Does subclinical hypothyroidism explain the increased susceptibility of women to torsades de pointes?

Among 20 consecutive patients (65% women) with drug-associated torsades de pointes, chemical evidence for hypothyroidism was found in only 10% of both women and men. Subclinical hypothyroidism is therefore unlikely to account for the consistently observed sex difference in the propensity to torsades de pointes.

Age-gender influence on the rate-corrected QT interval and the QT-heart rate relation in families with genotypically characterized long QT syndrome.

OBJECTIVES: We sought to analyze age-gender differences in the rate-corrected QT (QTc) interval in the presence of a QT-prolonging gene. BACKGROUND: Compared with men, women exhibit a longer QTc interval and an increased propensity toward torsade de pointes. In normal subjects, the QTc gender difference reflects QTc interval shortening in men during adolescence. METHODS: QTc intervals were analyzed according to age (< 16 or > or = 16 years) and gender in 460 genotyped blood relatives from families with long QT syndrome linked to chromosome 11p (KVLQT1; n = 199), 7q (HERG; n = 208) or 3p (SCN5A; n = 53). RESULTS: The mean QTc interval in genotype-negative blood relatives (n = 240) was shortest in men, but similar among women, boys and girls. For genotype-positive blood relatives, men exhibited the shortest mean QTc interval in chromosome 7q- and 11p-linked blood relatives (n = 194), but not in the smaller 3p-linked group (n = 26). Among pooled 7q- and 11p-linked blood relatives, multiple regression analysis identified both genotype (p < 0.001) and age-gender group (men vs. women/children; p < 0.001) as significant predictors of the QTc interval; and heart rate (p < 0.001), genotype (p < 0.001) and age-gender group (p = 0.01) as significant predictors of the absolute QT interval. A shorter mean QT interval in men was most evident for heart rates < 60 beats/min. CONCLUSIONS: In familial long QT syndrome linked to either chromosome 7q or 11p, men exhibit shorter mean QTc values than both women and children, for both genotype-positive and -negative blood relatives. Thus, adult gender differences in propensity toward torsade de pointes may reflect the relatively greater presence in men of a factor that blunts QT prolongation responses, especially at slow heart rates.

Probucol-associated tachyarrhythmic events and QT prolongation: importance of gender.

From published articles and adverse reactions reports filed with the FDA (available through the Freedom of Information Act), we analyzed occurrences of tachyarrhythmias and the magnitude of QTc prolongation associated with probucol therapy. Of 16 cases of tachyarrhythmic events reported in association with probucol, 15 (94%) occurred in women (p < 0.01 vs expected value of 58%). Tachyarrhythmias were specifically described as TdP in 11 (63%) cases, all women; additional potential contributory QT-prolonging factors (besides probucol) were not identifiable in 2 of the 11 cases. We also analyzed QTc responses in 359 probucol-treated patients, all having baseline QTc < or = 0.44 sec1/2. At doses of 500 to 1000 mg/day, probucol-associated prolongation of QTc to values > or = 0.45 sec1/2 was observed in 22% of women versus 7% of men (p < 0.001) and to values > or = 0.47 sec1/2 in 8% of women versus 2% of men (p < 0.03). Multivariate analysis identified baseline QTc (p < 0.0001) and female gender (p < 0.03), but neither age nor dose, as significant independent predictors of QTc prolongation to > or = 0.45 sec1/2 with probucol. These findings have relevance to the clinical use of probucol, provide further evidence that women have a relatively greater predisposition to development of acquired long QT syndrome, and carry implications for the design of trials involving QT-prolonging drugs.

T wave "humps" as a potential electrocardiographic marker of the long QT syndrome.

OBJECTIVES: This study attempted to determine the prevalence and electrocardiographic (ECG) lead distribution of T wave "humps" (T2, after an initial T wave peak, T1) among families with long QT syndrome and control subjects. BACKGROUND: T wave abnormalities have been suggested as another facet of familial long QT syndrome, in addition to prolongation of the rate-corrected QT interval (QTc), that might aid in the diagnosis of affected subjects. METHODS: The ECGs from 254 members of 13 families with long QT syndrome (each with two to four generations of affected members) and from 2,948 healthy control subjects (age > or = 16 years, QTc interval 0.39 to 0.46 s) were collected and analyzed. Tracings from families with long QT syndrome were read without knowledge of QTc interval or family member status (210 blood relatives and 44 spouses). RESULTS: We found that T2 was present in 53%, 27% and 5% of blood relatives with a "prolonged" (> or = 0.47 s, "borderline" (0.42 to 0.46 s) and "normal" (< or = 0.41 s) QTc interval, respectively (p < 0.0001), but in only 5% and 0% of spouses with a borderline and normal QTc interval, respectively (p = 0.06 vs. blood relatives). Among blood relatives with T2, the mean [+/- SD] maximal T1T2 interval was 0.10 +/- 0.03 s and correlated with the QTc interval (p < 0.01); a completely distinct U wave was seen in 23%. T2 was confined to leads V2 and V3 in 10%, whereas V4, V5, V6 or a limb lead was involved in 90% of blood relatives with T2. Among blood relatives with a borderline QTc interval, 50% of those with versus 20% of those without major symptoms manifested T2 in at least one left precordial or limb lead (p = 0.05). A T2 amplitude > 1 mm (grade III) was observed, respectively, in 19%, 6% and 0% of blood relatives with a prolonged, borderline and normal QTc interval with T2 in at least one left precordial or limb lead. Among the 2,948 control subjects, 0.6% exhibited T2 confined to leads V2 and V3, and 0.9% had T2 involving one or more left precordial lead (but none of the limb leads). Among 37 asymptomatic adult blood relatives with QTc intervals 0.42 to 0.46 s, T2 was found in left precordial or limb leads in 9 (24%; 5 with limb lead involvement) versus only 1.9% of control subjects with a borderline QTc interval (p < 0.0001). CONCLUSIONS: These findings are consistent with the hypothesis that in families with long QT syndrome, T wave humps involving left precordial or (especially) limb leads, even among asymptomatic blood relatives with a borderline QTc interval, suggest the presence of the long QT syndrome trait.

Routine withholding of digitalis for heart rate below 60 beats per minute: widespread nursing misconceptions.

OBJECTIVE: To describe the nursing practice of withholding digitalis solely on the basis of a heart rate less than 60 beats/min and to determine the rationale for this practice. DESIGN: Non-randomized survey. SETTING: Five hospitals in a midwestern metropolitan area, ranging from affiliates of a university medical center to a private community-based hospital. SUBJECTS: Two hundred twelve nurses, 53% from critical care units, 19% from step-down units, and 28% from nonmonitored units). RESULTS: Eighty-one percent of respondents either withheld digitalis unnecessarily or administered the drug without correctly indicating why they did so. Nurses with CCRN certification were more likely to answer correctly than those who were not certified (p = 0.0001). Categories for incorrect rationale were (1) incorrect understanding of the drug's mechanism of action (46%), (2) deference to physician's decision-making (28%), (3) adherence to hospital policy (18%), and (4) adherence to guidelines taught in nursing school (6%). CONCLUSIONS: The results document the need to correct widespread misconceptions regarding the mechanism of action for digitalis and subsequent nursing practice.