGY, VOL. 8, NO. 3, 1975

OVERDRIVE SUPPRESSION IN DIAGNOSIS OF SSS

~St

HBE

213

increased, and was increased up to 200 msec at a pacing rate of 110 beats/min. Finally, second degree A-V block developed at a rate of 120 beats/min or higher. H-V time, however, remained almost constant with increasing rates of pacing. Clinical course. Electrophysiological studies revealed not only serious depression of impulse formation of the sinoatrial node and subsidiary pacemakers in the atrium but serious depression of impulse conduction both in the atrium and A-V node. However, there was some hesitation in implanting the patient with a permanent pacemaker because of the following reasons: 1)he had never experienced syncope or dizziness, and 2) he was apparently a robust young man. He was followed up after discharge by occasional check-ups in the out-patient clinic, and was found dead in bed on May ]6, 1972, about two months later. Necropsy was not carried out.

RESULTS

Fig. 3: Simultaneous recordings of lead II and His b u n d l e e l e c t r o g r a m d u r i n g a t r i a l pacing (80 beats/min). Interval between pacing stimulus (St) and the initial steep deflection of A wave is defined as P-A time. P-A, A-H and H-V times are 140 msec, 132 msec and 50 msec, respectively. Note that P-A time is significantly prolonged but A-H and H-V times are lengthened no more than upper limits of normal values.

(0.24 - 0.28 sec) and a pattern of left ventricular hypertrophy. Right heart catheterization revealed normal right atrial and ventricular pressure and no evidence of left to right shunt. Overdrive pacing and recordings of His bundle electrogram were performed with the method as previously stated. The asystolic p a u s e a f t e r o v e r d r i v e pacing at 60 beats/min for 15 sec was greater than 5 sec. It attained a m a x i m u m of 7.1 sec following pacing at a rate of 100 beats/min for 15 sec (Fig. 2). In Fig. 2, the simultaneously recorded His bundle electrogram revealed that the first escape beat after the m a x i m u m p a u s e was A-V j u n c t i o n a l . Atrioventricular conduction of the patient was also a n a l y s e d by His bundle electrograms (Fig. 3). There was significant prolongation of P-A time (140 msec) at a pacing rate 80 beats/min while A-H (132 msec) and H-V time (50 msec) were not considerably prolonged. However, A-H time as well as P-A time was prolonged as the pacing rates were

J. ELECTROCARDIOLOGY, VOL. 8, NO. 3, 1975

Asystolic p a u s e s a f t e r s t o p p i n g t h e overd r i v e p a c i n g v a r i e d in l e n g t h w i t h c h a n g e in t h e p a c i n g r a t e a n d d u r a t i o n . F i g u r e 4A illust r a t e s t h e effect of t h e p a c i n g r a t e on t h e asystolic p a u s e in 10 p a t i e n t s w i t h SSS a n d t h e s a m e n u m b e r of p a t i e n t s w i t h NSR. In t h e f o r m e r group, r e s p o n s e s of t h e r e s p e c t i v e patients were plotted against the pacing rate. T h e y exceeded 1.9 sec a f t e r c e s s a t i o n of overd r i v e p a c i n g a t a low r a t e of 60 b e a t s / m i n ; especially, t h e y a m o u n t e d to m o r e t h a n 5.0 sec in 4 out of t h e 10 p a t i e n t s (cases 3, 4, 7, 10). T h e n , as t h e r a t e of the p a c i n g w a s increased, t h e asystolic p a u s e s t e n d e d to be l e n g t h e n e d in 7 of t h e SSS group, b u t t h e y a t t a i n e d t h e i r p e a k w i t h d i f f e r e n t r a t e s of p a c i n g t h a t w e r e v a r i a b l e f r o m p a t i e n t to p a t i e n t . T h e r e f o r e , no s i g n i f i c a n t c o r r e l a t i o n w a s o b t a i n e d bet w e e n t h e l e n g t h of t h e p a u s e a n d t h e r a t e of pacing. In the NSR group, the asystolic p a u s e s a r e i l l u s t r a t e d as t h e m e a n v a l u e of t h e 10 p a t i e n t s (Fig. 4A, solid circles). T h e y r e m a i n e d n e a r l y c o n s t a n t ( r a n g i n g f r o m 0.99 to 1.11 sec) w i t h all c h a n g e s in p a c i n g r a t e . Fig. 4B shows r e s p o n s e s to a fixed r a t e of 100 b e a t s / m i n for d i f f e r e n t d u r a t i o n s . I n 4 pat i e n t s (cases 1, 4, 5, 8) of t h e SSS group, t h e p a u s e w a s l e n g t h e n e d w i t h i n c r e a s e in d u r a t i o n of t h e pacing. B u t no s i g n i f i c a n t correlat i o n w a s f o u n d b e t w e e n t h e l e n g t h of t h e p a u s e a n d d u r a t i o n of t h e pacing. In t h e N S R g r o u p , t h e p a u s e also c h a n g e d l i t t l e w i t h d u r a t i o n of t h e pacing. T h u s , as no s t a t i s t i c a l l y s i g n i f i c a n t correl a t i o n w a s f o u n d b e t w e e n t h e l e n g t h of p a u s e a n d t h e i n c r e a s e in e i t h e r r a t e or d u r a t i o n of t h e o v e r d r i v e p a c i n g , to e v a l u a t e t h e a u t o m a ticity of t h e r e s p e c t i v e h e a r t s , we used t h e maximum (maximum pause) among all pauses that were obtained from the respective p a t i e n t s a f t e r c e s s a t i o n of v a r i o u s p a c i n g s

