QT interval as a marker for torsade
The incidence of torsade is unknown, but it is an uncommon cardiac abnormality. In the United States, torsade probably accounts for less than 5% of the 300,000 sudden cardiac deaths that occur each year. Because torsade de pointes is rare, regulatory agencies and clinicians use the QT interval as a surrogate ECG marker for risk of torsade de pointes. Heart rate can affect the QT interval, so various formulae are used to correct the QT interval for heart rate (QTc).
What is the QT interval? In a normal ECG (Figure 2), the P wave derives from right and left atrial electrical depolarization. The pacemaker of the heart is located in the sino-atrial node (SAN) in the superior portion of the right atrium. From the SAN, electrical signals travel down three intra-atrial pathways, activating the right atrium, then travel to the atrioventricular node (AVN). Bachmann’s bundle—a fourth atrial pathway—passes from the SAN to depolarize the left atrium. From the AVN, the electrical signal travels through the left and right bundle branches to activate their respective ventricles.
Electrical depolarization of the left and right ventricles produces the QRS complex. Most of the electrical forces making up this complex arise in the left ventricle, which is much larger than the right ventricle.
The electrical circuitry of the heart activates the left and right atria in such a fashion that these chambers eject blood into their respective ventricles just before these chambers contract. Optimal ventricular filling maximizes ventricular ejection of blood (Starling’s law). Ventricular repolarization (JT interval—electrical recovery) follows ventricular depolarization. On the surface ECG, the JT interval consists of an isoelectric event—the ST segment running from the end of the QRS complex to the beginning of the T wave—and the T wave itself (directional electrical recovery).
The QT interval, then, consists of both ventricular depolarization (QRS complex) and ventricular repolarization (JT interval). Ventricular repolarization makes up by far the greater portion of the QT interval.
Correcting the QT interval (QTc) In 1920, Bazett noted that as the heart rate slowed, the QT interval lengthened.12 From personal and reported observations, he derived an equation called the Bazett formula that corrects (or normalizes) the QT interval to a heart rate of 60 beats/min (QTc). In the Bazett formula, the QTc interval is the measured QT interval divided by the square root of the RR interval (time between sequential QRS complexes—the determinant of heart rate) measured in seconds (QTc = QT/RR).
The Bazett formula is most widely used to estimate the QTc interval, although at least 20 other formulae have been developed in response to the original’s perceived inadequacies.13-15 Bazett’s formula is used in most automated interpretations of the ECG.
Up to age 55, the normal QTc interval ranges from 350 to 430 msec for men and 350 to 450 msec for women, and it tends to increase with age. Most cases of torsade occur when the QT or QTc interval is greater than 500 msec.14 A QTc interval between 450 and 500 msec is cause for concern; a QTc interval that exceeds 500 msec is cause for alarm.
Factors that cause variations in QTc
Factors that can affect the QTc interval and increase the risk of torsade de pointes include electrolyte imbalances, medication use and overdose, cardiac disease, liver disease, endocrine disorders such as diabetes and hypothyroidism, and CNS injury (Table 1).
Table 1
Risk factors contributing to QTc interval prolongation
| Risk factor | Causes/implications |
|---|---|
| Sex (female) | QT intervals longer in women than in men QT interval longer during first half of menstrual cycle |
| Age (elderly) | Increased risk for CAD Multiple medications Pharmacokinetic/pharmacodynamic changes |
| Electrolyte imbalance Hypokalemia, hypomagnesemia Hypocalcemia | Diuretic use Excessive vomiting or diarrhea Postprandial hypokalemia |
| Congenital long QT syndrome | Associated with torsade and sudden death |
| Cardiac disease, with history of acute or chronic myocardial ischemia, CHF, cardiac arrhythmias, bradycardia | Increased risk of cardiac arrhythmias |
| Drugs known to prolong QTc interval | May potentiate QTc prolongation |
| Medication overdose with drugs that prolong the QTc interval | QTc prolongation generally dose-dependent |
| Concomitant medications, liver disease | Adverse events with cytochrome P-450 enzyme system inhibition, leading to increased drug levels that can increase QT interval |
| Endocrine/metabolic disorders Diabetes, obesity Hypothyroidism, pituitary insufficiency | Via electrolytes or cardiovascular disease |
| CNS injury Stroke, infection, trauma | Via autonomic nervous system dysfunction |
Circadian patterns The QTc interval varies throughout the 24-hour day, with nocturnal values about 20 msec greater than daytime measurements. These differences are driven by changes in autonomic (sympathetic and parasympathetic) tone.16,17 In 20 normal subjects, circadian variability was 76 ± 19 msec (range 35 to 108 msec) from day to night.17 This circadian variation may be accentuated in patients with cardiovascular disease.
Sex. At birth, QTc interval measurements do no vary by sex.18 At puberty, however, the male QTc interval shortens and remains shorter than its female counterpart by about 20 msec until age 50 to 55, coincident with a decline in male testosterone levels. This sex difference appears to be androgen driven. About 70% of torsade de pointes cases occur in women.18