Atrial Flutter Secondary to Digitalis Toxicity: Report of Three Cases

and Review of the Literature

ABNER J. DELMAN and EMANUEL STEIN
Circulation 1964;29;593-597
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 Atrial Flutter Secoiidary to Digitalis Toxicity
Report of Three Cases anid Review of the Literature
By ABNER J. DELMAN, MD. , AND EmANUEL SmihSN, M.D.
TIlE RARITY of atrial fIlutter du-e to digi- larged to the left. There erxrce o signs of coniges-
talis toxicity has been emphasized fre- tive heart failture. AIn electirocarridiogramn revealed
quiently.1-4 The present paper describes three atrial fibrillatioini witlh a rapidxventricular r-ate
cases of atrial flutter as a manitestation of (fig. 2a) \Withlin 40. liours hle eciv ed laniatoside
digitalis intoxication. The clinical characteris- C, 1.2 mg. initravelnouisly, (ligitoxin-i, 1.4 mig. orally,
and digoxini, 1.5 mg. orallv. At this time lhe dex 1
ties of this entity are reviexved. aped natusea anid vomitiing, an(ld an elcetrocatrdlio-
Case Reports gram rexvealed atrial flutter xvith vary ing bflack
(fig. 2b). Digitalis was stopped, anld in 4 days,
Case 1 rhythm reverted to atrial fibrillation xxith a veii-
A 50-year-old marn xvas admitted to Montefiore triclzular rate of 60 pe. minlute (fig. 2c). l-ie was
Hospital on juily 10, 1961, witlh a supraventricular
tachycardia. Thelre was a $35'-yeatr history of re-
current attacks, freqtuentl (loclmenited by electro-
cardiograms. He xxats n nio druCg thlerapxy. The
apical puilse rate wxas 200 per minullte and regular. J~~~~~~~~~~~~~~~
and the blood pressure xxas 155/110. Phvsical ex-
amination was otlherwise niormaml. Ani eXlectroLcardio-
gram slhoved a supraveIntricutlar tacvliveyiicliat with Li~~~~~
a rate of 200 per min-ute (fig. la). During the
next 16 hours, tlhe patient received 3.0( mg. of
lanlactoside C in-itraveniously anid initraimuiscutlaily1n
At this time, lhe became nauiseated; an electro-
cardiogram shoxved atrial tachyclardia xxwith varx- ~

inig block (fig. lb). Another 0.6 mg. of lanatosidle

CA was givexii in the next 6 houirs; tlheni an electro-
e
c.adiogram ieealed atrial fluitter xvith v arying
block (fig. lc). Digitalis was dlisconltinIuleld, aiid ** SIWJM iPt +_
there was spontaneous reveirsioni to regular sinuiis NA'BXw~d0fdUS.-M>1
o-
$ *...
L-
X . ~;.
--:.; .
n..._Z
'5. z'
R
.
:
' .........(..
_....
'9

rhytlm in :30 hours (fig. ld). No fturthelr dligitalis

was given]. He xvas discharged in regular siiniis
rhythm oni quiniidine, 0.2 Gm. ftii. times (laily.
Cornment. Massixve digitalls overdosage in this
patienit restulted in uince(luivocal digitalis toxicity7
manifested by lnausea auld atrial flutter xvitlh vari
ing block, and higlh degree of aitrioventriculai
llOck (4: 1).
Case 2
A 69-year ldanld with a histor.y of txwoa mva-
cardial infaretionis ani-d chlronic, slaxx atrial fibrilla-
tioI wvas admitted to Montefiore Hospital on Figure 1
December 27, 1954, with a 6-hotur history at
palpitations. He was on nio medication. Admission a, Lead II, ti/li 0 wdrtachyicoardia, Jioly 10,
blood pressusre was 120/60. The heairt xvas irreg- -196-1, S:30 p^. ., Lead.11, paroxysmal atrial tach_-
ulur at 150 per minutite andxwas modeiately eni- cardia wvith var~yinig block, Joiltl 11, 196R1, 12:3f~0.
c, Lead 11, atrial flaitter wcitl oai g block, veoitricni-
lar rote 70 per minniztte, 4. 1 oitrioveoitricnilor block,
From thce Calrdiovalscular Service, Division of Medi- Juily .11, 1961, 6:30 p.nm. d1, Lead 11, reversion to
cine, Monteflore Hospital, Nexx York, Nes\ Y oik. reC.dor "donsrhythm, july 13, 1961, 12:30 a,m.
C;ruIlatinon Volyin i XXIXv. Apri. 1964 593