214

TOYAMA ET AL

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'eo

8'o

i

L

ioo i:;o 14o 16o

1'8o

0

Pacing Rate (beats/min)

15

60

120

180

Pacing Duration (sec)

Fig. 4: Effect of pacing rate and duration on asystolic pause after cessation of the overdrive pacing. Responses of each of 10 patients with the SSS are plotted against pacing rate (A) and duration (B). Numbers in parentheses on the left side of each panel represent the case numbers of the respective patients. Double circles represent the maximum pauses which are obtained from the respective patients after cessation of various pacings with changes of their rates and durations. Dotted line illustrates the level of 5.0 sec. Responses of 10 patients with the normal sinus rhythm are expressed in mean values +- SD, and illustrated as solid circles and vertical bars.

with change of their rates and durations. The m a x i m u m pause of each patient in the SSS group is illustrated as double circle in Fig. 4; however, t h a t in the NSR group was not illust r a t e d in this figure. Fig. 5 illustrates the comparison between the m a x i m u m pauses in the NSR group and those in the SSS group. In the NSR group they ranged only from 0.7 to 1.5 sec (mean, 1.2 - 0.14), whereas in the SSS group from 5.6 to 9.0 sec (mean, 7.0 - L2). The m a x i m u m pauses in the SSS group were nearly 6 times as long as those in NSR group. This difference of the m a x i m u m pause between the two groups was statistically significant (p < 0.01). The simultaneously recorded His bundle electrogram revealed t h a t the initial spontaneous beat after the maxim u m pause was sinus-nodal (open circle in Fig. 5) in all of the NSR group but A-V junctional (double circle in Fig. 5) in 9 of the SSS group.

DISCUSSION Evaluation of cardiac automaticity by overdrive suppression E x p e r i m e n t a l studies 2~ have indicated t h a t suppression of pacemaker activity in the sinoatrial node after overdrive pacing depends upon both pacing rate and duration. However, several clinical results 1~22'23 have not yet disclosed data as clear cut as the previously reported a n i m a l experiments. Actually, we could not find a n y statistically significant correlation between the pause after cessation of overdrive pacing and either rate or duration of the pacing. This discrepancy between h u m a n and animal results m a y be partly explainable by assuming substantial differences of condition between the anesthetized experimental animal and the awake, unanesthetized human. However, the analysis of responses in patients with SSS offers the

J. ELECTROCARDIOLOGY, VOL. 8, NO. 3, 1975

OVERDRIVE SUPPRESSION IN DIAGNOSIS OF SSS

S-A

o

Nodal

~A-V

U}

9

I/1

@@

Junctional

@@ @

6

@ 0

215

ings with change of their rates and durations. In addition, as the first spontaneous beat following the m a x i m u m pause was the A-V junctional beat in 9 of 10 patients with SSS (shown as double circles in Fig. 5), the maxim u m pause m a y reflect degrees of depressed automaticity 49'2~'2~ of the whole heart including the sinoatrial node and subsidiary pacem a k e r r a t h e r than of the sinoatrial node alone.

