T-wave Alternans Testing in Pacemaker Patients

Comparison of Pacing Modes and Long-Term Prognostic Relevance

Marc Dorenkamp, M.D.; Christoph Breitwieser, M.D.; Andreas J. Morguet, M.D.; Joachim Seegers, M.D.; Steffen Behrens, M.D.; Markus Zabel, M.D.


Pacing Clin Electrophysiol. 2011;34(9):1054-1062. 

In This Article


Study Population

A prospective, single-center study was conducted in 63 patients with structural heart disease, preserved LV function (LV ejection fraction >40%), and a previously implanted dual-chamber pacemaker. Structural heart disease included coronary artery disease (n = 25), dilated cardiomyopathy (n = 8), valvular heart disease (n = 5), and hypertrophic cardiomyopathy (n = 2). Patients were enrolled consecutively at the device interrogation before discharge at our outpatient pacemaker clinic between April 1998 and August 2000. Indications for dual-chamber pacemaker implantation included sinus node dysfunction (n = 33), second-degree AV block (n = 27), and bifascicular block (n = 3). Patients with total AV block, atrial fibrillation, atrial flutter, or frequent ventricular ectopy were excluded. Patients were also excluded from the study if they were within 30 days of acute coronary syndrome, within 6 weeks of coronary revascularization, or were taking an antiarrhythmic drug at baseline. TWA testing was performed within a time range of 2–4 days after pacemaker implantation. While patients were tested, their chronic medication, including beta-blocking agents, was continued.[16] Written informed consent was obtained from all patients prior to the procedure.

Data Acquisition and Pacing Protocol

Microvolt TWA was measured using a Cambridge Heart CH 2000 system (Cambridge Heart Inc., Bedford, MA, USA) with stepwise increments in pacing rate up to a target heart rate of 105 beats per minute (bpm). After careful skin preparation, including mild abrasion for low skin-electrode impedance, special high-resolution electrodes were placed on standard precordial and orthogonal (X, Y, Z) ECG lead positions. After electrode placement, bidirectional AV conductivity was evaluated by programming the pacemaker rate below the intrinsic heart rate, and retrogradely via ventricular pacing increasing in rate up to the retrograde block cycle length. In case of confirmed antegrade AV conduction, pacing protocols were performed noninvasively via the pacemaker during single-chamber right atrial pacing (AAI mode) and subsequently during single-chamber RV pacing (VVI mode) in each patient. For both the atrial and ventricular pacing mode, microvolt TWA was assessed during paced heart rates at 80, 90, 100, and 105 bpm. The pacing rate was increased every 3 minutes. Atrially paced data were recorded if a 1:1 AV conduction was present. If Wenckebach block occurred, recordings were obtained at the highest possible heart rate. Accordingly, ventricular paced data were recorded at the same stable heart rate, and/or at 105 bpm, respectively. A recovery phase of 5 to 10 min was allowed between the two pacing modes. The order of atrial and ventricular pacing was not randomized. The possibility of an order effect was therefore investigated in a subgroup of patients (n = 34) by repeating the above pacing protocol on a separate day with reversed order of pacing modes. ECG signals were amplified and filtered (bandwidth, 0.05–250 Hz) and digitized (1,000 Hz with 16-bit resolution).

Analysis of Microvolt TWA

All tests were read and interpreted by two physicians blinded to the clinical information (C.B. and M.Z.). In case of disagreement, the grading result was discussed among all authors. Microvolt TWA was measured using the spectral method as described in detail elsewhere.[1,3] Briefly, the algorithm analyzes a 128-beat sequence of regular ECG complexes. Alternans at any point in time within the T-wave results in oscillations between beats. When applying a fast Fourier transform at 0.5 cycles/beat, these oscillations are represented as the spectral peak. The algorithm defines a microvolt TWA result as positive if the following criteria are present: (a) ≥1 min of sustained TWA amplitude (Valt) ≥ 1.9 μV, (b) alternans ratio (k-score) >3, and (c) present in at least one orthogonal or two adjacent precordial leads. Negative TWA is defined as absence of positive TWA as long as a heart rate of 105 bpm is achieved, whereas indeterminate TWA classifies other results. According to previous studies, positive and indeterminate test results were grouped as nonnegative.[17,18]

Long-term Prospective Follow-up

All patients were followed prospectively for a mean (± standard deviation) duration of 5.9 ± 1.9 (median 6.7, interquartile range 5.3–7.5) years starting with the date of microvolt TWA testing. Follow-up included review of all medical records, telephone questionnaires to patients and general practitioners, and information on deceased patients obtained systematically from the Berlin authorities. The end-point was predefined as all-cause mortality.

Statistical Analysis

All data are presented as mean ± standard deviation, except where noted. Concordance of microvolt TWA test results during atrial and ventricular pacing was calculated using Cohen's kappa statistic. Continuous variables were compared with Student's t-tests, and categorical variables were compared with the χ2 test or Fisher's exact test. Kaplan-Meier analysis was used to determine outcomes in a time-dependent fashion. Patient groups were compared using the log-rank method. Statistical analyses were performed with SPSS for Windows (Version 16.0, SPSS Inc., Chicago, IL, USA). A value of P < 0.05 was considered statistically significant.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.