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Home , Atrial tachycardia, Bradycardia, Sinus bradycardia

The - Syndrome Treatment with Cardiac Drugs and Adrenal Corticosteroid

Junichi FUJII, M.D., Nobumitsu TAKAHASHI,M.D., and Kazuzo KATO, M.D.

Seven patients of S-A block complicated by tachycardic paroxysms of atrial or flutter were described and the medical treatment in this syndrome was reappraised. Damage to S-A node and adjacent atrial tissue was assumed in all patients. All the patients had syncopal attacks associated with occurring especially at the termina- tion of tachycardia. Overdrive suppression of diseased S-A node and lower automatic pacemakers was demonstrated by ECG recordings. The term "bradycardia-tachycardia syndrome" or "syndrome of alternating bradycardia and tachycardia" seemed appropriate. In spite of difficulty of medical treatment reiterated by previous de- scriptions, 6 of 7 patients were improved with drug therapy, including adrenal corticosteroid. Adrenal corticosteroid in combination with or- ciprenaline or belladonna alkaloids was most helpful among the drugs used. Obviously, pacemaker implantation should be performed without delay in patients with frequent and prolonged attacks of . But not all patients have need of pacemaker implantation. A trial of drug therapy may be permitted in many patients of this syndrome before in- troduction of pacemaker. Additional Indexing Words: Sick sinus syndrome S-A block Atrial tachyarrhythmias Syn- cope Overdrive suppression

ECENTLY there have been some reports concerning the patients with S-A block or accompanied by paroxysmal atrial tachy- such as fibrillation, flutter and . As pointed out by several authors, these patients repeatedly exhibited syncopal attacks associated with following termination of the tachycardia. Short1) in 1954 advocated the term "the syndrome of alternating bradycardia and tachycardia" to distinguish these patients from those with bradycardia or tachyarrhythmia alone. Subsequently Ferrer2) described "the sick sinus syndrome" with wide clinical spectrum, ranging from sinus bradycardia with-

From the CardiovascularInstitute, 8-1-22 Akasaka,Minatoku, Tokyo. Receivedfor publicationJune 14, 1973. 414 Vol.14 No.5 BRADYCARDIA-TACHYCARDIA SYNDROME 415

out distressing symptoms to recurrent attacks of syncope. "Sluggish sinus

node syndrome"3) and "sino-atrial syncope"4) also were applied to much

the same group of patients. Though they were all characterized by depressed

sinus node function, episodes of cardiac arrest associated with syncope seem

to develop more frequently when tachyarrhythmias are complicated.

Frequent mention has been made of a great difficulty in medical treat-

ment of this group of patients. Antiarrhythmic drugs eliminating tachyar-

rhythmias are prone to develop more marked bradycardia or asystole, whereas

cardio-accelerators, favorable to bradycardia, may precipitate tachycardia

attacks. In 1966 Muller et al.5) reported a case treated successfully with the

use of artificial pacemaker, which has thereafter been increased perceptibly.

At present many investigators believe the application of pacemaker to be

the most efficacious method of therapy in this group of patients. Nevertheless

its use is not likely to be indicated to all patients. Although patients having

grave syncopal attacks of prolonged duration should unquestionably be aided by pacemaker without delay, treatment may be started with drugs in the

others.

As for the genesis of this syndrome, damage to the S-A node and the

adjacent atrial tissue around it was supposed to be responsible for both the

development of or sinus bradycardia and the occurrence of

tachyarrhythmia attack. Yet neither clinical nor pathological data have been

available enough to explain the special features of the syndrome. It may be

said that its genesis still remains to be investigated.

We have experienced 7 cases of this syndrome for the last 7 years. An

attempt was made to treat them mainly with drugs including adrenal cor-

ticosteroid with good success. Then the purpose of this paper is to reappraise

the effect of medical treatment on this syndrome and to review the discussion

on its clinical features.

MATERIAL

Seven patients having tachyarrhythmia attacks were selected from 62 cases of sinoatrial block who were seen in the Cardiovascular Institute Hospital from 1964 to 1971. Cases of sinoatrial block caused by drugs such as , , ƒÀ-blocker and the like were not included .

