Methods

The present study was a retrospective analysis of patients with Chagas cardiomyopathy and an ICD implanted for primary or secondary prevention at 14 Latin American centers included in the Fragmented ECG in Chagas Cardiomyopathy Study.

The inclusion criteria were (1) Chagas cardiomyopathy diagnosed by positive serologic tests and classic criteria, including living in endemic areas, ECG, and chest x-ray criteria, (2) ICD implanted for primary or secondary prevention of sudden cardiac death, and (3) sinus rhythm. Patients with history of AF were excluded. Demographics, clinical, and device follow-up were collected. The study protocol was approved by the ethics committee of each institution.

A standard 12-lead ECG (filter 150 Hz, 25 mm/s, 10 mm/mV) was obtained in all patients before the device implantation. The ECGs were directly scanned at 300 dpi and reviewed at a core laboratory center in Queen’s University by 2 blinded investigators (AE and AB). Disagreement was solved by consensus. The images were amplified ×10 and the P-wave duration was measured using semiautomatic calipers (Iconico, New York). The onset of the P wave was identified as the point of initial upward or downward deflection from the baseline and the P-wave offset as the returning point of the waveform to the baseline. Partial IAB was defined as a P-wave duration of >120 ms without biphasic morphology (±) in the inferior leads, and advanced IAB was defined as a P wave of >120 ms and biphasic morphology (±) in the inferior leads.

The ICD programing included therapy for ventricular tachycardia with antitachycardia pacing followed by shock for ventricular fibrillation. In all dual chamber or resynchronization devices, mode switch was turned on with an atrial rate cutoff of 170 or 175 beats/min. The ventricular tachycardia detection zones and number of antitachycardia pacing runs were selected in every center at the operator’s discretion.

The primary outcome was development of new-onset AF. In single-chamber devices, AF was defined as an irregularly irregular rhythm lasting at least 30 seconds with >80% match with the stored template. In devices with an atrial lead (dual-chamber pacemakers or resynchronization therapy), AF was defined as an episode of switch mode or atrial high rate lasting at least 30 seconds with electrograms compatible with fast and disorganized atrial rhythm. The secondary outcome was inappropriate ICD therapies, defined as antitachycardia pacing or shocks delivered by the ICD for any other rhythm rather than ventricular tachycardia or ventricular fibrillation. All patients attended regular follow-up visits, which were scheduled by the investigator at 3- to 6-month intervals. Clinical data and a full interrogation of the device’s memory, including programed parameters, stored measurements and electrograms, pacing threshold, and sensing tests, were collected at each visit.

Data are expressed as means and SDs for continuous variables and frequencies and percentages for categorical variables. Univariate comparisons (independent samples t tests and chi-square tests) and multivariate logistic regression analyses were performed to identify predictors of AF. Variables with p <0.10 on univariate analyses were entered into the model. p Values <0.05 were considered statistically significant.

Results

A total of 94 patients were analyzed of whom 14 were unable to be enrolled (atrial pacing, permanent atrial arrhythmias, and illegible ECGs), leaving 80 patients suitable for inclusion in the study. Baseline characteristics and medications are summarized in Table 1 . The indication for ICD was secondary prevention in 70% of patients. Devices implanted were single chamber in 31%, dual chamber in 65%, and resynchronization therapy in 4%.

Mean P-wave duration was 107.4 ± 12.6 ms, and IAB was detected in 15 patients (19%): 8 partial (10%; P-wave duration 126.2 ± 13.8 ms) and 7 advanced (9%; P-wave duration 129.7 ± 8.9 ms). Right bundle branch block was present in 42.5% of patients and left bundle branch block in 10%. Figure 1 shows a pattern of advanced IAB in a patient with typical electrocardiographic abnormalities of Chagas cardiomyopathy, which include right bundle branch block and/or left anterior fascicular block.

Inferior + V ₁ leads of a patient with Chagas cardiomyopathy and ICD. Please note advanced IAB (P wave of 160 ms with final negative component) + left anterior fascicular block + right bundle branch block (with fragmented QRS). This is the typical distal conduction disorder found in patients with Chagas cardiomyopathy.

During a follow-up of 33 ± 20 months, 11 patients (13.8%) presented with new AF. The occurrence of AF in the group with IAB was 11 of 15 (73.3%) versus 0 of 65 (0%) in patients with normal P-wave duration (p <0.0001). Fourteen patients (17.5%) presented with inappropriate therapies during the follow-up, all of them because of AF with rapid ventricular response. Seven patients (8.8%) died during the study period.

Table 2 lists a comparison of patients with and without AF. No significant differences were seen between the groups regarding age, gender, left ventricular ejection fraction, or medications, although age fell just short of significance at p = 0.08 and could be considered a trend. P-wave duration was significantly longer in patients that developed AF compared with those who did not (125.3 ± 7.8 vs 104.5 ± 10.8 ms, p <0.0001), and the prevalence of IAB was also significantly greater in the first group (100% vs 6%, p <0.0001). QRS was wider in patients with AF but fell short of statistical significance (p = 0.07).

In the multivariate analysis, IAB (partial + advanced) remained strongly associated with inappropriate therapies by the ICD (odds ratio 4.8, 95% confidence interval 1.3 to 16.9, p = 0.014). However, it was not possible to develop a multivariable model for AF because all 11 of the AF cases had IAB, resulting in an unstable model. Therefore the strong (p <0.0001) univariate results could not be adjusted for other covariates.