Increased ventricular repolarization heterogeneity in patients with ventricular arrhythmia vulnerability and cardiomyopathy: a human in vivo study

Abstract

Increased repolarization heterogeneity can provide the substrate for reentrant ventricular arrhythmias in animal models of cardiomyopathy. We hypothesized that ventricular repolarization heterogeneity is also greater in patients with cardiomyopathy and ventricular arrhythmia vulnerability (inducible ventricular tachycardia or positive microvolt T wave alternans, VT/TWA) compared with a similar patient population without ventricular arrhythmia vulnerability (no VT/TWA). Endocardial and epicardial repolarization heterogeneity was measured in patients with (n = 12) and without (n = 10) VT/TWA by using transvenous 26-electrode catheters placed along the anteroseptal right ventricular endocardium and left ventricular epicardium. Local activation times (AT), activation-recovery intervals (ARI), and repolarization times (RT) were measured from unipolar electrograms. Endocardial RT dispersion along the apicobasal ventricle was greater (P < 0.005) in patients with VT/TWA than in those without VT/TWA because of greater ARI dispersion (P < 0.005). AT dispersion was similar between the two groups. Epicardial RT dispersion along the apicobasal ventricle was greater (P < 0.05) in patients with VT/TWA than in those without VT/TWA because of greater ARI dispersion (P < 0.05). AT dispersion was similar between the two groups. A plot of AT as a function of ARI revealed an inverse linear relationship for no VT/TWA such that progressively later activation was associated with progressively shorter ARI. The AT-ARI relationship was nonlinear in VT/TWA. In conclusion, patients with cardiomyopathy and VT/TWA have greater endocardial and epicardial repolarization heterogeneity than those without VT/TWA without associated conduction slowing. The steep repolarization gradients in VT/TWA may provide the substrate for functional conduction block and reentrant ventricular arrhythmias.

Is there a significant transmural gradient in repolarization time in the intact heart?

“…In the human heart, no transmural gradients in ARIs 20 or repolarization times 21 (ie, the sum of activation time and ARI) were found and an analysis of the data from Franz et al 22 showed that epicardial repolarization occurred later than endocardial repolarization. 23 In the study of Chauhan et al, 24 repolarization time in the anteroseptal right ventricular endocardium in cardiomyopathy patients without arrhythmias was on average 288 ms, and left ventricular epicardial repolarization time adjacent to the septum was 287 ms.…”

Techniques for Ventricular Repolarization Instability Assessment From the ECG

“…Methods to estimate t d and w 1 can be found in [34], [35]. This approximated modeling to derive the T wave can be adapted to situations with increased dispersion of the RT s, as it happens in patients with increased vulnerability to ventricular arrhythmias [36]. In that case, the second order contribution in (6) becomes relevant and the following secondorder approximation of (4) can be used:…”

“…T6 T5 T3 T2 T1 T4 T7 T8 T6 T5 T3 T2 T1 T4 I II V6 V5 V3 V2 V1 V4 8 In order to obtain a suitable transformation matrix Υ the average ST-T complexes are canceled out by subtracting the previous complex from each complex x i,l = x i,l − x i−1,l . These detrended beats x i,l are used to build the matrices X and X (m) as in (35) and (36). Note that X and X (m) now contain K − 1 beats.…”

Arrhythmias in Dilated Cardiomyopathy

“…49 In addition to fibrosis, other factors, such as altered expression and distribution of connexin proteins and increased sympathetic activity, can further enhance the susceptibility to arrhythmias in DCM patients. 50,51 Poor cell-to-cell coupling promotes regions of conduction slowing, leading to functional and anatomic conduction block and causing reentrant excitation. In some scar regions an isthmus of slow conduction may have a complex 3-dimensional path for propagation within and/or across all 3 myocardial layers that causes sustained VT. 52 Much of our understanding of SMVT in DCM comes from studies of mapping and ablation in which scar is detected from evidence of low voltage (<1.5 mV in bipolar recordings) and abnormal electrograms.…”