RESULTS

Table I shows the clinical data on 7 patients . The patients of this series, 4 men and 3 women , were admitted to this 416 FUJII, TAKAHASHI, AND KATO ap. J.

Table

hospital, complaining of syncopal episodes with or arrhythmias, which began to develop an average of 1.7 years before admission. Ages varied from 18 to 79 years (average 61 years). All 7 patients exhibited documented episodes of sinoatrial block or sinus arrest with A-V junctional escape beats. The basic usually was between 32 and 54per minute with an average of 34per minute. In addition, 6 patients had paroxysms of , and 5 of , both lasting a few seconds to a few hours. The ventricular rate during these paroxysms was between 120 to 170per minute in all but 1 patient (Case 4), who showed paroxysms of atrial flutter with a ventricular rate of 66per minute. In 4 patients asystoles of 3.6 to 12.8sec duration were demonstrated at the termination of tachycardic paroxysms by long-term ECG recording, causing syncope and/or . Prolonged periods of asystole frequently

Table

J Vol.14 No.5 BRADYCARDIA-TACHYCARDIA SYNDROME 417

I

observed during the basic rhythm in another patient (Case 4) were also as- sociated with syncopal episodes. Other abnormalities than the rhythm en- countered in the routine electrocardiograms were slight depression of S-T segments of I, II (III) and left precordial leads in 5 patients and incomplete right with in 1. On X-ray 6 patients showed . Though a few of these com- plained of short breathness on exertion, otherwise no signs of congestive were noted. Laboratory examinations revealed increased sedimenta- tion rate, positive C-reactive protein and positive RA-test in 2 cases, respec- tively, and positive Wassermann reaction in 1 case (Table II). Serum potassium level was normal in all patients. Hypercholesterolemia was found in 1 patient. From these laboratory, electrocardiographic and historical evidences, the diagnosis of coronary disease was made in 4 patients, 1 of whom had

II Jap. Heart J. 418 FUJII, TAKAHASHI, AND KATO September, 1973 also rheumatoid arthritis and syphilis. Single case of hypertension and aortic regurgitation was also noted. No etiologic basis could be established in the remaining 1 case. Medical treatment including adrenal corticosteroid was successful in 6 out of 7 patients. In 5 cases the treatment was initiated with belladonna alkaloids or orciprenaline, or a combination of both. After the use of or- ciprenaline with or without extractum scopoliae, the atrial rate was increased to some extent but paroxysms of atrial fibrillation or flutter occurred more frequently in 4 patients. However, 1 patient (Case 7) was improved from oral administration of orciprenaline and extractum scopoliae without adverse effects. Extractum scopoliae alone employed in 1 patient was of little help in increasing the atrial rate. Oral therapy with a combination of prednisolone together with orciprenaline and/or extractum scopoliae was then instituted in 3 patients and from start of the treatment in 2 patients. In 4 of these, episodes of both sinoatrial block or asystole and tachycardia were practically abolished, the patients being essentially symptom-free. A was maintained without recurrence of after gradual decrease in prednisolone dose to 5-10mg every other day. One of 2 additional patients who received prednisolone alone had abbreviated asystole following tachy- cardic paroxysms, being asymptomatic. Quinidine and digitalis glycosides benefited 1 and 3 patients, respectively, by either decreasing the frequency of tachyarrhythmic paroxysm or controlling the ventricular response. However these drugs caused a deterioration of symptoms related to bradycardia, to sinus arrest, or to depression of the A-V junctional escape beats. None of this series of patients was given pacemaker therapy. All patients had been asymptomatic at follow-ups for 3 months to 7 years after discharge from hospital. Four patients showed sinus rhythm throughout the follow-up, while 2 had intermittent sinoatrial block or sinus arrest with A-V junctional escape rhythm. In another patient persistent atrial fibrilla- tion developed after 4 months. Only 1 patient died of cerebral thrombosis about 3 years later.

