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

Ahmad, Masood

Sanghi, Pramod

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Pramod Sanghi

Masood Ahmad

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Indian Pacing and Electrophysiology Journal

A Case of Atrial Fibrillation from Cyclosporine Toxicity

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Pramod Sanghi, Masood Ahmad, “A Case of Atrial Fibrillation from Cyclosporine
Toxicity”                                                                                                                                      40
A Case of Atrial Fibrillation from Cyclosporine Toxicity
Case Report
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.
Indian Pacing and Electrophysiology Journal (ISSN 0972-6292), 4(1): 40-42 (2004)
Pramod Sanghi, Masood Ahmad, “A Case of Atrial Fibrillation from Cyclosporine
Toxicity”                                                                                                                                      41
 
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.
Indian Pacing and Electrophysiology Journal (ISSN 0972-6292), 4(1): 40-42 (2004)
Pramod Sanghi, Masood Ahmad, “A Case of Atrial Fibrillation from Cyclosporine
Toxicity”                                                                                                                                      42
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
Indian Pacing and Electrophysiology Journal (ISSN 0972-6292), 4(1): 40-42 (2004)


al: Pressure Overload Induced Severe Hypertrophy in Mice Treated with Cyclosporine, an Inhibitor of Calcineurin. Circ Res

Atrial Fibrillation following Acute Overdose with Oral Cyclosporine. Ann Pharmacother

Cyclosporine-induced Coronary Artery Constriction-Dissociation between Thromboxane Release and Coronary Vasospasm. J Heart Lung Transplant

Factors Influencing Cyclosporine Blood Concentration-Dose Ratio. Ann Pharmacother

Neurological Complications of Immunosuppressive Cancer Therapy. Oncol Nurs Forum

Reduction in Blood Cyclosporine Concentrations by Orlistat.

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A Case of Atrial Fibrillation from Cyclosporine Toxicity

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