Are QT measurements on body surface ECG indicative of ventricular refractory patterns?

OBJECTIVE: Increased dispersion (DISP) of refractoriness (ERP) facilitates the induction of malignant ventricular arrhythmias. Accordingly, QT DISP on surface ECG, supposedly reflecting ERP DISP, has been proposed as a noninvasive marker for risk stratification. However, a comparative analysis of local ERPs and QT measurements is not available so far. METHODS AND RESULTS: In 19 healthy dogs, standard 12 lead surface ECGs were recorded to measure QT and RR intervals. Based on these measurements, corrected QT intervals (QTc, Bazett formula) and DISP (maximum difference) of both QT and QTc intervals (QT-DISP and QTc-DISP, respectively) were calculated. Subsequently, 60 custom-made needle electrodes (12 mm long, 4 bipolar electrodes per needle, interelectrode distance 2.5 mm) were inserted into the left (LV) and right ventricle (RV). At each bipole of 14 randomly selected needle electrodes (8 LV, 6 RV) local ERPs were determined (extrastimulus technique, basic cycle length 1000 ms). Interventricular DISP of ERP (LV-RV-DISP) was defined as the difference between the longest and shortest ERP within both ventricles. Respective values were calculated for each ventricle (LV-DISP; RV-DISP). Scatter plots and correlation analysis did not reveal a significant correlation between QT, QTc, QT-DISP, QTc-DISP and any of the ERP measurements or calculations. Although not statistically significant, the closest correlation was found between QTc and mean ERP and between QTc-DISP and LV-RV-DISP. CONCLUSION: QT measurements on surface ECG are poorly correlated with local ERPs. If anything, QT- or QTc-DISP might provide a rough estimate of interventricular, that is, global DISP of ERP. Local or even intraventricular DISP of ERP is definitely not reflected by these QT measurements.

Tridimensional activation patterns of acquired torsade-de-pointes tachycardias in dogs with chronic AV-block.

BACKGROUND: Dogs with chronic AV block exposed to type-III antiarrhythmic agents develop polymorphic ventricular tachycardias (PVT). Controversy exists regarding PVT mechanism and underlying pathophysiology. METHODS AND RESULTS: In dogs with acute (n = 10, AAVB) or chronic AV block (n = 14, CAVB, 62 +/- 5 days after AV-node ablation) 60 pins (12 mm long, 4 bipolar electrodes) were inserted into both ventricles. QT intervals and effective refractory periods (ERP) at 56 +/- 22 randomly selected sites (extrastimulus technique, 800 ms basic cycle length) were determined before and after Almokalant (0.34 micromol/kg). A multiplexer mapping system was used to reconstruct 3D activation patterns. The heart-to-body-weight index (HBWI) was obtained after the experiments. CAVB led to a significant increase in HBWI (11.3 +/- 1.5 vs. 9 +/- 1.2 g/kg BW, p < 0.001), and a significant increase in ERP (280 +/- 28 ms vs. 260 +/- 37 ms, p < 0.05) and QT interval (339 +/- 16 vs. 288 +/-12 ms, p < 0.05). Dispersion (DISP) of ERP was similar for AAVB and CAVB dogs. No AAVB dog, but 9 of 14 CAVB dogs developed PVTs in response to Almokalant. All PVTs originated from an endocardial focus. Consecutive beats continued to reveal centrifugal activation patterns in 8 of 10 episodes. In only 2 episodes was reentrant activation evident. CONCLUSION: Myocardial hypertrophy associated with CAVB predisposes the canine heart to drug induced PVTs. This seems to be primarily linked to prolonged repolarization. PVTs in this model are not only initiated, but also perpetuated by a centrifugal spread of activation.

Biventricular hypertrophy in dogs with chronic AV block: effects of cyclosporin A on morphology and electrophysiology.

Chronic atrioventricular (AV) block (CAVB) and biventricular hypertrophy in dogs increase susceptibility to drug-induced polymorphic ventricular tachycardia (PVT). In various rodent models, cyclosporin A (CsA) prevented hypertrophy. A similar effect in the CAVB model would allow us to determine whether hypertrophy represents an epiphenomenon, the cause of electrophysiological changes, and/or the anatomic substrate for PVTs. Upon AV node ablation, 6 dogs were studied acutely (AAVB), 25 dogs were kept for 6 (6W) and 12 wk (12W), receiving no treatment [CTL-CAVB-6W (n=6) and CTL-CAVB-12W (n=7)] or a daily oral dose of 10-20 mg/kg CsA directly (n=6, CsA-CAVB-6W) or 6 wk after radio-frequency ablation (n=6, CsA-CAVB-12W). For the final study, dogs were anesthetized, and 60 needles were inserted into both ventricles and connected to a multiplexer mapping system. Local effective refractory periods (ERPs) were determined at 56 +/- 22 randomly selected sites (extrastimulus technique, basic cycle length=800 ms). Arrhythmias within 30 min after application of almokalant (0.34 micromol/kg iv) were registered. The hearts were then excised to obtain the heart weight-body weight index (HBWI). Compared with AAVB, CTL-CAVB-6W and CTL-CAVB-12W showed increased HBWI and ERP associated with PVT inducibility in none of six AAVB dogs, four of six CTL-CAVB-6W dogs, and one of seven CTL-CAVB-12W dogs. Compared with CTL-CAVB-6W and CTL-CAVB-12W, CsA-CAVB-6W and CsA-CAVB-12W partially prevented hypertrophy or led to a regression of hypertrophy without reducing ERP prolongation. Despite ERP prolongation, PVTs were no longer inducible with CsA treatment. Thus prolongation of refractoriness seems to provide the trigger, but hypertrophy provides the essential substrate for the induction of PVTs in this model.