CASEREPORTS Case 1. A 71-year-old female admitted to this hospital on February 24, 1970, had experienced several episodes of arrhythmias, and syncope for 2 years. A recent increase in their frequency had been noted. She had sometimes showed signs of CHF also for the last 6 months. One of her sisters was treated of bradycardia of unknown etiology, but her own past history was non-contributory. On admission no abnormal physical findings were noted except for bradyarrhythmia of 36 beats per minute. Laboratory findings were shown in Table II. Ophthalmoscopic Vol.14 BRADYCARDIA-TACHYCARDIA SYNDROME 419 No.5

Fig. 1. Case 1.

examination revealed changes of KW-II. Chest X-ray film showed moderate cardiomegaly. The ECG at admission showed sinus and intermittent 2:1 to 3:1 sinoatrial block with paroxysms of atrial fibrillation, which was fre- quently initiated by atrial premature contraction. The paroxysm of atrial fibrilla- tion with the ventricular rate of about 170per minute persisted usually for 10-140 sec, then suddenly subsided. Its termination was often followed by asystole of 3 to 20sec duration, resulting in Adams-Stokes seizure. A period of asystole was interrupted by reappearance of A-V junctional escape or sinus beat (Fig. 1 A and B). Other ECG findings, ST-T changes were considered to be due to coronary sclerosis. With administration of orciprenaline, 10mg 4-6 times daily, and extractum scopoliae, 20mg 4 times daily, bradycardia was alleviated to some extent, but paroxysms of atrial fibrillation began to appear more frequently. Then prednisolone, 10mg 3 times daily, was added to the above-described medication . Two days later, a sinus rhythm was restored and maintained without episodes of atrial fibrillation (Fig. 1C). Prednisolone was given in doses of 15-30mg/day for 16 days, then discontinued after gradual decrease in the course of a week. Medication of orciprenaline and extractum scopoliae was continued. She has experienced Jap. Heart J. 420 FUJII, TAKAHASHI, AND KATO September, 1973

Fig. 2. Case 2. neither paroxysms of bradycardia nor tachycardia with syncope for the subsequent 6 months. Case 2. A 74-year-old housewife had been treated for pectoris and hypertension since 1958. She had syncopal and tachycardic paroxysms for the Vol.14 No.5 BRADYCARDIA-TACHYCARDIASYNDROME 421 last 5 months. Because of increased frequency of the attacks, the patient was ad- mitted to this hospital on January 5, 1965. On admission, physical findings were almost normal except for bradyarrhythmia of 54per minute and mild hypertension of 160/80mmHg. Laboratory findings were non-contributory. Fundoscopic examination showed changes of KW-II. Mild cardiomegaly was revealed on a chest X-ray film. ECG at admission showed sinus arrhythmia with 2:1 to 3:1 sinoatrial block, followed by A-V junctional escapes. A paroxysm of atrial fibrilla- tion with a ventricular rate of 150per minute occurred occasionally following atrial premature contraction. It was suddenly terminated with asystole, causing syncope (Fig. 2A, B). In Fig. 2B the asystole of 6sec was discontinued by nodal escaped rhythm, which soon changed into basic S-A block rhythm. At first orciprenaline 40-60mg/day was given for S-A block. Paroxysms of atrial fibrillation occurred more frequently and those of atrial flutter also occasionally appeared (Fig. 2C). Oral treatment with prednisolone, 5mg 3 times daily, was instituted. Since only a little improvement was effected with this therapy for 2 weeks, sulphate, 0.25mg 3 times daily, was added to it. A regular sinus rhythm with a rate of 58per minute was attained in a week. There was no re- currence of S-A block nor atrial fibrillation. Since 3 weeks later the prednisolone dose was decreased gradually to 5mg every other day. The patient has been essentially symptom-free for the subsequent 5 years. Her electrocardiogram showed a sinus rhythm of 50-60 beats per minute without any bouts of tachycardia (Fig. 2D).

