Bradycardia and reduced exercise capacity associated with chronic normotherpaeutic lithium therapy

To the Editor

Lithium has been the cornerstone of maintenance treatment in bipolar disorder for many years. The risk of toxicity is due to its narrow therapeutic range (0.6–0.8 mEq/L). We describe a 61-year-old man referred to the cardiology clinic for assessment of new electrocardiogram (ECG) findings of bi-fasicular block and bradycardia (Figure 1). His past medical history included asthma, hyperlipidaemia, hyperuricaemia and bipolar spectrum disorder. He took a budesonide inhaler, oral theophylline, aspirin, allopurinol and lithium.

Figure 1.

Twelve lead electrocardiogram showing bi-fasicular block with a heart rate of 40 beats/min.

Since starting lithium 2 years ago, he noted his resting heart rate (HR) drop from 60 beats/minute (bpm) to 40 bpm. There were no clinical signs of lithium toxicity. Thyroid function tests were normal and lithium levels were in the therapeutic range.

Upon exercise testing, he completed 16 METS and achieved 83% (136 bpm) of his predicted maximal HR. His holter monitor confirmed bradycardia to 33 bpm. A transthoracic echocardiogram showed normal left ventricular size and function. Although permanent pacing was discussed, lithium was ceased and replaced with lamotrigine.

Eight weeks later his ECG showed a 25% increase in his baseline HR to 50 bpm in sinus rhythm with a 38% shortening of the QRS duration to 100 ms (Figure 2), indicating more rapid activation of the ventricle. The patient’s peak exercise performance improved by 25%. He achieved 20 METS and 94% (151 bpm) of predicted heart rate on exercise ECG.

Figure 2.

Twelve lead electrocardiogram demonstrating improvement in the rate and normalisation of the QRS interval.

Lithium is known to have electrophysiological effects on the myocardium by displacing other cations upon entering the cardiac cells (Singer and Rotenberg, 1973). However, the published data for bradycardia associated with therapeutic lithium levels are limited. We report quantifiable chronotropic incompetence and bradycardia secondary to chronic lithium use at a therapeutic level. Other cases identify changes on the ECG such as inversion of T waves (Kochar et al., 1971). Unlike other cases, our case demonstrated diffuse effects within the conducting system as evidenced by a significant broadening of the QRS interval in addition to sinus node dysfunction, suggesting the effects of lithium are not limited to the SA node.

We conclude that cardiovascular complications of lithium can occur independent of the therapeutic level and duration of treatment. However its effect on the heart is reversible once withdrawn. We recommend a resting ECG before starting therapy as well as periodic monitoring of levels, ambulatory pulse recording and Holter monitoring, even with a normal ECG. An alternative medication to lithium should be considered when other causes for rhythm disturbances have been excluded.