Unexpected Cardiac Arrhythmia in an Older Woman
A 68-year-old woman with a history of hypertrophic cardiomyopathy, with an outflow gradient of 16 mmHg, occasional premature ventricular contractions (PVC), fibromyalgia, gastroesophageal reflux disease (GERD), and hypothyroidism visited the office for fatigue and dyspnea with minimal exertion. She was not symptomatic until about 2 weeks before her visit.
HISTORY
Exam was unchanged from 4 months prior except for a significant bradycardia, found on the ECG to be a sinus bradycardia at 42 per min. Her medications included a beta-blocker and thyroid replacement. This was a new finding, and a 24 Holter was recorded after reducing her beta-blocker. Thyroid function was normal. Holter showed sinus bradycardia with occasional periods of complete heart block, average rate 40 per min. Mulitfocal PVCs at 4 to 6 per min were present.
PHYSICAL EXAMINATION
Physical exam revealed a well-developed woman in no distress. Vital signs were normal except for a regular pulse rate of 48 to 52 per min. There were no distended neck veins, significant cardiac murmurs, or gallups. Chest revealed mild bibasilar rates that cleared with deep inspirations. Peripheral pulses were symmetrical and normal.
LABORATORY RESULTS
Routine CBC and basic metabolic panels were normal. A digoxin level was obtained which showed a level of 0.5 µgm/L.
Which of the following is the most effective next step in treating this patient?
A. Initiate emergency hemodialysis and monitor digoxin levels daily.
B. Administer CaCl2 intravenously and monitor digoxin levels daily.
C. Administer amiodarone 400 mg as a pharmacologic antidote to digitalis effect.
D. Placement of a pacemaker with setting 70 bpm.
(Answer and discussion on next page)
Correct Answer: D
Digitalis, an alkaloid derived from foxglove plants, has a long and storied history in the therapeutics of heart disease starting in the mid 19th century, when it was administered with apparent efficacy for “dropsy,” or what we now refer to as anasarca.
In a major landmark study1, the role of digoxin in CHF patients was clearly shown to be in reducing the rate of hospitalization overall and for worsening CHF, but without a mortality benefit.1,2 Evidence of digoxin toxicity was seen in 11.9% of patients, although only 2% of those cases were hospitalized over a 3.5-year study period.1 Those rhythms, which were statistically more frequent in digoxin toxicity (rather than being part of the natural history of advanced CHF itself) included supraventricular arrhythmias—2.5% incidence with digoxin vs. 1.2% in placebo, p<0.001—and even more so, second or third degree atrioventricular block—1.2% with digoxin vs. 0.4% in placebo, p<0.001. These rhythms occurred in 88.3% of patients who had therapeutic digoxin levels between 0.5-2.0 µgm/L, reinforcing the well known fact that such levels serve only as a rough guide and should not be used as definitive indicators of digoxin safety or toxicity.1 Although no single EKG abnormality is pathognomonic of digitalis toxicity, the combination of enhanced automaticity (i.e., PVCs) and impaired conduction (i.e., third degree block) is quite suggestive, even in patients with serum levels in the normal, therapeutic range.3 The improvement in EKG findings with cessation of digoxin further supports this hypothesis.
Causes of Digitalis
If we accept the clinical data presented, a new arrhythmia certainly consistent with the digitalis effect and a digoxin level demonstrating the presence of the agent in the patient, two questions need to be answered. First, where did the digitalis come from and second, how should the patient be managed?
Regarding this patient’s digitalis exposure, possibilities include her erroneously ingesting medicines confused by older prescriptions with mislabeled or unlabeled bottles. Surreptitious ingestion is another option and was not uncommon in the era when more patients used this medicine as part of a CHF or mitral stenosis/atrial fibrillation (AF) regimen. Finally, unusual sources such as herbs and flowers is a possibility that needs to be explored.4
Management of Digitalis
Management of digitalis intoxication is dependent upon the severity of effect. Common manifestations such as occasional ectopic beats, first-degree heart block, or AF with slow response require only the withdrawal of the agent and continued EKG monitoring. Dangerous ventricular tachycardia is usually an indication for Fab fragments of high affinity, polyclonal digoxin-specific antibodies to rapidly and specifically reverse digitalis effects.5 Sinus bradycardia, sinus arrest, and second- or third-degree AV block are frequently treated by pacing. The patient’s Holter findings are more consistent with the latter scenario and thus Answer D is the most appropriate in this setting.
Hemodialysis (Answer A) is not an effective therapy for digoxin toxicity due to the drug’s large volume of distribution and high level of tissue binding. CaCl2 (Answer B) actually enhances digitalis effects and is absolutely contraindicated in setting of digitalis intoxication. Similarly, the commonly used antiarrhythmic amiodarone (Answer C) is contraindicated because it increases the digoxin concentration, such that the dosage must be lowered if and when these meds are combined.
OUTCOME OF THIS CASE
On further history, the patient stated that she routinely harvested herbs from her garden, and had planted foxglove because of its pleasing flowers. A dig level was found to be 0.5 µgm/L. She again reiterated that she was not taking any digitalis-related medications. Because of symptoms and the persistent bradycardia, she received a pacemaker set at 70 bpm, and her fatigue and dyspnea resolved. ■
REFERENCES:
1.The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Eng J Med. 1997;336:525-533.
2.Packer M. End of the oldest controversy in medicine—are we ready to conclude the debate of digitalis? N Eng J Med. 1997;336-575-576.
3.Hauptman PJ, Kelly RA. Digitalis. Circulation. 1999;99:1265-1270.
4.Newman LS, Feinberg MW, LeWine HE. A bitter tale. N Eng J Med. 2004;351:594-599.
5.Hickey AR, Wenger TL, Carpenter VP, et al. Digoxin immune Fab therapy in the management of digitalis intoxication: safety and efficacy results of an observational surveillance study. J Am Coll Cardiol. 1991;17:590-598
Ronald Rubin, MD is professor of medicine at Temple University School of Medicine and chief of clinical hematology in the department of medicine at Temple University Hospital, both in Philadelphia.