Reentrant Atrioventricular Nodal Tachycardia Induced by Levothyroxine
Bernadette Biondi,
Serafino Fazio,
Fernando Coltorti,
Emiliano Antonio Palmieri,
Carlo Carella,
Gaetano Lombardi and
Luigi Saccà
Departments of Internal Medicine (S.F., F.C., E.A., L.S.) and
Endocrinology of University "Federico II" (B.B., G.L.); and
Department of Endocrinology of the 2nd University (C.C.) Naples,
Italy
Address all correspondence and requests for reprints to: Luigi Saccà, Medicina Interna, via Pansini, 5, 80131 Naples, Italy.
 |
Introduction
|
---|
SINUS tachycardia, atrial premature beats
and, in some cases, atrial fibrillation are frequent complications of
overt hyperthyroidism (1, 2, 3). Only recently these alterations of
cardiac rhythm also have been reported in patients with subclinical
hyperthyroidism. This condition may be the consequence of levothyroxine
(L-T4) treatment (exogenous hyperthyroidism) or may be of
endogenous origin, usually because of autonomously functioning thyroid
adenoma or multinodular goiter. Subclinical hyperthyroidism
induced by exogenous administration of L-T4 has been shown
to increase the average 24-h heart rate and the number of atrial
premature beats. Palpitations occur in some patients, and they may be
alleviated by the administration of a ß-adrenergic blocking drug (4, 5). Sawin et al. (6), in a large group of 2007 people 60 yr
of age or older, documented a 3-fold higher risk of atrial fibrillation
in the presence of low serum TSH concentrations caused by endogenous or
exogenous subclinical thyrotoxicosis (6).
Our report shows the possibility that thyroid hormones may also
induce other kinds of supraventricular arrhythmias not yet described in
hyperthyroid patients, such as reentrant atrioventricular (A-V) nodal
tachycardia.
 |
Clinical presentation
|
---|
We observed five women during the last 2 yr complaining of
increasingly frequent and prolonged episodes of palpitations during
substitutive L-T4 therapy (1.21.5 µg/kg per day) for
multinodular nontoxic goiter. Before the initiation of L-T4
therapy, the patients had a normal thyroid function as assessed by
serum free T4 (FT4), free T3
(FT3), and TSH levels in the normal range, and by a normal
TSH response to TRH. The age of the patients ranged from 3452 yr.
They had no evidence of cardiac disease except for the anamnestic
remark of previous episodes of palpitations in two patients, even
before L-T4 therapy. Assessment of cardiac rhythm and
thyroid function was performed to evaluate a possible relationship
between the presence of palpitations and L-T4 therapy.
The evaluation was performed by standard and 24-h ambulatory
electrocardiogram (ECG) monitoring (Holter ECG),
transoesophageal electrophysiological study, and thyroid hormone and
TSH assays during L-T4 therapy and 2 months after
L-T4 withdrawal. The patients took no medication other than
L-T4 during their evaluation.
Serum levels of FT4 and FT3 were in the normal
range, although they were higher during L-T4 therapy than
after L-T4 withdrawal, whereas TSH was lower during
L-T4 therapy than after withdrawal (Table 1
).
Four patients had abnormal conduction pathway as
demonstrated by a shortened P-R interval at the standard 12 lead ECG,
both during L-T4 therapy and after L-T4
withdrawal.
Holter ECG showed a clear increase of mean 24-h heart rate (82 ±
5 vs. 72 ± 6 beats/min) and atrial premature beats
(1435 ± 512 vs. 453 ± 145 beats/24 h) and
evidenced a greater number of episodes of reentrant A-V nodal
tachycardia (47 ± 33 vs. 9 ± 9 min/24 h) during
L-T4 therapy. These episodes were observed in all five
patients during therapy and persisted in only two patients after
discontinuation of therapy. In addition, they were started by atrial
premature beats.
