Two Types of T Wave Alternans in Long‐QT Syndrome

Abstract

A 5-year-old female child with bilateral hand syndactyly, QT prolongation, and 2:1 atrioventricular (AV) block was seen in consultation ( Fig. 1). The genetic testing identified a mutation in CACNA1C gene, confirming type 1 Timothy syndrome (LQT8). During ambulatory EKG monitoring, she had two types of T wave alternans (TWA): one occurred during a steady state in which RR intervals remained relatively unchanged (type 1), whereas the other developed during transition from 2:1 AV conduction to 1:1 conduction in which a sudden change in RR intervals and aberrant conduction were associated (type 2).During type 1 TWA, there was no significant beat-to-beat variation in PP interval (or RR interval) as well as in QRS duration ( Fig. 2A). In addition, there was an identifiable isoelectric interval between the end of previous T wave and P wave. Type 2 TWA, as shown in Figure 2B and C, was profound and developed likely secondary to a sudden change in heart rate and aberrant ventricular conduction from resumption of 1:1 AV conduction from 2:1 AV block during sinus arrhythmia (Fig. 2C). Type 2 TWA disappeared after a few seconds of 1:1 AV conduction from 2:1 AV block when the RR intervals remained stable and the mean QT ventricular became shorter. The relationship between QRS and QT during type 2 TWA is shown in Figure 2D. Previous studies have shown that TWA may herald development of malignant ventricular arrhythmia. However, two types of TWA in our case obviously developed at different mechanisms, from which different arrhythmogenic risks would be expected. Type 1 TWA, commonly reported in the literature, is unrelated to ventricular conduction and a change in RR intervals. It is probably due to abnormal intracellular Ca 2+ cycling that influences ventricular repolarization in an alternating pattern.1 Our recent basic research has shown that early afterdepolarization (EAD) alternans in left ventricular hypertrophy manifests as type 1 TWA on the ECG, which often precedes the development of EAD-initiating R-on-T ectopic beats.2 On the other hand, type 2 TWA was less commonly reported. It may occur as a consequence of an abrupt change in ventricular rate or aberrant ventricular conduction. "TWA" resulting from intermittent pre-excitation is the best illustration of activation-dependent change in T wave (Fig. 2E). A sudden change in RR intervals may also contribute importantly to type 2 TWA (Fig. 2B and C). Facilitation of TWA by an abrupt change in RR intervals in long-QT syndrome may be related to adaptation of time-dependent repolarizing currents to a new rate. Surprisingly, this female child was free of syncope and documented ventricular arrhythmias despite the fact that both types of TWA were commonly seen prior to the drug therapy. Even though, potential risks of both types of TWA to trigger TdP should not be ignored.

Mechanisms linking T‐wave alternans to spontaneous initiation of ventricular arrhythmias in rabbit models of long QT syndrome

“…; Shu et al . ), TWA is usually observed occurring at normal or slow heart rates in which the DI is long and thus most of the ion channels should have recovered or in their slowly recovery phase. Therefore, the refractoriness‐based mechanisms of alternans under rapid heart rates are probably not a candidate mechanism of TWA at normal or slow heart rates seen in LQTS patients.…”

Cardiac Alternans: From Bedside to Bench and Back

“…T-wave polarity alternans is also observed in LQTS patients with long TQ intervals and no QRSA (Figure 8D), 159,163 indicating that a non-CVR mechanism of SDA or regional alternans may be responsible. In Holter recordings, macroscopic T-wave polarity alternans episodes have been observed in up to 45% of congenital LQTS, 164 and often precede, sometimes immediately, episodes of Torsade de pointes, as illustrated in Figure 1B.…”

“…The mechanism of alternans could be EAD-induced alternans (Figure 2B), but steep APDR slope-induced alternans (Figure 2A) or Ca-driven alternans (Figure 5) are also plausible in view of the short preceding TQ intervals. T-wave polarity alternans is also observed in LQTS patients with long TQ intervals and no QRSA (Figure 8D), 159,163 indicating that a non-CVR mechanism of SDA or regional alternans may be responsible. In Holter recordings, macroscopic T-wave polarity alternans episodes have been observed in up to 45% of congenital LQTS, 164 and often precede, sometimes immediately, episodes of Torsade de pointes, as illustrated in Figure 1B.…”

“…Figure 8C, also obtained from an LQTS patient, 158 illustrates TWA with short TQ intervals and prominent T-wave polarity alternans, which is widely observed in LQTS. 19,22,[159][160][161][162] Moreover, QRSA is also present, indicating a high probability of SDA due to encountering CVR at the short TQ intervals. The mechanism of alternans could be EAD-induced alternans (Figure 2B), but steep APDR slope-induced alternans (Figure 2A) or Ca-driven alternans (Figure 5) are also plausible in view of the short preceding TQ intervals.…”

Dysfunctional Cav1.2 channel in Timothy syndrome, from cell to bedside

“…To date, there have been at least 60 typical or atypical TS patients, whose information are summarized in the Supplemental Table 1. 8–18 Six TS cases were followed over 24 years, suggesting that longer term survival of TS is possible; nevertheless, patients always require implantable cardioverter defibrillator (ICD) or pacemaker. 19 The most recent study of TS outcomes was conducted in 17 TS patients, whose rate corrected QT interval (QTc) was averagely 640 ms, mean longevity was 4.9 years old.…”