Provocation of sudden heart rate oscillation with adenosine exposes abnormal QT responses in patients with long QT syndrome: a bedside test for diagnosing long QT syndrome

Abstract

Aims: As arrhythmias in the long QT syndrome (LQTS) are triggered by heart rate deceleration or acceleration, we speculated that the sudden bradycardia and subsequent tachycardia that follow adenosine injection would unravel QT changes of diagnostic value in patients with LQTS.

Methods and results: Patients (18 LQTS and 20 controls) received intravenous adenosine during sinus rhythm. Adenosine was injected at incremental doses until atrioventricular block or sinus pauses lasting 3 s occurred. The QT duration and morphology were studied at baseline and at the time of maximal bradycardia and subsequent tachycardia. Despite similar degree of adenosine-induced bradycardia (longest R-R 1.7+/-0.7 vs. 2.2+/-1.3 s for LQTS and controls, P=NS), the QT interval of LQT patients increased by 15.8+/-13.1%, whereas the QT of controls increased by only 1.5+/-6.7% (P<0.001). Similarly, despite similar reflex tachycardia (shortest R-R 0.58+/-0.07 vs. 0.55+/-0.07 s for LQT patients and controls, P=NS), LQTS patients developed greater QT prolongation (QTc=569+/-53 vs. 458+/-58 ms for LQT patients and controls, P<0.001). The best discriminator was the QTc during maximal bradycardia. Notched T-waves were observed in 72% of LQT patients but in only 5% of controls during adenosine-induced bradycardia (P<0.001).

Conclusion: By provoking transient bradycardia followed by sinus tachycardia, this adenosine challenge test triggers QT changes that appear to be useful in distinguishing patients with LQTS from healthy controls.

Figures

Figure 1

Response of the R-R, QT, QTc, and QT(peak-end) to intravenous adenosine injection during sinus rhythm in patients with LQTS (black bars) and controls (white bars). All graphs show the mean (horizontal line) and SD (bar) during baseline, at the time of maximal adenosine-induced bradycardia, and the time that the maximal effect on the QT interval was observed during adenosine-induced tachycardia. QT(peak-end) is the interval between the peak of the T-wave and the end of the QT interval. *P< 0.01, **P<0.001.

Figure 2

Typical response of the QT interval to sudden changes in heart rate provoked by adenosine in a control. Following the injection of 18 mg adenosine, there is transient complete AV block leading to 3.5 s of ventricular asystole. Despite the marked bradycardia, there is little change in the QT duration and morphology. Ten seconds later, reflex sinus tachycardia occurs. The amplitude of the T-wave slightly decreases during tachycardia but the T-wave morphology remains normal.

Figure 3

Response of the QT interval to adenosine-induced bradycardia in two patients with LQTS. The top trace is from a 40-year-old female. Her baseline QTc is 480 ms and her T-waves have normal morphology. Following injection of 30 mg ATP, she developed 4 s of AV block (P-waves are marked with arrowheads). During the bradycardia, the T-wave become notched (T2 » T1). The bottom trace is from a 22-year-old female. Her baseline QTc is 500 ms. The T-wave in lead V2 is followed by a second wave that most probably represents a ‘physiologic U-wave’ because it is well defined, of small amplitude, and terminates much after the end of the QT interval defined from other leads (arrow). The maximal bradycardia, maximal tachycardia, and the maximal effects on the QT interval occur 20, 40, and 55 s after the ATP injection, respectively. During bradycardia, she develops notched T-waves in V2 [the amplitude of the second component increased and now terminates synchronously with the QT interval ends in other leads (arrow)]. During tachycardia, the T-wave assumes a bizarre morphology in lead V2, whereas abnormal ‘typical notched T-waves’ (T2 > T1) are noticed during tachycardia in lead V4.

Figure 4

Response of the QT interval to adenosine-induced tachycardia in three patients with LQTS. In the top trace (female, 47 years old), the QT interval not only fails to shorten during tachycardia but actually lengthens to the point that the end of the T-wave almost reaches the following P-wave. The middle trace is from a 50-year-old female with asymptomatic LQT2 mutation. Her QTc is only 430 ms at baseline and the T-wave morphology is normal. However, during the tachycardia phase of adenosine, the QT actually prolongs from 400 to 480 ms, the T-wave becomes frankly abnormal (*), and the QTc increases from 430 to 550 ms. The bottom trace is from a 56-year-old male. His baseline QT is only 420 ms. During the tachycardia phase of adenosine, he first developed notched abnormal T-waves (*) and eventually develops ventricular ectopy that looks typical of LQTS-related arrhythmias because the extrasystoles arise from the terminal part of the QT interval. Note that post-extrasystolic pauses trigger bizarre T-wave changes (**). The QTc reached a maximum of 560 ms before the onset of ventricular ectopy.

Figure 5

Provocation of T-wave alternans with adenosine. Adenosine test in an asymptomatic patient is considered to be an ‘obligatory carrier’ of LQTS because her mother and daughter have obvious LQTS with documented torsade de pointes (her daughter has been reported elsewhere). The QTc at baseline is borderline for a female (QTc = 450 ms). During the tachycardia phase of the adenosine challenge, she develops T-wave alternans (arrows).