Dynamic Conduction and Repolarisation Changes in Early Arrhythmogenic Right Ventricular Cardiomyopathy versus Benign Outflow Tract Ectopy Demonstrated by High Density Mapping and Paced Surface ECG Analysis

Aims: The concealed phase of arrhythmogenic right ventricular cardiomyopathy (ARVC) may initially manifest electrophysiologically. No studies have examined dynamic conduction/repolarization kinetics to distinguish benign right ventricular outflow tract ectopy (RVOT ectopy) from ARVC's early phase. We investigated dynamic endocardial electrophysiological changes that differentiate early ARVC disease expression from RVOT ectopy. Methods: 22 ARVC (12 definite based upon family history and mutation carrier status, 10 probable) patients without right ventricular structural anomalies underwent high-density non-contact mapping of the right ventricle. These were compared to data from 14 RVOT ectopy and 12 patients with supraventricular tachycardias and normal hearts. Endocardial & surface ECG conduction and repolarization parameters were assessed during a standard S1-S2 restitution protocol. Results: Definite ARVC without RV structural disease could not be clearly distinguished from RVOT ectopy during sinus rhythm or during steady state pacing. Delay in Activation Times at coupling intervals just above the ventricular effective refractory period (VERP) increased in definite ARVC (43±20 ms) more than RVOT ectopy patients (36±14 ms, p = 0.03) or Normals (25±16 ms, p = 0.008) and a progressive separation of the repolarisation time curves between groups existed. Repolarization time increases in the RVOT were also greatest in ARVC (definite ARVC: 18±20 ms; RVOT ectopy: 5±14, Normal: 1±18, p<0.05). Surface ECG correlates of these intracardiac measurements demonstrated an increase of greater than 48 ms in stimulus to surface ECG J-point pre-ERP versus steady state, with an 88% specificity and 68% sensitivity in distinguishing definite ARVC from the other groups. This technique could not distinguish patients with genetic predisposition to ARVC only (probable ARVC) from controls. Conclusions: Significant changes in dynamic conduction and repolarization are apparent in early ARVC before detectable RV structural abnormalities, and were present to a lesser degree in probable ARVC patients. Investigation of dynamic electrophysiological parameters may be useful to identify concealed ARVC in patients without disease pedigrees by using endocardial electrogram or paced ECG parameters

Prevalence of J-Point Elevation in Sudden Arrhythmic Death Syndrome Families

Objectives The purpose of this study was to assess the prevalence of J-point elevation among the relatives of sudden arrhythmic death syndrome (SADS) probands. Background J-point elevation is now known to be associated with idiopathic ventricular fibrillation. We hypothesized that this early repolarization phenomenon is an inherited trait responsible for a proportion of otherwise unexplained SADS cases. Methods Families of SADS probands were evaluated in an inherited arrhythmia clinic. Twelve-lead electrocardiograms were analyzed for J-point elevation defined as &gt; 0.1 mV from baseline present in 2 or more of the inferior (II, III, and aVF) or lateral (1, aVL, V(4) to V(6)) leads. Electrocardiographic data were compared with those of 359 controls of a similar age, sex, and ethnic distribution. Results A total of 363 first-degree relatives from 144 families were evaluated. J-point elevation in the inferolateral leads was present in 23% of relatives and 11% of control subjects (odds ratio: 2.54, 95% confidence interval: 1.66 to 3.90; p &lt; 0.001). Conclusions J-point elevation is more prevalent in the relatives of SADS probands than in controls. This indicates that early repolarization is an important potentially inheritable pro-arrhythmic trait or marker of pro-arrhythmia in SAD

Dynamic Conduction and Repolarisation Changes in Early Arrhythmogenic Right Ventricular Cardiomyopathy versus Benign Outflow Tract Ectopy Demonstrated by High Density Mapping & Paced Surface ECG Analysis

