British Heart_Journal, I970, 32, 453-457.

Use of propranolol in atrial flutter

Douglas A. L. Watt, W. R. Livingstone, R. K. S. MacKay, and E. N. ObinecheFrom Stobhill General Hospital, Glasgow N.I

Seven consecutive patients with atrial flutter are described, in six of whom sinus rhythm wasrestored by a combination of digoxin and propranolol. It is suggested that propranolol, used inthis way, is a valuable addition to the available measures for the control of this arrhythmia.

Atrial flutter is a notoriously difficult arrhyth-mia to control by pharmacological means. Itis a rhythm in which alterations in degree ofatrioventricular block may produce wild fluc-tuations in ventricular rate. At the same time,it may be regarded as unstable in nature, beingintermediate between sinus rhythm and atrialfibrillation, and capable of being transformed,either by therapeutic measures or spontane-ously, into one or other of these relativelystable rhythms.

It is generally accepted that atrial flutter,with these inherent potentially lethal proper-ties, is less desirable than either controlledatrial fibrillation, or the ideal, sinus rhythm,and various measures have been proposed toconvert it to one or other of these.The traditional drugs for this purpose are

digitalis and quinidine, either alone or to-gether. Classically, digitalis converts therhythm to atrial fibrillation, after which,quinidine restores sinus rhythm.Most observers, while accepting that this

course can occur, are disappointed by itsrarity. In fact three possible outcomes aremore commonly met. First, digoxin may, byitself, restore sinus rhythm. Secondly, itmay produce atrial fibrillation which does notconvert to sinus rhythm with sub-toxic dosesof quinidine. Thirdly, atrial flutter may bepersistent, and fail to respond to drug treat-ment except by ventricular slowing.

In contrast to this unpredictable and refrac-tory behaviour when challenged by drugs,atrial flutter responds gratifyingly easily todirect current (DC) countershock, so that incentres where this facility is available, it isthe treatment of choice. There are, however,still many situations in which DC counter-shock is not available. Even where it is avail-able, however, it may happen that atrial flutterhas been unrecognized and treated as atrialReceived 24 October I969.

fibrillation, or recognized and a preliminarytrial of digoxin given. In this situation, DCshock may be dangerous unless digoxin isdiscontinued for a period of days, a delaythat may be undesirable.

It is in these contexts that an alternativepharmacological approach to atrial flutterwould be desirable. The obvious drug fortrial is the fl-adrenergic blocking agent,propranolol.

Reports of its use, however, have been uni-formly disappointing. The manufacturers(Imperial Chemical Industries Ltd.) in theirI965 manual, quote complete control (i.e.restoration of sinus rhythm) in only one of sixcases. Their later manual (December I967)does not mention this arrhythmia.We have now treated seven successive

patients with atrial flutter, in six of whom acombination of digoxin and propranolol hasbeen followed by restoration and maintenanceof sinus rhythm.

Case reports

Case I A man of 54 years had sustained a myo-cardial infarction three years previously, followedby persistent angina pectoris. Hospital admissionfollowed a further antero-septal myocardial in-farction. He was moderately hypotensive and inearly congestive cardiac failure for which digoxinwas administered. On the ninth day, while receiv-ing digoxin O025 mg. twice daily, he was notedto have atrial flutter with an atrial rate of 300 perminute and 2: I AV block. Carotid sinus massageproduced no significant slowing. Propranolol, 3mg., was given intravenously without apparenteffect, but when carotid massage was repeated,sinus rhythm was restored. Oral propranolol,IO mg. 8-hourly, along with digoxin, was con-tinued until four days later, when it was with-drawn because of mild hypotension. Sinus rhythmremained unaltered over the next month, whenhe was discharged from hospital.

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454 Watt, Livingstone, MacKay, and Obineche

_4At

Use of propranolol in atrial flutter 455

20 April '6 bfore propranolol 20 April '68 after propronolol 21 April '68

FIG. 2 Electrocardiogram, Case 4.

admitted to hospital in mild congestive cardiacfailure. Six years previously he had experiencedpain in the arm, relieved by glyceryl trinitrate,and attributed to myocardial ischaemia. After ad-mission he was digitalized before a regular cardiacrhythm was identified as atrial flutter with 3:Iblock. After one week of digoxin, oral propranolol(io mg. thrice daily) was added to the regimen,and after 48 hours he was found to have returnedto sinus rhythm. Propranolol was then stopped,and sinus rhythm persisted. At review one monthlater, there had been no recurrence of atrialflutter.