Transoesophageal electrophysiological study was performed in only three
patients who gave their informed consent. A reentrant A-V nodal
tachycardia (diagnosed on the basis of a ventriculo-atrial interval
less than 70 ms) (Fig. 1
) was inducible
in all the three patients evaluated, both during L-T4
therapy and after L-T4 withdrawal, although it was less
easily induced in the latter case. Furthermore, the effective
refractory A-V nodal period was significantly shortened during
L-T4 therapy (230 ± 10 vs. 257 ± 6;
P = 0.015), as was the Wenckebach point (307 ± 6
vs. 333 ± 8; P = 0.004) (Table 2
).

View larger version (45K):
[in this window]
[in a new window]
|
Figure 1. Reentrant A-V nodal tachycardia triggered by
three consecutive electrical extrastimuli during transoesophageal
electrophysiological study.
|
|
 |
Discussion
|
---|
It is well known that thyroid hormones have electrophysiological
actions that are important in triggering supraventricular arrhythmias.
Indeed, thyroid hormones have direct positive chronotropic effect
because of a reduced time of repolarization phase of the action
potential, which results in shortening of the effective refractory
period (7, 8, 9, 10, 11). Recent data on sodium and potassium ion channel
currents have demonstrated that thyroid hormones up-regulate Kv 1.5
messenger RNA levels in the rat heart (12). Kv 1.5 is an ion channel
for IKur current that was also observed in the human atrial
cells (13). The molecular cloning of an individual cardiac ion channel
has provided important new information on the molecular basis of
cardiac excitability. The preferential atrial arrhythmogenic effect of
thyroid hormones could also be caused by the increased atrial
ß-adrenergic receptor density (14) in the presence of reduced
parasympathetic tone (15, 16). Thus, it is conceivable that
ß-adrenergic blockade might reduce the arrhythmogenic effect of
thyroid hormone in patients predisposed to supraventricular
tachycardia, when L-T4 treatment is considered
indispensable.
This report also shows that reentrant A-V nodal tachycardia may be
triggered by thyroid hormone in predisposed subjects. The reentrant A-V
nodal tachycardia is a relatively common cause of regular, narrow QRS
complex tachycardia, and it is more prevalent in women (7:3) than in
men (17, 18). Epidemiologically, it must be emphasized that both
thyroid disease and reentrant A-V nodal tachycardia are highly
prevalent in females. The symptoms of this arrhythmia are generally
mild and are described by patients as rapid heart beat, palpitation,
and dizziness, whereas older subjects may complain of presyncope.
In patients with reentrant A-V nodal tachycardia, at least two
functionally distinct A-V nodal conduction patterns are demonstrable
(19, 20). One pathway, referred to as the fast pathway, is
characterized by rapid conduction velocity and relatively long
refractoriness. The second or slow pathway typically shows slow
conduction velocity and short refractoriness. During sinus rhythm, the
electric impulse is expected to reach the His bundle and the ventricle
preferentially over the faster-conducting pathway with the frequent
evidence of a short P-R interval at the ECG. A-V nodal reentry of the
common type (slow-fast) is typically initiated by an atrial premature
beat that conducts down only through the slow pathway because of
functional block of the fast pathway, and reenters back through the
fast pathway because of recovery of its excitability (Fig. 2
).

View larger version (15K):
[in this window]
[in a new window]
|
Figure 2. Schematic description of induction of A-V
nodal reentry following an atrial premature beat in a subject with two
distinct functional pathways.
|
|
Conceivably, thyroid hormones might increase the occurrence of
reentrant A-V nodal tachycardia in predisposed subjects because of the
enhancement of atrial excitability, with consequent increase of the
number of atrial premature beats and the shortening of the refractory
period of the conducting tissues. Thus, reentrant A-V nodal tachycardia
might be triggered in patients in whom L-T4 is exogenously
administered to lower TSH. On this basis, a standard ECG may be
considered before starting L-T4 therapy to identify the
subjects with a short P-R interval who might be predisposed to this
kind of arrhythmia, and consequently, L-T4 therapy should
be given with caution to these patients.
Received February 11, 1998.
Revised March 26, 1998.
Accepted April 21, 1998.
 |
References
|
---|
-
Olshausen KV, Bischoff S, Kahaly G, et al. 1998 Cardiac arrhythmias and heart rate in hyperthyroidism. Am J
Cardiol. 63:930933.