Fig. 3. Case 3. Jap. Heart J. S 422 FUJII, TAKAHASHI,AND KATO eptember, 1973 Case 3. In November, 1965, this 79-year-old female had an episode of tachyar- rhythmia associated with palpitation and lasting for 3 days. But she had been symptom-free until February, 1966, when occasional episodes of palpita- tion and mild syncope were described. On admission to this hospital on March, 1966, her physical examination revealed heart rate of 43 beats per minute, blood pressure of 98/74mmHg and a grade 3/6 diastolic blowing murmur at 4L. The heart was moderately enlarged, but the lungs and the liver were not congested. Laboratory examinations were almost normal except increased total serum chole- sterol level as much as 323mg/ 100ml and a little retarded PSP-test. The first ECG showed advanced S-A block with sinus arrhythmia and nodal escaped rhythm, resulting occasionally in escape-capture (Fig. 3A). The S-T segment was slightly depressed in II, III, and left precordial leads. Occasionally a paroxysm of atrial flutter with a ventricular rate of 142/min occurred (Fig. 3B). The patient was initially treated with oral administration of extractum scopoliae, 10mg every 4 hours, prednisolone, 5-10mg and orciprenaline, 10mg 3 times daily, respectively. After 7 days an appreciable increase in the atrial rate was effected by this treatment, but accompanied by increased frequency of paroxysms of atrial flutter. Lanatocide-C of 0.4mg was injected intravenously at each paroxysm, which subsided spontaneously in 2-16 hours. It was noted that advanced S-A block recurred not infrequently after use of such a digitalis preparation. For the sub-

Fig. 4. Case 4. Vol.14 No.5 BRADYCARDIA-TACHYCARDIASYNDROME 423 sequent 37 days, a sinus rhythm of 50-60 beats per minute was preserved by pre- dnisolone, 5mg twice a day and extractum scopoliae, 10mg every 6 hours, without occurrence of paroxysmal atrial flutter. Paroxysms of atrial flutter reappeared, though in less frequency than previously, after the discharge in spite of the same treatment. The patient, however, had experienced no syncope until December, 1968, when she died of cerebral thrombosis. Case 4. An 18-year-old male student had experienced occasional episodes with vertigo and syncope lasting 2-30sec since August, 1963. The first ECG at the out-patient clinic of this institute in August, 1964 showed atrial flutter with a ventricular rate of 30-40per minute, left axis deviation, and incomplete RBBB (Fig. 4A). A moderately enlarged heart was revealed on a chest X-ray film but no detailed examinations had been made. In consequence of repeated syncopal at- tacks of 2 to 3min duration developing for 3 months the patient was admitted to the hospital in July, 1968. On admission bradyarrhythmia of 32per minute was found. All the laboratory examinations were non-contributory, except for moderate cardiomegaly on a chest X-ray film and the following abnormal ECG findings. An advanced degree of S-A block, associated with 3-5sec asystole mostly followed

Fig 5. Case 5. Jap. Heart J. 424 FUJII, TAKAHASHI,AND KATO September, 1973 by nodal escape, was found on an ECG (Fig. 4B). Continuous monitoring of ECG demonstrated the asystole occasionally lasting over 9sec, in particular, while sleeping at night. determined by right heart catheterization was found to be normal (6.67L/min). Oral treatment with orciprenaline, 10mg 3 times daily, and prednisolone, 10mg 3 times daily, were not effective in increasing heart rate. However, the patient had no further syncopal episodes during admission to this hospital. Subsequently, all medications were discontinued without recurrence of the atrial flutter or syncope. Implantation of the artificial pacemaker was recommended whenever necessary. Case 5. A 69-year-old male merchant was admitted to this hospital in March, 1971, complaining of occasional episodes of palpitations and syncopes lasting about 10sec. A similar type of palpitation with fainting had been present 2 months earlier, when the occurrence of alternating tachycardia and bradycardia was noted. Physical examination revealed a well developed, well nourished man in no acute distress. Blood pressure was 150/140mmHg, 38per minute and irregular. Laboratory data were non-contributory, except for moderate cardiomegaly on the