Case 7 A man of 56 years was admitted to asurgical ward because of swelling of ankles andabdomen, with hepatomegaly. He was found tohave congestive cardiac failure with tachycardia,and was digitalized. The electrocardiogramshowed atrial flutter. Two days later, atrial flutterpersisted with stable 4: I block. Intravenous pro-pranolol (3 mg.) produced no change, after whichoral propranolol, 5 mg., then IO mg. eight-hourly, had no effect over the next two days. Thedose of propranolol was raised to 20 mg. eight-hourly for the next two days, by which time thecardiac rhythm was atrial fibrillation with a ven-tricular rate of 64 a minute. Both propranolol anddigoxin were withdrawn, but six hours later,nodal bradycardia supervened which did notrespond to a total of 3 mg. atropine, and whichpersisted for six hours before giving way to sinusrhythm.On the following day he developed a left-sided

hemiparesis which seemed likely to be due tocerebral embolism, and which improved spon-taneously. Two further episodes of atrial flutteroccurred during the next IO days, both subsidingspontaneously. He developed bronchopneumoniaand progressively deteriorated, dying on the 26thday after admission.

DiscussionThese cases have been presented in detailbecause all but one follow an almost identicalpattern of behaviour in the presence of pro-pranolol. In each case the immediate effect wasenhanced sensitivity to vagal stimulation andincrease in atrioventricular block. In Case i,carotid massage restored sinus rhythm at thisstage. In all the others, however, the conver-sion to sinus rhythm occurred after an intervalof I2 to 48 hours.Had this sequence of events been noted on

only one occasion, the association betweenpropranolol administration and restoration ofnormal rhythm could well be disputed. Itsoccurrence in the identical fashion on fivesuccessive occasions appears reasonable evi-dence that there is a causal relation betweentreatment and outcome.

It is well recognized that the effects ofpropranolol are a mixture of fl-adrenergicblockade and 'quinidine-like' action, much ofthe anti-arrhythmic potential being attribu-table to the latter effect. It is also clear thatthese effects are not equally related to thedosage of the drug, the anti-arrhythmic dose,for example, may be homeopathic in com-parison with the anti-anginal dose. It appearsfrom these reports that there is, in addition, adifferent time factor involved, in that theP-adrenergic blocking, or vagus-potentiating,effect appears immediately, manifesting itselfas increased atrioventricular block, whereasthe quinidine-like effect on ectopic atrialactivity, to which we attribute the restorationof sinus rhythm, takes many hours to be mani-fest. Whether this is due to delay in action,

FIG. 3 Electrocardiogram, Case 5.

30:) Auag.'bB before propronolol 31 Aug.'68 after propranolol Sept.'68

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456 Watt, Livingstone, MacKay, and Obineche

or to cumulative effect, is, of course, notapparent in this series, nor did we try theeffect of using larger doses of propranolol tosee if they might be more rapidly effective.We are wary of the use of large doses of pro-pranolol in the presence of digoxin (Watt,I968).

It is apparent that most authors have re-garded conversion of atrial flutter to sinusrhythm with propranolol as an exceptionaloccurrence. It is also clear that in almost allof the successful occurrences, propranololhas been used in combination with other anti-arrhythmic agents, usually digitalis (Table).Rowlands, Howitt, and Markman (I965)

comment that in none of their cases did pro-pranolol influence the atrial rate in atrialflutter though the ventricular rate was slowed.This, however, was a study of response to asingle dose of propranolol. Harrison, Griffin,and Fiene (I965) restored sinus rhythm inone patient of 5 years with atrial flutter. Thispatient was already digitalized. Cherchi et al.(I966) showed increased AV block, but nocorrection of the arrhythmia in a group ofpatients treated both orally and intravenously.Nielsen and J0rgensen (I966) restored sinusrhythm in one patient after a week of com-bined digitalis and propranolol. Likewise,Luria, Adelson, and Miller (I966) report onepatient with paroxysmal flutter in whom treat-ment with digitalis and propranolol restoredsinus rhythm.