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.59t4 9DELN1AN, STEIN
Conmnent. ret'erthan-ax erage ruaniiiteianiice(-l
(ligitailis (h)saige plts prolbable in crieaisedl (ligitailis
sensitivity (1110 to hvdrochilorkotlhialzidle (witli pos-
C0. si1le
1 lypok.leir;ia) resiulted in dligitalis toxicitv
manifestc(l lv atrial flittel xvxithi Varyillg b)ht)ck,
slow venitiitilar rate (80 per minuite) and. 4:1
atriovenitr,icular1)lock.
Diseussion
The fir-st ease of atrial fltitter (tic to (ligi-
b. talis toxicity xvas reported by \\Vedd(1 ini 1924.
3 2.1 more cases were reported.'; 1 l
By 1959,
1959, Coffmani anid \\ hipple' listed the fol-
lowinig criteria for atrial flutter d(11e to (ligitalis
inltoxicati.onl: developm)ent of the arrhiythlmia

C.
d. 4w
Figure 2
a, Lead Vp, raipid/ atrial fibrillation wit/h aberrant toi-
trictelar conrduction, December 27, 1954, 5:0() pin. 1),
Lead V,, at rial fittter with varyling b)lock, ventricular
rate 70 per mintide, 4:1 atrioentrictilar block, De-
cemn/)er 29, 1954, 9:00 ami. c, Lead V, s/olw atrial
fibrillation, JanitaryJ 1, 1955, 9:00 ant.Yb
b.
giveni (ligoxili, 0.25 mg. orally twice claily 3 days
later and xvas lischarged.
Coamn rtt. Significant digitalis oxverdlosage in
this paitienit caused clearcut digitalis toxicity mani-
fested by nausea, vomitinig, and atrial fluitter xxith
Varlying bllock, wx iti a sloxx x entricular rate (80
per miniuite) and 4:1 atrioventriicuilar l)ock.
Case 3
C.4
A 63- veu -old manxwith a historx of airter io-
sclerotic heart (lisease with regular sinius rhythmn
(fig. :3a) aid moderate conigestive hear.t failrtiie
hatl been. on maintenance digoxiin, 0.75 mg. per
dly, anid livhdrochlorothiazide, 50 mg. (after initial
dligitalization with (ligoxin, 3.0 mg. orally, in 2
dlays) per (lay, for- 2 monithis. Oni examination
janaiiiriyv 13, 1962, his 10lood pressuire xvas 140/90
aild hlis ptulse irregular. Examination xvas other-
wxise unremarkable, with no sign-s of conigestive
heairt falihre. Ain electrocardiog.ram revealed atrial Figure 3
fluitter with varying hlock (fig. 3b). Digoxini and'
hvydr(ioelor-othia.izide xvere discoitinulled, aned the a, Lecad( I II, mm pu/tiar~sitms /tt/ntJatitary 7, 1962. b),
rhythnm reverted sponitanieously to atrial fibrillation Lca^. III, atrial jb(ttti uit/t tvarin/, block, uttici/at
(fig. 3c), theni to regular sin-ius rhythm (fig. 3d). f o( pcr itmitt , 4:1 atr^iocettti'ictlar block, Jamtt-
r(ale
He xxwas subsequentl restartedl oni digoxin, 0.2.5 ary 13, 1.9)62 c, Leadc III, atrtial fibr9illation,) Jamuiaryl
mg. pe- dayx, and remaitedl in reguilar siniiis /5, /1962. 31, Lexad III, regular mits iiil/tt/tti, Jrntiili1'ta
11\tIll hn . 16, /962l
(Biu/an,ilon. VI umeu \XI\X Alpn1 1964

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ATRIAL FLUTTER FROM DIGITALIS TOXICITY 595