Fig. 6. Case 6. Vol.14 No.5 BRADYCARDIA-TACHYCARDIA SYNDROME 425 chest X-ray film and ECG abnormalities. The initial ECG showed a sinus brady- cardia with occasional atrial premature contraction and a short run of atrial fibril- lation. There were no QRS-T changes. A follow-up tracing demonstrated atrial fibrillation with a ventricular response of 100-120per minute. Another record showed a paroxysm of atrial flutter. Each of these paroxysms of atrial fibrillation and flutter was followed by asystole of 4-8sec, then nodal escaped rhythm, associated with syncope (Fig. 5A): The treatment was initiated with prednisolone, 10mg 3 times daily, and ex- tractum scopoliae, 20mg every 6 hours. With this therapy a sinus rhythm was restored 3 days later, but an occasional atrial premature contraction was noted. After 7 days the prednisolone dose was decreased to 25mg/day and to 10mg/day after 20 days, when he had a recurrence of the paroxysmal atrial fibrillation. of 0.5mg was given to decrease the ventricular rate and the paroxysm ceased on the next day. With further decrease of the prednisolone dose, paroxysms of atrial flutter tended to recur more frequently. Oral administration of quinidine, 0.6Gm daily, together with digoxin, 0.25mg daily, did not control the paroxysms, aggravating the asystole and S-A block following them (Fig. 5B). Quinidine was discontinued and prednisolone, 40mg/day, was re-administered with good results. For 5 months the patient had no further syncopal episodes with prednisolone, 5-30mg daily, extractum scopoliae, 20mg 3 times daily, and digoxin 0.25-0.375mg/day. A sinus rhythm of 50-60per minute was maintained (Fig. 5C). Case 6. A 47-year-old male was admitted to this hospital on August 23rd , 1971, because of episodes of palpitation, fainting and flush for 1 to 2min, which he had sometimes experienced since 1969. On admission his heart rate was 45per

Fig. 7. Case 7. Jap. Heart J. S 426 FUJII, TAKAHASHI,AND KATO eptember, 1973 minute, irregular and blood pressure was 160/80mmHg. No other abnormalities were revealed on physical examination. A chest roentgenogram showed slight enlargement of the heart but the pulmonary vascularity was not increased. Routine laboratory examinations were within normal limits. An ECG showed frequent S-A block with nodal escape and occasional atrial premature contractions (Fig. 6A). There were no changes in QRS complexes but slight depression of the S-T segment in leads II, III, aVF, and V4-6 Oral administration of orciprenaline, 10mg 3 times daily, increased the atrial rate from 42 to 62 and produced a paroxysm of atrial fibrillation with a ven- tricular rate of 120per minute after 5 days, which was followed by asystole of 3sec terminating in nodal escape (Fig. 6B). The patient noted palpitation and vertigo. Orciprenaline was discontinued, and prednisolone, 10mg 3 times daily, was given. After 4 days with this treatment, the frequency of paroxysm of atrial fibrillation decreased to less than once a day, though S-A block was basic rhythm. The duration of asystole following paroxysm of fibrillation was not enough to cause fainting attacks. Because of gastric disturbance, one of side effects of prednisolone, its dose was gradually decreased until discontinued 42 days later without increase in frequency of atrial fibrillation. Since the patient had been essentially symptom- free for 2 months, though his electrocardiogram showed S-A block, no treatment was advised at his discharge from hospital (Fig. 6C). Case 7. A 70-year-old male was admitted on October 25, 1966, complaining of episodes of syncope with palpitation, dyspnea, and chest discomfort, which lasted about 2min. A similar type of episode had been experienced since 2 years before admission, its frequency being increased for the last 4 weeks. The patient described the development of right-sided hemiparesis, speech disturbance and numb feeling at the tongue after the episode in September 1965. On physical examination his heart rate was 58 beats per minute, irregular, blood pressure 122/58mmHg, and sclerotic. A grade 2/6 ejection systolic murmur was heard at the area. Laboratory data showed positive CRP and RA tests, KW-I change ophthalmoscopically and moderate cardiomegaly on a chest X-ray film. The ECG on admission showed a sinus bradycardia with occasional S-A block and atrial premature contractions (Fig. 7A). There were neither syncopal nor palpita- tion episodes during the following 2 weeks. On the 15th day of hospitalization, the patient had a paroxysm of atrial fibrillation with a ventricular rate of 120per minute, persisting for several hours (Fig. 7B). A sinus rhythm was restored spon- taneously. Before the nature of the syncopal episode was documented electrocar- diographically, he was discharged from hospital for his personal reasons. Oral treatment with digoxin, 0.25-0.5mg daily, together with extractum scopoliae and orciprenaline was effective in controlling syncopal episodes until March 1967, when he began to have persistent atrial fibrillation.