-
Presti CF, Hart RG. 1989 Thyrotoxicosis, atrial
fibrillation and embolism, revisited. Am Heart J. 117:976977.[Medline]
-
Forfar JC, Miller HC, Toft AD. 1979 Occult
thyrotoxicosis: a correctable cause of "idiopathic" atrial
fibrillation. 44:912.
-
Biondi B, Fazio S, Carella C, et al. 1993 Cardiac
effects of long-term thyrotropin-suppressive therapy with
levothyroxine. J Clin Endocrinol Metab. 77:334338.[Abstract]
-
Biondi B, Fazio S, Carella C, et al. 1994 Control
of adrenergic overactivity by beta-blockade improves quality of life in
patients on long-term suppressive therapy with levothyroxine. J
Clin Endocrinol Metab. 78:10281033.[Abstract]
-
Sawin CT, Geller A, Walf PA, et al. 1994 Low serum
thyrotropin concentration as a risk factor for atrial fibrillation in
older persons. N Engl J Med. 331:12491252.[Abstract/Free Full Text]
-
Klein I, Hong C. 1986 Effects of thyroid hormone
on cardiac size and myosin content of the heterotopically transplanted
rat heart. J Clin Invest. 77:16941698.[Medline]
-
Valente M, De Santo C, de Martino Rosaroll P, Di Maio
V, Di Meo S, De Leo T. 1988 The direct effect of thyroid hormone
on cardiac chronotropism. Arch Int Physiol Biochim. 97:431440.
-
Freedberg AS, Papp JG, Vougham Williams EM. 1970 The effect of altered thyroid state on atrial intracellular potential. J Physiol. 207:357369.[Medline]
-
Johnson PN, Freedberg AS, Marshall SM. 1973 Action
of thyroid hormone on the transmembrane potential from sinoatrial node
cells and atrial muscle cells in isolated atria of rabbits. Cardiology. 58:273289.[Medline]
-
Arnsdorf MF, Childers RW. 1970 Atrial
electrophysiology in experimental hyperthyroidism in rabbits. Circ Res. 26:575581.[Medline]
-
Nishiyama A, Kambe F, Kamiya K, Yamaguchi S, Murata Y,
Seo H, et al. 1997 Effects of thyroid and glucocorticoid hormones
on Kv 1.5 potassium channel gene expression in the rat left ventricle. Biochem Biophys Res Commun. 237:521526.[CrossRef][Medline]
-
Wang Z, Fermini B, Nattel S. 1993 Sustained
depolarization-induced outward current in human atrial myocytes.
Evidence for a novel delayed rectifier K+ current similar
to Kv 1.5 cloned channel currents. Circ Res. 73:10611076.[Abstract]
-
Golf S, Lovstad R, Hansson V. 1985 ß-Adrenoreceptor density and relative number of ß-adrenoreceptor
subtypes in biopsies from human right atrial, left ventricular and
right ventricular myocardium. Cardiovasc Res. 19:636641.[Medline]
-
Klein I, Levey GS. 1996 The cardiovascular system
in thyeotoxicosis. In: Brawerman LE, Utiger RD, eds. Werner and
Ingbars the thyroid, 7th ed. Philadelphia: Lippincott Raven;
607615.
-
Cacciatori V, Bellavere F, Pezzarossa A, et al. 1996 Power spectral analysis of heart rate in hyperthyroidism. J
Clin Endocrinol Metab. 81:28282835.[Abstract]
-
Ganz LI, Friedman PL. 1995 Supraventricular
tachycardia. N Engl J Med. 332:162172.[Free Full Text]
-
Akhtar M, Jazayeri MR, Sra J, Blanck Z, Deshpande S,
Dhala A. 1993 Atrioventricular nodal re-entry. Clinical,
electrophysiological, and therapeutic considerations. Circulation. 88:282295.[Abstract]
-
Denes P, Wu P, Dhingra RC, Chuquimia R, Rosen KM. 1973 Demonstration of a dual A-V nodal pathway in patients with
paroxysmal supraventricular tachycardia. Circulation. 48:549555.[Medline]
-
Rosen KM, Metha A, Miller RA. 1974 Demonstration of
dual atrioventricular nodal pathway in man. Am J Cardiol. 33:291294.[Medline]