during digitalis therapy; absence of other which information was available suggests cer-
drugs that cause arrhythmias; and clearing of tain clinical clues useful in establishing the
arrhythmia after omission of digitalis. diagnosis (table 1).
Using these criteria, they reviewed the Seven patients were over 60 years of age.
previously reported 22 cases, accepted 15 Eight patients were in severe congestive heart
cases and added a sixteenth case. Since then, failure. Twelve patients had severe heart dis-
two additional cases meeting these criteria ease. Five patients had a significant preceding
have been reported.16' 17 diuresis. Two patients had azotemia. Ad-
The rarity of atrial flutter and its mecha- vanced age,4 7 severe congestive heart fail-
nism of development in digitalis intoxication ure,2,7 severe heart disease,18 preceding diure-
is unexplained. The indirect or vagal effect sis,4 8, 18 and azotemia 4, 18 are all factors that
of digitalis on the innervated atrial muscle is may increase digitalis sensitivity. The 12 pa-
a decrease in the refractory period, with an tients with severe heart disease had two or
increase in muscle excitability. It has been more of these associated factors.
postulated that the vagal effect of digitalis The type of digitalis preparation or the
may predispose to ectopic atrial foci and lead route of administration was not significant,
to atrial flutter during toxieity.3' 8, 14, 15, 17 since toxicity occurred with oral, intramuscu-
Digitalis is usually used in the therapy of lar, and intravenous administration, and with
atrial flutter. Failure to recognize its causative digoxin, digitoxin, whole digitalis leaf, tinc-
role in atrial flutter may result in disaster ture of digitalis, and lanatoside C. However,
when even more digitalis is given at a time 14 patients received significantly greater than
when discontinuance is indicated.' Analysis the accepted dosage range of these specific
of the 16 cases (including our three cases) in preparations.2' 19 One of the two patients on
Table 1
Clinical Data in Sixteen Patients
Age
Range 30-39 40-49 50-59 60-69 70-79
Number 3 2 4 4 3
Sex: Male-11 Female-5
Type of heart disease
Normal 3
Arteriosclerotic 6
Rheumatic 4
Syphilitic 1
Patent ductus arteriosus 1
Constrictive pericarditis 1
Congestive heart failure
None 5
Mild to moderate 3
Severe 8
Significant digitalis overdose 14
Previous rhythm
Regular sinus rhythm 11
Atrial fibrillation 5
Ventricular rate ( 14 cases recorded)
40-100/minute l1
120/minute 1
150/minute 2
Ratio of atrioventricular block
Ratio 2:1 3:1 4:1 8: 1 Varying
Number 3 4 6 3 10

Circulation, Voluime XXIX, April 106 4

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596
doses of digitalis within the accepted dosage
range had severe heart disease. Of the three
patients with no heart disease, two received
massive overdosage of digitalis, and the third,
significant overdosage.
Thirteen patients had symptoms usually as-
sociated with digitalis toxicity, i.e., nausea,
vomiting, diarrhea, confusion, and scotomata.
The recorded ventricular rate in 14 patients
ranged from 40 to 150 per minute, and was
100 or less per minute in 11. The degree of
atrioventricular block ranged from 2:1 to 8:1
in the 16 patients, and was 3:1 or greater in
13. Two patients had a ventricular rate of 150
per minute, and both had frequent premature
beats of the ventricle.
In spontaneous, untreated atrial flutter, the
degree of atrioventricular block is usually
2:1, with a ventricular rate of 130 to 160 per
minute, and frequent premature beats of the
ventricle are unusual. Ten patients had atrial
flutter with varying block. Paroxysmal atrial
tachycardia with varying block secondary to
digitalis toxicity is well known.'4 Whether
atrial flutter with varying block or atrial tachy-
cardia with varying block will occur in digi-
talis toxicity may depend on the rate of dis-
charge of an ectopic atrial focus, as first
postulated by Prinzmetal et al.20 Our first pa-
tient progressed to atrial tachycardia with
varying block and then to atrial flutter with
varying block during massive digitalis therapy.
It has been recently suggested that atrial flut-
ter with varying block in a patient on digitalis
is a contraindication to further digitalis. If
the drug is continued, severe atrioventricular
block or complete heart block with Stokes-
Adams attacks may develop.21 The appear-
ance of atrial flutter with varying block in a
patient on digitalis may be as useful a sign of
digitalis intoxication as the development of
atrial tachycardia with varying block.
Therapy in atrial flutter due to digitalis
toxicity consists of discontinuation of the drug.
The arrhythmia will clear when the toxicity
subsides. If a rapid ventricular rate is present,
a trial of oral or intravenous potassium may
be attempted, particularly if potassium defi-
ciency is suspected. Prompt dissolution of the
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DELMAN, STEIN
flutter points strongly towvard digitalis intoxi-
cation as the cause.14
Summary and Conclusions
Three cases of atrial flutter due to digitalis
toxicity are presented and the world literature
is reviewed. Sixteen cases are analyzed for
clinical and electrocardiographic features.
Significant digitalis overdosage, severe heart
disease with associated factors sensitizing to
digitalis, and symptoms of digitalis toxicity are
characteristic. Two of the three patients with
no heart disease had massive overdosage.
Thus, toxicity can be strongly suspected in
this arrhythmia on clinical grounds. In addi-
tion, every patient had one or more of the
following: a slow ventricular rate (less than
90 per minute), a high degree of atrioven-
tricular block (3:1 or more), varying atrio-
ventricular block, or frequent premature ven-
tricular beats with a rapid ventricular rate.
The presence of any combination of these
electrocardiographic features in a patient sus-
pected of digitalis toxicity by clinical criteria
is highly suggestive of intoxication. The diag-
nosis can be made only in patients who de-
velop the arrhythmia while receiving digitalis,
and who are receiving no other drugs that can
cause the arrhythmia. Diagnosis is confirmed
by clearing of the arrhythmia on cessation of
digitalis, with or without potassium therapy.
Atrial flutter with varying block occurred in
10 patients. It may be as useful a sign of
digitalis toxicity as atrial tachycardia with
varying block.
Acknowledgment
We would like to thank Drs. Ira Rubin, Sidney
Arbeit, and Sidney P. Schwartz for assistance ini 'the
preparation of this report.
References
1. SOMLYO, A. P.: The toxicology of digitalis. Am.
J. Cardiol. 5: 523, 1960.
2. FRIEDBERG, C. K.: Diseases of the Heart. Ed. 2.
Philadelphia, WV. B. Saunders Company, 1956.
3. BELLET, S.: Clinical Disorders of the Heart Beat.
Philadelphia, Lea and Febiger Company, 1953.
4. FRIEDBERG, C. K., AND DONOSo, E.: Arrhythmias
and conduction disturbances due to digitalis.
Progr. Cardiovas. Dis. 2: 408, 1960.
Circulation, Volume XXIX. April 1964
ATRIAL FLUTTER FROM DIGITALIS TOXICITY 597