DISCUSSION In 1954 Short1) first described the syndrome of alternating bradycardia and tachycardia associated with syncope. Birchfield et al6) subsequently reported a case with similar syndrome, including bradycardia, asystole, Vol.14 No.5 BRADYCARDIA-TACHYCARDIASYNDROME 427 syncope and paroxysmal atrial fibrillation. Since then an increasing number of patients having syncope associated with extreme bradycardia have been reported by many authors. The depression of sinus node activity was de- monstrated in all of those patients, but not always the concurrence of tachy- arrhythmia. In 1968 Ferrer2) described the sick sinus syndrome in atrial disease (SSS) resulting from a failing S-A node, which exhibited wide clinical spectrum, ranging from sinus bradycardia without symptoms to recurrent at- tacks of syncope. Though no reference was made in her article to atrial tachy- arrhythmia, more than half of the patients with SSS appeared to have com- plicating supraventricular tachyarrhythmias. Rubenstein et al7) considered the sick sinus syndrome to be present in patients exhibiting otherwise un- explained marked sinus bradycardia or sinus arrest with or without associated supraventricular tachyarrhythmias. The mechanism of bradycardia may be either disordered impulse generation within the sinus node or impaired con- duction of impulses from the sinus node into the . The other terms "inadequate sinus mechanism" ,8) "sluggish sinus node syndrome",3) and "sinoatrial syncope"4) have also been used to describe the same condition . When complicating tachyarrhythmias have been present, however, the condi- tion has been best termed "the syndrome of alternating bradycardia and tachycardia",1) or simply "the bradycardia-tachycardia syndrome".9) From these descriptions, the term bradycardia-tachycardia syndrome seems ap- propriate for our material. All patients presented herein exhibited episodes of S-A block or sinus arrest and were characterized by asystole and syncope occurring at the termination of supraventricular tachyarrhythmia. Patients without tachycardia attacks were not included in this series. Sino-atrial block may possibly be caused by damage to sino-atrial node or atrial tissue around it, either primary or secondary to . It is induced in the presence of arteriosclerotic processes involving the S-A node and sclerosis of the right coronary artery. James10) demonstrated that the sino-atrial junction is the site of maximal ischemic damage when there is occlusion of the artery to the . According to recent report by Rubenstein et al,7) the etiology of S-A block or sinus arrest was coronary disease in 20 of 56 patients. S-A block has also been found in infectious diseases, such as rheumatic , , influenza, dysentery, , and . Patients with primary myocardial disease or other atrial degenerative processes of unknown or metabolic origins oc- casionally develop S-A block. Increased has been said to be another important etiologic factor for S-A block and sinus arrest. It can occur with disease of the central nervous system, pulmonary tumor , gagging, hypersensitive carotid sinus, or various gastrointestinal disorders. In addi- Jap. Heart J. 428 FUJII, TAKAHASHI, AND KATO September, 1973 tion, the vagotonic depression of the S-A node by digitalis is not infrequently the cause for S-A block. In our cases 4 patients were diagnosed to have coronary sclerosis, one of whom had also lues and rheumatic disease. Single case of hypertension and aortic regurgitation was noted. None of the above- metioned etiologic factors could be exactly verified in the remaining 1 case. Whether paroxysms of supraventricular tachyarrhythmia occur inde- pendently or are secondary to the bradycardia has not been clear. Frequent association of tachyarrhythmia with bradycardia has not always been de- monstrated. The 7 patients presented here were experienced among 62 patients with S-A block, while there were 31 cases having episodes of tachy- cardia of 114 reported cases of S-A block in Japan. Levine11) reported tachycardia developed in 4 of 18 patients with S-A block and Rubenstein et al7) described 33 patients with supraventricular tachycardia among 56 patients meeting the criteria of SSS. The possible suppression of both arrhythmias by means of pacing suggests that may be related to the slow rate. In experimental study by Loomis12) and coworkers, atrial fibrillation was readily induced by acetylcholine or vagal stimulation in animals whose S-A node was destroyed or cooled. Han et al13) showed that asynchrony of refractory period in atrial muscle was prominent in bradyarrhythmia, so that reentry was easily generated with resultant atrial tachyarrhythmias. Neither S-A block nor atrial fibrillation was caused by occlusion of the S-A nodal artery alone. In animals with occluded artery, however, S-A block associated with atrial fibrillation could be constantly produced by norepine- phrine, Ca, or right atrial dilatation during vagal stimulation.10),14) Asyn- chronous refractory period and altered conduction in S-A nodal and adjacent atrial tissues, induced by damage and vagotomy, would facilitate reentrant excitation resulting in tachyarrhythmias. Syncopal episodes due to sino-atrial block have long been stated to be rare. The block is usually transient and accompanied by A-V junctional or ventricular escape beats, seldom leading to prolonged cardiac standstill. How- ever, a number of recent description of sick sinus syndrome and the bradycardia- tachycardia syndrome emphasized their frequent association with syncope. In addition, it appears that syncopes develop more frequently in patients