Is amiodarone safe in heart failure?BMJ 2006; 332 doi: https://doi.org/10.1136/bmj.332.7537.317 (Published 09 February 2006) Cite this as: BMJ 2006;332:317
All rapid responses
We wish to thank Varughese and Tahrani for their interest in our
editorial. However, the notion of amiodarone interfering with the
thyroid, mainly through an action on 5’-deiodinase, is not novel.
Extensive research has been conducted in this field and, not surprisingly,
a recent international survey has shown that cardiologists and
endocrinologists work closely in the management of patients taking
amiodarone and that thyroid function is periodically assessed in this
Varughese and Tahrani correctly point out that thyroid dysfunction is
associated with increased cardiovascular morbidity and mortality. Heart
failure in hyperthyroidism may be secondary to a cardiomyopathy, but
typically is precipitated by an increased workload in patients with a
preexisting cardiac disorder, such as hypertensive or ischaemic heart
disease.(2) Alternatively, excess thyroid hormone may lead to prolonged
sinus tachycardia or atrial fibrillation with a rapid ventricular response
and the subsequent development of a tachycardiomyopathy.(2) In the
setting of hyperthyroidism, an important role is attributed to increased
tone of the sympathetic nervous system,(3) which is also involved in the
genesis of malignant arrhythmias.
The risk of arrhythmias is inherent to hypothyroidism too, where QT
interval prolongation may facilitate ventricular ectopy and the appearance
of torsade de pointes.(2) Heart failure, on the other hand, is relatively
rare in hypothyroidism,(2) but a low level of triiodothyronine in cardiac
disease has been identified with poor prognosis.(4) Significant in this
context is the fact that amiodarone inhibits the peripheral conversion of
thyroxine into triiodothyronine.
Do the comments of Varughese and Tahrani mean that, by correcting any
concurrent thyroid dysfunction, amiodarone therapy can be continued in
heart failure patients? We would not subscribe to this position. The
main point in our editorial, being directed to both specialists and
generalists, is that amiodarone should not be used in heart failure,
regardless of the mechanisms underlying a potential adverse effect on
Michele Coceani, cardiology specialty trainee (firstname.lastname@example.org)
Rita Mariotti, professor of cardiology
Division of Cardiology, Cardiac and Thoracic Department, University
of Pisa, Via Paradisa 2, 56124 Pisa, Italy
1. Bartalena L, Wiersinga WM, Tanda ML, Bogazzi F, Piantanida E, Lai
A, et al. Diagnosis and management of amiodarone-induced thyrotoxicosis in
Europe: results of an international survey among members of the European
Thyroid Association. Clin Endocrinol (Oxf) 2004; 61: 494-502.
2. Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system.
N Engl J Med 2001; 344: 501-9.
3. Kaplan MM. The thyroid and the heart: how do they interact? J
Cardiovasc Med 1982; 7: 893.
4. Iervasi G, Pingitore A, Landi P, Raciti M, Ripoli A, Scarlattini
M, et al. Low-T3 syndrome: a strong prognostic predictor of death in
patients with heart disease. Circulation 2003; 107: 708-13.
Competing interests: No competing interests
The editorial by Coceani and Mariotti (BMJ 11 February 2006; 332:317-
8) gives more insight in to the safety of amiodarone in heart failure, a
common scenario encountered in the daily clinical practice of not only
specialists, but also generalists and primary care physicians. However, it
was also rather surprising to see that there was no mention anywhere in
the article about the complex story of amiodarone, the thyroid gland and
heart failure, more so on a background of atrial fibrillation (which can
itself result from hyperthyroidism) in a discussion which revolved around
the ‘complex clinical syndrome’. Interestingly, the interaction between
amiodarone and digoxin in such a setting was commented on.
Amiodarone is a benzofuranic-derivative iodine-rich drug widely used
for the treatment of tachyarrhythmias and in 14-18% of amiodarone-treated
patients, there is overt thyroid dysfunction, either amiodarone-induced
thyrotoxicosis or amiodarone-induced hypothyroidism, both of which may
develop in apparently normal thyroid glands . Indeed, amiodarone-
induced thyrotoxicosis is a difficult condition to diagnose and treat .
Thyrotoxicosis is associated with increased cardiovascular morbidity and
mortality, primarily due to heart failure . Clinical suspicion is
essential in the diagnosis of amiodarone-induced thyrotoxicosis, because
the antiadrenergic effect of the drug may conceal symptoms and
occasionally, long-standing hyperthyroidism may lead to heart failure even
in the absence of concomitant cardiac conditions . In fact the
assessment of thyroid status in patients with heart failure has been
stressed before , and the prevalence of abnormal thyroid functions has
been correlated with the New York Heart Association (NYHA) class I-IV
symptoms in patients with heart failure .
The BMJ is a journal with widespread coverage and a majority of the
readers would not be heart failure specialists, though many a time would
be involved in the care and management of such patients. We feel that a
brief mention of this important topic which is well recognized, but less
commonly perceived in clinical practice was pertinent in a discussion of
that nature. It is extremely important that readers of a medical journal
would have to be reminded of these situations in such circumstances.
1. Martino E, Bartalena L, Bogazzi F, Braverman LE. The effects of
amiodarone on the thyroid. Endocr Rev 2001; 22(2):240-54.
2. Basaria S, Cooper DS. Amiodarone and the thyroid. Am J Med 2005;
3. Roffi M, Cattaneo F, Brandle M. Thyrotoxicosis and the
cardiovascular system. Minerva Endocrinol 2005; 30(2):47-58.
4. Middleton SC, Spencer AP. Assessment of hypothyroidism in patients
with chronic heart failure. Pharmacotherapy 2004; 24(3):358-61.
5. Ascheim DD, Hryniewicz K. Thyroid hormone metabolism in patients
with congestive heart failure: the low triiodothyronine state. Thyroid
2002; 12(6): 511-5.
GIV and AAT are Specialist Registrars in Endocrinology & General (Internal) Medicine on the West Midlands rotational training programme in the U.K.
Competing interests: No competing interests