<div><p>Aims</p><p>The concealed phase of arrhythmogenic right ventricular cardiomyopathy (ARVC) may initially manifest electrophysiologically. No studies have examined dynamic conduction/repolarization kinetics to distinguish benign right ventricular outflow tract ectopy (RVOT ectopy) from ARVC's early phase. We investigated dynamic endocardial electrophysiological changes that differentiate early ARVC disease expression from RVOT ectopy.</p><p>Methods</p><p>22 ARVC (12 definite based upon family history and mutation carrier status, 10 probable) patients without right ventricular structural anomalies underwent high-density non-contact mapping of the right ventricle. These were compared to data from 14 RVOT ectopy and 12 patients with supraventricular tachycardias and normal hearts. Endocardial & surface ECG conduction and repolarization parameters were assessed during a standard S₁-S₂ restitution protocol.</p><p>Results</p><p>Definite ARVC without RV structural disease could not be clearly distinguished from RVOT ectopy during sinus rhythm or during steady state pacing. Delay in Activation Times at coupling intervals just above the ventricular effective refractory period (VERP) increased in definite ARVC (43±20 ms) more than RVOT ectopy patients (36±14 ms, p = 0.03) or Normals (25±16 ms, p = 0.008) and a progressive separation of the repolarisation time curves between groups existed. Repolarization time increases in the RVOT were also greatest in ARVC (definite ARVC: 18±20 ms; RVOT ectopy: 5±14, Normal: 1±18, p<0.05). Surface ECG correlates of these intracardiac measurements demonstrated an increase of greater than 48 ms in stimulus to surface ECG J-point pre-ERP versus steady state, with an 88% specificity and 68% sensitivity in distinguishing definite ARVC from the other groups. This technique could not distinguish patients with genetic predisposition to ARVC only (probable ARVC) from controls.</p><p>Conclusions</p><p>Significant changes in dynamic conduction and repolarization are apparent in early ARVC before detectable RV structural abnormalities, and were present to a lesser degree in probable ARVC patients. Investigation of dynamic electrophysiological parameters may be useful to identify concealed ARVC in patients without disease pedigrees by using endocardial electrogram or paced ECG parameters.</p></div

CART analysis

<p>. Panel A shows the optimum recursive partition tree. An increase in the time from the stimulus to the end of the paced QRS complex (J-point) of >48 ms gave a sensitivity of 67% and specificity of 88% for definite ARVC. B and C show raw data for the principal branches. These measurements were able to distinguish any ARVC patient from RVOT ectopy (RVOTE)/Normal patients with a sensitivity of 67% and specificity of 84%.</p

Endocardial Conduction and Repolarization Parameters.

<p>Significance codes:</p><p>* p<0.05 vs Normals.</p><p>** p<0.01 vs Normals.</p><p>***p<0.0001 vs Normals.</p>†<p>p<0.05 vs RVOT Ectopy.</p>††<p>p<0.01 vs RVOT Ectopy.</p><p>Note: Activation and Repolarization times are given as means±SD for all measurements throughout ventricle.</p><p>HR: Heart Rate, ERP: effective refractory period, ARI: Activation Recovery Index, AT: Activation Time, RT: Repolarization Time.</p

Typical ECG examples of J-point hysteresis.

<p>Three representative paced ECGs are shown with stimulus to J-point timings of steady state and pre-VERP beats. The ARVC patient has a markedly extended J-point hysteresis pre-VERP than either normal patient or the RVOT ectopy patient.</p

Receiver-operator characteristic (ROC) curves derived from logistic models of electrophysiological criteria.

<p>ROC curves are shown for the individual determinants of the most predictive model for definite ARVC derived from electrogram data. AT: Activation time, VERP: Ventricular effective refractory period, Repol Time: Repolarisation Time.</p

Paced Surface ECG parameters.

<p>Significance codes:</p><p>* p<0.05 vs Normals.</p><p>** p<0.01 vs Normals.</p>†<p>p<0.05 vs RVOT Ectopy.</p>††<p>p<0.01 vs RVOT Ectopy.</p

3D color maps of fractionation measured pre-ERP-distribution in Normal individuals, RVOTE and definite ARVC.

<p>There is a patchy distribution of fractionated electrograms in both RVOTE and in ARVC ventricles.</p