Indian Pacing Electrophysiol. J. 2004;4(1):40-42
Case Report
A Case of Atrial Fibrillation from Cyclosporine Toxicity
Pramod Sanghi, M.D., Masood Ahmad, M.D.
Department of Cardiology, University
of Texas Medical Branch
Address for correspondence: Masood Ahmad,
M.D., Professor of Medicine, Department of Cardiology, University of Texas
Medical Branch, 301 University Blvd, Galveston, TX 77555-0766.
Email: mahmad@utmb.edu
Abstract
We describe the
unusual occurrence of atrial fibrillation immediately after a seizure in
a young patient with cyclosporine toxicity. The new onset atrial fibrillation
was triggered by high levels of cyclosporine and possibly facilitated by
the electrolyte imbalances post seizure and the presence of underlying mild
left atrial enlargement.
Key words: atrial fibrillation,
cyclosporine, seizure
A twenty-four year old obese (100 kg) man with a past medical history of
pure red cell aplasia diagnosed 8 months ago was admitted for elective chemotherapy
after having failed outpatient therapy with high dose prednisone and azathioprine.
Upon admission, the patient was placed on IV cyclosporine (12 mg/kg/day divided
BID) and oral prednisone (1 mg/kg/day). On the 3rd hospital day, IV
anti-thymocyte globulin (4000 mg/day) infused with IV methylprednisolone
(125 mg/day) was initiated. On the 4th hospital day a serum cyclosporine
level returned elevated at 995 ng/ml. At this point the cyclosporine
dose was decreased to 8 mg/kg/day. He was also transfused 2 units of
leukocyte reduced packed red blood cells for his chronically depressed blood
counts (Hemoglobin 6.2 gm/dl). The patient had an uncomplicated hospital
course until the 8th hospital day when he was found in his room having a tonic-clonic
seizure that lasted approximately 1-2 minutes. Shortly afterwards,
he was found to be in atrial fibrillation with a ventricular rate of 160
bpm and hypotensive with a blood pressure of 90/50 mmHg. After a brief
postictal period, he denied any complaints but was aware of his tachycardia.
The patient was initially given a loading dose of dilantin, and his heart
rate was controlled with boluses of IV diltiazem. Laboratory values taken
immediately after his seizure showed a K+ of 3.0 mmol/l, Ca2+
of 6.7 mg/dl, Mg2+ of 1.0 mg/dl, and CO2 of 9 mmol/l,
but on repeat labs taken 2 hours later, the electrolyte imbalances had all
normalized. The patient’s heart rhythm spontaneously converted to normal
sinus about 5 hours after he was initially found to be in atrial fibrillation.
His cyclosporine level that had been drawn just a few hours prior to his
seizure returned as 1360 ng/ml, which is over 4 times the therapeutic dose
for this treatment. The cyclosporine was held and the following day
returned as 264 ng/nl. Echocardiogram performed the following day revealed
normal systolic function (LVEF 55 – 60%) with a mildly enlarged left atrium
(4.2 cm) and mild to moderate tricuspid regurgitation. His estimated
pulmonary artery pressure was 40 mmHg.
Fig 1: Electrocardiogram
showing atrial fibrillation in a 24 year old man taken immediately after
a witnessed seizure. His cyclosporine level was toxic at 1360 ng/ml.
Fig 2: Electrocardiogram showing normal
sinus rhythm taken the following morning after the initial onset of atrial
fibrillation. The cyclosporine level drawn at this time was 264 ng/ml.
Discussion
Although this
is not the first time atrial fibrillation has been reported in the literature
from an overdose of cyclosporine1, our case is
unusual for the following reasons. First of all, our patient received
an appropriate dose of cyclosporine but was still found to have toxic levels
of the drug. While he was given the correct dosages for his weight
(12 kg/mg/day), the patient was obese and some studies suggest that the dosages
of cyclosporine in these patients not be based on their actual body weight
2. Other potential causes of high blood cyclosporine
levels in this patient are increased gastrointestinal absorption secondary
to high dietary fat intake while in the hospital or an idiosyncratic drug
reaction 3.
What is also
unique about this case is that the patient suffered a seizure prior to the
onset of atrial fibrillation. Seizure is a well described complication
of cyclosporine toxicity 4. The electrolyte
imbalances assumed to be secondary to the seizure may have predisposed the
patient to atrial fibrillation in the face of cyclosporine toxicity.
Although atrial fibrillation is a known complication of cyclosporine toxicity
independent of seizure activity or electrolyte imbalances, the atrial fibrillation
seen in this case occurred at a relatively low level of cyclosporine toxicity
as compared to other case reports in the literature1.
In addition, the patient may have been at further risk of developing atrial
fibrillation due to the mild left atrial enlargement seen on his echocardiogram.
Although the mechanism by which cyclosporine causes atrial fibrillation
is unknown, cyclosporine is known to have some deleterious cardiac effects
including coronary vasospasm 5 and ventricular
hypertrophy 6. Further research is
needed to determine the mechanisms by which these potentially harmful cardiac
effects occur.
References
1. LoVechio FA, Goltz HR. Atrial
Fibrillation following Acute Overdose with Oral Cyclosporine.
Ann Pharmacother 2000; 34 405
2. Garcia-Saiz M, Lopez-Gil A, Alfonso I, et al. Factors
Influencing Cyclosporine Blood Concentration-Dose Ratio. Ann Pharmacother
2002; 36:193-199
3. Colman E, Fossler, M. Reduction
in Blood Cyclosporine Concentrations by Orlistat. N Engl J of Med 2000;
342:1141-1142
4. Furlong T. Neurological
Complications of Immunosuppressive Cancer Therapy. Oncol Nurs Forum
1993; 201:337-1352
5. Braun-Dullaeus
RC, Feussner M, Walker G, et al. Cyclosporine-induced Coronary Artery Constriction-Dissociation
between Thromboxane Release and Coronary Vasospasm. J Heart Lung Transplant
1999; 18:328-335
6.
Ding B, Price RL, Borg TK, et al: Pressure
Overload Induced Severe Hypertrophy in Mice Treated with Cyclosporine, an
Inhibitor of Calcineurin. Circ Res 1999; 84:729-734