with alternating bradycardia and tachycardia than in those with severe sino-atrial block alone. Rasmussen15) reported 21 cases of chronic S-A block, 15 of whom had Adams-Stokes attacks. Fourteen patients also had paroxysmal atrial tachyarrhythmia. In the series of Rubenstein et al,1) syncope was experienced in 18 of 33 patients with BTS, while 5 of 15 without tachycardia exhibited it. We experienced 7 patients with BTS, all of whom had syncopal attacks as mentioned above. The mechanism of the syncopal Vol.14 No.5 BRADYCARDIA-TACHYCARDIASYNDROME 429 attacks has been established in 4 patients by ECG recording as episodes of cardiac arrest occurring at the termination of the tachycardia. Only 1 patient exhibited asystole which appeared frequently during the basic rhythm. These results suggest that the overdrive suppression of diseased S-A node and lower automatic pacemakers by tachyarrhythmias may be the major cause for cardiac arrest with syncope. Recently Mandel et al16)and Narula et al17) evaluated sinus node function in patients by determining the duration of the pause after cessation of atrial pacing with high frequency. Patients with sick sinus node were shown to have a longer pause following cessation of overdrive pacing than normal control patients. Moreover, some authors have pointed out that not infrequently more than S-A node is diseased in patients with SSS. Rosen et al18) showed evidence of generalized dysfunction of the conduction system with His bundle recordings and with atrial pacing. Thus, impaired impulse formation by lower automatic centers may be frequently associated with default of escape beats, in particular, at the termination of tachycardia. On the other hand, delayed conduction through the atrial and specialized tissues may facilitate the development of reentrant mechanisms in the atrium, resulting in atrial tachycardia. As described by many contributions, the bradycardia-tachycardia syn- drome pose a therapeutic dilemma. Treatment with cardiac depressant drugs may abolish the tachyarrhythmias but can accentuate bradycardia and in- crease syncope. Cardiac stimulant drugs, on the other hand, may improve the slow heart rate but will precipitate atrial tachyarrhythmias. Most authors now emphasize that patients with SSS, including BTS, are best treated with pacemaker implantation.2),4),5),9),19)-25)Since its use was first described by Muller et al5) in 1966, an increasing number of reports have indicated its value in the treatment of this entity of patients. In addition, when pacing has failed to prevent attacks of tachyarrhythmias, combined treatment with pacing and drugs has been recommended. Pacemaker implantation will permit to use ordinary therapeutic dose of antiarrhythmic drugs or digitalis without dangers of severe bradycardia. However, it must be recognized that not all patients have need of pacemaker implantation. It should be made with deliberation on the symptoms and prognosis of individual patient . Frequent and prolonged syncopal episodes undoubtedly require immediate use of pace- maker, and bradycardia leading to refractory heart failure and angina pectoris as well. But solitary attack of syncope does not seem merit it . In spite of reiterated difficulties of medical treatment , 6 of 7 patients described herein were successfully treated with drugs including adrenal cor- ticosteroid. Not only episodes of S-A block or sinus arrest but also those of tachyarrhythmia were abolished in 4 patients who received adrenal cortico - Jap. Heart J. S 430 FUJII, TAKAHASHI, AND KATO eptember, 1973 steroid in combination with orciprenaline or belladonna alkaloid. Other 2 patients were improved with adrenal corticosteroid alone or orciprenaline with belladonna alkaloid, respectively. In most of them, a sinus rhythm has been maintained without recurrence of atrial tachycardia nor syncope for up to 7 years. All but one patients have not experienced adverse side effects with the doses of adrenal corticosteroid used at this study. Moreover, when given in combination with adrenal corticosteroid, neither of orciprenaline and bel- ladonna alkaloid seemed to precipitate the atrial tachycardia. Although adrenal corticosteroid appeared of greatest benefit among the drugs used, attempts have been rarely made to treat S-A block or sinus arrest with it up to this day. Patients with complete A-V block, especially those following acute , have been occasionally treated with some success by it. But since the efficacy of artificial pacing was firmly established, little attention has been paid to its use in complete block, too. In addition to having antiinflammatory and sympathomimetic action, adrenal corticosteroid has been presumed to augment the growth of collateral vessels and to alter the potassium content in the specialized tissues. Whatever may be the major factor responsible for its effect, our results show that adrenal corticosteroid will possibly deserve to be tried in this category of patients. On the other hand, digitalis and quinidine were not useful also in our patients. They were sometimes associated with more frequent syncopal attacks. From these considerations, we are now impressed that treatment can be initiated with a variety of drugs in most patients of this syndrome. When this approach is not successful, a therapeutic trial of temporary pacing, fol- lowed by pacemaker implantation, is warranted. The combination of drugs and a pacemaker should also be considered. It is obvious, however, pace- maker implantation should be made without delay in patients with frequent syncopal attacks or severe congestive heart failure.

