Hypokalemia in women and methadone therapy are the strongest non-cardiologic factors associated with QT prolongation in an emergency department setting

Abstract

Background Our primary objective was to determine the adjusted quantitative associations of clinical predictors with QT prolongation, a defining cause of Torsades de Pointes (TdP). Methods A retrospective cohort study was performed on consecutive emergency department patients identified by ECG acquisition date, and heart rate corrected QT (QTc) and QRS durations. QTc was modeled as a function of clinical predictors with multiple linear regression. Results 1,010 patients were included. The strongest predictors of QTc and their coefficients were: antidysrhythmic (26.1ms, 95% CI 15.6–36.6) and methadone (43.6ms, 95% CI 28.1–59.2) therapies, and genetic long QT syndrome diagnosis (32.6ms, 95% CI −4.7–70.0). The association of QTc with serum potassium was approximated by a two piecewise linear function that differed by sex. For potassium below 3.9 mmol/L, QTc increased by 43.0ms (95% CI 26.2–59.7) and 29.5ms (95% CI 19.1–40.0) for every 1 mmol/L decrease in potassium in women and men, respectively. TdP occurred in only 4/686 (0.6%) of patients with QTc>500 and QRS<120, but mortality during the visit including hospitalization was 8.0%. Conclusions QTc duration is highly sensitive to hypokalemia, particularly in women. Methadone prolongs QTc remarkably compared to other non-cardiologic medicines. QTc>500 with normal QRS often signifies profound illness and substantial mortality risk, though not necessarily imminent TdP.

The QTc interval and risk of cardiac events in bulimia nervosa: A long‐term follow‐up study

“…Moreover, we expected that potassium derangements in purging patients with BN would be associated with an increased risk of a prolonged QTc (Marill & Miller, 2017). Surprisingly, only 2.4% of patients with BN had hypokalemia, and the frequency did not differ among the subgroups based on purging frequency.…”

“…Since hypokalemia is a well‐known consequence of purging, (Mehler & Walsh, ) we expected to find a higher frequency of hypokalemia in patients with BN, particularly among those who purge. Moreover, we expected that potassium derangements in purging patients with BN would be associated with an increased risk of a prolonged QTc (Marill & Miller, ). Surprisingly, only 2.4% of patients with BN had hypokalemia, and the frequency did not differ among the subgroups based on purging frequency.…”

Is myocardial repolarization duration associated with repolarization heterogeneity?

“…A two piecewise linear spline with inflection point knot at 3.9 mmol/L was used to model potassium dependence based on our previous investigation (Marill & Miller, 2017). Reliability of data abstraction of interval measurements was assessed with the intraclass correlation coefficient (ICC) using two way random models.…”

“…The Other secondary outcomes included the coefficients in two multiple linear regression models developed to assess the linear relationship of JTpkc and TpTe with major clinical variables associated with TdP occurrence. A two piecewise linear spline with inflection point knot at 3.9 mmol/L was used to model potassium dependence based on our previous investigation (Marill & Miller, 2017). These two models included coefficients for amiodarone and sotalol treatments as dummy binary independent variables.…”

Sudden Unexpected Death and the Mammalian Dive Response: Catastrophic Failure of a Complex Tightly Coupled System

“…Metabolic changes, particularly electrolyte imbalances, promote prolongation of the QT interval (Harris et al, 1992). Hypokalemia is the strongest non-cardiologic factor associated with QT prolongation (Marill and Miller, 2017). Within one minute, hyperventilation causes QT prolongation (Kannivelu et al, 2013), related to changes in blood pH and hypokalemia (Edwards et al, 1977).…”