Determination of indication for pacemaker implantation by evaluating the maximum pause

Q. 5 E -~ 4 E X

m 3 =E

.

.

.

.

0

N=IO

N =10

NSR

SSS

Fig. 5: Comparison of the maximum pause between the NSR and SSS groups. Open and dotted circles indicate that the first spontaneous beat following the maximum pause is the sinus nodal and A-V junctional, respectively. Solid circles indicate the mean values of the NSR and SSS groups. Dotted lines are drawn at the level of 1.5 and 5.0 sec, respectively. The former indicates the upper limit of the normal value, and the latter implies the critical level of so much marked depression of automaticity as to indicate pacemaker implantation.

following intricate problem. 24 As the sick sinus syndrome m a y frequently have sinoatrial exit block in association with depressed automaticity, it necessarily follows that all atrial depolarizations induced by the rapid overdrive pacing are not able to enter the sinoatrial node (entrance block of the atrial impulse into the sinoatrial node25). Therefore, the most effective rate for actual overdrive suppression of pacemaker cells in the sinoatrial node or the subsidiary pacemaker site can not be detected unless the potentials of the pacemaker cells are directly recorded, but so far this has not been successfully accomplished. In view of this point, it m a y become reasonable to evaluate depressed automaticity in the sick sinus syndrome by the maximum (maximum pause)among all pauses that were obtained with various pacJ. ELECTROCARDIOLOGY, VOL. 8, NO. 3, 1975

Since Muller 1~ described the first case of the sick sinus syndrome treated with pacem a k e r implantation, m a n y reports l~-ls have followed. According to these reports, there seems to be no precise method to judge indications for p a c e m a k e r i m p l a n t a t i o n by any laboratory examination, b u t it has been determined exclusively by severity of clinical symptoms. In the nine patients investigated in this paper, similarly, d e t e r m i n a t i o n of pacemaker implantation was performed according to t h e i r clinical s y m p t o m s alone. These patients, however, were subjected to examination of overdrive suppression before implantation of the pacemaker, and all had a m a x i m u m asystolic pause over 5.0 sec. This prolongation of the pause m a y reflect dep r e s s e d a u t o m a t i c i t y in t h e s e p a t i e n t s enough to explain their serious symptoms which necessitated pacemaker implantation. Another patient (case 7) also had a significantly long pause (7.1 sec) after overdrive pacing (at 100 beats/min for 15 sec). Howe.ver, as he was not only free of any serious symptoms b u t also apparently a h e a l t h y y o u n g man (20 years old) except for the prolongation of the m a x i m u m pause detected, the following decision was made in our laboratory: significant depression of a u t o m a t i c i t y might be highly suspected, but pacemaker implantation should be postponed until any remarkable symptoms appeared. He was then followed in the outpatient clinic, but unfortunately was found dead two months later. The possible cause of sudden death m a y have been prolonged asystole following cessation of paroxysmal tachycardia. From this, it may be reasonable to suspect t h a t extraordinary prolongation of the pause after overdrive pacing predicted the danger of his sudden death earlier t h a n any appearance of overt clinical symptoms. In view of this point, determining pacemaker implantation for sick sinus syndrome by severity of clinical symptoms alone, however useful, is not enough. Therefore, some supplementary examination of cardiac automaticity m a y be indispensable. ~9'2a2s In conclusion, overdrive s u p p r e s s i o n is con-

216

TOYAMA ET AL

s i d e r e d to be a useful m e t h o d for t h e p u r p o s e a t t h e p r e s e n t t i m e , a n d p r o l o n g a t i o n of t h e p a u s e o v e r 5.0 sec is t h e critical level for clinical a p p l i c a t i o n of p a c e m a k e r i m p l a n t a t i o n . Acknowledgments: The authors express their gratitude to Prof. Kazuo Yamada and to Dr. Toshiji Kobayashi for many helpful discussions. We also t h a n k Prof. D. H. Spodick for his correction of the English in this paper.

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J. ELECTROCARDIOLOGY, VOL. 8, NO. 3, 1975