Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs

Makkar, Raj; Fromm, Barbara S.; Steinman, Russell T.; Meissner, Marc D.; Lehmann, Michael H.

doi:10.1001/jama.270.21.2590

Cited by 508 publications

(333 citation statements)

References 114 publications

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“…Makkar et al examined 332 cases of antiarrhythmic induced TdP, and found that 70% of these patients were women, even though only 44% of the drug prescriptions were registered to women. 24 Multiple other studies have shown that women account for the majority of reported cases of drug-induced TdP. 25 -28 Brugada Syndrome Brugada syndrome is 7 to 8 times more prevalent in men compared to women.…”

Section: Long Qt Syndromementioning

confidence: 98%

Arrhythmias in Women

Curtis

Narasimha

2012

Clinical Cardiology

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There are important gender differences in cardiac electrophysiology that affect the epidemiology, presentation, and prognosis of various arrhythmias. Women have been noted to have higher resting heart rates compared to men. They also have a longer QT interval, which puts them at an increased risk for drug-induced torsades de pointes. Women with atrial fibrillation are at a higher risk of stroke, and they are less likely to receive anticoagulation and ablation procedures compared to men. Women have a lower risk of sudden cardiac death and are less likely to have known coronary artery disease at the time of an event compared to men. Both men and women have been shown to derive an equal survival benefit from implantable cardioverter defibrillators and cardiac resynchronization therapy, although these devices are significantly underutilized in women. Women also appear to have a better response to cardiac resynchronization therapy in terms of reduced numbers of hospitalizations and more robust reverse ventricular remodeling. Further studies are required to elucidate the underlying pathophysiology of these sex differences in cardiac arrhythmias. IntroductionSex differences in cardiac electrophysiology affect the epidemiology, presentation, and prognosis of various arrhythmias. These sex differences can have important clinical and therapeutic implications. Although the exact reason for these differences is not known, the potential mechanisms include differences in cardiac size, structure, and the different ways in which hormones, drugs, and electrolytes affect cardiac ion channels in men and women. The purpose of this review is to provide a synopsis of the important gender differences with respect to arrhythmias and to summarize updates from recent studies.

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Section: Long Qt Syndromementioning

confidence: 98%

Arrhythmias in Women

Curtis

Narasimha

2012

Clinical Cardiology

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“…These fell under three domains: basic demographic (age, gender10, 11), biochemistry (capillary glucose at the time of the ECG,12 potassium,13 calcium and magnesium concentrations10, 14 obtained closest temporally to ECG acquisition within 12 hours) and medications prescribed within 7‐days of the index ECG. Community‐issued medications are obtained by pharmacist reconciliation with primary care.…”

Section: Methodsmentioning

confidence: 99%

Incidence and outcomes of long QTc in acute medical admissions

et al. 2018

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SummaryAimsProlonged QT interval on electrocardiogram (ECG) increases the risk of ventricular arrhythmia. Patients admitted to acute medical units (AMU) may be at risk of QT prolongation from multiple, recognised risk factors. Few data exist regarding incidence or outcomes of QT prolongation in acute general medical admissions.The aims were to determine the incidence of Bazett's‐corrected QT (QTc) prolongation upon admission to AMU; the relationship between QTc and inpatient mortality, length of stay and readmission; proportion with prolonged QTc subsequently administered QT interval‐prolonging drugs.MethodsRetrospective, observational study of 1000 consecutive patients admitted to an AMU in a large urban hospital. Exclusion criteria: age <18 years, ventricular pacing, poor quality/absent ECG . QTc determined manually from ECG obtained within 4‐hours of admission. QTc prolongation considered ≥470 milliseconds (males) and ≥480 milliseconds (females). In both genders, >500 milliseconds was considered severe. Study end‐points, (a) incidence of QTc prolongation at admission; (b) inpatient mortality, length of stay and readmission rates; (c) proportion with QTc prolongation subsequently administered QT interval‐prolonging drugs.ResultsOf 1000 patients, 288 patients were excluded, therefore final sample was n = 712. Patient age (mean ± SD) was 63.1 ± 19.4 years; females 49%. QTc prolongation was present in n = 50 (7%) at admission; 1.7% had QTc interval >500 ms. Of the 50 patients admitted with prolonged QTc, 6 (12%) were subsequently administered QT interval‐prolonging drugs. QTc prolongation was not associated with worse inpatient mortality or readmission rate. Length of stay was greater in those with prolonged QTc, 7.2 (IQR 2.4‐13.2) days vs 3.3 (IQR 1.3‐10.0; P = 0.004), however, in a regression model, presence of QTc did not independently affect length of stay.Conclusions QTc interval prolongation is frequent among patients admitted to AMU. QT interval‐prolonging drugs are commonly prescribed to patients presenting with prolonged QTc but whether this affects clinical outcomes is uncertain.

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“…Drug-induced prolongation of repolarization as an antiarrhythmic mechanism was first described 35 (23). Most of these drugs (if not withdrawn) have seen their respective monographs modified to include appropriate warnings about QT interval prolongation and proarrhythmic potential.…”

Section: Acquired Lqts: a Common And Intriguing Disordermentioning

confidence: 99%

“…These include female sex (35), heart disease (left ventricular hypertrophy or dysfunction, heart failure and myocardial infarction) (10), hypokalemia (which not only reduces baseline I Kr (36), but also increases sensitivity of the current to drug-blocking effects [37]), high drug levels (due to excessive dosage or impaired elimination) and drug interactions (most often involving inhibition of P450 hepatic metabolizing enzymes) (10). Indeed, we identified the P450 enzymes involved in the biotransformation of domperidone, a potent I Kr blocker (38), which led to a warning of potential life-threatening drug interactions.…”

Section: Other Risk Factorsmentioning

confidence: 99%