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Circulation. 2018;138:e272–e391. DOI: 10.1161/CIR.0000000000000549 September 25, 2018 e341 CLINICAL STATEMENTS AND GUIDELINES

did not demonstrate any difference between men and women, although total outcomes improved.S10.6-17 The proportion of ischemic heart disease-associated SCAs among women surviving out-of-hospital cardiac arrest was significantly lower than in men, but ischemic heart disease remained the most powerful predictor etiologically,S10.6-18 and women were also significantly less likely to have severe LV dysfunction (LVEF ≤35%) or previously recognized ischemic heart disease.S10.6-19 Women appear to be less likely to benefit from therapeutic hypothermia postcardiac arrest; however, in the younger age group, neurologic recovery in women was better than in older women.S10.6-20 Women are less likely to have SCA during competitive athletic events. A large study including both recreational and competitive athletes across a large age range noted that SCA in women during athletic events was 1 in 20 of that in men.S10.6-21 A large literature review from 1980 to 1992 demonstrated that women accounted for 70% of recorded cases  of cardiovascular medication–related arrhythmias.S10.6-22 This is consistent with QT interval differences among men and women. A retrospective analysis of quinidine discontinuation reported a significant difference in discontinuation between men and women (66% versus 84%) largely due to prolonged QT.S10.6-23 A study of catheter ablation for VT reported that overall outcome was similar between men and women.S10.6-24 The only sex difference was the greater probability of women having RVOT VT and a greater probability of men having LV outflow tract VT.

10.7 Medication-Induced Arrhythmias

Recommendations for Medication-Induced Arrhythmias References that support the recommendations are summarized in Online Data Supplements 52 and 53. Digoxin

COR LOE Recommendation

I B-NR 1. Administration of digoxin antibodies is recommended for patients who present with sustained VA potentially due to digoxin toxicity.S10.7-1,S10.7-2 Medication-induced QT prolongation and torsades de pointes

COR LOE Recommendations

I B-NR 2. In patients with recurrent torsades de pointes associated with acquired QT prolongation and bradycardia that cannot be suppressed with intravenous magnesium administration, increasing the heart rate with atrial or ventricular pacing or isoproterenol are recommended to suppress the arrhythmia.S10.7-3

I C-LD 3. For patients with QT prolongation due to a medication, hypokalemia, hypomagnesemia, or other acquired factor and recurrent torsades de pointes, administration of intravenous magnesium sulfate is recommended to suppress the arrhythmia.S10.7-4,S10.7-5 I C-LD 4. For patients with torsades de pointes associated with acquired QT prolongation, potassium repletion to 4.0 mmol/L or more and magnesium repletion to normal values (eg, ≥2.0 mmol/L) are beneficial.S10.7-6,S10.7-7

Sodium channel blocker–related toxicity

COR LOE Recommendations

IIa C-LD 5. In patients taking sodium channel blockers who present with elevated defibrillation or pacing thresholds, discontinuing the presumed responsible medication or reprogramming the device can be useful to restore effective device therapy.S10.7-8,S10.7-9

III: Harm B-NR 6. In patients with congenital or acquired long QT syndrome, QT-prolonging medications are potentially harmful.S10.7-10

Recommendation-Specific Supportive Text

1.	 Typical arrhythmias related to digoxin toxicity include enhanced atrial, junctional, or ventricular automaticity (with ectopic beats or tachycardia) often combined with atrioventricular block.S10.7-11 VT that is fascicular or bidirectional in origin is suggestive of digoxin toxicity.S10.7-12 Severe digoxin overdose causes hyperkalemia and cardiac standstill. The diagnosis is established by the combination of characteristic rhythm disturbances, ancillary symptoms (visual disturbances, nausea, changes in mentation), and elevated serum concentrations. Potentiating factors may include hypothyroidism, hypokalemia, or renal dysfunction.S10.7-12 Treatment of digoxin toxicity is based on the severity. In mild cases, discontinuing the medication, monitoring rhythm, and maintaining normal serum potassium may be sufficient.S10.7-11 Intravenous magnesium is often administered if VAs are present.S10.7-12 Occasionally, temporary pacing may be needed for atrioventricular block or asystole.S10.7-13 For more severe intoxication (serum digoxin concentrations exceeding 4 ng/mL and with serious arrhythmias such as VT), the treatment of choice is digoxin-specific Fab antibody.S10.7-1 In 1 series of 150 severely intoxicated patients, response was rapid (30 minutes to 4 hour), and 54% of patients presenting with a cardiac arrest survived hospitalization.S10.7-1 Adverse effects include worsening of the underlying disease (increased ventricular rate during AF, exacerbation of HF) and hypokalemia. Doses lower (and less expensive) than the full neutralizing dose are sufficient as long as cardiac arrest is not imminent.S10.7-2

Recommendations for Medication-Induced Arrhythmias (Continued)

COR LOE Recommendations

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