Prolonged action potential duration and dynamic transmural action potential duration heterogeneity underlie vulnerability to ventricular tachycardia in patients undergoing ventricular tachycardia ablation

Abstract

Aims: Differences of action potential duration (APD) in regions of myocardial scar and their borderzones are poorly defined in the intact human heart. Heterogeneities in APD may play an important role in the generation of ventricular tachycardia (VT) by creating regions of functional block. We aimed to investigate the transmural and planar differences of APD in patients admitted for VT ablation.

Methods and results: Six patients (median age 53 years, five male); (median ejection fraction 35%), were studied. Endocardial (Endo) and epicardial (Epi) 3D electroanatomic mapping was performed. A bipolar voltage of <0.5 mV was defined as dense scar, 0.5-1.5 mV as scar borderzone, and >1.5 mV as normal. Decapolar catheters were positioned transmurally across the scar borderzone to assess differences of APD and repolarization time (RT) during restitution pacing from Endo and Epi. Epi APD was 173 ms in normal tissue vs. 187 ms at scar borderzone and 210 ms in dense scar (P < 0.001). Endocardial APD was 210 ms in normal tissue vs. 222 ms in the scar borderzone and 238 ms in dense scar (P < 0.01). This resulted in significant transmural RT dispersion (ΔRT 22 ms across dense transmural scar vs. 5 ms in normal transmural tissue, P < 0.001), dependent on the scar characteristics in the Endo and Epi, and the pacing site.

Conclusion: Areas of myocardial scar have prolonged APD compared with normal tissue. Heterogeneity of regional transmural and planar APD result in localized dispersion of repolarization, which may play an important role in initiating VT.

Keywords: Action potential duration; Dispersion of repolarization; Transmural dispersion of repolarization; Ventricular tachycardia.

Figure 1

Restitution studies in a patient with previous myocarditis and predominant epicardial scar (Patient 1). (A) Endocardial and epicardial bipolar voltage maps highlighting a large region of anterior epicardial scar. Position of catheters simultaneously placed endocardially and epicardially for transmural recording is shown. (B) The Wyatt method was used to analyse RT. AT measured as dV/dt_min of the QRS and RT as the dV/dt_max of the unipolar intracardiac electrogram T-wave. ARI (ARI = RT − AT), was measured as a surrogate marker of APD. (C) ARI restitution during endocardial pacing, across epicardial normal voltage tissue, epicardial scar borderzone, and epicardial dense scar. APD, action potential duration; ARI, activation recovery interval; AT, activation time; Endo, endocardium; Epi, epicardium; NS, non-significant; RT, repolarization time.

Figure 2

(A) Restitution studies in a patient with ischaemic cardiomyopathy and predominant endocardial anterior/apical scar of the left ventricle due to previous myocardial infarction (Patient 3). Catheters position for transmural recordings during restitution studies while pacing (B) the Endo and (C) Epi are shown. ARI, activation recovery interval; AT, activation time; Endo, endocardium; Epi, epicardium; NS, non-significant; RT, repolarization time.

Figure 3

(A) Restitution studies in a patient with ARVC across a region of transmural scar in the RVOT (Patient 6). Catheters are positioned transmurally in the anterior RVOT during restitution studies while pacing (B) the Endo and (C) Epi. ARI, activation recovery interval; ARVC, arrhythmogenic right ventricular cardiomyopathy; AT, activation time; Endo, endocardium; Epi, epicardium; NS, non-significant; RT, repolarization time; RVOT, right ventricular outflow tract.

Figure 4

Box and whisker plot of epicardial (A) and endocardial (B) ARI in relation to the tissue voltage characteristic. Tissue characteristic is denoted on the x-axis. Statistical significance between box plots is shown above the plots. ARI, activation recovery interval; b, scar borderzone; d, dense scar; n, normal tissue.

Figure 5

(A) Box and whisker plot displaying paired endocardial and epicardial scar pattern, and their association to endocardial subtracted by epicardial ARI (ΔARI), endocardial subtracted by epicardial RT (ΔRT) during endocardial pacing (B) and epicardial pacing (C). Scar tissue characteristic is denoted on the x-axis, the first letter is the characteristic of the endocardium and the second letter is the characteristic of the epicardium. Statistical significance is assessed as a comparison against normal endocardial and epicardial tissue (n_n), with statistical significance denoted above the boxplot. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. ARI, activation recovery interval; b, scar borderzone; d, dense scar; n, normal tissue; NS, non-significant; RT, repolarization time.

Figure 6

DOR and initiation of VT in an example patient (Patient 6). (A) S1–S2 restitution protocol, showing 12-lead ECG and sample unipolar electrograms from the RV endocardium and RV epicardium. Following a train of S1 pacing, an S2 beat is delivered, following this an RV ectopic beat triggers sustained VT. (B) RV Endo geometry and activation mapping of the sustained VT showing earliest activation (red area), in the RVOT, along with location of transmurally opposed Endo and Epi decapolar catheters from the restitution study. Poles 3 and 4 of Epi catheter were located over a region of late potentials in sinus rhythm (inset). (C) DOR at Epi catheter pole location 3–4 (where fractionation was recorded), in the neighbouring Epi poles to 3–4, and in the neighbouring adjacent linear Endo poles. DOR is shown for the last S2 beat (above panel) and for the ectopic beat subsequent to this which initiates sustained VT. Circles represent activation time, triangles represent repolarization time. DOR, dispersion of repolarization; Endo, endocardial; Epi, epicardial; RV, right ventricular; RVOT, right ventricular outflow tract; VT, ventricular tachycardia.