Gianelly, Griffin, and Harrison (i967) con-verted atrial flutter to sinus rhythm in one outof seven patients. Wolfson and his colleagues(I967) restored sinus rhythm in one patientwith post-operative flutter by combined digi-talis and propranolol.McLean, Stoughton, and Kagey (I967) suc-

ceeded only in reducing the ventricular rate

in two patients with atrial flutter. Irons, Ginn,and Orgain (I967) had no conversions to sinusrhythm among six patients with flutter treatedwith propranolol, though three showed ven-tricular slowing.

Reynolds and VanderArk (I967) describesuccessful treatment of two patients withparoxysmal atrial flutter with a combinationof quinidine and propranolol.Sloman and Stannard (i967) record one

success with propranolol where digoxin failedto control atrial flutter.We believe that, in combination with dig-

oxin, propranolol is an effective drug in themanagement of atrial flutter, both chronic andparoxysmal.

It lacks the speed and effectiveness ofdirect current countershock which must re-main the most satisfactory procedure in atrialflutter. Where, however, this facility is notavailable, or where circumstances render itsuse undesirable, we feel that pre-treatmentwith digitalis followed by propranolol con-version may well be the treatment of choice.

We are grateful to Dr. J. B. Rennie and Dr. J. L.Markson for perm ssion to treat patients undertheir care.

ReferencesCherchi, A., Lixi, M., Mazza, B., and Camoglio, E.

(I966). Prime osservazioni cliniche sull'azione anti-aritmica di un nuovo bloccante dei recettori beta:il propranololo. Minerva Medica (Parte sci.), 57,317.

Gianelly, R., Griffin, J. R., and Harrison, D. C. (1967).Propranolol in the treatment and prevention ofcardiac arrhythmias. Annals of Internal Medicine,66, 667.

Harrison, D. C., Griffin, J. R., and Fiene, T. J. (I965).Effects of beta-adrenergic blockade with proprano-lol in patients with atrial arrhythmias. New England3'ournal of Medicine, 273, 4IO.

TABLE Effect of combined therapy with propranolol on response of atrial flutter

Propranolol alone Propranolol+ quinidine Propranolol+ digoxinNo. No. No. restored No. No. No. restored No. No. No. restored

Authors improved sinus rhythm improved sinus rhythm improved sinus rhythm

Harrison et al. (I965) I I - - 4 2 ICherchi et al. (966) 2 2Nielsen and J0rgensen (I966) 4 3 - I - ILuria et al. (I966) - I IGianelly et al. (I967) 5 5 - - 2 I IWolfson et al. (I967) I I - I IMcLean et al. (I967) 3 2Irons et al. (I967) 6 3Reynolds and VanderArk (I967) - 2 2 -Sloman and Stannard (I967) - I ICurrent series - - 7 6

Total 22 I7 0 2 0 2 I7 3 12

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Use of propranolol in atrial flutter 457

Irons, G. V., Ginn, W. N., and Orgain, E. S. (I967).Use of a beta adrenergic receptor blocking agent(propranolol) in the treatment of cardiac arrhyth-mias. American journal of Medicine, 43, I6I.

Luria, M. H., Adelson, E. I., and Miller, A. J. (I966).Acute and chronic effects of an adrenergic beta-receptor blocking agent (propranolol) in treatmentof cardiac arrhythmias. Circulation, 34, 767.

McLean, C. E., Stoughton, P. V., and Kagey, K. S.(I967). Experiences with beta-adrenergic blockade.Vascular Surgery, i, io8.

Nielsen, B. L., and J0rgensen, F. S. (I966). Pro-pranolol ('Inderal') in cardiac arrhythmias. ActaMedica Scandinavica, I8o, 63I.

Reynolds, E. W., and VanderArk, C. R. (1967). Treat-ment of quinidine-resistant arrhythmias with the

combined use of quinidine and propranolol.Circulation, 36, Suppl. 2, p. 22I.

Rowlands, D. J., Howitt, G., and Markman, P. (I965).Propranolol ('Inderal') in disturbances of cardiacrhythm. British Medical Journal, i, 89I.

Sloman, G., and Stannard, M. (I967). Beta-adrenergicblockade and cardiac arrhythmias. British MedicalJ7ournal, 4, 5o8.

Watt, D. A. L. (I968). Sensitivity to propranolol afterdigoxin intoxication. British Medical Journal, 3,413.

Wolfson, S., Herman, M. V., Sullivan, J. M., andGorlin, R. (I967). Conversion of atrial fibrillationand flutter by propranolol. British Heart J7ournal,29, 305.

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