REFERENCES 1. ShortDS: BritHeart J 16: 208,1954 2. FerrerMI: JAMA206: 645,1968 3. TabaznikB et al: Circulation40 (SupplIII): 200,1969 4. EasleyRM et al: AmJ Med50: 166,1970 5. MullerOF: AmJ Cardiol17: 433,1966 6. BirchfieldRI et al: Circulation16: 20, 1957 7. RubensteinJJ et al: Circulation46: 5, 1972 8. SilvermanLF et al: J ThoracCardiovasc Surg 55: 264,1968 9. ZipesDP et al: Ann Int Med70: 885,1969 10. JamesTN : Circulation24: 761,1961 11. LevineSA: ArchInt Med17: 153,1916 12. LoomisTA et al: CirculatRes 3: 390,1955 Vol.14 No.5 BRADYCARDIA-TACHYCARDIA SYNDROME 431

13. Han J et al: Am Heart J 71: 481, 1966

14. James TN et al: Am Heart J 63: 196, 1962

15. Rasmussen K: Am Heart J 81: 38, 1971 16. Mandel W et al: Circulation 44: 59, 1971

17. Narula OS et al: Circulation 45: 140, 1972

18. Rosen KM et al: Circulation 43: 836, 1971

19. Cohen HE et al: Am J Cardiol 20: 735, 1967 20. Cheng TO: Am J Cardiol 22: 874, 1968

21. Adelman AG et al: Canad Med Ass J 100: 75, 1969

22. Hornbaker JH et al: Circulation 39: 189, 1969

23. SandƒÓe E et al: Acta Med Scand 186: 111, 1969. 24. Rokseth R et al: Brit Heart J 32: 93, 1970

25. Beller BM et al: JAMA 215: 589, 1971