5. WEDD, A. M.: Clinical auricular flutter. Ann.
Clin. Med. 3: 69, 1924.
6. CROUCH, R. B., HERRMANN, G. R., AND HEJT-
MANCIK, M. R.: Digitalis intoxication. Texas
M. J. 52: 714, 1956.
7. SHRAGER, M. W.: Digitalis intoxication; a review
of 40 cases. Arch. Int. Med. 100: 881, 1957.
8. MCMILLAN, T. MI., AND BELLET, S.: Auricular
flutter; clinical manifestations and treatment.
Am. J. M. Sc. 184: 33, 1932.
9. IMELIO, L., AND TALTWELL, R. J.: Calcificacion
pericardica y flutter auricular digitalico. Rev.
med. Rosario 30: 1195, 1940.
10. ZUBILLAGE, R.: Flutter auricular precipitado por
una ampolleta de oubaina en un paciente
previamente digitalizado. Bol. Hosp. Caracas
41: 145, 1942.
11. COLE, S. L.: Digitalis intoxication-chronic effects
manifested by diarrhea and atrial flutter. Am.
Heart J. 39: 900, 1950.
12. BICKEL, G., PLATTNER, H., AND EDELSTEIN, H.:
Intoxication digitalique massive terminee par
la guerison. Arch. mal. coeur 44: 61, 1951.
13. HEJTMANCIK, M. R., HERRMANN, G. R., AND
BRADFIELD, J. R.: Flutter auriculaire. Arch.
mal. coeur 44: 16, 1951.
14. LOWN, B., AND LEVINE, H. D.: Atrial Arrhythmi-
as, Digitalis and Potassium. New York, Lands-
berger Company, 1958.
15. COFFMAN, J. D., AND WHIPPLE, G. H.: Atrial
flutter as a manifestation of digitalis toxicity.
Circulation 19: 188, 1959.
16. ARAVANUS, C., AND MICHAELMES, G.: Atrial flut-
ter and right bundle-branch block following
digitalis therapy. Am. J. Cardiol. 4: 124, 1959.
17. BREST, A. N., DURGE, N. G., AND GOLDBERG, H.:
Conversion of atrial fibrillation to atrial flutter
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Cardiol. 6: 682, 1960.
18. CRAIG, L. G., LOWN, B., AND LEVINE, S. A.:
Resistance and sensitivity to digitalis. J.A.M.A.
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logical Basis of Therapeutics. Ed. 2. New York,
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OBLATH, R. W., AND DREUGER, H. E.: The
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1961.

William Withering
At first Withering used a decoction of the foxglove leaves which he soon dis-
carded in favor of an infusion. Gradually he gave this up and came to depend al-
most entirely on the powdered leaves. He recommended gathering the leaves just
before blossoming time, removing the midrib, and using only the powdered leaf
blade. This was dried either in the sun or before a fire and then rubbed down
to a "beautiful green powder" which weighed about one-fifth of the original
weight of the undried leaf. The dose for an adult was one grain twice a day. He
gave this powdered leaf either alone, or made with a pill with soap or gum am-
moniac as an excipient, with sometimes aromatics added. He did not believe
in giving digitalis oftener than twice a day. Time should be allowed for each
dose to act. He continued the drug until it acted upon the "kidneys, the stomach,
the pulse, or the bowels; let it be stopped upon the appearance of any one of
these effects."
Withering not only used digitalis extensively himself, keeping careful case
reports and notes, but he spread the gospel of its use among his medical friends
with the result that it soon became known and quite generally used.-Louis H.
RoDDIs, M.D. William Withering: The Introduction of Digitalis Into Medical
Practice. New York, Paul B. Hoeber, Inc., 1936, p. 57.

Circulation, Volutme XXIX, April 1964

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