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Electrical Storm Caused by Complementary Medication with Ginkgo Biloba Extract

      To the Editor:
      Ginkgo biloba extract is a top-selling alternative drug for the treatment of cognitive impairment and peripheral vascular disease, with annual worldwide sales estimated at $1 billion.
      • Rimmer C.A.
      • Howerton S.B.
      • Sharpless K.E.
      • et al.
      Characterization of a suite of ginkgo-containing standard reference materials.
      Although many patients taking Ginkgo biloba suffer from concomitant ischemic cardiomyopathy, little is known about the safety of this herbal remedy in this patient population. We here report a case of Ginkgo biloba-induced electrical storm in a patient with ischemic cardiomyopathy.

      Case Report

      A 72-year-old man presented at our outpatient clinic for routine interrogation of his implantable cardioverter defibrillator (ICD). He had a history of ischemic cardiomyopathy with reduced left ventricular ejection fraction (LVEF 35%) due to infero-lateral myocardial infarction 9 years prior. Recurrent symptomatic ventricular tachycardias (VT) prompted the implantation of an ICD 7 years ago. Under standard medication including aspirin (100 mg/day), bisoprolol (5 mg/day), ramipril (5 mg/day), simvastatin (40 mg/day), torasemide (10 mg/day), and the anti-anginal drug molsidomin (16 mg/day), the patient was free of angina and had a stable course with only sporadic sustained VT, rarely requiring antitachycardia pacing. Three weeks before admission, standardized Ginkgo biloba extract (120 mg/day) was prescribed by a general practitioner because of tinnitus.
      On admission, the patient complained about frequent episodes of dizziness and epigastric discomfort. Physical examination, electrocardiogram, and laboratory testing including electrolyte status were unchanged. Interrogation of the ICD, however, revealed a total of 1440 episodes of sustained VT since the last interrogation 4 months earlier (Figure, A). Analysis of the recordings of the last 10 days documented up to 33 episodes of incessant VT per day. All episodes were initiated by premature extra beats, exhibited a similar cycle length of 350-360 ms (170 beats per minute), and were successfully terminated by antitachycardia pacing, thus suggesting reentry as the underlying arrhythmia mechanism. A pro-arrhythmic effect of Ginkgo biloba was suspected and the drug was discontinued. After stopping Ginkgo biloba, the patient's condition markedly improved. Interrogation of the ICD 3 months later documented only 7 VT episodes, whereas 6 episodes occurred within the first week after withdrawal of Ginkgo biloba (Figure, B).
      Figure thumbnail gr1
      FigureCumulative registration of ventricular tachycardias (VT) by ICD. (A) Clustering of VT episodes between December and March 2007, the period Ginkgo biloba medication was taken. (B) Daily episodes of VT that required ICD intervention during Ginkgo biloba intake (horizontal bar). Substantial decrease of VT episodes immediately after Ginkgo biloba discontinuation with subsequent event-free follow-up.

      Discussion

      The obvious temporal coincidence of electric instability and Ginkgo biloba intake strongly suggests a pro-arrhythmic effect of Ginkgo biloba in this patient. Other destabilizing factors such as hypokalemia or hypomagnesemia could be excluded. The complete disappearance of VT episodes within days after Ginkgo discontinuation is in line with the kinetics of Ginkgo biloba extract that exhibits an elimination half-life of up to 10 hours.
      • Ang-Lee M.K.
      • Moss J.
      • Yuan C.S.
      Herbal medicines and perioperative care.
      Experimental data support our clinical hypothesis by showing distinct effects of Ginkgo biloba and its constituents on action potential duration and cationic currents in rodent ventricular myocytes.
      • Satoh H.
      Comparative electropharmacological actions of some constituents from Ginkgo biloba extract in guinea-pig ventricular cardiomyocytes.
      Alteration of action potential duration facilitates the generation of reentry circuits that constitute the basis of recurrent VT in ischemic cardiomyopathy.
      • Ebinger M.W.
      • Krishnan S.
      • Schuger C.D.
      Mechanisms of ventricular arrhythmias in heart failure.
      To date, clinical data about the association of Ginkgo biloba intake and arrhythmia are scarce. The continuous rhythm monitoring via intracardiac electrogram provided in this case documents for the first time a tight correlation between the intake of Ginkgo biloba extract and ventricular arrhythmias. Because Ginkgo biloba is increasingly popular in patients with generalized atherosclerosis, the herein reported pro-arrhythmic potential of this alternative medicine deserves further investigation.

      References

        • Rimmer C.A.
        • Howerton S.B.
        • Sharpless K.E.
        • et al.
        Characterization of a suite of ginkgo-containing standard reference materials.
        Anal Bioanal Chem. 2007; 389: 179-196
        • Ang-Lee M.K.
        • Moss J.
        • Yuan C.S.
        Herbal medicines and perioperative care.
        JAMA. 2001; 286: 208-216
        • Satoh H.
        Comparative electropharmacological actions of some constituents from Ginkgo biloba extract in guinea-pig ventricular cardiomyocytes.
        Evid Based Complement Alternat Med. 2004; 1: 277-284
        • Ebinger M.W.
        • Krishnan S.
        • Schuger C.D.
        Mechanisms of ventricular arrhythmias in heart failure.
        Curr Heart Fail Rep. 2005; 2: 111-117