The response of the QT interval to the brief tachycardia provoked by standing: a bedside test for diagnosing long QT syndrome

Abstract

Objectives: This study was undertaken to determine whether the short-lived sinus tachycardia that occurs during standing will expose changes in the QT interval that are of diagnostic value.

Background: The QT interval shortens during heart rate acceleration, but this response is not instantaneous. We tested whether the transient, sudden sinus tachycardia that occurs during standing would expose abnormal QT interval prolongation in patients with long QT syndrome (LQTS).

Methods: Patients (68 with LQTS [LQT1 46%, LQT2 41%, LQT3 4%, not genotyped 9%] and 82 control subjects) underwent a baseline electrocardiogram (ECG) while resting in the supine position and were then asked to get up quickly and stand still during continuous ECG recording. The QT interval was studied at baseline and during maximal sinus tachycardia, maximal QT interval prolongation, and maximal QT interval stretching.

Results: In response to brisk standing, patients and control subjects responded with similar heart rate acceleration of 28 +/- 10 beats/min (p = 0.261). However, the response of the QT interval to this tachycardia differed: on average, the QT interval of controls shortened by 21 +/- 19 ms whereas the QT interval of LQTS patients increased by 4 +/- 34 ms (p < 0.001). Since the RR interval shortened more than the QT interval, during maximal tachycardia the corrected QT interval increased by 50 +/- 30 ms in the control group and by 89 +/- 47 ms in the LQTS group (p < 0.001). Receiver-operating characteristic curves showed that the test adds diagnostic value. The response of the QT interval to brisk standing was particularly impaired in patients with LQT2.

Conclusions: Evaluation of the response of the QT interval to the brisk tachycardia induced by standing provides important information that aids in the diagnosis of LQTS.

Figure 1. Box Plots of Results Obtained in LQTS Patients and Controls

The colored boxes represent the interquartile range (25th to 75th percentiles). (A to F) The red boxes represent long QT syndrome (LQTS) patients; the blue boxes represent control subjects. (G and H) The orange boxes represent LQT1 patients; the purple boxes represent LQT2 patients. The thick black line in the box is the 50th percentile, and the bars represent the range of results excluding outliers. Solid black circles indicate outliers and * indicates extreme outliers. ΔQT = QT interval change from baseline; ΔQTc = corrected QT interval change from baseline.

Figure 2. QT Interval Stretching in Healthy Control Subject and in LQT2 Patient

(Top trace) A 39-year-old healthy volunteer. At baseline (left panel), heart rate is 65 beats/min, QT interval is 400 ms, and corrected QT interval (QTc) is 420 ms. Six seconds after standing (right panel), the shortest RR interval is 570 ms; by then, the QT interval has shortened to 360 ms. Since the RR interval shortened more than the QT interval, the QTc interval increased to 480 ms. Maximal QT interval stretching (when the end of the T-wave is nearest the next P-wave) is marked (*). (Bottom trace) A 38-year-old man with long QT syndrome mutation LQT2. At baseline, heart rate is 60 beats/min, QT interval and QTc interval are 440 ms. Note the fairly normal T-wave morphology. Shortly after standing (right panel), motion artifact is visible; the shortest RR interval is 640 ms, and by then the QT interval actually increased to 460 ms. Consequently, the QTc interval increased to 570 ms. Note the development of classic T-wave notching while standing.

Figure 3. QT Interval Stretching in LQT1

A 22-year-old woman with long QT syndrome mutation LQT1. (Left panel) At baseline, heart rate is 68 beats/min, QT interval is 480 ms, and corrected QT interval (QTc) is 512 ms. (Middle panel) Immediately after standing, there is movement artifact; heart rate increases to 82 beats/min but the QT interval fails to shorten, and the QTc interval increases to 582 ms (the QT interval stretches all the way to the next P-wave). (Right panel) At the end of the test, heart rate returns to baseline but the QT interval remains prolonged, and the QTc interval is 565 ms long and has abnormal morphology.

Figure 4. Provocation of Ventricular Arrhythmias by Standing in LQTS

A 34-year-old woman with previous cardiac arrest and documented pause-dependent torsades de pointes. (Left panel) At baseline, heart rate is 83 beats/min, QT interval is 400 ms, and corrected QT interval (QTc) is 470 ms. (Middle panel) During maximal tachycardia (8 s after standing), heart rate is 115 beats/min, QT interval is 440, and QTc interval is 461 ms. (Right panel) Ventricular extrasystoles appear during maximal QT interval stretching 15 s after standing. Note that the post-extrasystolic pauses (*) expose the small amplitude of P waves (arrows). It is therefore evident that during sinus tachycardia there is a late component of a very long QT interval on top of the P-wave (arrowheads).